eLFH and blue book Flashcards
Cardiac output increases with:
A. Increase in HR
B. Increased systemic vascular resistance
C. A decrease in dp/dt
D. Hyperkalaemia
E. An increase in LVEDV
A. True. CO = HR X SV. An iB. ncrease in heart rate will increase cardiac output until the point where filling time is compromised.
B. False. Increased SVR results in increased afterload and a reduced cardiac output.
C. False. dp/dt represents contractility.
D. False. Hyperkalaemia has a negative ionotropic effect.
E. True. LVEDV represents preload.
Concerning the cardiac cycle:
A. Aortic blood flow is lowest at the end of diastole
B. Aortic pressure is highest in mid systole
C. Atrial contraction can account for 40% of ventricular filling
D. The QRS complex on the ECG occurs immediately before the rapid ejection phase
E. The aortic valve opens at the start of ventricular systole
A. False. It is lowest in early diastole.
B. True.
C. True. At rest it is normally closer to 20%, but increases to as much as 40% with tachycardia.
D. False. The QRS complex occurs immediately before isovolumetric contraction.
E. False. The initial phase of ventricular contraction is isovolumetiric, with the aortic valve closed. Once LV pressure exceeds aortic pressure, the aortic valve opens.
Responses to acute haemorrhage may include:
A. Reduced ADH secretion
B. Increased sympathetic output
C. Reduced baroreceptor discharge
D. Increased glucagon release
E. Increased interstitial fluid formation
A. False. AdH secretion increases
B. True. Initially, sympathetic nerve activity is increased. When blood volume is critically depleted, peripheral sympathetic drive falls steeply.
C. True. The baroreceptors increase efferent output in response to stretch.
D. True.
E. False. Fluid enters the capillaries from the interstitium as a result of reduced hydrostaic capillary pressure.
In the fetal circulation at birth:
A. The pulmonary vascular resistance halves
B. Systemic vascular resistance rises
C. Left atrial pressure rises
D. The ductus arteriosus should close within 48 hours
E. The foramen ovale fuses
A. False. With the first gasp, PVR falls by > 80%.
B. True. Largely due to intense vasoconstriction of the umbilical vessels.
C. True. Due to increase pulmonary blood flow.
D. True. A High PaO2 appears to initiate closure. Prostaglandins maintain its patency.
E. False. It closes as left atrial pressure rises, but does not fuse for around 48 hours.
The following increase the movement of fluid out of capillaries:
A. Venous hypertension
B. Decrease in oncotic pressure
C. Arteriolar vasoconstriction
D. Hypotension
E. Decrease in hydrostatic pressure in capillaries
A. True.
B. True.
C. False.
D. False.
E. False.
Factors which increase flow out of capillaries are increased capillary hydrostatic pressure, increased interstitial colloid osmotic pressure, reduced interstitial hydrostatic pressure or reduced colloid oncotic pressure. In certain conditions (eg sepsis) the permeability coefficient may be altered.
The a-wave in the jugular venous pulse:
A. Is caused by atrial filling during ventricular systole
B. Is elevated in tricuspid stenosis
C. Is elevated in atrial fibrillation
D. Is elevated in tricupid regurgitation
E. When enlarged are known as canon waves
A. False. This would be the v-wave. The a-wave is due to atrial contraction.
B. True.
C. False. It is absent in atrial fibrillation due to the lack of atrial contraction.
D. False. The v-wave is
elevated in tricupid regurgitation.
E. True. Canon waves are large waves corresponding to atrial contraction against a closed tricuspid valve. They are seen in complete heart block or junctional arrhythmias.
In cardiac ventricular muscle:
A. Cells exhibit automaticity
B. The cells membranes are largely impermeable to negatively charged ions
C. Depolarization is followed by a plateau potential lasting about 200 ms
D. Rapid depolarzsation is mainly due to calcium influx throught transient (T-type) calcium channels.
E. Cannot be tetanized
A. False. This behaviour is exhibited primarily by pacemaker cells allowing spontaneous depolarisation. However if this apparatus is disrupted an escape rhythm may originate from in/below the AV node in a junctional escape rhythm, or in the Purkinje fibres in a ventricular escape rhythm.
B. True. These include proteins, sulphates and phosphates which thus remain intracellularly and contribute to the negative RMP.
C. True. Due to Calcium influx via slow L-type calcium channels.
D. False. Rapid depolarization of myocardial cells is due to sodium influx. Depolarisation of slow-response action potentials of pacemaker cells is due to calcium influx throught transient (T-type) calcium channels.
E. True. The prolonged refractory period prevents tetany.
Concerning coronary blood flow:
A. It is increased during hypoxia
B. It is approximately 25% of the cardiac output at rest
C. Significant right coronary artery perfusion occurs during systole
D. The coronary cirulation has the highest A-V oxygen difference of all the major organs
E. Coronary blood flow is regulated via the baroreceptor reflexes
A. True. Hypoxia increases coronary blood flow 2-3 fold.
B. False. Normal coronary blood flow at rest is approximately 250 ml/min or 5% of the cardiac output.
C. True. Unlike the left ventricle, the right ventricle receives most perfusion during systole due to its lower wall pressures.
D. True. The myocardium extracts 70% of oxygen.
E. True. Aortic pressure provides the main driving force for coronary blood flow and this pressure is controlled by baroreceptor reflexes. Flow is also affected by many local factors, including systolic compression and local metabolic factors.
Cardiac excitation in the normal heart:
A. Is initiated spontaneously in the sino-atrial (SA) node
B. Transmission through the atrium takes 0.4 s
C. The AV node allows rapid transmission of electrical excitation to the ventricle
D. The preferential route of transmission from right to left atrium is via Bachmann’s bundle
E. Gap junctions allow the myocardium to act as a single contractile unit
A. True.
B. False. Transmission through the atrium and the AV node to the venticular myocardium takes 0.2 s.
C. False. Transmission is slowest at the AV node.
D. True. Also known as the anterior interatrial band.
E. True. Gap junctions are located at the intercalated disc and allow electrical impulses to propagate freely.
The Valsalva Manoeuvre:
A. At the onset of the Valsalva manouvre arterial pressure rises
B. The reduced arterial pressure seen during the Valslva manouvre will be exagerated in hypovolaemia
C. Heart rate changes are mediated via the aortic chemoreceptors
D. The bradycardia seen after the termination of the manouvre is absent in most long-standing diabetics
E. Increases the intensity of the heart mumur associated with aortic stenosis.
A. True. Due to the the effect of increased intrathoracic pressure on the aorta.
B. True. After the initial rise, BP then falls due to the effect of raised intrathoracic pressure on venous return - this will be more pronounced in the hypovolaemic and can result in cardiovascular collapse.
C. False. Pressure changes are detected by baroreceptors.
D. False. Autonomic neuropathy results in an absence of heart rate changes, but this is seen in only 20-40% of long-standing diabetics.
E. False. It increases the murmur of mitral regurgitation, but most other mumurs are decreased.
Breathing spontaneously in the lateral position:
A. Perfusion is greater in the dependent lung
B. Ventilation is decreased in the uppermost lung
C. V/Q is higher in the dependent lung
D. Dependent lung has a lower PO2
E. Non-dependent lung has a higher PCO2
A True.
B. True.
C. False. In the awake adult, ventilation and perfusion are greater in the lower (dependent) lung although perfusion is slightly better than ventilation and so V/Q < 1.
D. True. V/Q is < 1, ie there is a degree of shunt. In areas of shunt alveolar gas tends toward mixed venous so PAO2 is low and PACO2 slighlty raised.
E. False. In the non-dependent lung V/Q > 1, ie a degree of dead space. Alveolar gas now tends toward inspired gas and so PO2 is raised but PCO2 is low.
FRC can be measured using:
A. Body plethysmography
B. Nitrogen wash-out
C. Spirometry
D. Helium wash-in
E. Intra-oesophageal balloon
A. True.
B. True.
C. False.
D. True.
E. False. Intra-oesophageal balloons are used to measure intra-pleural pressure.
Spirometry will measure all lung volumes except FRC, residual volume and TLC. This is because on the y-axis of the spirometry trace, it is not possible to say where zero lies (although it is often labelled as such in text books).
Concerning 2,3, DPG:
A. It binds the beta chains of deoxyhaemoglobin
B. It is formed from a product of glycolysis
C. An increased concentration increases oxygen utilisation by cells
D. Its red cell concentration is increased by circulating thyroid hormones
E. Is strongly bound by fetal haemoglobin
A. True.
B. True. 2,3-DPG is formed in red blood cells from phosphoglyceraldehyde, a product of glycolysis.
C. True. 2,3 DPG shifts the O2 dissociation curve to the right, reducing oxygen binding to haemoglobin and thus increasing oxygen availability for tissue utilization.
D. True. Thyroid hormones, along with growth hormone and angrogens increase 2,3,DPG concentration.
E. False. Fetal Hb does not contain beta chains.
Dipalmitoylphosphatidylcholine:
A. Is a mucopolypeptide
B. Causes an increase in surface tension
C. Causes an increase in chest wall compliance
D. Production is reduced in low cardiac output states
E. Maintains the same surface tension for different sized alveoli
A. False. It is a phospholipid, found in lung surfactant.
B. False. Surfactants role is to decrease surface tension.
C. False. It increases lung compliance, not chest wall compliance.
D. True. As it is derived from free fatty acids carried in the blood stream.
E. False. It is more effective at reducing surface tension in small alveoli. This reduces the effect of Laplace’s law, which would otherwise cause small alveoli to collape.
Peripheral chemoreceptors:
A. Are found in the carotid sinus
B. Are downregulated in the presence of chronic lung disease
C. Are stimulated by elevated levels of carboxyhaemoglobin
D. Give rise to increased afferent signals when PaO2 falls below 13 kPa
E. Maintain PaCO2 within the range 4.5-6.0 kPa
A. False. They are located in the carotid and aortic bodies.
B. False. Central chemoreceptors in the medulla respond to a rise in PaCO2 and CSF pH.
C. False.
D. True. The carotid body is the prime O2 sensory organ.
E. False. see part D.
Ventilation is predominantly controlled by central chemoreceptors in the medulla which respond to a rise in PaCO2 and CSF pH.
Carbon dioxide:
A. Freely diffuses across the blood : brain barrier
B. Is lagely transported unchanged
C. Gives rise to the same pH change in CSF as it does in blood
D. Transport by haemoglobin is inhibited by rising oxygen saturation
E. Has direct sympathomimetic activity
A. True. Unlike H+ ions and HCO3-.
B. False. Most is transported as bicarbonate. Around 5% is transported unchanged in the blood.
C. False. pH changes are greater in the CSF due to the lack of buffers.
D. True. By the Haldane effect.
E. False. But it does increase activation of the sympathetic system.
Pulmonary blood flow:
A. Is normally less than the cardiac output
B. Has a mean arterial pressure of 25-30 mmHg
C. In West zone 1, occurs mainly during diastole
D. Of 6000 ml/min with a minute ventilation of 4000 ml/min suggests the presence of a shunt
E. Is maximal in zone 2
A. True. A small proportion of the cardiac output will be anatomical shunt.
B. False. Mean pressure is around 15 mmHg. 25 -30mmHg would be the systolic pressure.
C. False. In West zone 1 pA>pa>pv therefore the pulmonary capillary is completely compressed by by the alveolus ceasing. This results in a very high V/Q ratio
D. True. As perfusion is significantly greater than ventilation.
E. False. It is maximal in zone 3.
Restrictive lung disease is characterized by:
A. A fall in FEV1
B. A fall in arterial PO2
C. A fall in FEV1/FVC ratio
D. Carbon dioxide retention
E. A fall in vital capacity
A. True. Pulmonary function tests generally reveal a decrease in both FEV1 and FVC with a normal FEV1/FVC ratio.
B. True. A fall in FRC causes alveolar collapse with a resultant shunt.
C. False.
D. False.
E. True. As does TLC and FRC.
During intermittent positive pressure ventilation:
A. Mean intrathoracic pressure will be lower than during spontaneous breathing
B. Right ventricular filling falls compared with spontaneous ventilation
C. PEEP will reinflate collapsed alveoli
D. Right ventricular workload may increase
E. Left ventricular workload may decrease
A. False.
B. True. Which will reduce cardiac output.
C. False. PEEP will prevent collapse, but would not normally be high enough to re-inflate collapsed lung.
D. True. PVR may rise during IPPV due to hyperinflation or alveolar collpase (PVR is lowest at FRC and rises above or below this).
E. True. IPPV reduces LV afterload by decreasing LV cavity size and transluminal wall tension.
Hyperventilation produces:
A. Muscle spasm
B. A raised pH
C. Decreased cerebral blood flow
D. Peripheral vasodilatation
E. Increased cardiac output
A. True. Alkalosis decreases the proportion of ioised calcium, causing tetany.
B. True.
C. True.
D. False. Hypocarbia causes vasoconstriction by a direct effect.
E. False. Hypercarbia causes an increase in cardiac output due to increased sympathetic activity. The direct effect of vasoconstriction from hypocarbia will reduce cardiac output.
Concerning the enteric nervous system:
A. It contains pre-ganglionic cholinergic fibres
B. Vagal fibres are post-ganglionic
C. It contains post-ganglionic sympathetic fibres
D. Many sympathetic fibres end on cholinergic neurones
E. Many sympathetic fibres end directly on intestinal smooth muscle
A. True. Generally, the parasympathetic supply to the GIT is via pre-ganglionic vagal fibres.
B. False.
C. True. The sympathetic supply is post-ganglionic, but may end on cholinergic neurones or on smooth muscle fibres directly.
D. True.
E. True.
Concerning nerve conduction:
A. A-delta fibres are the slowest as they are unmyelinated
B. A-beta fibres exhibit saltatory conduction
C. C fibres are myelinated
D. A-alpha fibres conduct at 30-70 m/s
E. A-delta fibres provide sensory innervation to muscle spindles.
A. False. A and B fibres are myelinated and therefore have fast conduction velocities due to saltatory conduction.
B. True.
C. False.
D. False. A-alpha fibres conduct at 70-120 m/s
E. False. But A-gamma fibres provide motor supply to muscle spindles.
Hemisection of the spinal cord causes:
A. Ipsilateral paralysis
B. Ipsilateral loss of proprioception
C. Contralateral loss of pain sensation
D. Ipsilateral loss of vibration sense
E. Contralateral loss of temperature sensation
A. True.
B. True.
C. True.
D. True.
E. True.
Brown-Sequard syndrome (hemisection of the spinal cord) causes ipsilateral paralysis and loss of proprioception, touch and vibration sensation, with contralateral loss of pain and temperature sensation.
Concerning synaptic transmission:
A. The synaptic cleft is 100 nm wide
B. Temporal summation may occur
C. Synaptic delay is normally 0.1 ms
D. IPSPs are depolarising
E. EPSPs are depolarising
A. False. The synaptic cleft is 30-50 nm wide.
B. True. Summation of excitatory postsynaptic potentials may be both spatial and temporal.
C. False. Synaptic delay is normally 0.5 ms.
D. False. IPSPs are hyperpolarising.
E. True.
Concerning the knee jerk reflex:
A. It is monosynaptic
B. The synaptic transmitter is glutamate
C. The sensory organ is the muscle spindle
D. It involves spinal roots L2,3,4
E. Glycine inhibition occurs in fibres to antagonistic muscles.
A. True.
B. True.
C. True.
D. True.
E. True.
The sensory organ is the muscle spindle, which when stretched sends signals to the CNS where a single synapse occurs with the motor supply to the muscle. In addition the Ia fibre from the muscle spindle synapses with an inhibitory interneurone (golgi bottle neurone) which releases inhibitory glycine at the motor neurone to the antagonistic muscle - known as reciprocal innervation.
Concerning the visual pathway:
A. Optic tract lesions will cause a bitemporal hemianopia
B. Optic chiasm lesions will cause a bitemporal hemianopia
C. Occipital lesions may spare the macula
D. Optic nerve lesions will cause bilateral loss of vision
E. Field defects start as scotomas.
A. False. Optic tract lesions cause homonymous hemianopia since the optic tracts carry fibres that supply the same field (ie left or right) from both eyes.
B. True. As at the Optic chiasm, temporal fibres cross the midline.
C. True. As the macula fibres are separated from the rest of the cortex subserving vision.
D. False. They will cause unilateral loss of vision.
E. True. These are small areas of visual loss.
Concerning pain pathways:
A. A-delta have cell bodies within the vental root ganglion of the spinal cord
B. A-delta fibres synapse with cells of the substantia gelatinosa of the spinal cord
C. C fibres synapse with cells in laminae IV and V in the dorsal horn
D. Most ascending neurones are in the anterolateral columns
E. The substantia gelatinosa projects directly to higher levels
A. False. A-delta have cell bodies within the dorsal root ganglia.
B. False. A-delta fibres synapse with cells in laminae I and V of the dorsal horn.
C. False. C fibres synapse with cells in laminae II and III in the dorsal horn.
D. True. Most second order neurones cross within a few segments and ascend in the anterolateral columns (spinothalamic tract).
E. False. The SG does not project directly to higher levels but contains multiple interneurones involved in pain modification.
Concerning sensory receptors:
A. Meissners corpuscles are associated with nociception
B. Ruffini corpuscles are associated with proprioception
C. Pacinian corpuscles are associated with vibration
D. Ruffini corpuscles are associated with nociception
E. Pacinian corpuscles are associated with proprioception
A. False. Meissners corpuscles are associated with touch.
B. True.
C. True. Pacinian corpuscles are associated with proprioception and vibration.
D. False. Free nerve endings are associated with nociception
E. True. Pacinian corpuscles are associated with proprioception and vibration.
Concerning the cranial nerves:
A. VII provides taste sensation to the posterior third of the tongue
B. V provides motor fibres to the jaw and tongue
C. IV innervates the inferior oblique muscle
D. III performs most eye movements
E. XII provides motor innervation to palatoglossus
A. False. Taste sensation to the posterior third of the tongue is provided by the glossopharyngeal (IX), the rest being supplied by the chorda tympani accompanying the facial nerve (VII).
B. False. The trigeminal nerve (V) supplies the muscles of mastication and sensation to the forehead and face in the distribution ophthalmic, maxillary and mandibular branches. This includes sensation from the cornea.
C. False. IV innervates the superior oblique muscle.
D. True. With IV and VI supplying superior oblque (to look down and inward) and lateral rectus (abduction) respectively.
E. False. XII innervates all tongue muscles except palatoglossus, which is innervated by X.
In the EEG, delta waves occur:
A. With increased cortical activity
B. Normally during sleep
C. Prominently over the frontal area
D. Upon closing the eyes
E. Normally in children
A. False.
B. True.
C. False.
D. False.
E. True.
Delta waves are abnormal 4Hz waves, though they can be normal in children and during sleep. Alpha waves are prominent on closing the eyes or with increased cortical activity whilst beta waves prominent over the frontal area.
At birth:
A. The foramen ovale closes because of a reversal of the pressure gradient between the left and right atria
B. The ductus arteriosus closes because of a respiratory acidosis
C. Blood flow in the IVC falls
D. Hypoxia will favour a right to left shunt
E. The first breath generates a negative pressure of about 50 cmH2O
A. True.
B. False. The ductus arteriosus closes functionally soon after birth (usually within 24 hours) due to exposure to oxygenated blood and reduced prostaglandin-E2.
C. True.
D. True. Any stimulus increasing Pulmonary Vascular Resistance will favour a right to left shunt and hence a Persisitent Fetal Circulation. These stimuli include hypoxia, hypercarbia, acidosis and hypothermia.
E. True.
At birth, pulmonary vascular resistance falls markedly as the lungs expand and fill with air. This decreases pulmonary artery pressures and increases blood flow to the left atrium. Umbilical vessels constrict and placental circulation ceases resulting in increased systemic vascular resistance and arterial pressure. Left atrial pressure becomes higher than right atrial pressure and this closes the foramen ovale.
Left ventricular end diastolic pressure (LVEDP):
A. Gives an index of preload
B. Will be raised if left ventricular compliance increases
C. Is increased in aortic regurgitation
D. Is a determinent of myocardial oxygen consumption
E. Is measured using a pulmonary artery flotation catheter
A. True. The best measure of preload in LVEDV, however this will correlate with LVEDP - the exact numerical relationship being dependent on left ventricular compliance.
B. False. Pressure will be lower for a given volume if compliance is increased (Complaince = Vol/Pressure)
C. True. Because regurgitant blood re-enters the ventricle increasing volume and pressure.
D. True. Raised LVEDP increases myocardial work and therefore oxygen requirement.
E. False. A pulmonary artery flotation catheter can measure the left atrial pressure (wedge pressure).
An increase in right atrial pressure:
A. Decreases systemic arterial pressure
B. Will increase type A atrial stretch receptor discharge during atrial systole
C. Causes an increase in urine volume
D. Can increase the heart rate via the Bainbridge reflex
E. Can decrease the heart rate via the baroreceptor reflex
A. False. An increase in preload will increase LVEDV and therefore stroke volume and consequently cardiac output and arterial blood pressure (unless in heart failure).
B. True. Atria have Type A stretch receptors that discharge predominantly during atrial systole and Type B receptors that discharge predominantly during atrial diastole.
C. True. Stimulation of atrial stretch receptors causes the release of atrial naturetic peptide (ANP) which has a diuretic action.
D. True.
E. True. Increasing RA filling produces 2 opposing reflexes that control HR. The resultant increased blood pressure can decrease HR via the baroreceptor reflex, however the atrial stretch receptors can increase HR via the Bainbridge reflex. Whether the HR increases of decreases after a sudden increase in intravascular volume is thought to be related to the initial heart rate (decreasing if it is high and increasing if it is low).
In diastole:
A. Myocardial relaxation is metabolically active
B. Hypercalcaemia causes positive lusitropy
C. Left atrial contraction occurs just before right atrial contraction
D. The greater part of left coronary artery blood flow occurs during diastole.
E. Diastasis shortens first with increasing heart rate
A. True. Myocardial relaxation is a metabolically active phase when calcium re-uptake occurs by the sarcoplasmic reticulum.
B. False. Lusitropy is a term that decribes myocardial relaxation. Catecholamines have a positive lusitropic action (allowing rapid relaxation) whilst hypercalcaemia inhibits relaxation due to incomplete calcium reuptake (an essential process in diastole).
C. False. RA contration preceeds LA contraction, however LV contaction precedes RV contraction.
D. True. Whereas in the Right Coronary Artery, the greater part of blood flow occurs during systole.
E. True. Diastasis is the slow ventricular filling phase of diastole. There is only a small increase in ventricular volume during this time.
In the first 24 hours after major trauma:
A. Sodium is retained
B. Glomerular filtration rate increases
C. Patients will be immunosuppressed
D. Urinary nitrogen levels will rise
E. Insulin secretion is decreased
A. True. Aldosterone levels increase, promoting sodium reabsorption.
B. False. GFR decreases.
C. False. Immunusuppression is a late feature following trauma.
D. True. Due to protein breakdown in the initial catabolic phase.
E. True. Glucagon secretion also increases briefly.
Afterload:
A. Equals systemic vascular resistance
B. If increased, will result in decreased LVEDV
C. Is likely to be low in heart failure
D. Will be low in a dilated ventricle
E. Is decreased in mitral regurgitation
A. False. Afterload is the tension developed in the LV wall during systole. SVR is however the commonest index of afterload used clinincally, but it is only one component that determines afterload.
B. False. If afterload increases, SV initially falls. SV is then (partially) restored by an increase in LVEDV. This is known as the Anrep effect.
C. True. Afterload is the tension developed in the LV wall during systole and as such can be related to pressure by Laplaces law. Thus in the failing heart afterload is likely to be low due to low intraventricular pressure.
D. False. Using Laplaces law, the increased radius will increase tension.
E. True. The left ventricle requires less tension to eject blood through this low pressure pathway.
Concerning the splanchnic circulation
A. The adult liver normally receives approximately one third of its blood supply from the coeliac axis
B. Beta 1 adrenergic receptors cause mesenteric arteriolar vasodilatation
C. Positive end expiratory pressure (PEEP) decreases portal blood flow
D. Arcades of arterioles supplying mucosal villi terminate and branch at the tip supplying well oxygenated blood to the mucosa
E. The splanchnic venous system can contain 1/3 of the total blood volume
A. True. The hepatic artery is a branch of the coeliac axis. There is an inverse ratio of the flow between the hepatic artery and portal vein but under normal conditions 1/3 of hepatic blood comes from the hepatic artery.
B. False. Beta 2 adrenergic receptors mediate vasodilation.
C. True. Portal blood flow does not autoregulate well. PEEP increases hepatic venous pressure and reduces portal flow.
D. False. The countercurrent exchange of oxygen between parallel arterioles and submucosal venules makes oxygen delivery to the tips of mucosal villi poor.
E. True. The splanchnic and skin circulations are the major reservoirs of available blood in times of stress.
Concerning cardiac tissue:
A. Myocardial cells have a RMP of -60mV
B. Myocardial cells do not possess gap junctions
C. Conduction velocity of action potentials is greatest in the bundle branches and Purkinje system
D. Calcium within the sarcoplasmic reticulum is released in response to rising intracellular sodium levels
E. Both the SA and AV nodes blood supply is derived from the right coronary artery
A. False. This is the RMP of pacemaker cells. Myocardial cells have a RMP of -90 mV.
B. False. Gap junctions connect the cytosol of adjacent myocardial cells allowing rapid transmission of electrical cells.
