A- Main Study Deck Flashcards

Question 1

Q

Re: Providone/Iodine as an antispectic/disinfectant - what are its main action, onset/duration, advantages & limitations and spectrum of activity?

Answer

A

Main action: Oxidative damage.
Onset/Duration: Onset: Iodine is bacteriocidal in 1 minute and kills spores in 15 minutes. However in povidine compounding it has a delayed onset/Duration: No sustained effect
Advantages:
1. Sporicidal
2. Cheap
3. Broad spectrum
Most effective for intact skin

Limitations:
1. Hypersensitivity reactions
2. Delayed onset without residual activity
3. Stains clothes and dressings

Spectrum of activity:
- Bacteria (G+ve and –ve and acid fast)
- Sporicidal
- Viruses
- Fungi

Ineffective against:
Prions
Hydrophilic viruses

Other:
Can be used as antiseptics or disinfectants (latter contains more iodine)

Question 2

Q

4 types of lung receptors (peripheral afferents)

Respiratory

Answer

A

Pulmonary stretch receptors - discharge in response to distension of lung & activity is sustained with lung inflation - ie. They show little adaptation
Irritant receptors - Rapidly respond to airway irritants - eg. Cigarette smoke/noxious gases/cold air
J receptors - respond to chemicals injected into the pulmonary circulation –> results in rapid, shallow breathing
Bronchial C fibres - respond to chemical injected into the bronchial circulation –> results in rapid, shallow breathing

Question 3

Q

Hering-Bruer reflex

Respiratory

Answer

A

Stimulation of pulmonary stretch receptors results in slowing of respiration due to increase in expiratory time

[Opposite is true for expiration]

Question 4

Q

Normal compliance

Respiratory

Answer

A

100mL/cmH₂O
* C_(lung)= 200mL/cmH₂O; C_{(chest wall)}= 200mL/cmH₂O

Specific compliance = 0.05/cmH₂O

Question 5

Q

Malignant hyperthermia incidence

Pharmacogenetics

Answer

A

1:5,000 - 1:50,000

Question 6

Q

What is porphyria?

Pharmacogenetics

Answer

A

Mutation of haem synthesis enzymes which causes a build-up of neurotoxic intermediate metabolites (porphyrin precursors) in response to various drugs (anticonvulsants, antibiotics, thiopentone)
○ Autosomal dominant

Question 7

Q

Malignant hyperthermia mechanism

Pharmacogenetics

Answer

A

Mutation of the ryanodine calcium channel receptor which causes a hypermetabolic crisis in response to volatile anaesthetics

Question 8

Q

Malignant hyperthermia signs/symptoms

Pharmacogenetics

Answer

A

○ Initial - tachycardia, masseter spasm, hypercapnoea, arrhythmia
○ Intermediate - hyperthermia, sweating, combined metabolic and respiratory acidosis, hyperkalaemia, muscle rigidity
○ Late - rhabdomyolosis, coagulopathy, cardiac arrest

Question 9

Q

Malignant hyperthermia Mx

Pharmacogenetics

Answer

A

Cease volatile, start TIVA, give dantrolene 2.5mg/kg increments to 10mg/kg, Rx of complications

Question 10

Q

Atypical plasma cholinesterase/pseudocholinesterase

Congenital/acquired/both/neither?

Pharmacogenetics

Answer

A

Fails to metabolise suxamethonium and causes “sux apnoea”
○ Congenital - autosomal recessive
○ Acquired - due to loss of plasma cholinesterase. Can occur in pregnancy, organ failure (hepatic, renal, cardiac), malnutrition, hyperthyroidism, burns, malignancy, drugs (OCP, ketamine, lignocaine and ester Las, metoclopramide, lithium)
○ Note: acquired disease will have normal dibucaine no but just decreased quantity of enzyme

Question 11

Q

How to test for atypical plasma cholinesterase/pseudocholinesterase?

Pharmacogenetics

Answer

A

○ Measured by dibucaine number. Dibucaine is an amide LA, which inhibits plasma cholinesterase. Greater inhibition indicates a less severe mutation - so normal:normal dibucaine no = 80 (80% inhibited). Dibucaine resistant:resistant has a no of 20 (20% inhibited)

Question 12

Q

G6PD deficiency

Pharmacogenetics

Answer

A

Mutation of glucose 6-phosphate dehydrogenase which produces acute haemolysis in response to oxidative stress due to dapsone, methylene blue, fluoroquinolones, antimalarialas and rasburicase

Question 13

Q

Normal cardiac output and cardiac index values

Answer

A

CO = 5L/min; CI = 2.5-4L/min

Question 14

Q

LaPlace’s Law (cardiac)

Answer

A

sigma = Pr/2h

where sigma = myocardial wall stress
P = transmural pressure
r = radius
h = ventricular wall thickness

Question 15

Q

Features of SA node and ventricular myocyte action potentials: resting, threshold, peak potentials

Answer

A

Ventricular myocyte:
* Resting potential: -90mV
* Threshold: -70mV
* Peak: +50mV

SA node:
* Max diastolic (nil real resting potential): -70mV
* Threshold: -40mV
* Peak: +20mV

Question 16

Q

Structure of fast cardiac Na+ channel

Answer

A

2xβ subunits
1x α subunit
* Has 4 domains - I-IV
* The N- & C- terminus are both intracellular
* Each domain has 6 transmembrane segments linked by intracellular and extracellular peptides
–Extracellular peptides linking segments 5-6 form the ion pore (responsible for ion selectivity - the Ca channel has similar structure but is Ca selective)
–Domain IV undergoes a conformational change in response to voltage & opens the pores (activation gate - ‘m’)
– The intracellular peptide loop connecting domain III & IV forms the inactivation gate ‘h’

Question 17

Q

What membrane potential does the absolute refractory period of a cardiac action potential go up to?

Answer

A

Absolute refractory period is up to ~-50mV. At this value, some fast Na+ channels have recovered from inactivation enough to permit response to stimulation

Question 18

Q

Time constant equation

Answer

A

(tau) = compliance x resistance

Question 19

Q

What are the functions of the FRC?