C. True.
D. False. It is released in response to rising intracellular calcium levels.
E. True.
During moderate exercise:
A. Cerebral blood flow increases
B. Increased cardiac output is achieved mainly from an increased heart rate
C. Central venous pressure rises
D. Intravascular volume is usually reduced
E. Haematocrit tends to fall
A. False. Caridac output by upto seven times resting values, but cerebral blood flow is maintained at normal levels.
B. True.
C. False. At moderate levels of exercise, increased venous return matched increased cardiac output and thus CVP does not significantly change. CVP does rise at maximal exertion.
D. True. Due to increased insensible losses and increased capillary filtration.
E. False. There is often a slight rise in haematocrit due to the reasons in Part D.
Regarding electrolyte changes:
A. Hypokalaemia increases automaticity
B. Hypokalaemia increases the QT interval
C. Hyperkalaemia brings the RMP closer to the threshold potential
D. Hypercalcaemia makes the threshold potential more negative
E. Hypermagnesemia prolongs the PR interval
A. True. Hypokalaemia makes the cardiac muscle RMP more negative, resulting in it being less excitable but with increased automaticity.
B. True.
C. True. Hyperkalaemia makes the RMP less negative.
D. False. Hypercalcaemia makes the threshold potential less negative, decreases conduction velocity and shortens the refractory period.
E. True. Hypermagnesemia delays AV conduction.
Partial agonists:
A. Act as both agonists and antagonists
B. Have similar intrinsic activity to full agonists
C. Include buprenorphine
D. Include pentazocine
E. Include clozapine
A. True. Partial agonists act as agonists in isolation, but can act antagonistically when given in combination with a full agonist.
B. False. Full agonists have an intrinsic activity of 1, whereas a partial agonists have an intrinsic activity of <1.
C. True.
D. False. Pentazocine is a mixed agonist-antagonist.
E. True. Clozapine is a partial agonist at D2 receptors.
Antagonists:
A. Have intrinsic activity, but lack affinity
B. Competitive antagonism reduces Emax
C. Competitive antagonists bind to a site distal to the receptor involved
D. Non-competitive antagonism is overcome by increasing agonist dose
E. May also act as agonists
A. False. They have affinity, but an intrinsic activity of zero.
B. False. Maximum efficacy (Emax) remains the same, but the dose-response curve is shifted to the right. Non-competitive antagonism reduces Emax
C. False. Competitive antagonists compete for a receptor with agonists. Non-competitive antagonists bind to a distal site, and induce a change at the receptor.
D. False. This is competetive antagonism.
E. True. Mixed agonists-antagonists can act as agonists at some receptors and antagonists at others e.g. pentazocine.
Regarding the log dose-response curve:
A. The ED50 is the drug concentration that induces a response halfway between zero and maximum
B. Therapeutic index = Lethal Dose 50 / Effective Dose 50
C. Drugs with a narrow therapeutic window do not require monitoring
D. It is shifted to the left with the addition of a competitive antagonist
E. Potency is represented by the height of the curve
A. False. ED50 refers to the dose of drug - this question defines the Effective Concentration 50.
B. True.
C. False. Drugs with a narrow therapeutic window often require close monitoring as the risk of reaching toxic levels is greater.
D. False. The curve is shifted to the right as a higher dose of agaonist is required to produce an equivalent response.
E. False. It is represented by the position of ED50, much like the position of P50 on the oxy-Hb dissociation curve.
Receptors and 2nd messengers:
A. G-protein receptors have alpha, beta and delta subunits
B. Insulin receptors are G-protein coupled
C. Opioid receptors are G-protein coupled
D. cAMP is a hydrophobic molecule
E. Nitric oxide acts via cAMP
A. False. G-proteins consist of alpha, beta and gamma subunits.
B. False. The Insulin receptor utilises tyrosine kinase.
C. True.
D. False. It is hydrophilic.
E. False. It acts via cGMP.
The following antagonists have agonist properties:
A. Ranitidine
B. Prazosin
C. Pindolol
D. Naltrexone
E. Xameterol
A. False. It is an H2-receptor antagonist.
B. False. It is a selective alpha1-adrenoreceptor blocker.
C. True. It is a non-selective Beta-blocker with partial beta-agonist activity. It also has partial agonist / antagonist activity at the 5-HT1A receptor.
D. False. It is an opioid receptor antagonist.
E. True. It is a mixed beta-agonist/antagonist.
Mixed agonist-antagonists are drugs that can exert both agonistic and antagonistic properties. Such drugs include: Opioids (Pentazocine, Nalbuphine and Buprenorphine), Mirtazepine, Pindolol and Xameterol.
Regarding negative exponential processes:
A. The rate of decay varies with time
B. The time constant is longer than the half-life
C. The time constant is the natural logarithm of the half-life
D. Is converted into a straight line by a semi-log plot
E. The time constant is the time for the process to complete if the rate continued at its initial speed
A. True. In an exponential process the rate of change of a variable is proportional to the magnitude of the variable at that moment in time. In a negative exponential process, the rate of decay is decreasing with increasing time.
B. True. An exponential process is said to be complete after 3 time constants, as opposed to 5 half-lives.
C. False. The time constant is the reciprocal of the rate constant.
D. True. This is true of other exponential processes also. It allows for easier interpretation.
E. True. It can also be defined as the time taken for an exponential process to fall to 37% or 1/e of its previous value.
Receptors:
A. Drug affinity depends on the attraction between receptors and drugs
B. Thyroid hormones bind to cell surface receptors
C. Acetylcholine receptors have 2 alpha and 2 beta subunits
D. Midazolam acts at GABAb receptors
E. Nicotinic hormones bind to intracellular receptors
A. True. Affinity is the ability of a ligand to bind to a specific receptor.
B. False. They bind to intracellular receptors.
C. False. The adult acetylcholine receptor has 2 alpha subunits (to which acetylcholine binds), a beta subunit, a delta subunit and an episilon subunit (this is replaced by a gamma subunit in the foetus).
D. False. It acts at GABAa receptors.
E. False. Nicotinic receptors are type 1 receptors according to Urquhart’s classification - membrane bound ligand gated ion channels.
Regarding chemical bond strength:
A. Van der Waals > Hydrogen > Ionic > Covalent
B. Covalent > Ionic > Hydrogen > Van der Waals
C. Covalent > Hydrogen > Ionic > Van der Waals
D. Ionic > Covalent > Hydrogen > Van der Waals
E. Van der Waals > Hydrogen > Covalent > Ionic
False.
False.
False.
True.
False.
Ionic bonds involve the electrostatic forces of attraction between oppositely charged ions after the complete loss or gain of electrons and are in general stronger than covalent bonds. Covalent bonds involve the sharing of electrons in order to gain full outer electron shells. Taken in isolation covalent bonds are generally weaker than an ionic lattice, however in complex molecules where there may be double or triple bonding they may become stronger than an ionic bond. For example a single covalently bonded carbon-oxygen required 350KJ/mol to break, but a triple-bonded carbon-oxygen requires 1080KJ/mol to break. A sodium-chloride ionic lattice requires 769KJ/mol to break.
Hydrogen bonding involves the forces of attraction between the postively charged nucleus of a hydrogen atom and an electronegative atom. Electron clouds have no definite shape, therefore at any moment one part of the cloud may be relatively more positively or negatively charged than the other - Van der Waals forces are the forces of attraction / repulsion between such areas.
The following processes are mediated by cAMP:
A. Decreased heart rate
B. Liver carbohydrate metabolism
C. Increased contractility
D. Triglyceride breakdown
E. Smooth muscle relaxation
A. True. Both increases and decreases in heart rate are mediated via cAMP. Beta1-adrenoreceptors are G-protein coupled - their stimulation causes increased cAMP and subsequent tachycardia. Muscarinic M2 receptors are Gi type g-protein coupled receptors and when stimulated decrease cAMP and reduce heart rate via opening of potassium channels
B. True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent glycogenolysis (also increases insulin and glucagon secretion).
C. True. Beta1-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent increase in contractility.
D. True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent lipolysis (also increases insulin and glucagon secretion). Beta 3-adrenoreceptors are also G-protein coupled and increase cAMP - they help regulation lipid metabolism.
E. True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent smooth muscle relaxation.
Which of the following may alter drug response:
A. Tachyphylaxis
B. Changes in receptor number
C. Hypersensitivity reactions
D. Idiosyncratic drug responses
E. Tolerance
A. True. Tachyphylaxis is defined as a decreased response following a single administration of a drug.
B. True. Whether this affects drug response depends on the degree of change in receptor number, and whether the drug response involves spare receptors (i.e. a full response is obtained despite some receptors not being occupied).
C. True. See below
D. True. Such reactions are not related to known pharmacological properties of a drug (i.e. not a common side effect, they are dose independent). They include anaphylaxis and anaphylactoid reactions.
E. True. Tolerance is the decreased responsiveness following repeated drug adminsitration.
The following are true regarding Volume of Distribution (Vd):
A. It is the amount of drug that distributes following administration
B. Can be greater than total body water
C. Is measured in kg/L
D. Is a constant for a given drug
E. Is equal to Clearance divided by Time Constant
A. False. It is the volume that a drug distributes into following administration.
B. True. TBW = 42L whilst Vd can be up to 1000L.
C. False. It is measured in L/Kg.
D. True.
E. False. Vd = Clearance x Time Constant.
Context sensitive half-time:
A. Is a decrement time
B. Shares a constant relationship with elimination half-life
C. Varies with duration of drug infusion
D. Is reliably used to describe time for recovery
E. Reflects the combined effects of absorption and distribution
A. True. Decrement time = the time taken of the plasma level for a drug to fall to a specified value (Context-Sensitive Half-Time is 50%).
B. False. There is no such relation.
C. True. This is the ‘context’.
D. False. It is the time for the plasma levels to fall to 50% of the value when the infusion is stopped.
E. False. It reflects the combined effects of distribution and metabolism.
The following influence Volume of Distribution (Vd):
A. Regional blood flow
B. Lipid solubility
C. Degree of tissue protein binding
D. Degree of plasma protein binding
E. Degree of ionisation
True.
True.
True.
True.
True.
Infusion kinetics:
A. It takes 5 half-times to reach steady state concentration
B. Steady state volume of distribution is dependent on lipid solubility and molecular weight
C. Loading Dose = Vd x Desired Plasma Concentration
D. Maintenance Dose = Steady State Vd x Clearance
E. Clearance = Input (mg/min) x Plasma Concentration (mg/ml)
A. False. It takes 5 Half-lives to reach steady state concentration.
B. False. Steady state volume of distribution is dependent on lipid solubility and clearance.
C. True.
D. False. Maintenance Dose = Steady State Concentration x Clearance.
E. False. In infusion kinetics at steady state Input = Elimination
Input (mg/min) is therefore equal to Clearance (ml/min) x Plasma Concentration (mg/min)
Therefore:
Clearance = Input (mg/min) / Plasma Concentration (mg/ml)
The following statements are true of Cytochrome P450 enzyme isoforms:
A. CYP2E1 is involved in metabolism of paracetamol
B. CYP3A4 is involved in metabolism of phenytoin
C. Are only found in the liver
D. Account for most phase 2 reactions
E. CYP2E1 is involved in the metabolism of chloride containing volatile agents
A. True.
B. False. CYP3A4 is important in the metabolism of both midazolam and alfentanil.
C. False. CYP2E1 is found in the kidneys.
D. False. Account for most phase 1 reactions.
E. False. CYP2E1 is involved in the metabolism of fluoride containing volatile agents.
The following are enzyme inducers:
A. Rifampicin
B. Metronidazole
C. Acute alcohol use
D. Carbamazepine
E. Chloramphenicol
A. True.
B. False. It is an enzyme inhibitor.
C. False. Acute alcohol use inhibits whilst chronic use induces.
D. True.
E. False. It is an enzyme inhibitor.
Phase 2 reactions include:
A. Oxidation
B. Acetylation
C. Sulphation
D. Hydrolysis
E. Glucuronidation
A. False. This is a Phase I reaction.
B. True.
C. True.
D. False. This is a Phase I reaction.
E. True.
Elimination:
A. Can only be by either distribution or metabolism
B. In 1st order kinetics, half-life is constant
C. In 1st order kinetics, a constant amount of drug is eliminated per unit time
D. Zero order kinetics is a linear process
E. In zero order kinetics, half-life increases with dose administered
A. False. Can also be by excretion.
B. True.
C. False. A constant proportion is eliminated per unit time.
D. False. Zero order kinetics is also known as non-linear kinetics.
E. True.
Hepatic clearance:
A. A drug with a high extraction ratio is not affected by protein binding
B. Lignocaine is an example of an enzyme limited drug
C. High extraction ratio implies significant 1st pass metabolism
D. Enzyme induction / inhibition can profoundly affect the clearance of drugs with a low extraction ratio
E. Warfarin is an example of an enzyme limited drug
A. True. It is not affected by enzyme level either.
B. False. Lignocaine has a high extraction ratio (>0.7) and is therefore flow / perfusion limited (as opposed to enzyme / capacity limited).
C. True. Most of the drug is extracted on the first pass through the liver, hence why changes in hepatic blood flow can drastically affect clearance.
D. True. Drugs with a low extraction ratio are enzyme / capacity limited drugs.
E. True. As are phenytoin, theophylline and most benzodiazepines and barbituates.
Bioavailability:
A. Of drugs administered via the IV route can be as high as 90%
B. Is the fraction of administered drug that reaches systemic circulaiton
C. Glycopyrrolate has >80% bioavailability
D. Is influenced by genetics
E. Is influenced by circadian rhythm
A. False. IV drug administration provides 100% bioavailability.
B. True.
C. False. Glycopyrrolates bioavailability is < 5%.
D. True. There are phenotypic variations in bioavailability.
E. True.
Isoflurane:
A. Is a stereoisomer of enflurane
B. Causes vasodilatation without reflex tachycardia
C. Has a saturated vapour pressure of 23.3 kPa at 20 degrees Celcius
D. 0.2% of isoflurane undergoes hepatic metabolism
E. The chloride group is attached to the chiral centre
A. False. It is a structural isomer.
B. False. A reflex tachycardia suggests that baroreceptor function remains intact with isoflurane use. The main cause of isoflurane induced hypotension is a reduction in systemic vascular resistance. Myocardial function and cardiac output see only a small decrease.
C. False. This is the SVP of enflurane. The SVP of isoflurane is 32 kPa.
D. True. Hepatic cytochrome P450 metabloizes the C - F bond. Renal toxicity is rare due to the low levels of fluoride ions produced.
E. True.
Factors that increase Minimum Alveolar Concentration:
A. Alpha-2 agonists
B. Hypernatraemia
C. Chronic alcohol intake
D. Acute alcohol intake
E. The premature neonatal period
A. False. These decrease MAC.
B. True.
C. True.
D. False. Acute alcohol intake decreases MAC.
E. False. The MAC is low in preterm neonates. For most agents MAC value peaks at 1-6 months.
Sevoflurane:
A. Has a chiral centre
B. Produces hydrofluoric acid if stored in glass
C. Has a blood:gas coefficient of 1.4
D. Causes coronary steal syndrome
E. Is metabolised by cytochrome isoform CYP3A4
A. False. It is achiral
B. True. This is highly toxic. Lewis acids degrade the ether and halogen bonds if sevoflurane is stored in water at concentrations less than 100ppm. The highly toxic hydrofluoric acid corrodes glass, driving Lewis acid production.
C. False. This is the blood:gas coefficient of isoflurane. 0.7 is the correct answer.
D. False. This is a side effect of isoflurane use.
E. False. This cytochrome isoform is responsible for the metabolism of opiates and benzodiazepines. CYP2E1 is responsible for sevoflurane / isoflurane / halothane metabolism.
Sevoflurane:
A. Is methyl-ethyl ether
B. Inhibits pulmonary vasoconstriction
C. Undergoes renal metabolism to produce inorganic fluoride ions
D. Compound A production is more likely in the presence of dry potassium hydroxide
E. Has a molecular weight higher than halothane
A. False. It is a polyfluorinated methyl isopropyl ether.
B. True.
C. False. This was a feature of methoxyflurane. 3.5% of sevoflurane undergoes hepatic metabolism to produce hexafluroisopropanol and fluoride ions.
D. True. The suggested nephrotxoic threshold for compound A is 150-200ppm. These are levels that far exceed what is seen in clinical practise.
E. True. Secoflurane 200.1, Halothane 197, Isoflurane / Enflurane 184.5, Desflurane 168, Xenon 131 and N2O 44.
Minimum alveolar concentration:
A. Is above 6% for desflurane
B. Is above normal atmospheric pressure for nitrous oxide
C. May be as low as 0.7 for sevoflurane in 70% nitrous oxide
D. Is 0.95 for Halothane
E. Is lower for enflurane than it is for isoflurane
A. True.
B. True.
C. True.
D. False. MAC of halothane is 0.75
E. False. Isoflurane 1.17, Enflurane 1.68
Halothane:
A. Is an halogenated ether
B. Has a SVP at 20 degrees celcius, similar to isoflurane
C. May be given safely with adrenaline infiltration at doses of 100 micrograms per minute
D. Its C-Br bonds are metabolised with greater ease than its C-F bonds
E. Is metabolised under hypoxic conditions to produce trifluoroacetyl chloride which is implicated in halothane hepatitis
A. False. Halothane is a halogenated hydrocarbon. There is no ether ‘link’.
B. True. Halothane 32.3 kPa, Isoflurane 33.2 kPa.
C. False. This dose of adrenaline should be administered over a 10 minute period. Halothane sensitises the heart to catecholamines, which may lead to arrhythmias - particularly ventricular tachycardias and bradyarrhythmias.
D. True. C-F bonds are the most stable carbon-halogen bond.
E. False. This metabolite is produced under oxidative conditions. In a hypoxic state reduced metabolites are produced e.g. inorganic fluoride.
Desflurane:
A. Has a boiling point of 39 degrees celcius
B. Is administered via the Tec 5 vaporiser
C. Induces tachycardia and hypertensions at MAC values greater than 1
D. Produces carbon monoxide on contact with soda lime
E. Has a blood gas coefficient higher than nitrous oxide
A. False. Its boiling point is 23.5 degrees celcius.
B. False. Is administered via the Tec 6. This heats the volatile to 39 degrees celcius under a pressure of 2 atmospheres.
C. True.
D. True. Volatile agents that contain a -CHF2 molecule (isoflurane, enflurane, desflurane) may produce carbon monoxide upon reaction with dry soda lime.
E. False. Blood gas coefficient of desflurane is 0.42; nitrous oxide 0.47
Nitrous Oxide
A. Has a critical pressure of 72 bar
B. Is stored in cylinders with a pin index configuration of 2 and 5
C. Increases cerebral blood flow
D. Inhibits methionine synthetase by reducing the cobalt ion in vitamin B12
E. Reduces that MAC of isoflurane to 0.5 when used at 70%
A. True. In addition to this, the critical temperature is 36.5 degrees celcius.
B. False. This is the pin index of oxygen. The configuration for nitrous oxide is 3 and 5.
C. True. It may also increase intracranial pressure.
D. False. It oxidises this cobalt ion. It may also inhibit methionine synthetase directly. Nitrous oxide therefore inhibits methionine, thymidine, tetrahydrofolate and DNA synthesis.
E. True.
Halothane:
A. Increases cerebral blood flow less than enflurane
B. Has a sweet odour
C. Has two bromide atoms
D. Is prepared with 0.01% thymol to prevent combustion
E. Causes vagal stimulation
A. False. In descending order; halothane, enflurane, nitrous oxide, isoflurane
B. True.
C. False. 1 bromide, 1 chloride and 3 fluoride ions.
D. False. It is prepared with 0.01% thymol to prevent decomposition by light.
E. True. It may also cause bradycardia by inhibiting atrioventricular conduction / activity.
In reference to inhaled anaesthetic agents:
A. Isoflurane does not increase cerebral blood flow at concentrations below 1 MAC
B. Xenon is hepatically metabolised
C. Oxygen has a critical pressure of 50 bar
D. Entonox seperates into its constituent parts below 7 degrees celcius
E. 0.1% of nitrous oxide is metabolised
A. True.
B. False. All clearance is by lung elimination.
C. True.
D. False. This is likely to occur at temperatures below -7 degrees celcius (pseudo-critical temperature) at pressures of 117 bar.
E. False. Less than 0.01% of nitours oxide undergoes metabolism.
Ingested lipids:
A. Are mainly triglycerides
B. Are composed of essential and non-essential fatty acids
C. Are broken down primarily in the terminal ileum
D. Are used as a source of ATP
E. Increase in the faeces with a decrease in bile secretion
A. True. Triglycerides make up to 90% of dietary lipids.
B. True. Alpha-linolenic acid and linoleic acid are examples of essential fatty acids. Humans do not possess the enzyme systems to synthesize them.
C. False. 10-30% are broken down in the stomach, the rest is broken down in the duodenum and upper jejunum. Bile salts are absorbed in the terminal ileum.
D. True. It is a relatively energy dense molecule, providing more than double that from glucose.
E. True. Bile salts are required solubilizing agents for fats and aid in their absorption.
Regarding Basal Metabolic Rate (BMR):
A. It is the lowest possible rate
B. BMR decreases with age
C. For every 1 degree centigrade rise in body temperature, the BMR increases by 8%
D. BMR is the energy output of an individual per unit time at rest, at room temperature
E. May be measured using an ergometer
A. False. It can be lower when asleep.
B. True. It is higher in children. There is also a gender difference with males having a higher BMR than females.
C. False. This is true for the cerebral metabolic rate not the body’s basal metabolic rate.
D. True. It must also be measured 12-14 hr after their last meal (a time when one is said to be thermoneutral).
E. False. It may be measured indirectly using a Wet Spirometer not an ergometer. An ergometer is used to measure energy expenditure whilst active.
Insulin:
A. Is antagonised by growth hormone
B. Facilitates protein anabolism
C. Promotes glycogen synthesis in the liver
D. Facilitates the deposition of fat
E. Inhibits the passage of potassium ions into cells
A. True. The 5 counter-regulatory hormones that antagonise insulin-induced hypoglycaemia are adrenaline, noradrenaline, glucagon, growth hormone and cortisol.
B. True. Insulin is the only major anabolic hormone. Hence it stimulates synthesis of proteins, fat and glycogen.
C. True.
D. True.
E. False. Insulin facilitates the passage of potassium ions into cells and is often used as a treatment for hyperkalaemia.
Considering lactate metabolism:
A. One molecule of lactate is produced for every glucose molecule during anaerobic metabolism
B. Fitness training does not affect the rate of rise in plasma lactate
C. Glucose metabolism to lactate releases ATP at the same rate as oxidation within the mitochondria
D. After exercise lactate is largely reconverted into glucose
E. Lactate filtered in the kidney is actively reabsorbed
A. False. Each glucose is converted to 2 pyruvate and these are converted to 2 molecules of lactate.
B. False. At a certain level of exercise the plasma lactate level rises sharply. This is at between 50-80% of maximal O2 consumption. In an untrained person plasma lactate will rise at a lower level of exercise than in the trained.
C. False. Glucose metabolism to lactate releases ATP at least twice as rapidly as mitochondrial metabolism and can optimally provide energy for 1.5 minutes of maximal muscle activity.
D. True. After exercise 80% of lactate present is reconverted to glucose in the liver via the Cori cycle.
E. True. Filtered lactate is actively reabsorbed by the nephron to a transport maximum of 75 mg/min.
Hyperglycaemia may result from the administration of:
A. Adrenaline
B. Thyroid stimulating hormone
C. Beta blockers
D. Thiazide diuretics
E. Glucagon
A. True. Adrenaline increases glucagon secretion and stimulates gluconeogenesis.
B. True. Thyroid hormone stimultaes: increased glucose absorption from the gut, glycogenolysis and gluconeogenesis.
C. False. Patients on beta blockers are at risk of hypoglycaemia under general anaesthesia.
D. True. Thiazide diuretics commonly precipitate Type 2 diabetes.
E. True.
Glucagon release:
A. Stimulates gluconeogenesis
B. Inhibits adenylate cyclase in liver cells
C. Stimulates secretion of growth hormone
D. Is inhibited by cortisol
E. Is stimulated by theophylline
A. True. Glucagon is gluconeogenic, glycogenolytic, and lipolytic.
B. False. It acts via G-protein linked receptors.
C. True. Glucagon is formed in the pancreatic alpha-cells. Secretion is stimulated by beta-mediated sympathetic nerves to the pancreas, acetylcholine, amino acids, CCK and gastrin.
D. False. Secretion is stimulated by cortisol and infection, but inhibited by alpha stimulation, insulin, glucose, ketones, phenytoin and somatostatin.
E. True. Theophylline and other phosphodiesterase inhibitors also stimulate its release.
In starvation:
A. Free fatty acid oxidation in the liver, muscle and heart is increased
B. Muscle glycogen and brain glycogen are replenished by gluconeogenesis
C. Ketone bodies produced in the liver from free fatty acids can be utilized by brain cells but glucose is still essential
D. Glucose can be formed from fatty acids
E. The odour of the breath is due to ketosis
A. True. In starvation, glycogenolysis occurs and the liver begins to use fatty acids as a source of energy.
B. False. As the glycogen is depleted, gluconeogenesis increases using amino acids from the breakdown of muscle protein. Glycogen is not replenished until the return of nutrients, this restorative process is under the control of cortisol.
C. True. Most tissues, including the brain, can ultimately adapt to the use of ketone bodies as a fuel source. However the brain cannot survive without glucose.
D. False. Glycerol can be used to produce glucose but the free fatty acids undergo beta-oxidation to produce ATP in the mitochondria.
E. True.
Insulin and growth hormone have directly opposing effects on:
A. Fat catabolism
B. Glucose utilisation
C. Fat anabolism
D. Protein anabolism
E. Glycogen production
A. True. Growth hormone causes fat breakdown.
B. True. Growth hormone inhibits glucose utilization, whereas insulin stimulates glucose absorption.
C. True. Insulin stimulates fat deposition.
D. False. Both insulin and growth hormone promote protein synthesis.
E. True. Insulin stimulates glycogen deposition, whereas growth hormone encourages glycogenolysis.
Consequences of starvation include:
Select true or false for each of the following statements.
True
False
A. Increased brain uptake of glucose
B. Reduction of the respiratory quotient
C. Elevated blood glucagon levels
D. Increased urinary nitrogen output
E. Development of metabolic alkalosis
A. False. Glucose supply to the brain is a priority in starvation as it is largely dependent on glucose as an energy substrate. The brain can however metabloise ketones.
B. True. As metabolism switches to the burning of fats the respiratory quotient drops towards 0.7.
C. True. Glucagon levels go up as the body enters a catabolic phase with increased glycogenolysis.
D. True. Increased protein breakdown leads to increased urinary nitrogen excretion.
E. False. The accumulation of acetyl-CoA leads to ketoacidosis, not alkalosis.
Considering ketone bodies:
A. The majority of amino acids can be converted into acetoacetate
B. The liver converts fatty acids into acetoacetate for transport to other parts of the body
C. Ketosis can arise from a diet composed almost entirely of fat
D. Citrate availability limits entry of acetyl-CoA into the citric acid cycle
E. Ketoacidosis causes hyponatraemia
A. True. The majority of amino acids after deaminationcan be converted into acetyl-CoA from which acetoacetate can be formed.
B. True. Fatty acid degradation occurs largely in the liver where aceyl-CoA is formed leading to acetoacetate production. This is transported at low levels but with efficient flux to the rest of the body.
C. True. Ketosis, the presence of excessive levels of acetoacetate, beta-hydroxybutyrate or acetone in the blood can arise in starvation, diabetes mellitus or in a very high fat based diet.
D. False. Sufficient oxaloacetate is needed to receive acetyl-CoA into the citric acid cycle.
E. True. Ketoacids are easily excreted by the kidney but being strong acids they are excreted combined with Na+ from the extracellular fluid. The resultant hyponatraemia leads to an increased acidosis beyond that occasioned by the direct rise in ketoacid levels.
Rotameters:
A. Are variable orifice flowmeters
B. Produce a constant pressure drop across the bobbin
C. Produce laminar flow at low flow rates
D. May produce turbulent flow at low flow rates
E. May be lined with gold
A. True. rotameters are variable orifice flowmeters whereas pneumotachographs are variable pressure, constant orifice flowmeters.
B. True.
C. True.
D. False. This is because the annulus of the bobbin is narrow, compared to its length against the flowmeter wall. Therefore it tends to act as a tube, and flow tends to be laminar. If the annulus was wide and the length was short, it would behave as an orifice and therefore flow would be turbulent.
E. True. It acts as an anti-static coating.
Concerning Flow:
A. If Reynold’s number exceeds 1500, turbulent flow is always present
B. The critical velocity is the gas velocity at which laminar flow changes into turbulent flow
C. Helium reduces the density of inspired gases and therefore the likelihood of turbulent flow within the respiratory system
D. Turbulent flow within blood vessels may be detectable by invasive techniques
E. Reynold’s number depends on tube thickness
A. False. If Reynold’s number is >2000, flow is likely to be turbulent. Under 2000 it is likely to be laminar.
B. True.
C. True. By reducing the density, the Reynold’s number is reduced and therefore the likelihood of turbulent flow.
D. True.
E. False.
Regarding the pneumotachograph:
A. The lumen expands into a small number of large tubes
B. It has a sensitive differential pressure transducer across the resistor
C. Output is unaffected by gas viscosity
D. It may give erroneous readings in the presence of water vapour
E. Works on the principle of Poiseuille’s Law
A. False. In a Fleisch pneumotachograph the lumen divides into a large number of smaller tubes.
B. True. The pressure gradient across the transducer is what allows flow to be calculated.
C. False. Flow is affected by viscosity, therefore the pressure difference across the transducer will also be affected.
D. True. Water vapour can block differential pressure transducers, or smaller tubes in a Fleisch pneumotachograph.
E. True.
The following statements are true of gas flow:
A. Gas flow is proportional to the fourth power of the radius in turbulent flow
B. Resistance is directly proportional to the length of a tube
C. A gas with low density is likely to develop turbulent flow
D. Flow is dependent on viscosity in laminar flow
E. A warmed gas flow is more likely to be laminar
A. False. This is related to the Hagen-Poiseuille equation, which applies ONLY to laminar flow.
B. True. According to the Poiseuille equation Flow is proportional to the pressure difference and fourth power of the radius and inversely proportional to viscocity and the length of the tube. From Ohms law, as resistance is pressure/flow, this means that it is directly proportional to the length of the tube.
C. False. The Reynold’s number is proportional to density, therefore the lower the density , the lower the Reynold’s number. Turbulent flow is more likely with a Reynold’s number >2000.
D. True. Laminar flow depends on fluid viscosity.
E. True. Increasing gas temperature reduces density, which therefore reduces Reynold’s number.
Regarding fluid flow:
A. Flow is laminar in tubes that are very long compared with their diameter
B. Flow is turbulent when Reynold’s Number is >2000
C. Flow through an orifice is influenced by the fluid or gas viscosity
D. Velocity is higher and pressure is lower at the point of constriction in a tube
E. At low haematocrit, blood flow is better in blood vessels
A. True. This is why at low flows, the flow across a bobbin in a rotameter is laminar. The bobbin makes the gas behave as it flowing through a tube, rather than an orifice.
B. True. Flow is laminar when Reynold’s number is <2000.
C. False. Flow through an orifice is always turbulent and therefore dependent on density.
D. True. This is the Bernouille principle and is due to conservation of energy.
E. True. Low haematocrit results in low viscosity, improving flow (but predisposing to turbulence).
Regarding gas or liquid flow:
A. In laminar flow, flow is determined by the pressure gradient divided by resistance
B. In laminar flow, resistance is constant and independent of flow
C. resistance decreases with flow in turbulent flow
D. Poiseuille’s law does not apply in turbulent flow
E. Flow through an orifice is always turbulent
A. True. This is shown in the Hagen-Poiseuille equation.
B. True. Whereas in turbulent flow resistance increases with flow in an exponential manner.
C. False. See above.
D. True. Poiseuille’s law only applies to laminar flow.
E. True.
Pressure:
A. Is force per unit distance
B. Can be expressed as the width of fluid in a column
C. Is force divided by area
D. Is work per unit volume
E. Has potential difference as its electrical analogue
A. False. Pressure is force per unit area
B. False. It can be expressed as the height of fluid in a column
C. True. Pressure is force per unit area
D. True. Pressure is work per unit volume
E. True. If we substitute pressure as voltage into Ohm’s Law, where current is flow, and resistance is unchanged
Resistance to laminar flow in a vessel is:
A. Proportional to wall thickness
B. Inversely proportional to the fourth power of the radius
C. Proportional to length
D. Independent of haematocrit
E. Proportional to the pressure drop
A. False. Wall thickness plays no role in resistance to laminar flow.
B. True. From the Poiseuille equation we see that flow is directly proportional to the fourth power of the radius which means that resistance is inversely proportional to the fourth power of radius. (V=IR Ohms law)
C. True. See above.
D. False. Laminar flow depends on fluid viscosity (haematocrit affects blood viscosity).
E. True. Flow = Pressure drop/Resistance, therefore Resistance = Pressure drop/Flow.
Bourdon Gauge’s:
A. Contain a Torcellian vacuum
B. Are always oval in cross-section
C. Makes use of Charles’ Law
D. Are easy to recalibrate
E. Cannot be used for temperature measurement
A. False. A barometer contains a Torrcellian vacuum.
B. False. As pressure increases, the cross-section becomes more circular.
C. True. When used to measure temperature.
D. False. They are very difficult to recalibrate.
E. False. They can make use of Charles’ Law to measure temperature
Units of Pressure:
A. 1 Bar is the equivalent of 10 atmospheres
B. 1 mmHg is the same as 1 Torr
C. Pressure increases by 1 Atmosphere for every 100 cmH2O
D. Readings in mmHg are numerically lower than cmH2O due to Hg’s greater density
E. 1 Atmosphere = 760 Torr
A. False. 1 Bar = 1 Atmosphere
B. True.
C. False. 1 Atmosphere = 1035 cmH2O
D. True. Hg is approximately 13 times denser than H2O
E. True. 1 Torr = 1 mmHg and 1 Atmosphere = 760 mmHg = 760 Torr
The Magill (Mapleson A) breathing system:
A. Is the most efficient Mapelson system for spontaneously breathing patients
B. Will work with minimal re-breathing at a fresh gas flow of 70% of minute volume in spontaneous ventilation
C. Makes scavenging of exhaled gases easier
D. The co-axial version is the Lack system
E. Is also efficient during controlled ventilation
A. True. This system is characteristically efficient for spontaneous ventilation but not controlled ventilation.
B. True.
C. False. Scavenging requires an appropriate system to be connected to the APL valve but this is not particularly more or less easy to achieve for the Mapleson A than other systems.
D. True.
E. False.
Breathing (reservoir) bags:
A. Have a capacity roughly equating the vital capacity of an 80 Kg adult
B. A standard 0.5L bag can be used with a Jackson-Rees system
C. Prevent wastage of fresh gas flow during expiratory pause
D. Provide a rough visual assessment of volume of ventilation
E. Act as a reservoir because the anaesthetic machine can not provide the peak inspiratory flow required in normal respiration
A. False. The reservoir bag for adult use has a volume of approximately 2L.
B. False. The Jackson-Rees modification to the Mapelson E (making it a Mapelson F) includes a specialised reservoir bag with an opening at the end to allow a controlled leak and variable PEEP.
C. True.
D. True.
E. True.
Regarding breathing systems used in anaesthesia:
A. The Magill system is most efficient for spontaneously breathing patients even at a fresh gas flow (FGF) of 70% of minute ventilation
B. D, E and F systems are all T pieces
C. The Bain system requires a FGF of 50-60 ml/kg during spontaneous breathing
D. The rate of change of vapour concentration in circle system depends on circle system volume, the FGF rate and net gas uptake
E. The Magill system is inefficient during controlled ventilation because much of the gases are vented via pop-off valve
A. True.
B. True.
C. False. The Bain system (a Mapelson D variant) requires a FGF 2-3x minute ventilation to prevent rebreathing.
D. True.
E. True.
Concerning absorption of carbon dioxide in breathing systems:
A. Soda lime granules are size 4-8 mesh
B. Baralyme contains calcium hydroxide in addition to barium hydroxide
C. Soda lime produces more compound A during low fresh gas flow
D. Dry soda lime absorbs more carbon dioxide
E. Carbon dioxide first reacts with sodium and potassium hydroxide of soda lime
A. True.
B. True.
C. True.
D. False. Water is generated by the overall reaction of CO2 with soda lime but it’s presence or absence does not influence it’s ability to absorb CO2.
E. True.
Regarding anaesthetic breathing systems:
A. Re-breathing does not occur in Mapleson D during controlled ventilation
B. With a fresh gas flow (FGF) <1.5 L, volatile concentration in the breathing system may be higher than the dial setting of the vaporiser at steady state
C. In the circle system with a FGF <1 L (N2O:O2=66:34), FIO2 in the circle may increase over time
D. A FGF of 3 times the minute volume may be needed to prevent re-breathing in Bain’s co-axial system during spontaneous ventilation
E. Dead space gas is preserved in Magill system during spontaneous ventilation
A. False. Re-breathing can be prevented from occurring in controlled ventilation with the Mapelson D but this is dependent on adequate fresh gas flow.
B. False. The delivered volatile concentration is, in practice, rarely the same as the dial setting but it cannot exceed it except in the few moments after the vapouriser is dramatically turned down or switched off and the system is re-equilibrating.
C. False. In low flow operation of the circle, particularly where the oxygen volume supplied falls towards or below metabolic requirements, the FiO2 will steadily fall and the circle will empty; N2O rapidly equilibrates and so uptake of N2O will not exceed that of oxygen so increase in oxygen concentration does not result.
D. True.
E. True.
Regarding nitrous oxide:
Select true or false for each of the following statements.
True
False
A. Has a MAC of 1.05
B. Can be safely administered via a Quantiflex mixer
C. Has a pseudocritical temperature of -5.5C
D. Is an inert gas
E. Is recognisable by French-blue cylinders and a pin-index of 3 and 5
A. False. Nitrous oxide has a MAC of 105% and so is not an anaesthetic suitable for use at STP as pure nitrous oxide would neither have a MAC of 1.0 nor deliver any oxygen to the patient.
B. True. It can be safely delivered via a Quantiflex mixer which allows a full range oxygen/nitrous oxide mixtures to be administered from 21-100% oxygen so avoiding accidental hypoxic mixtures.
C. False. A pseudocritical temperature is a property of gas mixtures such as entonox.
D. False. Nitrous oxide is not an inert gas and in fact with sufficient heat, dissociates to become an avid oxidant.
E. True.
The Mapleson A breathing system:
Select true or false for each of the following statements.
True
False
A. Is a non-rebreathing system
B. Must have the expiratory valve close to the patient
C. Requires a fresh gas flow equal to the dead space ventilation
D. Requires a higher fresh gas flow than a Mapleson D system in manual ventilation
E. Was modified by Magill from Mapleson’s original design
A. False. Re-breathing can occur with any Mapelson system if used incorrectly.
B. False. The position of the APL relative to the patient is not the critical factor and the Lack system is a Mapelson A where the APL is removed from the patient end of the system.
C. False. Fresh gas flow requirements are determined by the ventilation mode - 70% of MV in spontaneous ventilation, 200-300 ml/kg in controlled ventilation.
D. True.
E. False. William Mapelson classified the semi-open breathing systems by functional characteristics, he did not design them.
Activated charcoal, as used in the Cardiff Aldasorber:
A. Does not absorb nitrous oxide
B. Is effective in absorbing isoflurane
C. Increases expiratory resistance significantly
D. Can be reactivated by heating to remove the absorbed agents
E. Changes from white to blue when exhausted
A. True.
B. True.
C. False. The Cardiff Aldasorber is a low resistance device.
D. True.
E. False. There is no indicator dye; the only change the device undergoes during use is a small and gradual increase in mass as volatile substances are adsorbed onto the granules.
A canister of soda-lime:
A. Contains mostly calcium carbonate
B. Requires water for the absorption process
C. Contains 50% by weight of sodium hydroxide
D. Will absorb nitrous oxide
E. When packed will be 50% filled with granules
A. False. The principal ingredient in soda-lime is calcium hydroxide with others including sodium hydroxide (3%) and water (20%).
B. True. Though water does not change CO2 absorption characteristics, dry soda lime can generate carbon monoxide when using volatiles containing the CHF2 moiety
C. False.
D. False. Nitrous oxide is not absorbed.
E. True.
When using a circle system (with a CO2 absorber) and a vaporiser outside the circle:
A. A fresh gas flow of at least 2/3 of the minute volume is required
B. The actual inspired vapour concentration during maintenance may be higher than the vaporiser setting
C. The actual inspired oxygen concentration may be lower than that of the fresh gas at low fresh gas flows
D. Sevoflurane is a suitable agent to use
E. The system can only be used for patients breathing spontaneously
A. False. Due to the ability to largely recycle gases and a lack of leaks, modern circle systems can sustain very low flows; in a fully closed configuration, total gas flow can be reduced to 100% oxygen at a rate equivalent to the metabolic requirements of the patient (200-300ml/min).
B. False. During maintenance (i.e. at steady-state), the inspired volatile agent will eventually reach but never surpass the set concentration on the vapouriser.
C. True.
D. True.
E. False. The circle can be used equally well in spontaneous or controlled ventilation.
Propofol:
A. Is highly protein bound
B. Produces vasodilatation by nitric oxide production
C. Is only partly unionized at physiological pH
D. Has a hydroxyl group situated on its 4th carbon
E. Undergoes both phase 1 and phase 2 metabolism
A. True. 97% protein bound.
B. True. Propofol causes hypotension (reduction in sytsemic vascular resistance and cardiac output) without tachycardia. Bradycardia is common, especially with opiate co-administration.
C. False. The pka of propofol is 11, therefore at pH 7.4 it is almost entirely unionized.
D. False. The hydroxyl group is situated on the 1st carbon. Phase 1 metabolism into a quinol derivative involves hydroxylation of the 4th carbon.
E. True. Glucuronidation is the predominant metabolic pathway, hydroxylation by cytochrome P450 to a quinol derivative prior to conjugation is also an important pathway. The relative importance of each pathway varies amongst patients.
Propofol:
A. Is used at a dose of around 4 mg/kg for IV paediatric induction
B. Causes a reduction in cardiac output solely by reducing heart rate
C. Clearance is by hepatic metabolism alone
D. Acts as an anti-emetic by competitive antagonism of central serotonin receptors situated in the chemoreceptor trigger zone
E. Is a cause of hypertrigylcerideaemia
A. True. Approx double the typical adult dose.
B. False. Propofol also reduces myocardial contractility and sympathetic tone.
C. False. Extra-hepatic metabolism is significant, suggested by the fact that clearance is higher than hepatic bolod flow. Sites for extra-hepatic metabolism include the kidneys (responsible for about a third of extra-hepatic metabolism) and lungs (to 2, 6 - diisopropyl - 1, 4 - quinol).
D. False. The anti-emetic effect of propofol is probably mediated through dopamine receptor antagonism.
E. True. This may be a part of the metabolic syndrome seen in children after prologed infusion. Propofol infusions have been linked to organ fatty infiltration with severe bradycardias, metabolic acidosis and increased mortality.
With regards to IV induction agents:
A. Propofol has the same volume of distribution as ketamine
B. Propofol has the highest clearance rate
C. The clearance rate of etomidate is 5 ml/kg/min
D. Thiopentone has a higher percentage of protein binding that methohexitone
E. Thiopentone has a pKa of 10.6
A. False. Propofol 4 L/kg. Ketamine 3 L/kg. Etomidate 3 L/kg. Thiopentone 2.5 L/kg.
B. True. 30-60 ml/kg/min.
C. False. Etomidate 10-20 ml/kg/min, Ketamine 17 ml/kg/min, Thiopentone 3.5 ml/kg/min
D. True. Thiopentone 80%. Methohexitone 60%.
E. False. pKa of thiopentone is 7.6
Midazolam:
A. Is 68% protein bound
B. Is 40% unionized at physiological pH
C. Has inactive metabolites
D. Is metabolised by the same cytochrome P450 system as alfentanil
E. Is given in oral doses of up to 1 mg/kg in paediatric premedication
A. False. 98% protein bound.
B. False. Midazolam is a tautomeric molecule consisting of benzene and diazepine rings. In a pH > 4 the diazepine ring closes producing a lipid soluble unionized molecule. With a pKa of 6.5 around 89% of molecules are unionized at physiological pH.
C. False. The phase 1 metabolite 1-alpha-hydroxy-midazolam is active. This may then be conjugated (glucuronidation) prior to excretion.
D. True. CP450 3A3/4. The action of midazolam may be prolonged by co-administration of alfentanil.
E. True. 30 minues prior to induction. Monitoring is required if doses >0.5 mg/kg are used.
Ketamine:
A. Is a competitive antagonist of NMDA receptors
B. Is prepared as a racemic mixture in which the R- isomer is more potent than the S+
C. Is used as an oral premedication in doses of 2-5 mg/kg
D. Emergence phenomena is less common in the young and elderly
E. Undergoes cytochrome P450 de-methylation to the inactive metabolite norketamine
A. False. Non-competitive antagonist.
B. False. S+ is 2-3 times more potent than the R- isomer. It may also produce less intense emergence phenomena.
C. True. 20% bioavailability. Doses of up to 10 mg/kg have be used in extreme cases.
D. True.
E. False. Norketamine is active, this then undergoes glucuronidation to an inactive metabolite which is excreted.
Ketamine:
A. Is stored as an aciditc solution
B. Induces dissociative anaesthesia with predominant beta activity on EEG
C. Reduces cerebral oxygen consumption
D. Is 25-50% protein bound
E. Is a direct myocardial depressant
A. True. pH 3.5-5.5. Ampoules can contain 10, 50 or 100 mg/ml.
B. False. Theta and delta activity is pre-dominant during ketamine induced dissociative anaesthesia.
C. False. Cerebral oxygen consumption, blood flow and intracranial pressure are all increased by ketamine.
D. True.
E. True. Ketamine increases sympathetic tone and circulating levels of adrenaline and noradrenaline. This produces the cardiovascular effects seen clinically of tachycardia, increased cardiac output, increased / maintained blood pressure and elevated CVP. However, ketamine also produces a mild direct myocardial depressant effect that is masked, less so for the S+ isomer.
Etomidate:
A. Is prepared with 35% propylene glycol
B. Produces pain on injection in 75% of cases
C. Causes nausea and vomiting
D. Is given as an IV induction dose of 2-3 mg/kg
E. Produces excitatory movements with epileptiform activity on EEG
A. True.
B. False. Produces pain in around only 25%.
C. True.
D. False. The IV induction dose is 0.2-0.3 mg/kg
E. True. Etomidate is the most likely IV induction agent to cause myoclonic movements and epileptiform activity on EEG - in around 20% of cases.
Etomidate:
A. Has an ester bond
B. May be used in patients with porphyria
C. Is predominanlty protein bound
D. Inhibits adrenal medullary function
E. Has the same volume of distribution as ketamine
A. True. Etomidate is an imidazole derivative and an ester.
B. False. Etomidate is known to cause a porphyric crisis.
C. True. Around 75%.
D. False. Etomidate has been shown to inhibit 11-beta and 17-alpha hydroxylase function and impair aldosterone and cortisol synthesis for up to 24 hours after administration. Steroidogenesis occur in the adrenal cortex.
E. True. 3 l/kg
Thiopentone:
A. Is prepared as a hygroscopic yellow powder in 8% sodium carbonate
B. When reconstitued with water produces a 2.5% solution
C. At physiological pH 60% of the drug is unionized in blood
D. Is metabolised to pentobarbitone
E. When in solution is found predominantly in its keto form
A. False. 6% sodium carbonate.
B. True.
C. True.
D. True. Pentobarbitone is an active metabolite.
E. False. It is predominantly in its enol form when in solution. The enol form is soluble. Thiopentone is tautomeric and alkaline conditions promote the switch from keto to enol.
Thiopentone:
A. Has a sulphur group on its 2nd carbon
B. Is a bronchodilator
C. Stimulates anti-diuretic hormone release
D. Is an enzyme inhibitor
E. Is more active in alkalotic conditions
A. True. There is an oxygen group in this position in oxybarbiturates.
B. False. Thiopentone may produce laryngospasm and bronchospasm.
C. True. This is one of the reasons why thiopentone causes a reduction in urine output.
D. False. Thiopentone is an enzyme inducer.
E. False. Acidosis and hypoalbuminaemia increases the amount of free unionized drug. A lower dose is often needed in critically ill patients.
Remifentanil:
A. Undergoes hepatic metabolism
B. Has a half life of approximately 20 minutes
C. Has a short duration due to rapid redistribution
D. Has a potency similar to fentanyl
E. Has a prolonged action in patients with pseudocholinesterase deficiency
The pharmacological effects of Morphine include:
A. Constipation
B. Biliary spasm
C. Histamine release
D. Cough
E. Release of antidiuretic hormone
Fentanyl:
A. Has a potency 10 times that of morphine
B. Is highly water-soluble
C. Has a large volume of distribution
D. Does not accumulate even after repeated doses
E. Is metabolised to norfentanyl
Diclofenac:
A. Works by inhibiting lipo-oxygenase
B. May increase renal blood flow
C. Has anti-pyretic properties
D. Reversibly promotes platelet aggregation
E. May be used in the last trimester of pregnancy
Alfentanil:
A. Is more lipid soluble than pethidine
B. Is less lipid soluble than fentanyl
C. Is highly protein bound
D. Is more potent than fentanyl
E. Has clinically important active metabolites
Tramadol:
A. Is a controlled drug
B. Can be administered intravenously
C. Has affinity for binding at the mu opoid receptor comparable to that of morphine
D. Acts predominantly by inhibiting the reuptake of noradrenaline and serotonin (5-HT)
E. May be used concurrently with a MAOI
The metabolism of morphine involves:
A. Acetylation
B. Demethylation
C. Oxidation
D. Methylation
E. Conjugation with glucouronide
Clonidine:
A. Is predominantly an alpha-1 adrenergic agonist
B. Is poorly absorbed orally
C. Lowers the MAC of volatile anaesthetic agents
D. Attenuates the stress response to endotracheal intubation
E. Can be used for spinal analgesia
The following drugs are antagonised by naloxone:
A. Bupranorphine
B. Dextropropoxyphene
C. Etomidate
D. Midazolam
E. Remifentanil
The following statements are true:
A. Paracetamol is oxidised to N-acetyl P-Benzoquinoneimine (NAPQI)
B. Paracetamol is antagonised by N-Acetyl Cysteine (NAC)
C. Paracetamol reduces prostaglandin synthesis
D. Aspirin overdose causes a metabolic alkalosis
E. Aspirin reversibly inhibits cyclooxygenase
A. True. NAPQI is a potent cell toxin. 10% of paracetamol is oxidised to NAPQI which is usually safely conjugated with glutathione. If glutathione is depleted, as in paracetamol overdose, it bonds to exposed protein SH groups causing inactivation and cell necrosis in a centrilobular pattern.