Answer

A

Oxygen reservoir - prevents rapid changes in alveolar oxygen tension and arterial oxygen content by maintaining gas exchange throughout expiration
- Maintenance of small airway patency (N2 splinting)
- Optimising respiratory workload - compliance maximal at FRC, WOB required from FRC is minimal
  ○ Keeps tidal volume over steep part of lung compliance curve
- Minimises pulmonary vascular resistance & hence RV afterload/work/oxygen demand

Question 20

Q

What are the factors affecting FRC

Question 21

Q

Normal WOB

Question 22

Q

Oxygen requirement of breathing

Answer

A

The oxygen requirement of breathing at rest is 2-5% of VO₂ or 3ml/min

(tidal breathing uses <2% of BMR)

Question 23

Q

Normal osmolarity

Answer

A

~285mOsm/kg

Question 24

Q

Baroreceptor reflex

Answer

A

Sensor/stimulus: carotid sinus & aortic arch - circumferential and longitudinal stretch receptors detect change in BP
○ Decreased BP decreases firing rate of baroreceptor
- Afferent: glossopharyngeal + vagus
- Processor: NTS & Caudal ventral medulla/RVLM
  ○ Decreased BR firing rate –> decreases GABA secretion from caudal VM. This decreases inhibition of sympathetic output from RVLM (ie SNS activity increased)
- Efferent/effectors: vagus nerve + sympathetic chain
  ○ Peripheral vessels - a1 mediated vasoconstriction
  ○ Decreased vagal input into SA
- Effect: increased HR and BP in response to fall in BP
- Note: Tends to override Bainbridge reflex when it comes to atrial stretch in hypovolaemia (except in spinal anaesthesia, where reverse Bainbridge reflex may predominate)

Question 25

Q

Bainbridge reflex

Answer

A

Sensor/stimulus: Stretch receptors in atria + pulmonary artery measure changes in pressure
- Afferent: vagus
- Processor: NTS & CVM
- Efferent:
  ○ Sympathetic fibres to heart
  ○ Vagal efferents to gardiac ganglion
- Effects
  ○ Increased RA pressure produces an increase heart rate

Question 26

Q

Chemoreceptor reflex

Answer

A

Sensor/stimulus: Carotid and aortic body detect low PaO2 and/or high PaCO2
- Afferent: glossopharyngeal + vagus
- Processor: NTS + Nucleus ambiguus
- Efferents/effectors:
  ○ Sympathetic fibres to heart and peripheral smooth muscle
  ○ Vagal efferents to cardiac ganglion
- Effects:
  ○ Primary effects - bradycardia, hypertension
  ○ Secondary effects - increased preload due to increased ventilation, thus activation of Bainbridge –> increased heart rate
  ○ Activation of pulmonary stretch receptors –> activation of Hering-Breuer reflex –> increases HR

Question 27

Q

Cushing reflex

Answer

A

Sensor/stimulus: intracranial pressure/cerebral ischaemia is detected by some unknown sensor
- Afferent:
  ○ Fibres from the medullary mechanosensory areas, to sympathetic ganglia
  ○ Fibres from cerebral hemispheres, which exert descending inhibitory control on the medullary vasomotor sensor
- Processor: rostral ventrolateral medulla
- Efferents/effectors: Sympathetic fibres to heart and peripheral smooth muscle
- Effects:
  ○ Hypertension + tachycardia
  ○ Secondary - baroreflex mediated bradycardia

Question 28

Q

Bezold-Jarisch Reflex

Answer

A

Sensor/stimulus: Multiple and heterogeneous stimuli interact with receptors in all cardiac chambers, including:
○ Mechanical: pressure and stretch (thus, inotropy preload and afterload)
○ Chemical: veratrum alkaloids, ATP, capsaicin, snake venom, other venoms
- Afferent: unmyelinated C-fibres of vagus
- Processor: NTS
- Efferents/effectors: sympathetic fibres to heart and peripheral smooth muscle, vagus via cardiac ganglion
- Effects: hypotension (vasodilation) & bradycardia

Question 29

Q

Occulocardic reflex

Answer

A

Sensor/stimulus: mechanoreceptors on the globe and in facial muscles detect pressure on the globe
- Afferent: long and short ciliary nerves to trigeminal nerve (via Gasserian ganglion) to sensory nucleus of TN. From here, short internuclear fibres to NTS
- Processor: NTS
- Efferents/effectors: vagus nerve via cardiac ganglion to SA + AV node
- Effects: bradycardia, if severe, to the point of arrest

Question 30

Q

Diving reflex

Answer

A

Sensor/stimulus: pain, temperature, chemical and mechanosensitive stretch receptors detect pressure to globe of eye, pain in trigeminal nerve distribution, cold temperature, or noxious stimulus of anterior ethmoidal nerve
- Afferent: trigeminal nerve
- Processor: NTS (vagal response), Rostral medulla (sympathetic response), ventral response (apnoea)
- Efferents/effectors: Vagus nerve via cardiac ganglion to SA, AV nodes; phrenic nerve to respiratory muscles
- Effects: bradycardia, cerebral vasodilation + systemic vasoconstriction, apnoea
  ○ Net effect is to prevent aspiration and maximise blood flow to CNS at the expense of skin, muscle and splanchnic organs

Question 31

Q

Barcroft-Edholm Reflex

Answer

A

Sensor/stimulus: Emotional distress/orthostatic changes, increased ITP (eg. Defecation, cough/sneeze, laughter)
- Afferent: unknown
- Processor: ?NTS/Nucleus ambiguus
- Efferents/effectors: vagus & SNS to SA, AV nodes, peripheral smooth muscle
- Effects: Vagal - bradycardia, sympathetic - systemic vasodilation

Question 32

Q

SvO2 from tissue beds: jugular, muscles, renal, IVC, SVC, Hepatic

Answer

A

Jugular - 55%
Muscles - 72%
Renal - 81%
IVC - 71%
SVC - 79%
Hepatic - 66%

Question 33

Q

Normal mixed venous PO2 & SvO2

Answer

A

40mmHg & 70-75%

Question 34

Q

Energy consumption of 1 MET

Answer

A

1 MET = 3.5 ml O2/kg/minute

Question 35

Q

Aortocaval compression syndrome

Answer

A

Seen as early as wk 20
Compression of IVC by gravid uterus - decreases venous return & reduced CO
* Blood returns to heart via paravertebral epidural veins draining into azygous
* Uterine perfusion diminished secondary to increased uterine venous pressure
Compression of aorta may be present & associated with uterine arterial hypotension + reduced uteroplacental perfusion
Can be relieved by positioning mother to left side