B. False. NAC replaces glutathione to allow safe metabolism of paracetamol.
C. True. Paracetamol reduces the COX enzyme to reduce prostaglandin synthesis.
D. False. Aspirin (Salicylic acid) causes a metabolic acidosis and respiratory alkalosis in adults. It is an acid in itself and promotes hyperventilation by a direct effect.
E. False. Aspirin irreversibly inhibits COX and therefore its effects on platelets last until the platelet is replaced as platelets do not have a nucleus and therefore lack capacity to produce new COX enzymes.
Plasma cholinesterase:
A. Acquired deficiencies of the enzyme in genotypically normal patients prolongs suxamethonium activity for several hours
B. The commonest genotype for cholinesterase activity is Eu:Eu
C. Deficiency occurs in pregnancy
D. Homozygotes always experience a prolonged suxamethonium block
E. Patients who are homozygotes for the fluoride resistant gene have a near normal dibucaine number
A. False. The prolongation of action in genotypically normal patients, i.e. with acquired deficiencies of the enzyme, is usually no longer than 30 minutes.
B. True. Eu:Eu is the commonest genotype and it is present in 96% of the population. These homozygotes have a completely normal recovery from suxemethonium.
C. True. Pregancy is an acquired factor associated with reduced plasma cholinesterase deficiency. Other causes are Liver disease, Renal and Cardiac Failure, Thyrotoxicosis, Cancer and a number of drugs.
D. False. Eu:Eu is a homozygote.
E. True. Their dibucaine number is around 70 (compared with 80 for Eu homozygotes).
Dibucaine is an amide local anaesthetic. The dibucaine number indicates the percentage that it inhibits the various forms of plasma cholinesterase. The normal Eu Eu genotype is most inhibited (80%), Ea Ea and Es Ea genotypes are least inhibited (20%).
The silent gene homozygotes Es Es have no plasma cholinesterase activity to inhibit and so do not have a dibucaine number.
Contraindications to suxemethonium include:
A. The presence of renal failure
B. 48 hours following major burns
C. Malignant hyperpyrexia
D. Pregnancy
E. Day case anaesthesia
A. False. Renal failure does not itself cause a hyperkalaemic response to suxemethonium, however hyperkalaemia secondary to acute renal failure would increase the risk of arrhythmias.
B. True. Burns patients (>10% of body surface) are at greatest risk of suxemethonium induced hyperkalaemia from 24 hours after the injury until around 18 months.
C. True. Along with all the volatile inhalational agents.
D. False. Though it’s action may be slightly prolonged.
E. False.
Malignant hyperthermia:
A. Exhibits autosomal recessive inheritance
B. Is associated with a defect on the ryanodine receptor encoded on chromosome 19
C. Diagnosis is based on response of biopsied skeletal muscle to 2% halothane and cafffeine (2mmol/L)
D. Without dantrolene the mortality can be as high as 70%
E. Each vial of dantrolene reconstituted with 60ml water produces a solution of pH 8.0
A. False. MH is a rare autosomal-dominant condition. Incidence in UK 1 in 200,000.
B. True.
C. True.
D. True.
E. False. Dantrolene is available as capsules and in vials as an orange powder containing 20 mg dantrolene, 3 g mannitol and sodium hydroxide. Each vial when reconstituted with 60 ml water has a pH of 9.5.
Safe drugs in malignant hyperthermia include:
A. Propofol
B. Fentanyl
C. Ketamine
D. Etomidate
E. Nitrous Oxide
True.
True.
True.
True.
True.
Sumemethonium and all volatile anaesthetic agents are the only triggers of MH.
The effects of non-depolarising musle relaxants are prolonged by:
A. Volatile anaesthetics
B. Hyperthermia
C. Lithium
D. Calcium channel antagonists
E. Hypomagnesaemia
A. True.
B. False. Action is prolonged by hypothermia.
C. True.
D. True. There is a reduced calcium influx resulting in reduced ACh release.
E. False. Effects are prolonged by hypermagnesaemia due to the decrease in ACh release caused by competition with calcium and by stabilization of the post juntional membrane.
Effects are also prolonged by aminoglycoside antbiotics, such as gentamicin or tobramycin.
Atracurium:
A. Has 4 chiral centres and 10 stereoisomers
B. Undergoes Hofmann elimination accounting for 60% of its metabolism
C. Hofmann elimination is potentiated by acidosis and hypothermia
D. A product of its metabolism is laudanosine, a glycine antagonist
E. Laudanosine is a breakdown product of both ester hydrolysis and Hofmann degradation.
A. True.
B. False. Hofmann elimination only accounts for 40% of atracurium’s metabolism.
C. False. Acidosis and hypothermia will slow down the process of Hofmann elimination.
D. True.
E. True.
Cis-atracurium:
A. Is one of the 10 stereoisomers present in atracurium
B. Is 10 times more potent than atracurium
C. Is predominantly eliminated by ester hydrolysis
D. Is safe for use in patients with renal failure
E. Has metabolites with neuromuscular blocking properties
A. True.
B. False. It is approximately 3 to 4 times more potent than atracurium.
C. False. It is predominantly eliminated by Hofmann elimination and its metabolites have no neuromuscular blocking properties.
T
D. rue. It can be used safely in both renal and hepatic failure.
E. False. It is predominantly eliminated by Hofmann elimination and its metabolites have no neuromuscular blocking properties.
The following are benzylisoquinolinium compounds:
A. Atracurium
B. Midazolam
C. Pancuronium
D. Tubocurarine
E. Mivacurium
A. True.
B. False. Midazolam is a benzodiazepine.
C. False. Pancuronium is an aminosteroidal compound.
D. True.
E. True.
Other effects of suxemethonium:
A. Sinus or nodal bradycardia secondary to sympathetic ablation
B. Myalgia, particularly in young women
C. Patients with severe burns or neuromuscular disorders are susceptible to sudden, massive release of potassium
D. Can cause a rise in intra-occular pressure by about 10mmHg for a matter of minutes following administration
E. Raises intragastric pressure by 10 cmH2O
A. False. Sinus or nodal bradycardia is caused via stimulation of muscarinic receptors in the sinus node.
B. True. Muscle pains are commonest in young females mobilizing rapidly in the post operative period.
C. True. May be large enough to provoke cardiac arrest.
D. True. Normal intraocular pressure is 10-15 mmHg making this a 100% rise in intra-ocular pressure which can be significant in the presence of globe perforation.
E. True. Though suxemethonium simultaneously increases lower oesophageal sphincter tone so there is no increased risk of reflux.
Vecuronium:
A. Is relatively cardio-stable
B. Is presented as a powder containing mannitol and sodium hydroxide.
C. May cause critical illness myopathy
D. Precipitates histamine release
E. Its chemical structure differs from pancuronium by a single methyl group
A. True. The aminosteroids are not assocciated with the histamine release seen with the benzylisoquinolinium compounds.
B. True. It is unstable in solution and therefore presented as a freeze-dried powder containing mannitol and sodium hydroxide.
C. True. As can all musle relaxants if used long term.
D. False.
E. True.
Esmolol:
A. Is useful in the treatment of essential hypertension
B. Has a half life of 2 minutes
C. Is largely excreted unchanged in the urine
D. Acts selectively on beta-1 receptors
E. Possesses intrinsic sympathomimetic activity
A. False. It is only given intravenously and has a short half life.
B. False. It is around 10 minutes.
C. False. It is rapidly metabolised by red-cell esterases.
D. False. It is non-selective.
E. False.
The following statements about selective phosphodiesterase (PDE) inhibitors are true:
Select true or false for each of the following statements.
True
False
A. Inhibition of isoenzyme family No. I effects a positive inotropic action
B. Inhibition of isoenzyme family No. III results in clinically important bronchodilatation
C. They increase myocardial oxygen consumption
D. Tachycardia is a common occurrence
E. Their use increases hblood pressure as a result of increased cardiac output and systemic vascular resistance.
A. False. Inhibition of isoenzyme family No. III results in positive inotropy.
B. False. Bronchodilatation does occur but not to a clinically significant degree.
C. False. There is unchanged or even slightly reduced myocardial oxygen consumption as systemic vasodilation reduces left ventricular systolic wall tension.
D. True. There is a reflex tachycardia.
E. False. Hypotension is often seen as a result of reduced systemic vascular resistance due to smooth muscle relaxation.
Milrinone:
A. Is one of the bipridine derivative group of phosphodiesterase inhibitors.
B. Is structurally related to amrinone
C. It’s short half life makes it well suited to use as an infusion
D. Doses should be reduced in end stage renal failure
E. Is incompatible with intravenous frusemide when given through the same cannula
A. True. Enoximone and piroximone are imidazolone derivatives.
B. False.
C. False. It is used in infusion form but has a terminal half life of 2.5 hours. A loading dose is required.
D. True. 80% is excreted unchanged via the kidneys and dose reductions are required when the creatinine clearance falls to less than 30 ml/min.
E. True.
Clonidine:
A. Is a selective partial agonist for the alpha-2 adrenoceptor with a ratio of approximately 200:1 (alpha2:alpha1)
B. Is rapidly absorbed when given orally
C. When given as premedication, it reduces the MAC by up to 50%
D. Discontinuation can result in hypertension
E. Has a diuretic effect in humans
A. True.
B. True.
C. False. It does reduce MAC but only the highly selective drugs such as dexmedetomidine have lowered anaesthetic requirements to this degree.
D. True. Rebound hypertension occurs on discontinuation of long term use.
E. True. It inhibits the release of ADH.
The following are indications for the use of ACE inhibitors:
A. Pre-eclampsia
B. Essential hypertension
C. Hypertension secondary to bilateral renal artery stenosis
D. Following acute myocardial infarction
E. Chronic congestive cardiac failure
A. False. ACE Inhibitors are contraindicated in pregnancy.
B. True.
C. False. ACE Inhibitors are contraindicated in bilateral renal artery stenosis or unilateral renal artery stenosis supplying a single kidney as renal failure may supervene.
D. True.
E. True.
Ephedrine:
A. Is a catecholamine
B. Causes the stimulation of both alpha and beta adrenoceptors
C. Acts directly and indirectly on adrenoceptors
D. Is a uterine relaxant
E. Can exist in four isomeric forms, two of which are pharmacologically active.
A. False. It does not have a hydroxyl substitution of the benzene ring, and therefore cannot properly be called a catecholamine.
B. True.
C. True. It’s main effects are from the release of noradrenaline but it also has some direct effect on receptors.
D. False. All anaesthetic vapours are uterine relaxants.
E. False. It can exist in four isomeric forms but the only active one is the l-form. Ephedrine is supplied as the racaemic mixture or simply in the l-form.
Regarding digoxin:
A. 25% of the oral dose is absorbed
B. 95% is bound to plasma proteins
C. It is largely excreted unchanged in the urine
D. Hyporkalaemia may cause raised serum levels of digoxin
E. Toxicity may result in Mobitz type II heart block
A. False. It is well absorbed orally.
B. False. There is insignificant binding to plasma proteins.
C. True.
D. True.
E. True. All forms of heart block have been recorded in digitalis toxicity.
The following drugs cause prolongation of the Q-T interval:
A. Sotalol
B. Quinidine
C. Verapamil
D. Flecainide
E. Disopyramide
A. True. Sotalol, a beta blocker, posesses class III activity, and both quinidine and disopyramide have class 1A actions with mild class III activity prolonging the cardiac action potential and hence the Q-T interval.
B. True.
C. False.
D. False. Flecainide, a class IC antiarrhythmic agent does not directly prolong the Q-T interval.
E. True.
The following drugs have potassium sparing diuretic effects:
A. Enalapril
B. Frusemide
C. Triamterene
D. Spironolactone
E. Flecainide
A. True. The angiotensin converting enzyme inhibitors have an anti-aldosterone effect They act as weak potassium sparing diuretics and concomittant use of such drugs should be undertaken with care.
B. False. Frusemide use can result in hypokalaemia.
C. True.
D. True.
E. False. It has no diuretic effect.
Sodium nitroprusside:
A. Acts by stimulating the release of nitric oxide in vascular tissue
B. Acts as an arteriolar and venous dilator
C. Is associated with a baroreceptor mediated rise in heart rate
D. Rapidy decomposes in the presence of light
E. Is broken down by non-specific plasma esterases
A. True.
B. True.
C. True. Is associated with a reflex tachycardia.
D. False. Its decomposition is surprisingly slow: 50% of its activity remains after 2 days exposure to light.
E. False. Breakdown occurs in red blood cells with production of cyanomethaemoglobin.
The following are recognised complications of amiodarone:
A. Peripheral neuropathy
B. Prologation of the Q-T interval
C. Hyperthyoidism
D. Reversible restrictive lung defect
E. Optic atrophy
A. True.
B. True.
C. True. Hypo or hyper-thyroidism may occur at higher doses.
D. True. Pulmonary fibrosis, if treated early and the amiodarone stopped, may regress.
E. False. Corneal microdeposits rather than optic atrophy occur in long term use.
The following Beta-blockers are metabolised predominantly by the liver:
A. Labetolol
B. Propranolol
C. Atenolol
D. Metoprolol
E. Sotalol
A. True.
B. True.
C. False. Atenolol and sotalol are water soluble and therefore predominantly metabolised by the kidney.
D. True.
E. False.
Labetolol:
A. Acts on alpha and beta receptors with higher affinity for alpha-receptors
B. May cause retrograde ejaculation by its beta-blocking action
C. Has significant intrinsic sympathomimetic activity (ISA)
D. Causes significant postural hypotension
E. Is contraindicated in pregnancy
A. False. It has more affinity for beta receptors: beta:alpha 3:1 following oral ingestion and 7:1 after IV administration.
B. False. This can occur secondary to it’s alpha action.
C. True. It does have significant ISA.
D. True.
E. False. It is one of the drugs used in pre-eclampsia.
Dopexamine hydrochloride:
A. Has significant alpha-adrenoceptor activity at higher doses
B. Acts mainly at beta-1 receptors to produce an increased cardiac output
C. Acts mainly at alpha-1 receptors to produce an increased cardiac output
D. Requires use of a loading dose
E. Improves renal blood flow at the expense of splanchnic blood flow
A. False. Dopexamine is an analogue of dopamine.
B. False. It acts mainly at beta-2 and DA-1/DA-2 receptors. It has no alpha activity. It also inhibits uptake-1.
C. False.
D. False.
E. False. It is a weak positive inotrope but powerful splanchnic vasodilator reducing afterload.
The following are natural precursors of adrenaline:
A. Aspartate
B. Glycine
C. Glutamine
D. Dihydroxyphenylalanine
E. Dobutamine
A. False.
B. False.
C. False.
D. True.
E. False. Dopamine is a precursor of adrenaline. Dobutamine is a synthetic compound.
The synthetic pathway is as follows:Tyrosine-DOPA-Dopamine-Noradrenaline-Adrenaline.
Hyoscine hydrobromide (Scopolamine):
A. Is a less potent anti-sialagogue than atropine
B. Does not cross the blood-brain barrier
C. Is largely excreted unchanged in the urine
D. Is an effective anti-emetic which can be delivered transdermally
E. May produce excitement and restlessness
A. False. It is a more potent anti-sialagogue than atropine.
B. False. It has central and peripheral effects, which include sedative, anti-emetic and anti-sialogogue actions.
C. False. Only 1% is excreted unchanged.
D. True.
E. True. Through paradoxical central stimulation.
Isoprenaline:
A. Has alpha and beta adrenergic activity
B. Increases peripheral vascular resistance
C. Is a naturally occuring catecholamine
D. May decrease mean arterial pressure
E. It’s effects are mediated via adenylate cyclase
A. False. It acts on beta-1 and beta-2 receptors only.
B. False. It causes a fall in peripheral vascular resistance via it’s beta-2 effets.
C. False. Isoprenaline is a synthetic catecholamine.
D. True.
E. True.
Hydralazine:
A. Dilates arterioles and veins equally
B. It’s first pass metabolism is dependent on the acetylator status of the patient
C. Increases cerebral blood flow
D. May cause a lupus-like syndrome
E. Is contraindicated in pre-eclampsia
A. False. Hydralazine is predominantly an arteriolar dilator.
B. True.
C. True.
D. True. After chronic usage. Peripheral neuropathies and blood dyscrasias have also been reported.
E. False.
Nitric oxide (NO):
A. Is synthesised exclusively by vascular endothelium
B. Is synthesised from L-asparagine
C. Is produced by the lung
D. Binds to haemoglobin with an affinity equal to that of carbon monoxide (CO)
E. Ultimately is metabolised to nitrate which is excreted by the kidneys
A. False. Nitric oxide is also produced by macrophages and thrombocytes.
B. False. It is synthesised from L-arginine.
C. True.
D. False. The haemoglobin molecule has an affinity 1500 times higher to NO than to CO. Nitrosyl haemoglobin is produced, which in the presence of oxygen, is oxidised to methaemoglobin.
E. True.
The following drugs exhibit tachyphylaxis:
A. Glyceryl trinitrate
B. Ephedrine
C. Suxemethonium
D. Trimetaphan
E. Hydralazine
A. True.
B. True.
C. False. Repeated doses can result in a prolonged dual block.
D. True.
E. False.
The following hormones are secreted by the anterior pituitary gland:
A. Thyrotropin releasing hormone
B. Growth Hormone
C. Vasopressin
D. Lutenising hormone
E. Prolactin
A. False. This is produced by the hypothalamus to stimulate release of TSH by the anterior pituitary.
B. True.
C. False. This is secreted by the posterior pituitary which is physiologically very different to the anterior part of the gland.
D. True.
E. True.
The anterior pituitary synthesisis the following hormones: prolactin, growth hormone (GH), adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), lutenising hormone (LH) and follicle stimulating hormone (FSH). The release of these hormones is dependent on stimulation from the hypothalamus via a complex portal vascular system.
Aldosterone:
A. Is a glucocorticoid
B. Is synthesised in the zona glomerulosa of the adrenal medulla
C. Secretion is stimulated by hyperkalaemia
D. Causes sodium retention predominantly in the loop of Henle
E. Increases intracellular cAMP
A. False. It is a mineralocorticoid.
B. False. It is synthesised in the zona glomerulosa of the adrenal CORTEX.
C. True. And by angiotensin II and ACTH.
D. False. This occurs primarily in the DCT.
E. False. It acts on intracellular receptors to propduce specific gene transcription. cAMP concentrations are altered due to agonist effects on extracellular 2nd messenger receptors.
Aldosterone is produced by the zona glomerulosa of the adrenal cortex in response to stimulation by angiotensin II, ACTH and a rise in serum potassium. It is a mineralocorticoid with 21 carbon atoms. It causes sodium retention and potassium loss at the DCT. Aldosterone levels are high in Conn’s syndrome and low in Addison’s disease.
Insulin:
A. Secretion produces anabolic conditions
B. Is a positive inotrope
C. Is secreted by alpha cells within the Islets of Langerhans
D. Causes triglyceride breakdown
E. Secretion is stimulated by somatostatin
A. True.
B. True.
C. False. It is secreted by beta cells.
D. False. It causes triglyceride formation and fat deposition.
E. False. False. It is inhibited by somatostatin (as is glucagon).
Insulin is a peptide hormone secreted by beta cells within the Islets of Langerhans in the Pancreas. Secretion is stimulated by a rise in plasma glucose, parasympathetic release of Ach, beta 2 adrenoceptor stimulation (adrenaline) and amino acids arginine and leucine. Release is inhibited by low glucose concertrations, noradrenaline (alpha 1) and somatostatin.
Regarding the posterior pituitary gland:
A. It is connected to the hypothalamus by a portal vascular system
B. It is responsible for synthesis of vasopressin and oxytocin
C. It produces lipid soluble hormones
D. Release of vasopressin is stimulated by an increase in osmolality
E. Vasopressin acts on aquaporin channels within the distal convoluted tubule
A. False. It communicates with the hypothalamus via specialised neurons. The ANTERIOR pituitary is connected to the hypothalamus via a portal vascular system.
B. False. Vasopressin and oxytocin are stored in the posterior pituitary but synthesised in the aforemetntioned specialised hypothalamic neurons.
C. False. They are peptide hormones and are water soluble, not lipid soluble.
D. True. Vasopressin is ADH. Increasing osmolality stimulates ADH release to produce water retention.
E. False. ADH acts primarily at V2 receptors in the collecting duct to upregulate aquaporin channels and resorb water. It has a minor role at the DCT
Regarding the renin angiotensin aldosterone system:
A. Renin is secreted by the macula densa
B. Angiotensin I is converted to angiotensin II in the lungs
C. Angiotensisn II is a vasoconstrictor
D. Aldosterone is responsible for a rapid increase in renal blood flow in response to renin secretion
E. A patient taking candesartan will have less circulating angiotensin II
A. False. It is secreted by the juxtaglomerular apparatus. The macula densa detects sodium concentration at the DCT.
B. True. Angiotensin converting enzyme (ACE) is found here.
C. True. It is thought to preferentially constrict the efferent arteriole producing an increase in GFR.
D. False. The effects of aldosterone take hours as it works via intracellular receptors to alter gene trascription.
E. False. Candesartan is an angiotensin II receptor blocker. It has no effect on ACE.
Renin is secreted by the juxtaglomerular cells in response to signals from the macula densa which detects a decrease in sodium concentration at the DCT. Renin stimulates conversion of angiotensinogen to angiotensin I, which is converted to angiotensin II (a2) by ACE in the lungs. A2 causes vasoconstriction of the efferent arteriole and stimulates release of aldosterone from the adrenal cortex.
In response to trauma the following will occur:
A. Increased plasma glucose concentration
B. Increased aldosterone secretion
C. Increased ACTH production in the anterior pitutary
D. A rise is serum glucagon secretion
E. Sodium retention as a result of vasopressin action on the DCT
A. True. Due to the inhibtion of insulin production and stimulation of glucagon production by the sympathetic nervous system resulting in mobilisation of glucose.
B. True. Part of the stress response is aldosterone secretion resulting in sodium and water retention.
C. True. Part of the stress response.
D. True. Sympathetic stimulation causes release of glucagon to mobilse glucose stores.
E. False. Vasopressin is released but it causes retention of water in the collecting duct
Adrenaline:
A. Is produced in the central part of the adrenal gland
B. Causes bronchoconstriction
C. Causes a rise in blood glucose levels
D. Acts on alpha adrenoceptors
E. Causes miosis
A. True. Anatomically the adrenal medulla is found in the centre of the gland.
B. False. It causes bronchodilatation.
C. True. Though adrenaline does stimulate a small amount of insulin release, overall it inhibits insulin secretion and stimulates glucagon therefore raising blood glucose levels.
D. True. It does, although it has greater effect on beta. Pharmacologically, higher doses are needed to produce alpha effects.
E . False. It causes mydriasis.
Adrenaline is a post gangionic neurotransmitter in the sympathetic nervous system and is a circluating hormone produced by the adrenal medulla. It acts on both alpha and beta adrenoceptors but predominantly beta to produce vasodilation, bronchodilation, tachycardia, increased contractility, hypertension, mydriasis and increased glucose concentration.
Regarding catecholamines:
A. Noradrenaline is synthesised by removal of a methyl group from adrenaline
B. The rate limiting step in catecholamine synthesis is conversion of L-Dopa to Dopamine
C. Isoprenaline is synthesised in the adrenal medulla
D. Phaeochromocytomas commonly secrete more adrenaline than noradrenaline
E. Phaeochromocytomas is treated with beta blockers as a first line
A. False. Noradrenaline is a precursor of adrenaline, so, adrenaline is synthesised by the addition of a methyl group to noradrenaline.
B. False. The rate limiting step is the hyroxylation of tyrosine
C. False. Isoprenaline is a synthetic compound of similar structure to adrenaline.
D. False. They most commonly secrete predominantly noradrenaline, though they can be predominanty adrenaline or dopamine secretors.
E. False. This could result in unoppsed alpha stimulation by the excess noradrenaline causing profound vasoconstriction.
The following are secreted by the adrenal cortex:
A. Noradrenaline
B. Aldosterone
C. Testosterone
D. Renin
E. Adrencorticotrophic hormone
A. False. This is secreted by the adrenal medulla.
B. True. This is secreted by the Zona glomerulosa.
C. True. The majority of testosterone is sectred by the testes or ovaries but roughly 5% comes from the adrenal cortex.
D. False. This is secreted by the juxtaglomerular apparatus in the kidney.
E. False. This is secreted by the pituitary, stimulating glucocorticoid and mineralocorticoid production.
The following hormones are sectreted by the adrenal cortex: aldosterone (zona glomerulosa), cortisol and corticosterone (zona fasciculata) and androgens such as testosterone, dihydrotestosterone and androstenedione (zona reticularis)
Vasopressin:
A. Is secreted by the hypothalamus
B. Is a peptide hormone
C. Secretion is stimulated by increased plasma osmolality
D. Plasma levels are high in diabetes insipidus
E. Causes selective reabsorbtion of water in the distal convoluted tubule
A. False. It is synthesised in the hypothalamus but secreted into the circulation by the posterior pituitary.
B. True. It is a monopeptide hormone.
C. True.
D. False. Plasma levels of vasopressin are low in DI causing increased water loss via the kidneys.
E. False. Though it may have a small role at the DCT vasopressin causes selective reabsorbtion of water via aquaporin channels in the collecting duct
During pregnancy progesterone is responsible for the following changes:
A. Smooth muscle relaxation
B. Increased motility within the GI tract
C. An increase in basal temperature
D. Bronchodilatation
E. Generalised vasoconstriction
A. True.
B. False. It causes decreased GI motility
C. True. Progesterone is thermogenic.
D. True.
E. False. Progesterone causes generalised vasodilatation.
Progesterone is responsible for most of the hormonally mediated changes occuring during pregnancy including: smooth muscle relaxation, vasodilatation, bronchodilatation, renal tract dilatation, decreased GI motility and constipation.
Cardivascular changes during pregnancy:
A. Blood volume increases by approximately 25% at term
B. During pregnancy there is an increase in red cell volume with a decrease in haematocrit
C. Cardiac output increases as a result of increased heart rate
D. There is a decrease in blood pressure during normal pregnancy
E. Aorto caval compression becomes clinically significant at term
A. False. Blood volume increases by 45 - 50%.
B. True. Although there is an increase in red cell mass, there is a greater increase in plasma volume resulting in a net decrease in haematocrit.
C. False. Cariaic output increases predominantly as a result of increased stroke volume .
D. True. Despite the increase in cardiac outpu,t vasodilatation leads to a decrease in systemic vascular resistance and drop in BP.
E. False. Aortocaval compression can occur from 20 weeks gestation onwards.
There are many cardiovascular and haemodynamic changes during pregnancy, the main ones are: increased cardiac output due to an increase in stroke volume, an increase in red cell volume and plasma volume and a decrease in systemic vascular resistance.
Respiratory changes during pregnancy:
A. PaCO2 is decreased to approximately 4 kPa during the first trimester
B. Funtional Residual Capacity is increased by 20% at term
C. Oxygen consumption remains the same as pre-pregnancy levels
D. Minute ventilation increases during pregnancy
E. Progesterone and oestrogen both act as respiratory stimulants
A. True. The desired PaCO2 is reset to 4 kPa as a result of progesterone. This leads to a respiratory alkalosis.
B. False. FRC is decreased to 80% of normal. This leads to airway closure and rapid desaturation in the supine position during the latter stages of pregnancy.
C. False. The requirements of a growing fetus increase oxygen consumption to 35% above pre-pregnancy levels.
D. True. Leading to the aforementioned respiratory alkalosis.
E. True.
Gastrointestinal changes during pregnancy:
A. Lower oesophageal sphincter tone is increased to combat increased gastric motility
B. Intragastric pressure rises as a mechanical consequence of the enlarging uterus
C. Heartburn is suffered by roughly half of all pregnant women
D. Diarrhoea is common during pregnacy
E. Rapid sequence induction is required for general anaesthesia from the start of the 3rd trimester
A. False. Wrong on both counts. LOS tone is decreased as a result of smooth muscle relaxation. Gastric emptying is thought to remain unchanged (unless opiods have been given).
B. False.
C. False. Heartburn is suffered by most women (75-85%) as a result of decreased LOS tone.
D. False. The opposite is true - smooth muscle relaxation within the gut leads to constipation.
E. False. RSI is required from the start of the 2nd trimester as that is when LOS tone decreases and reflux becomes common.
Oxytocics:
A. Cause increased uterine contraction
B. Commonly cause vomiting
C. Should not be given in pre-eclampsia
D. Result in hypotension and tachycardia
E. Are given routinely after delivery during cesarian section
A. True. This is the reason for their use
B. False. Ergometrine (combined with syntocinon to form syntometrine or given alone to produce uterine contraction) reliably causes vomiting.
C. False. Ergometrine however should not as it causes a rise in BP.
D. True. They must therefore must be given slowly with caution.
E. True. They are routinely given after delivery of the baby to contract the uterus and reduce bleeding. Do not give it prior to delivery as it could result in profound fetal distress (paticularly hazardous during LSCS for twins!).
Oxytocics (such as syntocinon) are given to induce labour, to those in labour making slow progress, and after delivery of the fetus at C-section to ensure uterine contraction and reduce intrauterine bleeding
Drugs able to cross the placenta include:
A. Morphine
B. Non depolarising muscle relaxants
C. Glycopyrrolate
D. Warfarin
E. Lignocaine
A. True. Morphine is lipid solube and crosses the placenta - therefore babies delivered soon after high dose IV morphine may have respiratory depression.
B. False. These are large polar molecules therefore not lipid soluble and not able to cross the placenta.
C. False. Glycopyrrolate is a quaternary amine - therefore charged and unable to cross the placenta.
D. True. Crosses the placenta and is teratogenic, therefore not given during pregnancy.
E. True. Less protein binding than bupivicaine therefore more crosses the placenta. Also subject to ion trapping as a result of the lower pH within the fetus.
The following drugs cause tocolysis:
A. Salbutamol
B. Isoflurane
C. Sevoflurane
D. Nitrous oxide
E. Magnesium
A. True.
B. True.
C. True.
D. False. Nitrous has no effect on uterine tone making it useful during general anaesthesia for C-section.
E. True.
Tocolysis is the relation of uterine smooth muscle as a result of administration of a drug. The following drugs cause tocolysis: salbutamol, terbutaline, ritodrine, volatile agents, magnesium and GTN.
Regarding pre-eclampsia:
A. It is characterised by hypertension and proteinuria after 20 weeks gestation
B. It occurs in 1% of pregnancies
C. Eclamptic fits should be terminated with benzodiazepines
D. Eclamptic fits will not occur more than 24 hours after delivery
E. It commonly results in thrombocytopenia
A. True.
B. False. It occurs in 5-6% of pregnancies.
C. False. They should be terminated by magnesium which should then be continued and the fetus delivered as soon as possible.
D. False. They may occur up to a week after delivery.
E. True. Platelets must be checked regularly during labour.
Pre-eclampsia is a disorder characterised by hypertension and proteinuria (oedema is no longer a diagnostic requirement). It may progress to eclampsia (fitting) or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) or both
The following drugs cause uterine contraction:
A. Syntocinon
B. Ergometrine
C. Prostaglandin F2alpha
D. Ritodrine
E. GTN
A. True. see feedback Q6
B. True. It’s an agonist at alpha 1 adrenoceptors, 5HT and dopaminergic recptors. It is used to aid delivery of the placenta or help gain control of PPH with an atonic uterus. Causes hypertension and should not be used in pre-eclampsia.
C. True. Examples include carbaprost and haemabate. Side effects include bronchoconstriction, tachycardia and hypotension.
D. False. This relaxes the uterus
E. False. This also relaxes the uterus
The following are absolute contraindications to epidural analgesia during labour:
A. Platelet count <100
B. Temperature >38 degrees
C. Cellulitis at the site of intended placement
D. BMI >50
E. Spina bifida
A. False. The guidelines from the CMACE report state that patients with platelets of 80 or less are at increased risk of developing an epidural haematoma.
B. False. Bacterameia is a relative but not absolute contraindication.
C. True. Using a tuohy needle to push infection into the epidural space could lead to an epidural abscess and paralysis.
D. False. Some would say this is an indication rather than contraindication - a good working epidural could save you from a crash GA section in an obese patient.
E. False. Anatomical abnormalities such as spina bifida may make placement of an epidural impossible, but they are not absolute contraindications.
Absolute contraindications to epidural are: Patient refusal, allergy to local anaesthetic, infection (cellulitis) over the site of placement, coagulopathy, raised itracranial pressure, profound hypovolaemia. Relative contraindications include: bacteramia, nerological disorders (eg MS, syringomyelia), fixed cardiac output state (eg aortic stenosis, HOCM), previous spinal surgery, anatomica; abnormalities (eg spina bifida)
Verapamil:
A. Is a derivative of papaverine
B. Has poor oral absorption
C. Has a bioavailability following oral administration of about 75%
D. Is highly bound to plasma proteins
E. Is largely excreted by the kidney
A. True. Verapamil is a synthetic papaverine derivative.
B. False. It is well absorbed following oral administration, but undergoes extensive first pass metabolism with a bioavailability of 10-20%.
C. False.
D. True.
E. True. 70% of metabolites are excreted by the kidney.
Trimetaphan:
A. Blocks parasympathetic ganglia to produce hypotension
B. Is an arteriolar and venous dilator
C. Is inactivated by plasma cholinesterase
D. Has a long half life
E. May potentiate the effect of suxemthonium
A. False. Trimetaphan induces hypotension by blocking sympathetic ganglia but it also exhibits some direct vasodilatation.
B. True.
C. True.
D. False. It has a plasma half-life of only 2 minutes.
E. True. Side-effects include histamine release, mydriasis, and potentiation of suxemthonium, urinary retention and impotence due to the non-selective ganglion blockade.
Phenoxybenzamine:
A. Is a non-selective alpha-adrenergic antagonist
B. Acts predominantly on pre-synaptic alpha-1 receptors
C. Can be given orally or intravenously
D. May result in nasal stuffiness
E. Is useful in the management of craniopharyngioma
A. True. Phenoxybenzamine is a non-selective alpha blocker.
B. False. It predominantly acts post-synaptically.
C. True.
D. True. Doses are often limited by this, along with postural hypotension.
E. False. It is often used in the treatment of phaeochromocytoma’s.
The following are side effects of thiazide diuretics:
A. Hyperuricaemia
B. Hyponatraemia
C. Hypoglycaemia
D. Hypokalaemic, hypochloraemic acidosis
E. Hypercalcaemia
A. True.
B. True.
C. False. They can cause hyperglycaemia.
D. False. Thiazides tend to result in hypokalaemic, hypochloraemic metabolic alkalosis.
E. True.
Ephedrine is unlikely to be effective in reversing hypotension in patients chronically receiving the following medication:
A. Reserpine
B. Alpha-methyl dopa
C. Phenoxybenzamine
D. Clonidine
E. Propranolol
A. True. Indirectly acting sympathomimetics like ephedrine are unlikely to increase blood pressure in patients taking drugs which alter neuronal storage, uptake, metabolism or release of neurotransmitters. Reserpine depletes neuronal granules of noradrenaline.
B. True. Alpha-methyl dopa acts as a false transmitter.
C. True. Phenoxybenzamine and propranolol block peripheral receptors and industrial doses of directly acting sympathomometics may be required to overcome their blockade.
D. False.
E. True. Clonidine works on central adrenergic receptors and the peripheral effect of indirectly acting sympathomimetics is not decreased, in fact smaller doses may be required due to receptor up regulation.
The following statements are true:
A. ACE Inhibitors slow the onset of chronic renal disease secondary to hypertension
B. Angiotensin II causes glomerular afferent arteriolar vasodilatation
C. The fetus has high renin and angiotensin II levels
D. Angiotensin II stimulates the release of aldosterone from the adrenal medulla
E. All ACE inhibitors have similar antihypertensive efficacy at equipotent doses.
A. True. ACE Inhibitors do slow the onset of chronic renal disease secondary to hypertension and diabetes.
B. False. Angiotensin II causes glomerular arteriolar vasoconstriction (in the efferent arterioles to a greater extent than the afferent).
C. False. Renin levels are high, but angiotensin II levels are low due to the limited pulmonary blood flow.
D. False. Angiotensin II stimulates the release of aldosterone from the adrenal cortex.
E. True.
The following may be used to control the ventricular rate in atrial fibrillation:
A. Quinidine
B. Atenolol
C. Amiodarone
D. Digoxin
E. Disopyramide
A. False. Although it may be used in atrial arrhythmias, it has a slight vagolytic effect and may accelerate the ventricular rate in AF unless digoxin is given concomitantly.
B. True.
C. True.
D. True.
E. False. Disopyramide has both class Ia and III activity and an anticholinergic effect. For similar reasons to quinidine it should not be used for AF alone.
In the treatment of cardiogenic shock:
A. Enoximone increases the left ventricular end diastolic pressure
B. Adrenaline increases the systemic vascular resistance
C. Cardiac output is increased by noradrenaline
D. Isoprenaline reduceses myocardial oxygen consumption
E. Dobutamine reduces systemic vascular resistance
A. False. It reduces afterload and left ventricular end diastolic pressure due to its vasodilating effects.
B. True. Adrenaline acts on both alpha and beta receptors. At low doses, beta effects predominate (tachycardia, increased cardiac output, lower SVR) but at higher doses alpha effects take over with peripheral vasoconstriction.
C. False. Noradrenaline is mainly an alpha-agonist and increasing systemic vascular resistance and hence reducing cardiac output.
D. False. Isoprenaline produces a tachycardia viaits beta-agonist effect, increasing myocardial consumption.
E. True. Dobutamine vasodilates by acting on beta 2-adrenergic receptors.
The following have calcium antagonistic actions on smooth muscle:
A. Dantrolene
B. Diltiazem
C. Nicardipine
D. Hydralazine
E. Nitroglycerine
A. False. Dantrolene is a direct-acting skeletal muscle relaxant. It has no action on smooth muscle.
B. True.
C. True.
D. False.
E. False. Neither hydralazine nor nitrglycerine act as calcium antagonists.
Adenosine:
A. Is an effective treatment stable ventricular tachycardia
B. Has a half life of approximately 2 minutes
C. Should be given as a slow intravenous bolus
D. Can result in wheezing
E. Causes coronary vasoconstriction
A. False. Adenosine is effective in SVTs, depressing the SA node activity and blocking AV node conduction. Although ineffective in VTs, it can serve to distinguish SVT with associated bundle branch block from VT in a patient with broad complex tachycardia.
B. False. It has a very short half life (<10 seconds).
C. False. Beacause of it’s very short half life, it should be given as a rapid bolus.
D. True. Though all side effects should be short lived due to it’s short half life.
E. False. It is a potent coronary vasodilator and may cause coronary steal in susceptible patients.
Regarding the renal circulation
A. A renal blood flow of 1200 mls/minute is likely if the mean arterial pressure is 160 mmHg
B. Blood supply to the medulla is derived entirely from the vasa recta
C. Macula densa cells are located in the afferent arteriolar wall
D. Autoregulation of renal blood flow occurs in the dennervated kidney
E. Renal oxygen consumption is approximately 60 ml/minute
A. True. Renal blood flow is usually 25% of cardiac output, and is maintained by autoregulation, whilst mean arterial pressure remains in the range 80-200 mmHg
B. True. Capillaries close to the boundary of the cortex and medulla loop into the medulla and form the vasa recta. These surround the Loop of Henle.They are the only blood supply to the medulla.
C. False. Macula densa cells are located in the distal convuluted tubule
D. True. Autoregulation even occurs in the dennervated kidney
E. False. Renal oxygen consumption is only approximately 18 mls/min
Concerning the blood supply of the kidneys
A. The renal arteries divide into arterioles, then capillaries, then arterioles, then vasa recta
B. 90% of the blood entering the kidney supplies the medulla
C. Administration of non-steroidal anti inflammatory drugs to normal kidneys reduces the GFR by 20%
D. Symptomatic uraemia usually devlops when the GFR is about 15 ml/min
E. The normal young adult renal blood flow is about 600 mls/minute.
A. True. The renal system is the only system where capillaries drain into efferent arterioles, and then into peritubular and long vasa recta capillaries again.
B. False. 90% of the blood entering the kidneys supplies the cortex. It has a high blood flow-500 ml/min per 100 g of tissue. It has a low arteriovenous difference of approximately 2%.
C. False. NSAID’s do not influence GFR under normal circumstances but can cause significant loss of function if there is effective loss of circulating volume from any cause. PGI2 and PGE2 are released in hypovolaemia and may cause vasodilation helping prevent the kidney from ischaemic damage
D. True. The symptoms of uraemia occur late in the loss of renal function, and are caused by retained toxic products. They are non specific and include anorexia, nausea, vomiting, lethargy, poor sleep, pruritus
E. False. The normal renal blood flow is about 22-25% of cardiac output, approximately 1200 mls/minute.
In the normal human kidney
A. One would expect to find approximately 100,000 nephrons
B. Distal tubular cells do not posess brush borders
C. Proximal tubular cells possess fewer mitochondria than distal tubular cells
D. Only 20% of nephrons have a Loop of Henle
E. The slit membrane of the Bowman’s capsule has pores of 5 nm diameter
A. False. Each kidney contains approximately 1 million nephrons
B. True. The cells of the proximal convuluted tubule have brush borders. The distal tubular cels are similar to those of the tick ascending limb of the loop of Henle.
C. False. Proximal tubular cells are particulary rich in mitochondria
D. False. All nephrons possess a Loop of Henle. 20% will be juxtamedullary
E. True. The Bowmans capsule surrounds the glomerular capllaries and collects filtrate.
In the proximal tubule of the nephron
A. Sodium is actively reabsorbed
B. Bicarbonate is secreted
C. All of the reabsorption of glucose occurs
D. The vast proprtion of filtered water is reabsorbed
E. Water reabsorption is under the control of aldosterone
A. True. Sodium is actively transported out of all parts of the renal tubule except the thin portion of the Loop Of Henle. Sodium is pumped from tubular cells into the interstitium by the sodium-potassium-ATPase pump
B. False. Reabsorption of bicarbonate, chloride, glucose, sodium and potassium occurs in the proximal tubule.
C. True. Glucose is normally completely reabsorbed in the proximal tubule. If the renal threshold for glucose is exceeded, glucose will appear in the urine.
D. True. Up to 70% of filtered water is reabsorbed in the proximal convuluted tubule
E. False. Aldosterone mainly acts in the distal tubule by regulating sodioum reabsorption. Water then follows passively.
Consider the following statement regarding glucose reabsorption
A. The tubular transport maximum for glucose is 380 mg/minute
B. Glucose wil appear in the urine at a renal threshold of 110 mmol/L
C. Glucose is reabsorbed by counter transport with sodium
D. Glucose is usually reabsorbed in the distal convoluted tubule
E. Glucose is completely reabsorbed providing the plasma concentration is normal
A. True. There is a tubular transport maximum for glucose and it is 380 mg/minute.
B. False. The renal threshold for glucose is 11 mmol/L
C. False. Glucose is co transported with sodium
D. False. Glucose reabsorption is in the proximal convoluted tubule
E. True. Glucose has a tubular transport maximum that is not exceeded at normal plasma glucose concentrations
Transport processes in the kidney include
A. Tubular secretion of ammonia in both proximal and distal tubules
B. Glomerular filtration of all molecules under 5nm diameter
C. Reabsoprtion of proteins by pinocytosis
D. Reabsorption of 160 g glucose per day.
E. Excretion of bicarbonate ions, buffered by phosphate
A. True. Ammonia is produced in tubular cells by metabolism of glutamine.Its main role is in the buffering processes promoting the excretion of hydrogen ions.
B. False. Glomerular filtration is partly determined by molecular size, charge and protein binding.
C. True. In health, large molecules do not pass through the glomerular membrane. Any protein molecules that do are taken up by pinocytosis at the luminal membrane
D. True. 99% of glucose is reabsorbed by a saturable co-transport mechanism in the proximal tubule
E. False. Hydrogen ions are buffered intraluminally by phosphate, not bicarbonate ions.
Consider the following statements regarding renin
A. Release is controlled by the macula densa in response to a low sodium flux
B. It is released from macula densa cells
C. Release is increased by hypotension
D. Release is inhibited by beta blockers
E. Release is increased by antidiuretic hormone
A. True. When less filtrate reaches the macula densa, sodium concentration around the cells is reduced. This is detected by the macula densa cells and an increase in rennin secretion is triggered
B. False. Renin is released from juxtaglomerular cells located in the wall of the afferent arteriole
C. True. Renin is released in response to the low cardiovascular pressures which occur in hypotension
D. True. Renin release is increased in response to beta-1-receptor stimulation
E. False. Release is decreased by antidiuretic hormone which acts to conserve sodium and water
Primary active transport in the renal tubules
A. Is involved in the movement of 3 sodium ions into the cell.
B. Involves a carrier protein which removes energy from the transported substances
C. Involves the activation of ATPase
D. Provides gradients for secondary active transport
E. Establishes a net positive voltage inside the cell
A. False. 3 sodium ions are pumped outwards for 2 potassium ions inward.
B. False. In primary active transport, energy is imparted which allows the substance being transported to be moved against its electrochemical gradient
C. True. When 3 sodium ions and 2 potassium ions bind to the carrier protein, the ATPase function of the protein is activated
D. True. Gradients are set up via the sodium-potassium ATPase pump to allow the reabsorption of sodium ions via secondary active transport.
E. False. 3 sodium ions are pumped out for 2 potassium ions pumped inward.
Consider the following statements about clearance
A. Clearance of para-amino hippuric acid estimates renal plasma flow
B. Clearance of inulin is greater than that of glucose
C. Clearance of inulin is greater than that of free water
D. Clearance of an actively reabsorbed substance must exceede that of inulin.
E. Clearance of a renally inert indicator can be used to measure GFR
A. True. Para amino hippuric acid (PAH) is 90% cleared by the kidneys from the plasma. PAH clearance is therefore used to estimate RPF. The amount of PAH still in the blood can be corrected for.
B. True. Inulin is almost completely cleared. Its rate of excretion is very close to its filtration rate. Glucose is reabsorbed up to its transport maximum.
C. True. A majority of filtered water is reabsorbed by the renal tubules
D. False. If a substance is actively reabsorbed its clearance must be below that of inulin
E. True. An ideal substance for the measurement of GFR will be freely filtered, neither secerted or reabsorbed, nor metabolised
Consider the following statements about aldosterone
A. Production is increased by sodium chloride ingestion
B. Trauma leading to hypovolaemia will result in aldosterone release
C. Aldosterone reduces the sodium content of sweat
D. Aldosterone production increases urinary potassium excretion
E. Aldosterone increases urinary sodium concentration
A. False. Sodium chloride ingestion increases plasma osmolality and will decrease aldosterone prouction. One of the main roles of aldosterone is in sodium reabsorption
B. True. Hypovolaemia causes renin release, and thus angiotensin II release. This causes aldosterone release, with the ultimate effect of increasing sodium and water reabsorption
C. True. Aldosterone increases sodium reabsorption from the gut, sweat and saliva.
D. True. Aldosterone stimulates the production of potassium channels in the luminal membrane of the cortical collecting duct.Potassium is lost through these.
E. False. Aldosterone is the main determinant of sodium reabsorption
Sodium valproate:
A. Is contraindicated in children
B. Is used to treat petit mal seizures
C. Is used to treat grand mal seizures
D. Can be used safely in liver disease patients
E. Acts by enhancing concentrations of the neurotransmitter GABA
A. False. Valproate can be safely used in children down to 1 month of age.
B. True. It is used to treat generalised, mixed and partial seizures.
C. True.
D. False. It is contraindicated in severe hepatic or renal failure.
E. True. Sodium valproate acts by weakly blocking sodium ion channels. It inhibits GABA transaminase, which would deactivate gamma-Aminobutyric Acid (GABA) and may also stimulate GABA synthesis.
Valproic acid:
A. Is metabolised in the liver
B. Is a liquid fatty acid at room temperature
C. Enhances platelet aggregation
D. Takes at least 3 weeks to have it’s effect
E. Has been used to treat migraines
A. True. 75% is metabolised by the CYP450 system.
B. True. Valproate is a liquid at room temperature but can be reacted with a base to form a solid salt.
C. False. Valproate interferes with platelet aggregation and can cause blood dyscrasias.
D. False. It is effective 14 days after treatment commences.
E. True. Though mainly in the US.
Phenytoin:
A. Inhibits the enzyme intestinal conjugase
B. Has a half life of about 4hrs
C. Is an CYP450 enzyme inhibitor
D. Can cause Vitamin B2 deficiency
E. Causes hypotension
A. True. Phenytoin does inhibit intestinal conjugase, which causes folate deficiency, not vitamin B2 deficiency.
B. False. Phenytoin’s half life is 6 to 24 hours.
C. False. It is an enzyme inducer.
D. False.
E. True. When administered IV, Phenytoin can cause hypotension and arrhythmias and should be administered with cardiac monitoring.
Phenytoin:
A. Does not cause glycosuria
B. Is highly protein bound
C. Undergoes zero order kinetics with a wide therapeutic index
D. Toxicity can cause diminished tendon reflexes
E. Oral bioavailability is high and absorption is rapid
A. False. Phenytoin can cause hyperglycaemia & glycosuria due to insulin inhibition.
B. True. It is mainly bound to Albumin.
C. False. Phenytoin follows saturatable first order kinetics which converts to zero order kinetics when the enzyme system is overwhelmed. It has a narrow therapeutic index and blood levels are therefore monitored.