Question 36

Q

Changes in afterload during pregnancy

Answer

A

Afterload (reduced) –> TPR decreases by 30% by wk 12& 35% (by 20th wk, then remains at 30% below non-pregnant values)
* Vasodilation mediated by progesterone, prostaglandins & downregulation of alpha-receptors
* SBP + DBP - decrease (~10%) & reach nadir at 20wks
* Vascular system as whole becomes more refractory to vasoconstrictors
* Note re: RV afterload
□ CVP + PCWP - remain stable throughout pregnancy. PCWP balance by decreased PVR

Question 37

Q

Changes in preload during pregnancy

Answer

A

○ Preload (increased) –> By term, maternal blood volume increased by 35-40% (approx 1-1.5L)
§ Plasma volume increases by 45% - Na + H2O retention by oestrogen stimulation of RAAS
§ RBC volume increases by 20% due to renal erythropoietin synthesis
§ Disproportionate rise in plasma volume vs red cell mass accounts for fall of haematocrit to 33% (“anaemia of pregnancy”)

Question 38

Q

Changes in CO, HR and SV during pregnancy

Answer

A

CO increases by 40-45% by 12-28wks, peaks at 50% 32-36wks, then reaches 47% at term
- Heart rate: HR increases by 17% at end of first trimester,(increases to 25% at middle of third trimester);
- Stroke volume increases by 20-30% (predom in 1st trim)

Question 39

Q

Changes to distribution of CO in pregnancy (regional flow changes)

Answer

A

Distribution (regional flow changes)
○ Renal blood flow - increases by 80% in first trimester (may fall slightly towards term)
○ Large proportion of blood flow is directed to uteroplacental circulation, that increases its blood flow 10-fold to 750mL/min at term
○ Increased blood flow to breasts, GIT, skin

Question 40

Q

Physical and mechanical changes to heart during pregnancy

Answer

A

Physical/mechanical changes:
- LV mass increases by 40g by 3rd trimester
- Heart is more rotated to left
○ May see Q waves + TWI in inferior leads
- Colloid oncotic pressure falls by 14% - may predispose to oedema

Question 41

Q

CVS changes during PARTUITION + Post delivery:

Answer

A

Pressure:
○ Maternal SBP + DBP increase 10-20mmHg during uterine contraction
- Volume:
  ○ Each uterine contraction squeezes ~300mL blood from uterus into central maternal circulation
- Cardiac output:
  ○ CO increases by ~15% during latent phase of labour, by 30% during the active phase & 45% during the expulsive stage
  ○ Immediately after delivery, CO ~60-80% above pre-labour values as a consequence of autotransfusion & increase venous return associated with uterine involution
- CO & SBP/DBP return to non-pregnant values by 2 wks post delivery

Question 42

Q

How long after birth do pregnancy-induced respiratory changes settle?

Answer

A

After birth:
* FRC and RV return to normal within 48h
* Vt returns to normal within 5 days

Question 43

Q

Effect of pregnancy on lung mechanics

Answer

A

Compliance
○ increased adipose tissue and breast mass –> decreased chest wall compliance (lung compliance unchanged)
- Resistance
  ○ Increases in early pregnancy - mucosal oedema
  ○ Progesterone-mediated bronchodilation - decreased resistance in later pregnancy (35%)

Question 44

Q

Storage functions of the liver

Answer

A

Storage
- Metabolic fuel: Glycogen- ~100g & fat
- Fat soluble vitamins
  ○ Vitamin A → stored in stellate cells –> converted to retinol (active form). Contains 1-2yr supply
  ○ Vitamin D → ~ 1-4 month supply
  ○ Vitamin E & vitamin K - minimal
- Vitamin B12 + folate (50% of body’s storage for both)
- Trace elements - iron (as ferritin), zinc, copper, selenium
- Blood reservoir - ~ 500mL of blood

Question 45

Q

Synthetic functins of the liver

Answer

A

Synthetic
- Plasma proteins- albumin, α+ β globulins, fibrinogen
- Nutrients - glucose, ketones, lipids, cholesterol, amino acids
- Regulatory molecules (thrombopoetin, angiotensinogen)
- Bile acids → stored in gallbladder

Question 46

Q

Metabolic functions of the liver

Answer

A

Metabolic
- Carbohydrate metabolism
○ Liver is a glucostat –> maintains strict BSL
§ in conditions of ↑ glucose, glycogenesis & FFA synthesis will normalise BSL
§ in conditions of ↓ glucose, gluconeogenesis will normalise BSL
- Lipid metabolism → free fatty acids (FFA). synthesised & packaged with as lipoproteins be transported to adipose tissue for storage
§ FFA oxidation will also produce energy.
- Protein Metabolism - amino acids can be transaminated, deaminated or decarboxylated to give acetyl- CoA

Question 47

Q

Detoxification/excretory functions of the liver

Answer

A

Detoxification & excretion
- Immunological detoxification:
○ Kupfer cells act as scavengers & phagocytes & secrete prostaglandins
- Ammonia → urea conversion via urea cycle
- Conjugation of bilirubin & excretion in bile
- Processing of drugs via:
○ Phase I (oxidation & hydrolysis) and
○ Phase II (conjugation) reactions

Question 48

Q

Length, diameter, origin and termination of trachea

Answer

A

Length: 10-16cm
Diameter: (internal) 2.5cm
Origin: C6
Termination: carina, T4 (sternal angle)

Question 49

Q

Classify generations of bronchial tree

Answer

A

Generation 1-4 - Bronchi (cartilaginous)
Generation 5-14 - bronchioles (non-cartilaginous)
Gen 15-18 - Respiratory bronchioles (some gas exchange)
Gen 23 - alveolar sacs

Question 50

Q

Describe the muscles in the larynx involved with phonation, inspiration, expiration and effort closure

Answer

A

Muscles - various muscles attaching to the various structures. Important movements:
* Phonation: cricothyroid (brings cords together by moving thyroid down), interarytenoid (transverse + oblique), vocalis (subset of muscles from thyroarytenoid) - mediates tension in vocal ligament to modulate pitch
* Inspiration: + cricoarytenoid (posterior + lateral) - rotate arytenoids outwards
* Expiration: thyroarytenoid adduct cords to increase resistance and provide intrinsic PEEP (3-4 cmH2O), which maintains patency of small airways & maintains FRC
* Effort closure - aryepiglottic muscles contract strongly to act as a sphincter, allowing airway to withstand up to 120cmH2O pressure

Question 51

Q

What is Dalton’s Law

Answer

A

Dalton’s Law:
* In a mixture of gases, the pressure exerted by each gas is the same as the pressure exerted if the gas was the only gas in that mixture:
* PTOTAL = PGas1 + PGas2 + PGas3

Question 52

Q

What is Boyle’s Law?