D. False. Toxicity causes blurred vision, mydriasis and brisk tendon reflexes.
E. False. Bioavailability is good, but oral absorption is slow, variable & can be only partial. Volume of distribution is approx 70% of body weight.
Phenytoin:
A. Causes megaloblastic anaemia due to Vitamin B12 deficiency
B. Is a class Ia antiarrhythmic
C. Has no effect on Thyroid function
D. Is absorbed rapidly via IM or IV routes
E. Phenyotin is carcinogenic
A. True. Phenytoin causes macrocytic, megaloblastic anaemia due to vitamin B12 and/or folate deficiency.
B. False. It is a class Ib antiarrhythmic agent, like Lidocaine.
C. True. Causes falsely low TFTs after long term treatment.
D. False. Not effective IM, only PO (slowly) and IV.
E. False. There is no good evidence that Phenytoin is carcinogenic.
Phenytoin:
A. Can be used to treat Digoxin induced dysrhythmias
B. Is metabolised in the liver by the enzyme rhodanase
C. Can cause significant side effects including nystagmus
D. Is effective with the oral contraceptive pill
E. Stabilises excitable membranes
A. True.
B. False. Phenytoin is metabolised by hepatic microsomal enzymes.
C. True. It can cause horizontal gaze nystagmus, gum overgrowth, acne as well as blood disorders.
D. True. Phenytoin is effective in the presence of the OCP but the contraceptive effect may not be effective due to enzyme induction.
E. True.
Phenobarbitone/Phenobarbital:
A. Is the most widely used anticonvulsant
B. Lasts longer than Phenytoin
C. Is used in the treatment of generalised seizures
D. Is ineffective in absence seizures
E. Is highly protein bound
A. False.
B. True. Phenobarbital is extremely long acting, with a half life of 50 - 100 hours or more.
C. True. It is effective in all seizure activity except absence seizures.
D. True.
E. False. Protein binding is in the order of 20 - 45%.
The following statements are correct:
A. Phenytoin only very rarely provokes an allergic reaction
B. Phenytoin is mainly excreted in the urine
C. Phenytoin can be used to treat trigeminal neuralgia
D. Sodium valproate can cause tremors
E. 10% of people treated with Sodium valproate experience hair loss
A. False. Phenytoin can cause severe allergic reactions and must be given with vigilance.
B. False. Primarily, Phenytoin is excreted in the bile, but some is excreted renally.
C. True.
D. True.
E. True.
Carbamazepine:
A. Is safe in pregnancy
B. Can be used in chronic pain
C. Has a short half life
D. Can cause severe thrombocytopenia
E. Increases the risk of developing Lupus in women
A. False. Carbamazepine can cause spina bifida & other neurodevelopmental problems after intrauterine exposure.
B. True.
C. False. Half life is in the order of 25 - 65 hours
D. True. Carbamazepine can reduce serum sodium & WBC levels at normal drug levels, but also cause life-threatening loss of platelets.
E. True. Lupus risk increases by nearly 90% (probably only in women).
The following statements are correct:
A. Phenytoin is safe in pregnancy
B. Fetal Hydantoin syndrome is associated with Carbamazepine treatment only
C. Phenobarbital is also a sedative agent
D. Phenytoin act to stabilise active voltage gated sodium channels in the CNS
E. Phenytoin can cause skin rashes
A. False. Phenytoin is teratogenic and can cause Fetal Hydantoin Syndrome (like Carbamazepine).
B. False. FHS causes intra-uterine groth retardation, microcephaly, craniofacial abnormalities and limb defects.
C. True. Use of Phenobarbital as a sedative has largely been superceded by benzodiazepines.
D. False. Phenytoin stabilises sodium channels in their inactive state
E. True.
Metformin:
A. Undergoes liver metabolism
B. Is effective in overweight diabetics
C. Overdose can lead to lactic acidosis
D. Has a half life of 6 hours
E. Causes ketonuria
A. False. Metformin is not metabolised and is excreted unchanged in the urine. It is undetectable in plasma at 24 hours after a single dose.
B. True. It does not cause weight loss but decreases weight gain in combination with lifestyle modifications.
C. True.
D. True. Peak concentrations are reached within one to three hours, but it’s duration of action is between 8 & 12 hours, and is therefore administered up to 3 times a day.
E. True.
Metformin is a Biguanide hypoglycaemic agent. It enhances the peripheral action of insulin (endogenous), decreases intestinal glucose uptake & decreases peripheral glucose utilisation.
Biguanides:
A. Stimulate pancreatic insulin secretion
B. Are teratogenic
C. Are used in all ages of diabetics
D. Metformin has an oral bioavailability of 50-60%
E. Metformin is highly protein bound
A. False. Biguanide action involves decreased gluconeogenesis, increased glycolysis & decreased intestinal glucose reabsorption.
B. False. They are not recommended in pregnancy, though are not teratogenic.
C. False. Ketonuria can occur in young diabetics treated with Insulin & Biguanides, and so Metformin is usually only used in adult onset diabetes.
D. True.
E. False. Metformin has negligible protein binding.
The average half-life is 3 hours but the hypoglycaemic effect can last to between 6 & 14 hours.
Sulphonylureas:
A. Are used in adult onset diabetes
B. Can cause hypoglycaemia
C. Cause lactic acidosis in toxicity
D. Act by increasing insulin release
E. Act by increasing insulin production
A. True.
B. True.
C. False. Unlike Metformin, they do not cause lactic acidosis.
D. True.
E. False. They act by increasing insulin release (not production) from the pancreatic beta cells, by binding to specific receptors.
Sulphonylureas, such as Gliclazide, unlike Metformin, can cause hypoglycaemic episodes and blood sugars must be checked regularly. They also enhance Insulin’s effect of taking up glucose into muscle & fat. Other examples include glibenclamide, tolbutamide &, the older preparation, chlopropramide.
Sulphonylureas:
A. Have a hypoglycaemic effect potentiated by thiazide diuretics
B. Are highly protein bound
C. Displace bound Insulin from pancreatic islet 13 cells
D. Include the drug Phenformin
E. Include the drugs Chlorpropramide & Metoclopramide
A. False. Sulphonylureas’ hypoglycaemic effect is antagonised by thiazide diuretics.
B. True.
C. True. Act by displacing bound Insulin from the pancreas &, therefore, they are only effective if endogenous insulin still exists (i.e. not absolute insulin loss/pancreatic beta cell destruction, as in type 1 DM).
D. False. Phenformin is a Biguanide similar to Metformin.
E> False. Despite the identical suffix (-pramide), Metoclopramide is a Benzamide anti-emetic.
Sulphonylurea hypoglycaemics:
A. Tend to cause weight loss
B. Can be used to treat ketoacidosis
C. Are safe for use in pregnancy
D. Are potentiated by Sulphonamides
E. Have shorter half lives than Biguanides
A. False.
B. False. Oral hypoglycaemics have no role in the management of acute diabetic ketoacidosis.
C. False.
D. True.
E. False.
They have longer half lives than the Biguanides and are not recommended for use in pregnancy. They act by binding to a receptor coupled to increased Calcium entry into the pancreatic beta cells, which enhances Insulin secretion.
Insulin:
A. Neutral insulin has a pH of 7
B. Different preparations exist lasting from less than 2 hrs to more than 36 hours
C. 60 - 80% of insulin can be lost due to binding to the IV fluid container & tubing
D. 80% of the secreted insulin is degraded by the liver & kidneys
E. Half life of endogenous insulin is 45 mins
A. True.
B. True.
C. True.
D. True. The liver enzyme, hepatic glutathione transhydrogenase breaks the insulin molecule down into it’s constituent peptide chains.
E. False. Endogenous insulin has a very short half life of 10 - 20 mins and is fixed to many tissues, except RBCs & brain.
Sulphonylureas:
A. Are effective orally & parenterally
B. Can cause pancytopenia
C. Chlorpropramide is metabolised & excreted by the kidneys
D. Gliclazide protects pancreatic beta cells from hyperglycaemic damage
E. Gliclazide reduces atheromatous build up
A. False. Sulphonylureas are only effective when administered orally. There is no IV preparation.
B. True. Tolbutamide & Chlorpropramide can cause leucopenia, agranulocytosis and thrombocytopenia in rare cases.
C. False. Chlorpropramide undergoes no significant metabolism & is excreted, very slowly, largely unchanged in the urine.
D. True.
E. True.
Gliclazide has been proven to be protective in hyperglycaemia-induced beta cell apoptosis and have an antiatherogenic effect.
Regarding insulin:
A. It’s action involves a second messenger system
B. It is a polypeptide formed of 4 chains
C. It increases cAMP levels in the liver
D. Insulin increases potassium uptake into cells
E. Insulin increases protein synthesis in ribosomes
A. True.
B. False. It is formed of 2 chains, A and B.
C. False.
D. True.
E. True.
Insulin decreases cAMP in the liver and causes a shift of potassium intracellularly, therefore effectively decreasing serum potassium levels in acute hyperkalaemia. It also inhibits hormone sensitive lipase, increases protein synthesis in ribosomes and increases glucose uptake in the peripheral tissues.
Insulin facilitates glucose uptake into:
A. The pituitary
B. Red Blood Cells
C. Peripheral tissues inc. muscle & fat
D. Fibroblasts
E. Intestinal mucosa
A. True.
B. False.
C. True.
D. True.
E. False. It decreases reabsorption in the intestine, which can lead to glycosuria.
Insulin increases glucose uptake into the liver (to form glycogen), peripheral tissues (especially muscle & fat cells), the pituitary and fibroblasts. It has a molecular weight of 5600 Da and is composed of 2 polypeptides, called A and B chains, strongly bound by 2 covalently bonded disulphide bridges.
Insulin secretion:
A. Can be blocked by Atropine
B. Is inhibited by the hormone Somatostatin
C. Is inhibited by the phosphodiesterase inhibitor Theophylline
D. Is stimulated by leucine
E. Is increased by Beta 2 adrenergic receptor activation
A. True.
B. True.
C. False. Theophylline stimulates Insulin secretion but Somatostatin opposes it’s secretion.
D. True.
E/ True. The Sympathetic nervous system has conflicting effects on Insulin release, Alpha 2 agonists decrease Insulin release, whilst Beta 2 agonists increase it’s secretion.
The amino acids, Leucine & Arginine, stimulates insulin secretion, whereas the anticholinergics, including Atropine, can block it’s release.
The following are safe to use in patients with severe penicillin allergy:
A. Piperacillin
B. Teicoplanin
C. Cefradine
D. Clarithromycin
E. Imipenem
A. False. Piperacillin is a penicillin.
B. True. Teicoplanin is a glycopeptide.
C. False. Cefradine is a cephalosporin.
D. True. Clarithromycin a macrolide.
E. False. Imipenem is a carbapenem.
Cross-reactivity between penicillins, cephalosporins and carbapenems occurs in upto 10% of penicillin allergic patients.
The following are effective against anaerobic bacteria:
A. Imipenem
B. Metronidazole
C. Trimethoprim
D. Aztreonam
E. Vancomycin
A. True. Imipenem covers a very broad spectrum of bacteria including some anaerobes.
B. True. Metronidazole only covers anaerobes and parasites.
C. False.
D. False. Aztreonam is a monobactam with no useful activity against anaerobes or gram-positive organisms; it covers a wide range of gram-negative bacteria.
E. False.
The following antibiotics are bactericidal:
A. Piperacillin
B. Cefotaxime
C. Imipenem
D. Clindamycin
E. Rifampicin
A. True.
B. True.
C. True.
D. False. Clindamycin is a bacteriostatic lincosamide antibiotic
E. True.
Examples of bacteriocidal antibiotics include:
Penicillins, cephalosporins, carbapenems, aminoglycosides, quinolones, metronidazole, vancomycin.
Examples of bacteriostatic antibiotics include:
Sulphonamides, tetracyclines.
Note macrolide antibiotics can be bacteriocidal OR bacteriostatic depending on their plasma concentration.
Which of the following statements regarding antibiotics and their mechanism of action are true?
A. Benzylpenicillin inhibits cell wall synthesis
B. Ceftriaxone binds to the ribosomal subunit to halt bacterial protein synthesis
C. Gentamicin arrests bacterial protein synthesis by binding to the 30S ribosomal RNA subunit
D. Ciprofloxacin inhibits DNA gyrase
E. Rifampicin inhibits cell wall synthesis
A. True.
B. False. Cephalosporins, including Ceftriaxone, inhibit cell wall synthesis as do all beta-lactam antibiotics. Their beta-lactam ring binds to proteins and prevents peptidoglycan cross-linkage in the bacterial cell-wall thus weakening it.
C. True.
D. True.
E. False. Rifampicin binds to the beta-subunit of DNA-dependent RNA polymerase, preventing bacterial protein synthesis.
The following antibiotics can be used in the treatment of MRSA:
A. Clindamycin
B. Imipenem
C. Vancomycin
D. Flucloxacillin
E. Gentamicin
A. True.
B. False. Carbapenems do not cover MRSA.
C. True.
D. False.
E. False.
Examples of agents that cover MRSA include: Meropenem, Ciprofloxacin, Vancomycin, Clindamycin, Fusidic acid and Teicopleinin.
The following can be used to treat clostridium difficile infection:
A. Ciprofloxacin
B. Vancomycin
C. Metronidazole
D. Meropenem
E. Rifampicin
A. False. Ciprofloxacin is thought to increase susceptibility to C.difficile infection.
B. True. Metronidazole & Vancomycin are commonly used to treat c.difficile.
C. True.
D. False.
E. False.
The following antibiotics provide good gram-negative cover:
A. Vancomycin
B. Gentamicin
C. Ciprofloxacin
D. Aztreonam
E. Metronidazole
A. False. Vancomycin provides only very limited gram-negative cover.
B. True.
C. True.
D. True. Aztreonam provides gram-negative aerobic cover only.
E. False. Metronidazole is effective solely against anaerobes and parasites.
Regarding antifungals:
A. Amphotericin B acts by creating pores in the fungal cell membrane
B. Miconazole is absorbed well orally
C. Amphotericin B can be administered orally
D. Azoles work by affecting fungal ergosterol synthesis
E. Dose adjustment of ketoconazole is required in patients with renal failure
A. True.
B. False. All azoles are well absorbed orally except Miconazole which is given intravenously.
C. False. Amphotericin B is only administered intravenously.
D. True.
E. False. Ketoconazole is metabolised in the liver and inactive metabolites are excreted in the bile, hence no dose adjustment is required in renal failure.
The following statements are true regarding antimicrobial agents:
A. Vancomycin can cause ototoxicity
B. Fusidic acid causes red discolouration of body fluids
C. The effects of non-depolarising muscle relaxants can be prolonged by the use of aminoglycoside antibiotics
D. Tetracycline can cause discolouration of teeth in children
E. Metronidazole causes Red Man Syndrome?
A. True. Rifampicin causes red discolouration of body fluids.
B. False. Rifampicin causes red discolouration of body fluids.
C. True. Aminoglycosides increase potency of NDMRs by decreasing pre-junctional release of ACh and reducing the sensitivity of post-junctional receptors to ACh.
D. True.
E. False. Vancomycin causes histamine release and associated symptoms including widespread rash known as Red Man Syndrome.
The following antibiotics are significantly sensitive to beta-lactamases produced by bacteria:
A. Erythromycin
B. Meropenem
C. Flucloxacillin
D. Piperacillin
E. Benzylpenicillin
A. False. Erythromycin is a macrolide and hence not sensitive to beta-lactamases.
B. False.
C. False.
D. True.
E. True.
Beta-lactam antibiotics are sensitive to beta-lactamase enzymes produced by resistant bacteria; different antibiotics in this class have differing degrees of sensitivity. Benzylpenicillin and Piperacillin are sensitive. However Meropenem is very resistant to beta-lactamases, and Flucloxacillin is moderately beta-lactamase resistant.
Regarding acid-base balance in the body:
A. A pH of 7.0 equates to a hydrogen ion concentration of 100 nmol/L
B. pH is defined as the negative Loge of the hydrogen ion concentration in mol/L
C. Albumin is an important intracellular buffer
D. Carbonic anhydrase catalyses the reaction between water and CO2
E. Alkalosis lowers the free ionized calcium concentration
A. True. A pH of 7.0 indicates a hydrogen ion concentration of 10-7 mol/L or 100 nmol/L.
B. False. pH calculation uses Log10 and not Loge.
C. False. Albumin is an extracellular buffer.
D. True. Carbonic anhydrase, present at many sites throughout the body, is essential for the reaction between water and CO2 to occur rapidly.
E. True. Alkalosis, e.g. from hyperventilation, encourages free Ca2+ ions to bind to proteins, and can lead to tetany.
The mechanisms of respiratory system control:
A. A low PO2 in the blood directly stimulates medullary chemoreceptors
B. CO2 in the blood directly stimulates medullary chemoreceptors
C. H+ ions the blood directly stimulate medullary chemoreceptors
D. H+ ions the blood directly stimulate carotid body chemoreceptors
E. The baroreceptor response to hypotension includes respiratory stimulation
A. False.
B. False. Medullary chemoreceptors respond directly to CSF pH rather than CO2. However, CSF pH does change rapidly in response to CO2, which readily crosses the blood brain barrier and there is then minimal buffering in CSF.
C. False. H+ ions the blood cannot cross the blood brain barrier, but stimulate respiration via peripheral chemoreceptors.
D. True.
E. True. In addition to the cardiovascular changes seen in response to the baroreceptor reflex, there is an increase in respiratory rate.
The following represent typical oxygen content values that would be expected from each of these sites:
A. Renal vein - 125 mL/L
B. Coronary sinus - 90 mL/L
C. Radial artery - 200 mL/L
D. Umbilical vein - 130 mL/L
E. Pulmonary artery - 150 mL/L
A. False.
B. True.
C. True.
D. True.
E. True.
The following values would be compatible with a healthy person having lived at 5,000 m for 7 days:
A. [HCO3-] of 31 mmol/L
B. PaO2 of 10.6 kPa
C. PaCO2 of 3.9 kPa
D. Resting heart rate of 95/min
E. Right shift of Hb-O2 dissociation curve
A. False.
B. False.
C. True.
D. True.
E. True.
At 5,000 m the atmospheric pressure is approximately half that at sea level, which would produced a maximum PaO2 of around 5-6 kPa. This stimulates hyperventilation, lowering the PaCO2, and by day 7 there will have been metabolic compensation by excreting (rather than retaining) bicarbonate. A modest tachycardia would still be present and an increase in 2, 3 DPG moves the Hb-O2 dissociation curve to the right.
Sodium 142 mmol/L. Potassium 4.7 mmol/L. Chloride 108 mmol/L. Bicarbonate 12 mmol/L. The above values for plasma concentrations would be compatible with:
A. A normal anion gap
B. Stage 4 chronic kidney disease
C. Diabetic ketoacidosis
D. Hypoalbuminaemia
E. Pyloric stenosis
A. False.
B. False.
C. True.
D. False.
E. False.
These values show a metabolic acidosis with a raised anion gap (27), indicating an organic acid cause for the disturbance, such as DKA. There would a normal anion gap with CKD. Pyloric stenosis produces a metabolic alkalosis (raised bicarbonate). A low albumin reduces the anion gap as it is one of the main unmeasured anions.
Which of the following are true about acid-base regulation?
A. The pKa of H2CO3 is 6.1 at 37 degrees Celcius
B. The majority of filtered HCO3- is reabsorbed in Loop of Henle
C. Phosphate is an important extracellular buffer
D. The distal convoluted tubule determines the final urine pH
E. H+ ions are exchanged for K+ ions in the kidney
A. True. The pKa for the main dissociation pathway of H2CO3 at body temperature is 6.1.
B. False. Almost all H2CO3 is reabsorbed in the PCT.
C. False. Phosphate is one of the main intracellular buffers.
D. True.
E. True. The intercalated cells in the DCT regulate the final urine pH, excreting or reabsorbing H+ ions in exchange for K+ as circumstances require.
With regard to oxygen binding:
A. Affinity for haemoglobin is higher than for methaemoglobin
B. Affinity for fetal haemoglobin is higher than for haemoglobin
C. Affinity for myoglobin is higher than for haemoglobin
D. Each molecule of myoglobin can bind up to 4 molecules of oxygen
E. The normal P50 for Hb is approximately 5.3 kPa
A. True. Met-Hb is unable to bind oxygen.
B. True. The fetal Hb dissociation curve is to the left of that for Hb, so has a higher O2 affinity.
C. True.
D. False. Myoglobin is a single ferroprotein chain, and can bind only 1 molecule of oxygen; it has a very high affinity for oxygen, releasing it only at extremely low PO2 levels.
E. False. The normal P50 for Hb is approximately 3.5 kPa.
Carbon dioxide:
A. Is 5 times more soluble in plasma than oxygen
B. Content in venous blood is approximately 500 mL/L
C. Is carried in blood largely as bicarbonate
D. Conversion to carbamino compounds requires carbonic anhydrase
E. Content in blood increases as Hb unloads oxygen
A. False. CO2 is 25 times more soluble than oxygen.
B. True. 90% of it is carried as bicarbonate, with a content of 510 mL/L in venous blood.
C. True.
D. False. Carbamino compound formation is rapid and does not require enzyme activity.
E. True. This is the Haldane effect.
The following are buffers in renal tubular fluid?
A. Albumin
B. Ammonia
C. Bicarbonate
D. Phosphate
E. Urea
A. False.
B. True.
C, True.
D. True.
E. False.
Ammonia, bicarbonate and phosphate buffer hydrogen ions secreted into renal tubular fluid. Urea is not a buffer and albumin should not be present in tubular fluid.
Acutely reducing the inspired oxygen concentration to 10% at sea level will cause:
A. Increased urinary pH
B. Increased cardiac output
C. Increased capacity of Hb for oxygen
D. A respiratory acidosis
E. Increased erythropoietin secretion
A. True. Hyperventilation will cause a respiratory alkalosis and consequently the urinary pH will increase in attempt to correct this.
B. True. Mild degrees of hypoxia will cause sympathetic stimulation with a consequent increase in heart rate and cardiac output.
C. True. Alkalosis causes increased affinity of Hb for oxygen due to the shift of the oxygen-haemoglobin dissociation curve.
D. False. Hyperventilation will cause a respiratory alkalosis.
E. True. Erythropoietin is secreted in response to hypoxia but its effect is not seen acutely.
The following would be expected at the peak of vigorous exercise:
A. Oxygen consumption increased 10 fold
B. Overall oxygen extraction ratio increased to 0.75
C. Coronary oxygen extraction ratio doubled
D. Cardiac output increased 10 fold
E. Minute ventilation increased 10 fold
A. True.
B. False.
C. False.
D, False.
E. True.
Maximum O2 consumption increases approximately 10 fold during vigorous exercise, and this is met by an increase in cardiac output of 5 times, minute ventilation 10 times and a doubling of the oxygen extraction ratio to 0.5. The heart already has a high extraction ratio and must meet increased demand by increasing coronary flow.
Haemoglobin:
A. Contains 2 alpha chains
B. Carries 4 molecules of oxygen per chain
C. Is a 4-chain structure
D. Contains a ferrous ion
E. Is a polypeptide
A. True. Haemoglobin is a molecule comprised of four polypeptide chains, 2 alpha and 2 beta.
B. False. Each haemoglobin molecule carries 4 molecules of oxygen.
C. True.
D. True. Each polypeptide chain contains a porphyrin ring with a ferrous ion at its centre.
E. True.
Each polypeptide chain contains a porphyrin ring with a ferrous ion at its centre.
The oxygen content of blood is decreased in:
A. COHb
B. Methaemoglobinaemia
C. Anaemia
D. Chronic renal failure
E. Hyperbaric conditions
A. True.
B. True.
C. True.
D. True. CRF causes anaemia
E. False.
The oxygen content of blood is calculated by adding together the amount of oxygen carried by haemoglobin and the amount of oxygen carried in solution. In states of anaemia the former is reduced, as it is in methaemoglobinaemia and in the precence of carboxyhaemoglobin. Dissolved oxygen only represents about 1% of the total and is a function of PO2. It therefore increases under hyperbaric conditions.
The oxygen-haemoglobin dissociation curve moves to the right:
A. With an increase in temperature
B. When 2,3-DPG levels increase
C. When carbon dioxide concentration increases
D. With an increase in hydrogen ion concentration
E. On exercise
A. True.
B. True.
C. True.
D. True.
E. True.
Factors causing a right shift are: Hyperthermia, decreased pH, increased 2,3,DPG, increased PaCO2, pregnancy, haemoglobin S and after altitude acclimitisation.
The following drugs are bases:
A. Atracurium
B. Bupivacaine
C. Diclofenac
D. Morphine
E. Thiopental
A. True.
B. True.
C. False.
D. True.
E. False.
It is important to understand the ionization of drugs with changing pH (and hence membrane transfer). As a guide to identifying whether a drug is an acid or base, think of its salt when prepared.