Answer

A

Boyle’s Law:
* For a fixed mass of gas at constant temperature, the pressure (P) and volume (V) are inversely proportional, such that P ×V = k, where k is a constant.

Question 53

Q

Henry’s Law

Answer

A

Henry’s Law
* The amount of a given gas dissolved in a given liquid is directly proportional to the partial pressure of the gas in contact with the liquid:

P = Hv × M

Where
* P is pressure
* M is the molar concentration of gas
* Hv is Henry’s Proportionality Constant

Question 54

Q

Graham’s Law

Answer

A

Graham’s Law:

* The rate of diffusion is inversely proportional to the √MW

Question 55

Q

Fick’s Law of diffusion

Answer

A

Fick’s Law of diffusion:
* Passive movement of molecule from an area of high concentration to low
- There are many different iterations of Fick’s Law
- V_gas∝A/T D (P_1− P_2)

V_gas  = Flow of gas
D∝ Solubility/√MW
MW = molecular weight 
A = surface area
P_1  − P_2= difference between partial pressure in alveolus vs capillary
T = diffusion distance (or thickness of membrane)

Question 56

Q

Third gas law (Gay-Lussac’s Law)

Answer

A

The pressure of a fixed mass of gas at constant volume is directly proportional to its absolute temperature (P/T = k).

Question 57

Q

Avogadro’s Law

Answer

A

Equal volumes of gases at the same temperature and pressure contain the same number of molecules (6.023 × 1023, Avogadro’s number).

Question 58

Q

Universal (Ideal) Gas Law

Answer

A

The state of a fixed mass of gas is determined by its pressure, volume and temperature (PV = nRT)

Question 59

Q

The Bohr equation for measuring dead space

Answer

A

VD/VT = (FACO2 - FECO2) / FACO2

Where:

VD = dead space volume
VT = tidal volume
FECO2 = fraction of expired CO2
FACO2 = fraction of alveolar CO2

		*Note: Enghoff modification: P_A 〖CO〗_2  is substituted by P_a 〖CO〗_2  as arterial CO2 is measurable (and arterial CO2 is the mixed product of all lung units (theoretically representative of the average CO2 of all alveoli put together))

Question 60

Q

Alveolar gas equation

Answer

A

PAO2 = (FiO2 × (Patm - PH2O)) - (PaCO2 / RQ)

Where 

PAO2= Partial pressure of alveolar oxygen
FiO2 = fraction of inspired oxygen
Patm = Atmospheric pressure (usually 760 mmHg)
PH2O = partial pressure of water vapour at the alveolus (usually 47 mmHg)
PaCO2  = Partial pressure of arterial carbon dioxide
RQ = respiratory quotient, usually 0.8

Question 61

Q

Oxygen content equation

Answer

A

(sO2 × ceHb × BO2 ) + (PaO2 × 0.03)

Where:

ceHb = the effective haemoglobin concentration (conc of hb species capable of carrying & releasing O2)
PaO2 = the partial pressure of oxygen in arterial blood
0.03 = the content, in ml/L/mmHg, of dissolved oxygen in blood (for a PaO2 of 100 mmHg, the O2 content is 0.03 × 100 = 3ml/L
BO2 =  the maximum amount of Hb-bound O2 per unit volume of blood (normally 1.39 of dry Hb, or 1.30 in "real" conditions)
sO2 = oxygen saturation:

Question 62

Q

The shunt equation

Answer

A

Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2)

Where
    Qs/Qt = shunt fraction (shunt flow divided by total cardiac output)
    CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content
    CaO2 = arterial O2 content
    CvO2 = mixed venous O2 content

Question 63

Q

Starling equation

Answer

A

J_v=L_p S [(P_c − P_i) - σ(π_c− π_i)
Where:
Jv = filtration rate
Lp = Hydraulic permeability
S = Surface area
Pc = Capillary hydrostatic pressure
Pi = Interstitial hydrostatic pressure
σ = Reflection coefficient (protein permeability, range 0-1)
πc = Intracapillary plasma oncotic pressure
πi = Interstitial oncotic pressure

*Note: LpS = K = kf = capillary filtration constant*
**Note2: πi becomes πegl in the revised Starling model to represent the endothelial glycocalyx layer**

Question 64

Q

Starling forces in lung

Answer

A

○ LpS - surface area ~140m2 (compared to 4000-7000m2 in systemic circulation)
○ Pc = 4-12mmHg
○ Pi = interstitial hydrostatic pressure - essentially equal to alveolar pressure = atm pressure. Increases during PPV
§ Surfactant decreases hydrostatic pressure by decreasing surface tension
○ πc = 25mmHg throughout circulation; affectd by blood protein count
○ πi = ~3mmHg at alveoli
○ σ= 0.5-0.7 in lung

Answer 63

A

2mLH2O/L/s

Answer 64

A

Bind to 30s Ribosomal subunit, which interferes with protein synthesis by causing misreading and premature termination of mRNA translation.
Diffuse through porin channels in the outer membrane into periplasmic space. Transport through inner membrane is oxygen dependent (/electron dependent). Antimicrobial activity is markedly reduced in anaerobic conditions (eg. Abscess).
Concentration dependent killing - higher the concentration, the greater the rate at which bacteria are killed.
Post-antibiotic effect exists (bactericidal effect persists after conc<MIC). The duration of this effect is also concentration dependent

Answer 65

A

Disinfectants are chemical agents or physical procedures that inhibit or kill microorganisms
Antiseptics are disinfectants with sufficiently low toxicity to host cells that can be used directly on skin, wounds or mucosa

Answer 66

A

Main action: Likely act by denaturing proteins. Optimal bacteriocidal concentration is 60-90%
Onset/duration Rapid/ Lack residual action because they evaporate completely
Advantages: Evaporative effects are useful when sinks with running water are not available
Limitations: Flammable- must be allowed to dry fully before diathermy or laser surgery 2. Corneal damage; 3. Skin drying; 4. Ineffective against C. Dif spores
Spectrum of activity: - Gram positives and negatives, Acid fast bacteria are susceptible, - Lipophilic viruses may be susceptible, Many fungi
Ineffective against: Spores and prions. Hydrophilic viruses are less susceptible

Answer 67

A

Main action:Cationic biguanide -strongly adsorbs to bacterial membranes causing leakage of small particles and precipitation of cytoplasmic proteins
Onset/Duration: Delayed/Sustained residual activity
Advantages: Resistant to inactivation by blood and organic material; Low skin irritation
Limitations:
1. Neurotoxic
2. Delayed effect
3. No direct spore activity
4. Agents in moisturisers, neutral soaps, and surfactants may neutralised its action

Spectrum of activity
- Bacteria (G+ve>G-ve)
- Moderate fungal and viral activity
- Inhibits spore germination

Ineffective against
Spores and prions
Hydrophilic viruses are less susceptible

Other
Can be combined with 70% alcohol
Preferred antiseptic for central venous access
Not absorbed orally

Answer 68

A

Potency is defined as the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect/a specified response in 50% of the population
○ Two drugs may have the same efficacy but one may achieve the effect at a lower dose
○ A drug with lower EC50 or ED50 has higher potency

Answer 69

A

Efficacy - a measure of the magnitude of the effect once the drug is bound
○ Different agonists produce varying responses, even when occupying the same proportion of receptors
○ Efficacy can be expressed numerically - as a ratio of the drug’s maximal efficacy to the maximal efficacy of some known potent agonist (aka intrinsic activity or maximal agonist effect)

Answer 70

A

A compound that competes with endogenous agonists for the same binding site - it may be reversible or irreversible
○ In the presence of a competitive antagonist, the Emax of the agonist is unaffected, but the potency is reduced

Answer 71

A

A compound that binds at a different site to the natural receptor and produces a conformational change that prevents receptor activation

Answer 72

A

The volume of air in the lungs at end of expiration during tidal breathing. It is the point at which alveolar pressure = atmospheric pressure, and is equal to expiratory reserve volume (ERV) plus residual volume (RV).

Answer 73

A

Blood supply:

Upper half: superior branch of the super thyroid artery
Lower half: inferior branch of the inferior thyroid artery

Venous drainage:

Upper half: superior branch of the superior thyroid vein
Lower half: inferior branch of the interior thyroid vein –> brachiocephalic vein

Nerve supply:

All muscles are supplied by the recurrent laryngeal nerve except cricothyroid muscle, which is innervated by the external laryngeal

Lymphatics

Upper and lower groups of deep cervical nodes

Answer 74

A

This is specific to laminar flow (fastest velocity at centre of vessel, little to no movement at periphery)

Answer 75

A

If Re<2000, flow more likely to be laminar, 2000-4000 = transitional & >4000 turbulent

Answer 76

A

PaO2 = partial pressure of oxygen in arterial blood (measured value, in mmHg)
- This is the pressure that ‘dissolved’ oxygen (ie oxygen unbound to Hb) exerts on the measuring oxygen electrode
- Although the pressure of oxygen is an important indicator of Hb saturation and total oxygen content, it is not a measure of content (ie mass or volume)
SaO2 = oxygen saturation (measured value, in %)
- This is the percentage of all the heme sites in all the available haemoglobin that is taken up by an oxygen molecule
- Similarly to above, this is an important surrogate measure for oxygen availability however is also not a measure of content
CaO2 = blood content of oxygen (can be measured directly, or calculated by the oxygen content equation, in mL of oxygen/100ml or 1000mL of blood - ie mL/dL or mL/L)
- This measures total oxygen content (dissolved plus bound)

Answer 77

A

The maximal volume of gas in the lungs at which small airways begin to collapse in dependent parts of the lung

Answer 78

A

The heat required to convert a substance from liquid to vapour at a given temperature. Latent heat of vapourisation decreases as ambient temperature increases, and is reduced to zero at the critical temperature of that substance.

Answer 79

A

Vapour pressure = pressure exerted by a vapour above the surface of a liquid.
- The more solutes you add to a solution, the lower vapour pressure, at any given temp + pressure
Saturation vapour pressure = pressure exerted by a vapour in equilibrium with liquid of the same substance. It is influenced by temperature and pressure
- AKA equilibrium vapour pressure. It is the point at which the rate of evaporation = rate of condensation
- Substances with a higher vapour pressure is more volatile. (eg. Sevo has SVP of 157mmHg at sea level, room temp vs H2O which is 18.6mmHg)
- SVP increases with increasing temp - at body temp, H2O SVP is 47-48mmHg

Answer 80

A

The temperature at which vapour pressure equals atmospheric pressure. A lower atmospheric pressure will result in a lower boiling point temperature
* Note: evaporation different to boiling - evaporation takes place from surface; bubbles form within the liquid when boiling.

Answer 81

A

Critical temperature is the temperature above which it is not possible to liquefy a given gas by increasing its pressure
- A substance is a gas when it is above its critical temperature, and a vapour when it remains in gaseous phase below its critical temperature
- Nitrous has a critical temp of 36.5o and a critical pressure at this temp of 73atm. At 20O (temp of normal operating room), its critical pressure is 55atm

Answer 82

A

Minimum pressure which would suffice to liquefy a substance at its critical temperature

Answer 83

A

The point of minimum pressure and maximum temperature at which both a gaseous and a liquid phase of a given compound can coexist

Answer 84

A

Volume of space occupied by 1kg of a gas at its critical point

Answer 85

A

Absolute humidity is the mass of water vapour present in a given volume of air.
Relative humidity is the percentage ratio of the mass of water vapour in a given volume of air to the mass required to saturate that given volume of air at the same temperature

Answer 86

A

The amount of a substance filtered per unit time

Answer 87

A

Any weakly ionised acid or base in equilibrium with its fully ionised salt that can resist changes in pH when a stronger acid or base is added.