Sodium-drug (or similar) = acid
Drug-sulphate (or similar) = base
Bases: Atracurium besylate, bupivacaine hydrochloride, Morphine sulphate
Acids: Sodium diclofenac, sodium thiopental
The oxyhaemoglobin dissociation curve is shifted to the left in:
A. Pregnancy
B. Stored blood
C. Fetal haemoglobin
D. Cyanide poisoning
E. Carbon monoxide poisoning
A. False. The P50 is higher in normal pregnancy.
B. True. Due to lower 2,3 DPG levels.
C. True.
D. False.
E. True.
Factors causing a left shift are: Hypothermia, increased pH, decreased 2,3,DP and decreased PaCO2. The curves for fetal, carboxyhaemoglobin and methaemoglobin are also shifted left.
The following are normal for an adult at rest:
A. Anion gap of 12 mmol/L
B. Carbon dioxide production of 500mL/min
C. Hydrogen ion concentration of 40 mmol/L
D. Carboxy-Hb of 0.5%
E. Fetal-Hb of 0.5%
A. True.
B. False.
C. False.
D. True.
E. True.
The normal anion gap is 8-16 mmol/L. Carbon dioxide production is around 200 mL/min (with an RQ of 0.8). Hydrogen ion concentration is 40 nmol/L (not mmol). Up to 2% of Hb can be bound to CO even in non-smokers. A small amount of HbF is still produced in adult life, the amount varying considerably, and can be as high as 5%.
The following would be compatible with a 10 day history of pyloric stenosis
A. Raised aldosterone level
B. Serum Chloride of 86 mmol/L
C. Serum Potassium of 5.5 mmol/L
D. Arterial PCO2 of 5.9 kPa
E. Arterial pH of 7.54
A. True.
B. True.
C. False.
D. True.
E. True.
Pyloric stenosis results in a loss of water, chloride and hydrogen ions (making B and E true). Hypoventilation is a respiratory compensation for the metabolic alkalosis (so D is true), and a rise in aldosterone secretion is part of the response to volume loss. In the DCT Hydrogen ions are retained in exchange for K+ excretion, and so hypokalaemia would be expected.
The Haldane Effect:
A. Enhances carbon dioxide unloading in the lungs
B. Is due mainly to enhanced formation/breakdown of carbamino compounds
C. Is more effective in a patient breathing 100% Oxygen
D. Is related to the Hb-Oxygen interaction
E. Results directly in part from changes in 2,3 DPG
A. True.
B. True.
C. False.
D. True.
E. False.
The Haldane Effect improves Carbon dioxide uptake in the peripheries and unloading in the lungs and results mainly (70%) from the more rapid formation of carbamino compounds by deoxyhaemoglobin. 2, 3 DPG has a direct action towards the Bohr but not the Haldane Effect and breathing 100% Oxygen will not have any influence.
The following are true about renal acid-base regulation:
A. Aldosterone is the main regulator of urinary pH
B. Filtered bicarbonate acts as a buffer in tubular fluid
C. Hydrogen ions are secreted by the incalated cells in the PCT
D. Hydrogen ion secretion in the PCT is dependent on carbonic anhydrase
E. The kidney excretes the body’s largest acid load
A. False.
B. True.
C. False.
D. True.
E. False.
Aldosterone has no significant role in acid-base balance. Filtered bicarbonate is the main intraluminal buffer for secreted Hydrogen ions in the PCT, production of which requires the action of carbonic acid. The intercalated cells are in the DCT. The largest acid load produced by the body is respiratory acid, in the form of carbon dioxide, and is excreted by the lungs.
The rate of drug absorption from the stomach is
A. lower for fentanyl than diclofenac
B. greater for weak acids than weak bases for drugs with a pKa of 6
C. increased in the presence of metoclopramide
D. always increased by omeprazole
E. less important than absorption from the small intestine for most oral medication
A. True. fentanyl is a weak base with a pKa of 8.4 so is almost entirely ionized in the stomach; diclofenac is a weak acid with pKa of 4 and will be largely unionized in the stomach
B. True.
C. False. metoclopramide increases gastric emptying, so reduces drug concentration in the stomach, which reduces rate of absorption from the stomach. Overall. Absorption may be increased, especially for basic drugs - but this is not what the question asks
D. False. The absorption of weak acids in the stomach will be slowed by PPIs
E. True. In general the greater absorptive area of the small bowel accounts for a greater proportion of drug absorption
When considering absorption of drugs from the gastrointestinal (GI) tract
A. fentanyl is better absorbed from the small intestine than the stomach
B. thiopental cannot be administered through a GI tract route
C. atracurium cannot be given orally
D. Neostigmine is better absorbed than physostigmine
E. Ketoconazole absorption is increased in patients taking omeprazole
A. True. The pH of the small bowel is higher than the stomach, so weak bases are better absorbed
B. False. Thiopental can be administered rectally; it is absorbed fairly well
C. True. Atracurium is a bis-quaternary molecule that is permanently charge and not absorbed from the GI tract
D. False. Neostigmine is quaternary and charged, physostigmine is a tertiary amine
E. False. Ketoconazole is a weak base but is so lipophilic that oral preparations cannot dissolve in hydrophilic gastric juice unless they can be ionized. By increasing gastric pH PPIs reduce the degree of ionization and so the solubility of ketoconazole
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin
A. diazepam
B. fentanyl
C. phenytoin
D. ibuprofen
E. lidocaine
A. False.
B. True.
C. False.
D. False.
E. True.
In general acidic/neutral drugs bind to albumin and basic drugs or those with a quaternary nitrogen, to alpha-1 acid glycoprotein. Lidocaine and fentanyl are basic drugs, ibuprofen is acidic and diazepam/phenytoin are neutral - they are not water soluble
Which of the following are true of plasma protein binding of therapeutic drugs
A. displacement of protein-bound drug by a second drug will necessarily cause toxic effects
B. drugs with a low hepatic extraction ratio and high degree of protein binding are most affected by changes in protein binding
C. drugs that show flow-dependent hepatic extraction are unaffected by changes in protein binding
D. the interaction between amiodarone and warfarin is entirely due to competition for plasma protein binding sites
E. the renal filtration rate of a drug is increased when plasma protein binding is decreased
A. False. Toxic effects seen only if the therapeutic ratio is small and hepatic extraction ratio is very low
B. True.
C. True.
D. False. This interaction is mainly due to a metabolic interaction: amiodarone inhibits CYP2C9
E. True.
Regarding the distribution of drugs through the body
A. the volume of distribution at steady state for a drug is dependent only on its lipid solubility
B. in a one-compartment model, volume of distribution is directly proportional to drug clearance
C. drugs with greater than 95% protein binding have a relatively small volume of distribuition
D. volume of distribution at steady state is approximately equal to total body water for most drugs
E. non-depolarizing muscle relaxants have a smaller volume of distribution than induction agents
A. False. although lipid soluble drugs can have very large volumes of distribution, if a drug is rapidly metabolized then it will have a much smaller volume of distribution that might be expected from its lipid characteristics : eg remifentanil
B. True. volume of distribution is given by clearance divided by rate constant for elimination (Vd = Cl/k)
C. False. propofol has a very large volume of distribution but also is greater than 98% bound - so this is clearly untrue
D. False. volume of distribution varies greatly between drugs: large for propofol, small for atracurium
E. True. ndmrs are charged molecules and do not cross lipid membranes so have relatively small volumes of distribution
Which of the following describe the distribution of propofol
A. it has a volume of distribution of approximately 1.4 L/kg
B. it is an acidic drug so binds to albumin in plasma
C. the volume of distribution is very large as it is essentially unionized at plasma pH
D. the initial volume of distribution in adults is age-dependent
E. the volume of distribution is high because propofol is highly protein-bound
A. False. Its Vd at steady state has variously been estimated to be as high as 20-60 L/kg, but lower values are found for short infusions. However, in general it has a volume of distribution of at least 4 L/kg
B. True.
C. True.
D. False. None of the kinetic models identify age as an independent variable for predicting initial Vd
E. False. Vd is high because it is extremely lipid soluble and essentially unionized
Which of the following are metabolites of atracurium
A. cisatracurium
B. desmethylatracurium
C. laudanosine
D. 3,17-dihydroxy atracurium
E. a monoquaternary alcohol derivative
A. False. this is just one of the 10 isomers of atracurium, not a metabolite
B. False.
C. True. a product of the minor (Hofmann) metabolic pathway
D. False. the aminosteroids are broken down by deacetylation at the 3 and 17 positions
E. True. a product of the major (ester hydrolysis) pathway
Which of the following enzymes demonstrate important pharmacogenetic variation
A. CYP2E1
B. CYP2D6
C. CYP3A5
D. CYP2C9
E. CYP1A2
A. False.
B. True. This is responsible for codeine conversion to morphine. 10% of Caucasians are poor metabolizers
C. False.
D. True. This is responsible for the metabolism of S-warfarin
E. False.
Which of the following drugs have an oral bioavailability of more than 75%
A. aspirin
B. paracetamol
C. oramorph
D. diclofenac
E. ibuprofen
A. False. about 65%
B. True. about 90%
C. False. about 25%
D. False. about 50%
E. True. more than 80%
Which of the following routes of elimination are the major route for the named drug
A. lungs: sevoflurane
B. renal: benzylpenicillin
C. red cell esterases: esmolol
D. tissue esterases: remifentanil
E. non-enzymic plasma degradation: mivacurium
A. True. >95% excreted unchanged
B. True. rapid excretion by tubular secretion
C. True.
D. True. plasma esterase activity also contributes, but tissue (especially muscle) esterases are most important
E. False. mivacurium is broken down by butyrylcholinesterase, cisatracurium and atracurium are degraded by the Hofmann process
In a one-compartment model for the kinetics of a drug
A. the volume of distribution at steady state can be calculated using a single bolus dose of drug
B. if volume of distribution stays the same, clearance increases if the time constant decreases
C. the context sensitive half time is proportional to the duration of an infusion
D. after giving an intravenous bolus dose, the rate of elimination at a particular time is dependent only on the clearance
E. the behaviour of the drug can be predicted as long as the clearance is known
A. True. There is just one volume to consider
B. True.
C. False. the CSHT is always constant and equal to the half-life
D. False. it is proportional to plasma concentration - an exponential relationship - whereas clearance is constant
E. False. you need two parameters to describe the behaviour of the drug: volume of distribution and time constant (or rate constant for elimination). Clearance simple gives you the ratio of these two values To describe behaviour completely, you need to know both parameters individually, not just the ratio
If a drug given by continuous intravenous infusion behaves according to a three-compartment model
A. the volume of distribution at steady state is the most important determinant of the variability of the context sensitive half time
B. the second compartment has three rate constants associated with it
C. if the plasma level has reached steady state, then clearance out of the body can be calculated from the infusion rate and concentration
D. drug can be removed from the system from any of the three compartments
E. the effect compartment equilibrates with the central compartment
A. False. the duration of the infusion and the ratio of elimination to redistribution rather than Vdss are most important: if elimination is very rapid and redistribution from compartments 2 and 3 is slow, then CSHT will not vary as much as if elimination were rapid and redistribution also rapid
B. False. elimination occurs only from the first (central) compartment, so there are just two: k12 and k21
C. True.
D. False. in the 3-C model, we adopt a mammilary, not a catenary model; elimination is allowed only from the central compartment
E. True.
When considering elimination of drug from the body
A. the rate of elimination is equal to the clearance
B. if glomerular filtration rate doubles, then the amount of free drug excreted through the urine also doubles
C. CYP450 enzymes are found only in hepatocytes
D. hepatic enzymes involved in xenobiotic metabolism are exclusively associated with the smooth endoplasmic reticulum
E. more than 99% of the drug will have been eliminated after three half-lives
A. False. rate of elimination = clearance multiplied by drug concentration
B. False. urinary elimination depends also on tubular secretion
C. False. CYP450 enzymes are expressed in many tissues
D> False. there are CYP enzymes in the SER, but metabolic enzymes are also found in the cytoplasm (alcohol dehydrogenase) and associated with mitochondria (MAO)
E. False. after 5 half-lives or 3 time constants
For a simple one-compartment model
A. the half-life is longer than the time constant
B. the rate constant for elimination is found from the slope of the graph that plots log(concentration) against time
C. clearance is the ratio of the volume of distribution to the time constant
D. the volume of distribution multiplied by the rate constant for elimination divided by plasma concentration is equal to the clearance
E. the shape of the curve that describes the rise of drug concetration with time on starting a constant rate infusion is a negative exponential
A. False. the time constant is always longer than the half-life
B. True.
C. True. Clearance = Vd/tau = Vd k, where tau is the time constant and k the rate constant for elimination
D. False. this is the rate of elimination
E. True. wash-in curves are negative exponentials because the rate at which concentration changes decreases with time[ Css(1 - exp(-kt))]
In patients with hepatic failure and acsites
A. the volume of distribution for hydrophilic drugs is reduced
B. the metabolism of all drugs is reduced
C. the bioavailability of drugs with a moderate heptic extraction ratio is increased
D. the terminal elimination half-life for remifentanil is unaffected
E. the dose of non-depolarizing muscle relaxants required for intubation is increased
A. False. In general Vd increases with ascites
B. False. many drugs are affected, but not all
C. True. metabolic capacity will be reduced as may hepatic flow, so it is likely that bioavailability will be increased
D. True.
E. True. Mainenance doses may need reducing, but the increased initial Vd means a larger initial dose may be needed
Which of the following will increase hepatic extraction of propofol
A. dobutamine
B. ciprofloxacin
C. carbamezepine
D. noradrenaline
E. chronic alcohol intake
A. True. increases hepatic blood flow
B. False. ciprofloxacin inhibits CYP1A2, not those enzymes primarily responsible for propofol metabolism (CYP2B6 and CYP2C9). Though they may interact to produce QT prolongation
C. False. CYP inducer, but hepatic ER already approaches 1
D. False. cardiac output not necessarily increased, so hepatic flow not increased
E. False. propofol is not metabolized by CYP2E1
A mammilary three-compartment model used to model effect-site targeting of drug concentration
A. elimination occurs from the effect site
B. the volume of the effect site is not included in the volume of distribution at steady state
C. there are two inter-compartmental clearances included in the model
D. the t1/2keo describes the rate of equilibration between plasma and effect compartments
E. clearance from the system can be found from steady-state infusion rate and plasma concentration
A. False. The effect site is considered to have a negligible volume and so elimination from this compartment is not a part of the 3-C model
B. True.
C. True. In a 3-C model there are three clearances to consider: two inter-compartment clearances and one out-of-system (body) clearance
D. True. This parameter describes the lag between plasma concentration changes and effect compartment changes
E. True. Input = output principle applies for steady state infusions - the difficulty lies with knowing when steady-state has been reached
Which of the following drugs readily cross the placenta
A. S-bupivacaine
B. diazepam
C. fentanyl
D. succinylcholine
E. isoflurane
A. True.
B. True.
C. True.
D. False.
E. True.
Lipid soluble drugs cross the placenta more rapidly than drugs that are ionized at plasma pH; permanently charged drugs do not cross the placenta so muscle relaxants will not affect the fetus
When measuring bioavailability
A. drug behaviour must be fitted to a known model in order to calculate bioavailability
B. bioavailability refers only to oral compared with intravenous administration
C. oral bioavailability can be found by dividing clearance of the drug when given orally by the clearance found when given IV
D. the same dose of drug must be given orally and intravenously to find oral bioavailability
E. interindividual variability must be expected
A. False. A non-model-based method is used: AUC(oral)/AUC(IV) if looking at oral bioavailability
B. False. Any route can be assessed for bioavailability compared with the standard route of administration (usually IV)
C. False. Clearance should be the same for a drug whether it is given orally or intravenously: bioavailability is the ratio of the area under the concentration-time curve (AUC) for the oral route divided by the AUC for the IV route
D. True.
E. True. Bioavailability of a given drug for a particular patient will differ depending on many factors including health problems and concurrent medication
Which of the listed drugs have a volume of distribution at steady state greater than total body water
A. cisatracurium
B. neostigmine
C. atropine
D. noradrenaline
E. sevoflurane
A. False.
B. False.
C. True.
D. False.
E. True.
Permanently charged molecules do not distribute across lipid membranes so the muscle relaxants and neostigmine have small volumes of distribution. Atropine and sevoflurane are very lipid soluble and will distribute into lipid areas. Noradrenaline is ionized at body pH and modeling is consistent with rapid metabolism so calculated Vd is small
On a flow volume loop in a spontaneously ventilating patient:
A. peak inspiratory flow rate is less than the peak expiratory flow rate
B. flow increases and then reduces as inspiration progresses
C. expiratory flow is constant throughout expiration
D. the area within the loop is greater in emphysema than normal
E. there is a limitation of inspiratory flow (‘a flattened top’) with sub-glottic laryngeal narrowing
A. True.
B. True. Flow during inspiration depends mostly on inspiratory muscle strength and is a smooth U shape. It increases in the first half of inspiration, reaching a rounded plateau, and then falls.
C. False. Initial expiratory flow rates are high and decrease during exhalation
D. False. Airways resistance is increased and tidal volume is reduced, so the area within the loop is smaller than normal.
E. True. The flow-volume loop is an excellent test for large airway narrowing, e.g. sub-glottic stenosis. The patient’s attempts at breathing in are attenuated by the stenosis, which limits flow.
A capnograph can be obtained by:
A. infra-red spectrometry
B. Raman spectrometry
C. mass spectrometry
D. gas chromatography
E. photoacoustic spectrometry
A. True. The response is sufficiently rapid to produce a trace.
B. True. Raman scattered light is light emitted at a different but characteristic wavelength from incident light and depends on the gas present. It is a rapidly responding system.
C. True.
D. False. The slow response time of gas chromatography makes it unsuitable for displaying a real-time capnograph
E. True. Photoacoustic spectrometry uses ultrasound and is a rapid-response system.
This question focuses on carbon dioxide - identifying which different methods of gas analysis allow measurement of rapidly changing values of the gas in a mixture.
When measured by a sphygmomanometer, systolic blood pressure is:
A. abnormally high with a narrow cuff
B. lower in the leg than in the arm in the sitting position
C. inaccurate if the patient is hypothermic
D. usually 20 mm Hg lower by comparison with direct arterial recordings
E. directly related to the loudest Korotkoff sound on auscultation
A. True. A cuff that is too narrow over-reads; a cuff that is too wide under-reads.
B. False. Blood pressure in the leg is a little higher than in the arm.
C. False. Hypothermia does not alter the accuracy of blood pressure measurement.
D. False. This is clearly not the case; there should be a reasonable agreement between the two methods.
E. False. Systolic blood pressure occurs when the Korotkoff sound is first heard.
Pulse oximeters:
A. can cause burns to the skin under the probe.
B. are inaccurate in the presence of foetal haemoglobin
C. are inaccurate in the presence of methaemoglobin
D. are inaccurate in patients with pigmented skin
E. have a slower response time than transcutaneous oxygen electrodes
A. True. Burns are rare but have been reported.
B. False. HbF has an identical absorption spectrum to HbA.
C. True. Methaemoglobin absorbs light equally at wavelengths of 660 and 940 nm, independent of PO2. This 1:1 ratio of absorption is also seen when Hb is 85% saturated, so the oximetry reading will show a saturation of 85%, whatever the true saturation, and so is inaccurate in the presence of methaemoglobin.
D. True. Skin pigmentation can alter values for saturation.
E. False. Transcutaneous oxygen electrodes have slower response times than pulse oximeters.
The concentration of isoflurane in an anaesthetic breathing system can be measured by:
A. an infra-red analyser
B. a mass spectrometer
C. an ultrasonic analyser
D. a refractometer
E. a paramagnetic analyser
A. True. Infrared analysis is the commonest method of measuring vapour concentrations in the theatre environment
B. True. Mass spectrometry is the gold standard for measurement of any gas/vapour in the laboratory and may be used in theatres.
C. True. Historical only.
D. True. Refractometry is bulky but will measure vapour concentrations - most commonly in commercial situations where very accurate measurement is needed.
E. False. Isoflurane is not paramagnetic and so cannot be measured with these analysers.
When testing a transducer-catheter system used for the measurement of pressures:
A. optimal damping is about 0.8 of critical
B. frequency response should be 5 times the fundamental frequency
C. catheter systems used for measurement of arterial pressure should be long and narrow
D. mean pressures are unaffected by damping
E. application of a square-wave pressure signal is a method of assessment
A. False. Optimal damping occurs when the damping coefficient (D) is 0.64. A value of D = 1 implies critical damping.
B. False. The frequency response should ideally be above the first 8-10 harmonics of the fundamental frequency (heart rate), i.e. ten times the heart rate.
C. False. Catheter systems should be short, stiff and wide bore.
D. True.
E. True. The application of a square wave is one method of testing a clinical catheter-transducer system connected to an amplifier.
Oesophageal Doppler cardiac output measurement:
A. requires a probe between 50 and 60 cm long
B. depends on blood flow in the ascending aorta
C. is influenced by body temperature
D. is calibrated by using cold saline
E. requires the ultrasound beam to be at 90 degrees to the direction of blood flow
A. False. Oesophageal Doppler measures blood flow (or, more accurately, red blood cell velocity) in the descending rather than the ascending aorta with the probe usually inserted to the 40 cm mark.
B. False. Flow is measured in the descending aorta.
C. False. Body temperature affects cardiac output measurement using pulmonary artery catheters, not oesophageal Doppler technology.
D. False. Cold saline boluses are required for the pulmonary artery catheter, but not oesophageal Doppler technique, of measuring cardiac output.
E. False. If blood flow were at 90 degrees to the ultrasound beam, no change in wavelength would occur and so there would be no Doppler shift.
The following statements are true of diathermy:
A. it utilises a high frequency current
B. the degree of burning depends upon current density at the diathermy tip
C. the same high frequency current flows through the diathermy tip and the return plate
D. bipolar diathermy coagulation does not require a separate skin electrode
E. the diathermy cannot pass current if the return plate becomes detached
A. True. Diathermy uses a high-frequency current greater than 1 MHz.
B. True. This is the basic principle of diathermy.
C. True. This is literally true for monopolar diathermy, but in bipolar diathermy the ‘return plate’ is effectively one of the tips of the probe.
D. True. See answer to c.
E. False. Current can flow if the plate is detached and any part of the patient is touching an earthed metal object.
The bispectral index (BIS):
A. is derived from blood pressure and the heart rate
B. decreases during normal sleep
C. predicts the response to surgical incision
D. shows similar changes with most anaesthetic agents
E. predicts brain damage during cardiopulmonary bypass
A. False. The bispectral index (BIS) is one of a number of systems using information from the electroencephalogram (EEG).
B. True.
C. False. No system can predict such a response.
D. True. The BIS shows similar changes with most (but not all) anaesthetic agents, ketamine being a typical exception.
E. False. The BIS falls with both deepening sedation and ischaemia; it cannot differentiate between the two.
The rate of diffusion of a gas is:
A. inversely proportional to the square root of its molecular weight
B. slowed as membrane thickness is increased
C. directly proportional to its tension gradient
D. decreased as its temperature increases
E. unaffected by ambient pressure
A. True. Graham’s Law states that the rate of diffusion of a gas is inversely proportional to the square root of its molecular weight.
B. True. The rate of diffusion is inversely proportional to membrane thickness.
C. True. The rate of diffusion is proportional to the concentration gradient (Fick’s Law). The law is modified to describe the rate of movement across a membrane or surface area, where tension gradient replaces concentration gradient.
D. False. As temperature increases, the velocity of movement of molecules increases, so the rate of diffusion also increases.
E. True. Ambient pressure does not affect rate of diffusion.
Cholesterol:
A. is a steroid precursor
B. has hormonal activity
C. is a constituent of cell membranes
D. is present in the blood mainly as the ester
E. is increased in myxoedema
A. True. Cholesterol is a precursor in the synthesis of both steroid hormones and bile acids.
B. False. Cholesterol has no intrinsic hormonal activity.
C. True. Cholesterol is a component of the lipoprotein matrix of animal cell membranes.
D. False. Cholesterol circulates in the blood in lipoprotein complexes; cholesterol esters are found in these complexes, but do not form the major part.
E. True. Thyroid hormones decrease plasma cholesterol by increasing levels of low density lipoprotein (LDL) receptors, which bind and take up LDL, including cholesterol. Increased cholesterol levels therefore occur in myxoedema (hypothyroidism).
Total body water:
A. is increased during pregnancy
B. can be measured using deuterium oxide
C. is half to two-thirds of body weight in young adults
D. is a smaller proportion of body weight in men than in women
E. is a lower proportion of body weight in neonates than in young children
A. True. In pregnancy, fat is laid down, but in terms of total body water (TBW) this is generally outstripped by increases in extracellular fluid volume and uterine size.
B. True. TBW is measured using a substance such as radiolabelled water (deuterium oxide,2H2O), which distributes throughout the entire compartment.
C. True. In adults, TBW is approximately 60% of body weight, or about 42 L in a 70 kg male.
D. False. As fat contains less water per unit mass than muscle, this percentage is lower in obese individuals and in women, who generally have proportionately more fat than men.
E. False. Neonates have a lower percentage of body fat and a greater circulating volume per unit mass than older children. TBW in the term neonate is approximately 75% of total body weight, falling progressively to the adult proportion by about two years of age
Characteristics of active transport across cell membranes include:
A. independence of temperature
B. movement against a concentration gradient
C. expenditure of energy
D. an upper limit to the rate of transport
E. insensitivity to anoxia
A. False. The rate of most metabolic reactions, including active transport, increases as body temperature increases.
B. True. Active transport is the passage of a substance from one side of a cell membrane to the other, against its electrical or chemical (concentration) gradient.