Answer 88

A

Bicarbonate
Phosphate (note: conc too low)
Protein (note: conc too low)

Answer 89

A

HCO3
Hb
Plasma protein
Phosphate (note: conc too low)

Answer 90

A

Urinary:
- Phosphate
- Ammonia

Bone:
- Ca carbonate

Answer 91

A

HCO3 (important as low proteins, & negligible PO4)

Answer 92

A

RBCs phagocytosed by macrophages in liver or spleen, or haemolysed in circulation. Heme is degraded to bilirubin, Fe 2+ is recycled

Answer 93

A

Heme synthesised in mitochondria & cytosol of immature RBCs, globin synthesised by ribosomes in cytosol

Answer 94

A

Normal range
10-13s

Therapeutic values
20-30s (warfarin)

Coagulation pathway assessed
Extrinsic & common

Method
- Sample collected in citrated blood tube & centrifuged (only plasma analysed)
- Recombinant tissue factor added

Abnormal in:
○ Problems with:
§ Vit-K dependent factor eg.warfarin
§ FVII eg. haemophilia
§ Factor Xa eg. apixaban
§ Thrombin eg. dabigatran

Answer 95

A

Normal range
30-40 sec

Therapeutic values
usually 50-90 or 60-100s

Coagulation pathway assessed
Intrinsic & Common

Method
- Collected + centrifuged as per PT
- Phospholipid & negatively charged FXII activator added

Abnormal in:
- Factor deficiency (XII, XI, X, IX, II), heparin therapy, direct thrombin inhibitor therapy, direct Xa inhibitor therapy, antiphospholipid syndrome

Answer 96

A

Normal range
110-130sec

Therapeutic values
200sec for ECMO, 400sec for bypass

Coagulation pathway assessed
Whole clotting cascade & platelet function

Method
- Whole fresh blood collected
- Point of care test - contact activator (eg. Kaolin) added
- Endogenous platelets are used as the source of phospholipid

Abnormal in:
Any coagulopathy. Most useful when there is one single predictable source of clotting dysfunction

Answer 97

A

Cytochalasin D (platelet inhibitor) - isolates fibrinogen testing

Answer 98

A

tissue factor

Answer 99

A

Phospholipid & ellagic acid

Answer 100

A

Ellagic acid & heparinase

Answer 101

A

500IU of Factor IX
500IU of Factor II (prothrombin)
500IU of Factor X

Answer 102

A

Factor VII (will reduce PT)
Factor IX, XI (will reduce aPTT)
Factor X, II
200IU of Factor VIII per adult dose

Answer 103

A

Adsorption of coagulation factors from plasma onto an ion exchange medium –> selective elution

Answer 104

A

Separation (by centrifuge) from whole blood, either by donation or by apheresis. Must be prepared within 6-18hrs

Answer 105

A

25-50IU/kg
Warfarin: INR < 2 - 20U/kg, 2-4: 30U/kg, >4: 50U/kg

Answer 106

A

Glycogen: 100g
Fat: 75g

Answer 107

A

○ Vitamin A → stored in stellate cells –> converted to retinol (active form). Contains 1-2yr supply
○ Vitamin D → ~ 1-4 month supply
○ Vitamin E & vitamin K - minimal

Answer 108

A

Primary: Formed in liver from cholesterol (by action of cholesterol 7α hydroxylase)
□ Cholic + Chenodeoxycholic acid

Secondary: formed by bacterial action on primary bile acids
□ Deoxycholic + Lithocholic acid

Answer 109

A

Tolerance is the requirement of higher doses of a drug to produce a given response

Answer 110

A

Pharmacokinetic tolerance
- Pharmacodynamic tolerance
  ○ Receptor downregulation
  ○ Receptor deactivation
  ○ Receptor subunit modification
  ○ Second messenger systems
  ○ Drug target depletion
- Physiological tolerance
- Learned/behavioural tolerance
- Others:
  ○ Sensitisation
  ○ Cross-tolerance

Answer 111

A

Persistent exposure makes drug clearance mechanisms more active; classically by induction of metabolic enzymes (eg. Effect of ethanol on CYP450 enzymes)

Answer 112

A

Persistent exposure to the drug produces and adaptive homeostatic response that results in a decreased pharmacological effect
○ Receptor downregulation - receptors are inactivated or endocytosed in response to sustained stimulation
○ Receptor deactivation - receptor protein is phosphorylated in response to excess stimulus (eg. Nicotine and nicotinic receptor)
○ Receptor subunit modification - modified receptor complex is selectively expressed, with diminished selectivity for the drug but maintained sensitivity for the endogenous ligand (eg. GABA-A receptor and benzodiazepines)
○ Second messenger systems - deactivation of post receptor second messenger systems (eg. B-agonists)
Drug target depletion - some key molecule is used up in the drug action. Subsequent drug dosing will have diminished effect until the key molecule is regenerated (eg noradrenaline depletion due to ephedrine therapy)

Answer 113

A

Tolerance to the effects of the drug rather than to the drug itself at the receptor level. Physiological adaptive mechanisms may maintain homeostasis. Eg. Vasodilator antihypertensives may be offset by increased heart rate and CO, which maintains BP

Answer 114

A

The development of learned behavioural adjustments that compensate for the drug’s effects

Answer 115

A

“reverse tolerance” - subsequent dosing increases the drug effect (eg. Amphetamines)

Answer 116

A

Development of tolerance to multiple drugs belonging to the same class, after exposure to only one of them (eg. Nitrates)

Answer 117

A

Decreased response to a drug with repeated short-term use. It occurs over minutes-hours & cannot easily be overcome with increase dose

Answer 118

A

(DR SVC)

Diuretics
- Carbonic anhydrase Inhibitors
- Loop diuretics
- Thiazides
- K+ sparing diuretics

RAAS antagonism
- ACE Inhibitors
- ARBs
- Direct renin inhibitors

Sympatholytics
- alpha blockers
- beta blockers
- mixed alpha + beta
- centrally acting (eg clonidine)

Vasodilators
- Arterial - hydralazine
- Arterial + venous - nitrates

Ca channel blockers

Answer 119

A

○ 37 kDa proteolytic enzyme with half life 40-120min
○ Produced in and released from juxtaglomerular (granular) cells in juxtaglomerular apparatus

Role:
○ Cleaves angiotensiongen into angiotensin-I
○ Rate-limiting step in RAAS

Answer 120

A

Stimulus for release:
○ ↓ Na delivery to macula densa
○ ↓ blood pressure or renal perfusion pressure (sensed by intrarenal baroreceptors) –> likely cell stretch-mediated mechanism of renin release
○ Activation of β1 receptors on juxtaglomerular cells

Inhibits release:
○ Negative feedback: ↑ Renin –> ↑ Angiotensin II (ATII) –> binds AT1 receptors on juxtaglomerular cells –> ↓ renin secretion

Answer 121

A

Class/chemistry: Catecholamine/Endogenous sympathomimetic
Preparation/administration: Clear, colourless solution in 0.1mg/ml or 1mg/ml - can be administered IV/subcut; 1% ophthalmic solution; aerosol (280mic/MD)

Answer 122

A

Indication/Dose:
– Anaphylaxis - 0.1-0.5mg subcut
– Cardiac arrest - 1mg IV;
– Low CO states: 0.01-0.1mic/kg/min as infusion in shock
– Glaucoma
– Local vasoconstrictor (added to LA solutions to prolong duration)

Answer 123

A

Absorption - inactivated with oral administration; slower subcut vs IM. Well absorbed from tracheal mucosa.pKa 9.7
Distribution - Vd = 0.1-0.2L/kg; 12 % protein bound

Answer 124

A

Metabolism - Metabolised rapidly by COMT (liver)–> metadrenaline + noradrenaline; MAO (neurons); final common products (normetadrenaline + VMA) are inactive.
Excretion - urine; half life ¬2min

Answer 125

A

Mechanism of action - directly acting sympathomimetic amine. Agonist of α + β adrenoceptors, with ¬equal activity at both. At α1 - results in release of IP3 –> vasoconstriction. β1 + 2 –>cAMP

Onset: immediate
Duration: 1-5min

Answer 126

A

Effects +/- side effects
– CVS - Positive ionotrope + chronotrope. Increases cardiac output, myocardial O2 consumption, coronary blood flow. May result in tachycardia, dysrhythmias, ischaemia
– Resp - mild resp stimulant (increases both tidal volume and respiratory rate). Potent bronchodilator but tends to increase the viscosity of bronchial secretion
– CNS - Increases cutaneous pain threshold and enhances neuromusclar transmission. Little overall effect on CBF. Cerebral haemorrhage may result
– Renal - decreases renal blood flow by up to 40%, but filtration rate remains mostly the same. Inhibits contraction of pregnant uterus
– Metabolic/other - elevated BSL (increases glucagon secretion, stimulates gluconeogenesis, decreases insulin secretion. Plasma renin increased (B1 effect), plasma conc of FFAs increase (activates triglyceride lipase). Increases BMR by 20-30%
Special points:
– Dose decrease with volatile anaesthetics (risk of ventricular dysrhythmias - mainly halothane, enflurane + isoflurane)

Answer 127

A

Naturally occurring sympathomimetic amine

Answer 128

A

Indication/Dose:
– Hypotension occurring in general, spinal or epidural anaesthesia - 3-7.5mg (max 9mg), repeated every 3-4 min to a max of 30mg, titrated to response
– Nasal decongestant
– Other: Nocturnal enuresis, narocolepsy, diabetic autonomic neuropathy, hiccups

Answer 129

A

Absorption - rapidly and completely absorbed via all routes
Distribution - rapidly and extensively absorbed. Vd = ~4L/kg. Crosses placenta & excreted to breast milk

Answer 130

A

Metabolism - resistant to MAO + COMT metabolism. Small amount metabolised to norephedrine (may produce central stimulant effect) in liver
Excretion - 55-99% excreted unchanged in urine. Half life 6hrs

Answer 131

A

Mechanism of action - acts both indirectly (causes release of NA from sympathetic nerve terminals) and directly by stimulating α & β-adrenoceptors

Onset: rapid
Duration: 1hr

Answer 132

A

Effects +/- side effects
– CVS - Similar to adrenaline but more prolonged - positive ionotrope + chronotrope–> increases cardiac output, myocardial work and myocardial oxygen consumption
– Resp - resp stimulant + marked bronchodilation
– CNS - stimulatory effect similar to amphetamine. Increases CBF
– Renal - constricts renal blood vessels - decreases renal blood flow & GFR
– Metabolic - stimulates glycogenolysis, may increase BMR, thermogenesis

Special points:
– Tachyphylaxis occurs with prolonged use. Dysrhythmias with halothane
– Clonidine premedication enhances pressor effects of ephedrine

Answer 133

A

Class/chemistry: Catecholamine/endogenous sympathomimetic
Preparation/Administration: Clear, colourless liquid containing 2mg/ml. Administered via CVC in 40mic/ml conc infusion

Answer 134

A

Dose: titrated to effect. Usually 0.1-0.4ug/kg/min
Indication: refractory hypotension

Answer 135

A

Absorption: Undergoes significant first pass metabolism and is inactive when administered orally
Distribution: VD 0.1-0.4L/kg; 25% protein bound

Answer 136

A

Metabolism: Endogenous NA is metabolised via 2 pathways:
- oxidative deamination to aldehyde by mitochondrial MAO (in liver, brain, kidney) and
- methylation by cytoplasmic catechol-O-methyl transferase(COMT) to normetanephrine. Predominant metabolite is VMA
Excretion: half-life is ~2minutes, 5% of dose excreted unchanged

Answer 137

A

Mechanism of action: non-selective sympathomimetic - acts on α & β adrenoceptors. Effect of action depends on distribution of these receptors throughout the body. It is generally a poor β2 agonist. Adrenoceptors are G-protein coupled receptors (GPCR) and binding causes a chain of downstream effects
- Onset: immediate
- Duration of action: 5-10minutes; tachyphylaxis with prolonged administration