C. True. Active transport across cell membranes requires energy, almost entirely in the form of ATP hydrolysis.
D. True. Transport across cell membranes is limited by the number of carrier proteins present, so is a saturable process.
E. False. As 19 times as much ATP is generated by aerobic rather than anaerobic metabolism of glucose, active transport is decreased under hypoxic conditions.
Lactate dehydrogenase:
A. utilises pyruvate as a substrate
B. catalyses the hydrolysis of lactose
C. is synthesised in skeletal muscle
D. requires ATP as a coenzyme
E. is an enzyme of the citric acid cycle
A. True. Lactate dehydrogenase (LDH) catalyses the reaction: Pyruvate + NADH + H+ Lactate + NAD+. NAD+ is required during glycolysis, and conversion of NADH to NAD+ through the action of LDH allows glycolysis to continue under anaerobic conditions.
B. False. Lactose is a disaccharide and is therefore not a substrate for LDH.
C. True. LDH is found in skeletal muscle, but isoenzymes are also present in liver and heart.
D. False. ATP is not required for the reaction catalysed by LDH.
E. False. Under aerobic conditions, pyruvate is metabolised to acetyl CoA, which then enters the citric acid cycle.
The carotid bodies:
A. have a smaller blood supply per gram than the brain
B. are more influenced by oxygen tension than by oxygen content
C. are stimulated by a fall in pH
D. send afferent signals mainly by the vagus nerve
E. contain baroreceptors
A. False. The carotid bodies have an exceptionally high blood supply of approximately 2000 ml per 100 g tissue per minute compared with the brain (approximately 50 ml per 100 g per minute).
B. True. Although indifferent to arterial oxygen content, thecarotid bodies are stimulated by a decrease in arterial oxygen tension, a rise in PaCO2and a fall in pH.
C. True.
D. False. The carotid bodies send afferent signals via the glossopharyngeal nerve; the aortic bodies send afferent signals via the vagus nerve.
E. False. Although the carotid and aortic baroreceptors are located close to the carotid and aortic bodies, they are entirely separate receptors.
Likely findings in a patient breathing room air whose haemoglobin is 5.0 g 100 ml-1 include:
A. an arterial PCO2of 5.5 kPa (42 mm Hg)
B. an oxygen content of 19.5 ml per 100 ml blood
C. an oxygen saturation of 97%
D. an arterial PO2of 12.5 kPa (95 mm Hg)
E. a mixed venous PO2 of 5.3 kPa (40 mm Hg)
A. True. Assume that the anaemia is longstanding, so PaCO2 will be normal; during acute haemorrhage, hyperventilation will occur as a compensatory response and PaCO2 will fall.
B. False. Oxygen content is calculated by adding oxygen bound to haemoglobin (Hb) to dissolved oxygen: (Hb concentration x 1.34 x SaO2 ) + (PaO2 x 0.023). For a Hb concentration of 5.0 g 100 ml-1, a saturation of 97% and a PaO2 of 12.5 kPa, oxygen content will be (5.0 g 100 ml-1x 1.34 ml g-1 x 0.97) + (12.5 kPa x 0.023 ml 100 ml-1 kPa-1) = (6.5 + 0.3) ml 100 ml-1 = 6.8 ml dl-1 blood (take care with units for Hb).
C. True. In the absence of other pathology, PaO2, and hence oxygen saturation, will be normal.
D. True.
E. False. If cardiac output, oxygen consumption and hence oxygen extraction remained unchanged, mixed venous oxygen content would be only about 1.8 ml dl-1, with a very low mixed venous oxygen saturation and a partial pressure well below 5.3 kPa. With such severe anaemia, a compensatory increase in cardiac output with decreased oxygen extraction would only partially offset this.
Normal terminal bronchioles (1 mm diameter) characteristically:
A. offer lower resistance to airflow as lung volume increases
B. collapse with forced expiration
C. have abundant smooth muscle
D. participate in transmural gas exchange
E. contain type-2 pneumocytes
A. True. Terminal bronchioles contain no alveoli and represent the last division of the conducting airways. With increasing lung volume, radial traction by surrounding lung tissue causes an increase in bronchial diameter, leading to a decrease in airway resistance.
B. True. These airways may collapse completely at low lung volumes. Closing volume is the volume above residual volume at which measurable small airways closure occurs.
C. True.
D. False. Terminal bronchioles subdivide into respiratory bronchioles, which do participate in gas exchange.
E. False. Surfactant is produced by type-2 pneumocytes, which are alveolar epithelial cells.
Lung compliance:
A. varies with lung volume
B. is decreased in the elderly
C. is approximately linear in the normal tidal volume range
D. is measured in units of cm H2O L-1
E. measured dynamically is frequency-dependent
A. True. Compliance of the lung is given by the slope of the graph of volume vs pressure. The pressure-volume curve is sigmoid, not linear, so compliance varies with lung volume.
B. False. Compliance is decreased by pulmonary oedema and pulmonary fibrosis and is increased in the elderly and in emphysema.
C. True. The sigmoid relationship between lung volume and intrapleural pressure is roughly linear in the middle range, which includes normal tidal ventilation.
D. False. The compliance of the lung is 0.1 L cm H2O-1.
E. True. Dynamic compliance is inversely related to frequency of ventilation.
Physiological dead space:
A. is greater than anatomical dead space
B. remains constant with changes in tidal volume
C. accounts for the difference in composition between alveolar and mixed expired gas
D. is increased during general anaesthesia
E. can be calculated from tidal volume and the CO2 concentrations of expired and alveolar gas
A. True. Physiological dead space = anatomical dead space + alveolar dead space.
B. False. Changes in lung volume affect conducting airway diameter and pulmonary vascular resistance, altering regional pulmonary blood flow and V/Q ratios throughout the lung.
C. True. Mixed expired gas comprises gases from the anatomical dead space, alveolar dead space and ventilated alveoli.
D. True. General anaesthesia inhibits hypoxic pulmonary vasoconstriction and interferes with optimal matching of ventilation with perfusion, resulting in increased physiological dead space.
E. True. Physiological deadspace is measured using the Bohr equation: VD/VT = (PaCO2 - PECO2)/PaCO2 (PACO2 is assumed to equal PaCO2)
The arterial baroreceptors:
A. are located only in the carotid sinus
B. are stretch receptors
C. increase their discharge rate in response to increased blood pressure
D. respond to changes in PaO2
E. influence the secretion of thyroxine
A. False. Arterial baroreceptors are stretch receptors located in the walls of the aortic arch and carotid sinuses (small dilatations of the internal carotid arteries just above the carotid bifurcation).
B. True.
C. True. Arterial baroreceptors are stimulated by distension and increase their discharge frequency in response to an increase in arterial pressure.
D. False. The carotid and aortic bodies are responsive to PaO2, not the baroreceptors.
E. False. The baroreceptors do not influence thyroxine synthesis or release.
Adenylyl cyclase:
A. is indirectly coupled to beta-adrenoceptors
B. is a membrane-bound enzyme
C. catalyses the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).
D. is inhibited by aminophylline
E. is activated by salbutamol
A. True. Adenylate cyclase is activated indirectly by catecholamines binding to beta-adrenoceptors on the cell surface. The drug receptor complex then associates with a regulatory G-protein, which, once activated, will increase or decrease adenylate cyclase activity.
B. True. Adenylate cyclase is a membrane-bound enzyme, which catalyses the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). There is also a soluble form of the enzyme, found within the cytoplasm.
C. True.
D. False. Aminophylline is an inhibitor of phosphodiesterase, which breaks down cAMP to inactive 5’-AMP.
E. True. Salbutamol is an agonist at beta-2-adrenoceptors, resulting in adenylate cyclase activation.
The following drugs act mainly by altering cell membrane sodium permeability:
A. mannitol
B. bupivacaine
C. triamterene
D. bumetanide
E. glyceryl trinitrate
A. False. Mannitol is a 6-carbon sugar alcohol, which acts as an osmotic diuretic; it has no effect on cell membrane permeability to sodium.
B. True. Local anaesthetic drugs such as bupivacaine cause blockade of sodium channels in nerve cell membranes, thereby reducing the rate of depolarisation without affecting the resting membrane or threshold potentials.
C. True. Bumetanide and triamterene both decrease membrane permeability to sodium by inhibiting the active transport of sodium in renal tubular cell membranes. Triamterene acts at the distal renal tubule to inhibit sodium reabsorption in exchange for potassium and hydrogen ions.
D. True. Bumetanide acts predominantly at the ascending limb of the loop of Henle by binding reversibly to the Na+/K+/2Cl- transport protein to inhibit sodium and chloride reabsorption.
E. False. Glyceryl trinitrate has no effect on cell membrane permeability to sodium; it is converted to nitric oxide, which activates cytoplasmic guanylate cyclase in vascular smooth muscle cells, causing vasodilatation.
The fraction of a drug bound to plasma proteins:
A. comprises the active portion of the drug
B. is the ionised fraction
C. is unrelated to the amount of unbound drug
D. constitutes a depot of drug that will prolong action
E. influences the initial volume of distribution
A. False. Most drugs do not act while in plasma, but need to reach their effect site. Bound and unbound drug are in equilibrium, but only free drug can leave plasma. Once free drug leaves the plasma, equilibrium is restored by some bound drug being released from its binding sites. Thus, extensive protein binding can slow the rate at which active drug can reach its site of action, but bound drug is not inactive.
B. False. The ionised fraction is not the fraction bound to plasma proteins, it is the proportion of drug that has either acquired (if a weak base) or given up (if a weak acid) a proton.
C. False. The bound and unbound portions of a drug are in equilibrium and therefore closely related. The degree of binding depends on the physicochemical properties of the drug.
D. True. Drug bound to plasma proteins is not available for immediate action, and the pharmacological effect is prolonged.
E. True. The initial volume of distribution is determined largely by the extent of protein binding. The more highly protein bound, the lower the initial volume of distribution. However, the volume of distribution at steady state is largely determined by lipid solubility and tissue binding for drugs that are not tightly bound to plasma proteins.
The following are true for intravenous anaesthetics:
A. clearance may be defined as the volume of a body compartment from which a drug is completely removed per unit time
B. clearance is independent of the drug concentration
C. the main site of drug clearance is the liver
D. clearance is linearly related to body weight
E. context-sensitive half-time is dependent on the plasma concentration at the end of an infusion
A. True. Clearance is that volume of a body compartment (often blood or plasma) from which a drug is completely removed per unit time, usually expressed in ml min-1.
B. True. Clearance simply identifies that volume of the compartment from which drug is removed; however, the amount of drug removed in unit time does vary with the concentration (clearance x concentration = amount of drug removed in unit time).
C. True. Drugs are cleared by several routes, including the kidney and lung, but the main site of drug clearance is the liver, either by metabolism, biliary excretion or both.
D. False. Although clearance is often reported as indexed to body weight, this relationship is not always predictable.
E. False. Context-sensitive half-time (CHST) is the time taken for a 50% decrease in the plasma concentration of a drug, after termination of an infusion which has been designed to maintain steady-state plasma concentrations. It is a function of the duration of the infusion.
The following drugs are hydrolysed by esterases
A. edrophonium
B. aspirin
C. diamorphine
D. tetracaine (amethocaine)
E. propofol
A. False. Edrophonium has a quaternary nitrogen, which binds to the anionic site of acetylcholinesterase, but it is not an ester, so cannot bind to or be metabolised by the enzyme. It is excreted unchanged or as the glucuronide conjugate.
B. True. Aspirin is an ester and is metabolised by esterases to acetic acid and salicylate, the active moiety.
C. True. Diamorphine is an ester (diacetylmorphine) and is deacetylated by plasma and tissue esterases to monoacetylmorphine and morphine.
D. True. Tetracaine (amethocaine) is an ester local anaesthetic and is extensively hydrolysed by plasma cholinesterase and other tissue esterases.
E. False. Propofol is not an ester; some propofol is metabolised to the quinol derivative, and both propofol and its quinol are largely glucuronidated.
The MAC of sevoflurane will be decreased in a patient:
A. premedicated with temazepam
B. with a PaCO2 of 2.5 kPa (19 mm Hg)
C. with a raised plasma magnesium concentration
D. with a raised rectal temperature of 43 ° C
E. with a haemoglobin of 100 g/L
A. True. MAC is decreased by concurrent use of CNS sedative drugs including benzodiazepines, opioids and clonidine.
B. False. MAC is not affected by haemoglobin concentrations, arterial CO2 tensions or plasma magnesium concentrations.
C. False. See b above; administration of Mg2+ potentiates NMDA antagonists and possibly opioids, but an effect on MAC has not clearly been established.
D. False. MAC is increased by hyperthermia.
E. False. See b above.
The following are true of the metabolism of volatile anaesthetic agents:
A. sevoflurane is metabolised by hepatic microsomes
B. bromide ions are produced as a product of desflurane metabolism
C. chronic barbiturate therapy will induce the drug enzyme system for metabolism of halothane
D. cigarette smoking influences the choice of volatile agent for maintenance of anaesthesia
E. enflurane is hepatically metabolised to a greater extent than halothane
A. True. Volatile anaesthetic agents are metabolised to a small extent by microsomal CYP P450 enzymes. Approximately 3% of inhaled sevoflurane is metabolised by the isoform CYP2E1.
B. False. Desflurane is a fluorinated ether, which is minimally (0.02%) metabolised to produce trifluoroacetate and fluoride ions. Only halothane contains bromine atoms.
C. True. Chronic intake of barbiturates, alcohol or cigarettes induces CYP enzymes, including those responsible for the metabolism of halothane.
D. False. Cigarette smoking does not affect, the choice of anaesthetic agent for maintenance of anaesthesia, despite its effect on CYP enzymes.
E. False. 20 to 25% of inhaled halothane is metabolised compared with 2 to 2.5% of enflurane.
The blood/gas partition coefficient of an anaesthetic agent
A. is a dimensionless measurement
B. is a ratio of solubilities
C. is important to the speed of induction of anaesthesia
D. determines the alveolar partial pressure required for anaesthesia with the agent
E. is a factor in the rate of recovery from anaesthesia with the agent
A. True. The blood/gas partition coefficient of an anaesthetic agent reflects its solubility in blood. It is expressed numerically as the ratio of the amount of anaesthetic in blood and gas at a given temperature (37 C), when the two phases are at equal partial pressures and of equal volume. Being a ratio, it has no units of measurement.
B. True.
C. True. Blood gas solubility determines the rate of onset and offset of effect of inhalational anaesthetic agents; alveolar concentrations of agents with a low blood/gas partition coefficient increase quickly to equilibrate with inspired concentrations. Thus, diffusion into both pulmonary capillaries and the CNS, and the onset of anaesthesia, occur more quickly than for a more soluble agent (higher blood/gas partition coefficient).
D. False. The alveolar partial pressure required to maintain anaesthesia and MAC are related to lipid solubility, as expressed by the oil/gas solubility coefficient.
E. True. See c above.
Ketamine:
A. has more than one chiral centre
B. causes postural hypotension
C. increases intracranial pressure
D. blocks the ion channel associated with the NMDA receptor
E. is a bronchodilator
A. False. Ketamine has one chiral centre and is presented as a racemic mixture of its two enantiomers, S (+)-ketamine and R (-)- ketamine.
B. False. Unlike other intravenous anaesthetic drugs, ketamine has positive inotropic effects, so heart rate, arterial pressure and cardiac output are increased.
C. True. Ketamine increases cerebral blood flow, CMRO2 and intracranial pressure.
D. True. Ketamine is a non-competitive inhibitor of ion channels associated with NMDA receptors
E. True. Ketamine causes bronchodilatation.
Competitive neuromuscular blockade may be prolonged in the presence of:
A. pyrexia
B. carbamazepine
C. lithium
D. edrophonium
E. neomycin
A. False. Competitive neuromuscular blockade may be prolonged by several factors, including hypothermia, hypokalaemia, hypocalcaemia and metabolic acidosis.
B. False. Carbamazepine is a hepatic enzyme inducer and shortens the duration of action of competitive neuromuscular blockers.
C. True. Lithium acts like a sodium ion and may prolong competitive neuromuscular blockade.
D. False. Edrophonium is an acetylcholinesterase inhibitor which antagonises competitive neuromuscular blockade.
E. True. Drugs which reduce pre-synaptic calcium entry, such as calcium channel blockers and aminoglycosides (gentamicin, neomycin), will prolong blockade.
The devices used to measure gas flow based on the measurement of pressure gradient across a resistance include:
A. Wright peak flowmeter
B. pneumotachograph
C. Wright’s respirometer
D. wet spirometer
E. rotameter
A. False. The Wright Peak flowmeter relies on hte variable orifice principle
B. True. The measurement of pressure drop across a resistance is exactly how a pneumotachograph measures gas flow
C. False. Wright’srespirometer measures gas volume, not gas flow
D. False. the wet spirometer also measures gas volume, not gas flow
E. False. A rotametermeasures gas flow by variable orifice principle
The content of the following cylinders when full are liquid at room temperature:
A. nitrous oxide
B. oxygen
C. helium
D. Entonox (50:50 nitrous oxide in oxygen)
E. nitric oxide in nitrogen
A. True. A full nitrous oxide cylinder contains liquid at room temperature, it has a critical temperaure of 36.5oC.
B. False. Oxygen is always gaseous at room temperature, independent of ressure, since its critical temperature is -118.4oC.
C. False. The critical temperature of heluim is below room temperature
D. False. Entonox behaves as agas at room temperature
E. False. The mixture of nitric oxide and nitrogen behaves as a gas at room temperature
A reservoir of liquid inhalational (volatile) anaesthetic agent is allowed to come into equilibrium with a mixture of gases in an enclosed container. Under these conditions, the partial pressure of the agent in the resulting gas mixture depends on:
A. the atmospheric pressure
B. the surface area of the liquid
C. the volume of the liquid
D. the temperature of the liquid
E. the composition of the gas mixture
A. False. Saturated vapour pressure (SVP) does not change with the atmospheric pressure but the resulting concentration does change
B. False. since equilibrium as been reached, the surface area will not influence the partial pressure
C. False. Since the equilibrium has been reached, the volume of the liquid will not influence the partial pressure
D. True. SVP varies with the temperature of the liquid and reaches atmospheric pressure at its boiling point
E. False. gas composition does not affect partial pressure of the agent, provide that no chemical reaction occurs
The following are true of the pressure/force relationship:
A. for a given force applied to a syringe,doubling the diameter of the syringe will reduce the pressure generated a factor of four
B. the pressure required to open an expiratory valve at its minimum setting is approximately 50 Pa
C. the pressure of a full oxygen cylinder is approximately 138 atmospheres
D. Entonox requires only a single-stage reducing valve
E. gauge pressure is equivalent to the measured value plus the atmospheric pressure
A. True. Pressure is force per unit area applied. If you double the diameter, you increase the area by factor of four (area = Pi*r2)
B. True.
C. True.
D. False. Entonox requires a two-stage valve to allow on-demand delivery only when a negative pressure is developed in the second-stage delivery
E. False. Gauge pressure is the absolute pressure minus atmospheric pressure
Critical pressure is:
A. the pressure required to liquefy gas at its critical temperature
B. 5100 kPa
C. the pressure above which a liquid cannot be boiled
D. dependent upon the molecular weight of the gas
E. the same for all gases
A. True. this is the definition of critical pressure
B. False. Critical pressure depends on the gas; it is not constant
C. False. see a for definition
D. False. molecular weight does not correlate with critical pressure
E. False. Critical pressure is different for different substances
The Doppler effect:
A. applies to both electromagnetic radiation and sound
B. changes the velocity of reflected ultrasound
C. depends on the piezo-electric properties of some crystals
D. shows a shift to lower frequency if the source is moving away from the receiver
E. can indicate the velocity of the red blood cells
A. True. The Doppler effect applies to all waves, both sound and elecromagnetic radiation
B. False. The wavelength and frequency, not the velocity, of the reflected wave is changed
C. False. The piezo-electric effect is the ability of certain crystals to contract slightly when subjected to a potencial difference. Such a crystal will vibrate when an alternating current is applied and can be used to create a waveform for use in ultrasound that exploits the Doppler effect
D. True.
E. True. The Doppler effect is used to measure the velocity of moving particles as red blood cells, the frequency of the reflected wave decreases with blood moving away from the people
Magnetic resonance imaging:
Select true or false for each of the following statements.
A. involves placing the patient in a magnetic field which causes the alignment of atoms with an even number of protons and neutrons
B. uses radiofrequency pulses that causes the atoms to absorb energy
C. uses a magnetic field of about 6 Tesla
D. involves a superconducting magnet cooled by liquid helium
E. requires special monitoring devices which contain desensitised ferrous materials
A. False. The magnetic field of an MRI scanner aligns atoms with an odd number of protons plus neutrons
B. True.
C. False. The strength of the magnetic field is usually less that 2 Tesla
D . True.
E. False. Ferrous materials should not be near a strong magnetic field for safety reasons; they will also affect the resulting image
We are increasingly asked to provide care in the MRI environment, and so some understanding of how images are generated and important anaesthetic implications, is necessary. The magnetic field of an MRI scanner aligns atoms with an odd number of nucleons (the number of protons plus neutrons). Bursts of radiofrequency energy are then applied ,which are taken up by hydrogen nuclei in water and knocked out of alignment. The energy is subsequently released again as the hydrogen ions ‘relax’ and is picked up by an external radiofrequency coil. This information forms the basis of the resulting image.
the following are true of osmolality:
A. the depression of the freezing point of a solution is proportional to its osmolality
B. the water vapour pressure of a solution varies with its osmolality
C. the normal urine osmolality can be as high as 1400 mOsm/kg
D. a urinary osmolality of 700 mOsm/kg corresponds to a specific gravity of 1040
E. the main determinant of intracellular osmolality is protein
A. True. If you add salt to a container containing water and ice in equilibrium, the rate at which water molecules move from ice into water is initially unchanged, but that from water to ice is reduced. Therefore, the freezing point is reduced in proportion to the molar concentration of solute(Raoult’s Law)
B. True. The osmolality of a solution refers to the number of osmotically active particles per kilogram of solvent. At liquid/ vapour interface, water molecules will move from liquid to gas and vice versa; as the number of osmotically active particles increases in the liquid, the number of water molecules leaving the liquid is reduced
C. True. Concentrated urine canhave an osmolality of up to 1400 mOsm/kg
D. False. An osmolality of 700 corresponds with a specific gravity of 1020, not 1040
False. Protein only accounts for a very mnor portion of intracellularly osmoticall active particles
A drug has an initial volume of distribution = 0.1 Litre Kg-1 and a rate constant of elimination k = 0.1 min-1. It obeys a one-compartment model. An intravenous bolus dose of 500 mg is given to a healthy 50 Kg subject.
Which of the following is the most likely plasma drug concentration after two minutes?
A. 1.0 mcg mL-1
B. 25.2 mcg mL-1
C. 81.9 mcg mL-1
D. 98.8 mcg mL-1
E. 100.0 mcg mL-1
C. 81.9 mcg mL-1
The initial concentration = Dose/Vd = 500 000 mcg/5 000 mL = 100 mcg.mL-1. Approximate calculation: after one minute, 10% (k expressed as %) of plasma will be cleared of drug, giving a concentration = 90 mcg.mL-1. Assuming a one compartment model, one minute later, a further 10% will give a concentration = 81 mcg.mL-1. Exact calculation: ln (C/C0) = -kt. C=81.9 mcg mL-1.
The non-depolarising neuromuscular blocker rocuronium is sometimes used for its rapid onset of action.
Which of the following is the most important reason for its more rapid onset compared with vecuronium?
A. Priming doses are not required for rocuronium
B. Rocuronium has a lower volume of distribution
C. Rocuronium has lower potency
D. Rocuronium has pre-junctional action at the NMJ
E. Rocuronium is an aminosteroid
C. Rocuronium has lower potency
The rapid onset of action of Rocuronium is because of its low potency, since the higher dose required for intubation will enhance the diffusion gradient between plasma and neuromuscular junction (Bowman principle).
A 50-year-old woman is anaesthetised for cystoscopy and injection of botulinum toxin into the bladder for detrusor instability.
Which of the following best explains the therapeutic effect of botulinum toxin?
A. Antagonism of acetylcholine at the post-junctional receptor
B. Increased neuronal re-uptake of acetylcholine
C. Inhibition of acetylcholine release
D. Inhibition of acetylcholine synthesis
E. Potentiation of acetylcholinesterase
C. Inhibition of acetylcholine release
Botulinum toxin is an exotoxin produced by the anaerobic bacterium Clostridium botulinum and now used as a therapeutic drug. It inhibits acetylcholine release from nerve terminals.
In an experimental situation, a giant squid axon is bathed in an electrolyte solution containing chloride, potassium and sodium ions.
Which of the following changes would have the greatest effect in making the resting membrane potential less negative?
A. Decreasing the extracellular concentration of potassium ions
B. Decreasing the extracellular concentration of sodium ions
C. Increasing the extracellular concentration of chloride ions
D. Increasing the extracellular concentration of potassium ions
E. Increasing the extracellular concentration of sodium ions
D. Increasing the extracellular concentration of potassium ions
The question simply tests knowledge of the Nernst equation and the fact that the resting membrane is relatively impermeable to sodium.