Answer 138

A

Adverse effects: (inc toxicity)
Link above to organ systems:
- CNS - not much change to cerebral blood flow (mildly reduced) + reduction in O2 consumption.
○ Toxicity/Adverse effects: Anxiety, headache, photophobia
- CVS - positive ionotrope - works on the β1 receptor in heart to increase contractility, however does not increase HR like adrenaline (reflex vagal stimulation leads to compensatory bradycardia). CO remains the same or decreases slightly
○ Vasopressor effect - α agonist causing vasoconstriction and raised peripheral vascular resistance, causing rise in SBP + DBP
○ Coronary vasodilation (unclear how/why - possibly β2 stimulation mediated, although NA usually poor β2 agonist)
○ Adverse: chest pain
- Resp - increased minute volume, very slight bronchodilation
- GU - increases contractility of uterus (may induce fetal bradycardia + asphyxia), increases tone of bladder neck, reduces renal blood flow (GFR well maintained)
- Skin: significant cutaneous vasoconstriction. Adverse: pallor; Toxicity: Gangrene. Extravasation - sloughing + tissue necrosis

And others:
- Serious cardiac dysrhythmias during halothane anaesthetics
- Co-administration with MAOIs or tricyclic antidepressants can precipitate serious hypertensive episodes

Answer 139

A

Class/chemistry: Propanedinitrile derivative
Preparation/administration: Clear, yellow or orange solution for injection – 2.5mg/mL in 5 & 1-mL ampoules

Answer 140

A

Severe decompensated heart failure unresponsive to other therapies.
Cardiogenic shock post cardiac surgery in pts with EF <40%
Infusion at 0.05-0.2microg/kg/min. Used for ~24/24

Answer 141

A

MoA: Increases calcium sensitivity by binding to myocardial troponin C, leading to stabilisation and increased duration of calcium binding. This results in increased myocardial contractility without impairment of myocardial relaxation or increased oxygen demand. Also stimulates ATP-sensitive K+ channels leading to vasodilation

Answer 142

A

— CVS – Increases myocardial contractility via increased calcium sensitivity without increased myocardial oxygen demand. Also causes coronary and peripheral vasodilation. Hypotension

Answer 143

A

Class/chemistry: Synthetic isoprenaline derivative
Preparation/administration: 12.5mg or 50mg/mL of dobutamine (diluted prior to infusion)

Answer 144

A

For low cardiac output states eg: acute heart failure & cardiogenic shock. Dose: 2.5-20mic/kg/min (~100-3000mic/min)

Answer 145

A

Predominately selective β-1 agonist, weak β2 agonist. Acts directly on catecholamine receptors to activate adenylate cyclase, which catalyses the conversion of of ATP to cAMP

Answer 146

A

— CVS – activate cardiac β-1-adrenoceptors. SA automaticity increased and AV nodal conduction velocity also increased. Also has activity at α- and β2-adrenoceptors. It decreases LVEDP and SVR
— CNS – stimulation occurs at high dose ranges. Fatigue/nervousness/headache

Other
Should not be used in people with cardiac outflow obstruction. Tachyphylaxis can occur during prolonged infusion

Answer 147

A

Synthetic sympathomimetic amine

Answer 148

A

Adjunct in treatment of hypotension. 0.5-2mg bolus dose. Infusion 0.5-10mg/hr

Answer 149

A

Absorption: -
Distribution: Does not cross BBB. Vd = 4L/kg; 45% PB. Distributes into catecholamine storage vesicle - persists for days

Answer 150

A

Metabolism: Not metabolised

Excretion: Eliminated slowly over hrs/days - distribution t1/2 rapid. Half life - minutes

Answer 151

A

Direct and indirect acting sympathomimetic. Agonist effect at alpha-1 adrenoceptor, but also some beta-adrenoceptor activity. Causes noradrenaline release from intracytoplasmic stores, in addition to causing adrenaline release
Duration of action - 20-60min; onset 1-2min

Answer 152

A

CVS - Sustained increase in systolic and diastolic blood pressures due to increase in systemic vascular resistance. Reflex bradycardia. Indirect increase in coronary artery flow
CNS - cerebral blood flow decreased
Renal - renal blood flow decreased

Other:
- Excessive hypertension may occur when administered in patients with hyperthyroidism or those receiving MAOIs

Answer 153

A

Synthetic catecholamine

Answer 154

A

Complete heart block, bradycardia with haemodynamic compromise
0.5-10mic/min1

Answer 155

A

Non-selective Beta-adrenergic agonist. Its actions are mediated by membrane-bound adenylate cyclase and subsequent formation of cAMP
Onset: immediate
DoA: 10-15min

Answer 156

A

CVS - Positive ionotrope + chronotrope –> increased CO; decreased, PVR (B2 effect) & DBP
- Side effects = tachycardia, hypotension, arrhythmias, angina
Resp - Potent bronchodilator
CNS - CNS stimulant

Other
- Tachyphylaxis may occur with prolonged use

Answer 157

A

Naturally occurring catecholamine

Answer 158

A

Low cardiac output states, especially post cardiac surgery. Initial 2-10mic/kg/min; maintenance up to 50mic/kg/min

Answer 159

A

Stimulates adrenergic and dopaminergic receptors. Lower doses mainly dopaminergic stimulating (renal + mesenteric vasodilation), higher doses both dopaminergic & β1 stimulating, large doses stimulate α-adrenergic receptors
Onset: 5 min
Duration: <10min

Answer 160

A

CVS - Dose dependent - increased ionotropy, CO, coronary BF (beta effects); increased vasoconstriction, SBP (alpha effects)
Resp - may decrease ventilatory response to hypoxia
CNS - Nausea (direct stimulation of CTZ). Does not cross BBB
Renal - in low doses, marked reduction in renal vascular resistance –> increases flow. Diuresis via D1 receptors at luminal and basal membranes of PCT

Other
- Reduce dose in people who have taken recent MAOIs

Answer 161

A

Synthetic sympathomimetic amine

Answer 162

A

hypotension, nasal decongestant, mydriatic agent. 50-100microg bolus doses

Answer 163

A

Direct acting selective alpha-1-adrenoceptor agonist (nil B-effects)
Duration of action 15-20min IV; onset immediate

Answer 164

A

CVS - rapid increase in SBP + DBP, SVR. Reflex brady - may reduce CO
CNS - mydriasis
Renal - RBF decreased

Answer 165

A

(Argipressin is synthetic compound which is identical to endogenous human vasopressin)

Class/chemistry:
- Naturally occurring nonapeptide prohormone produced in posterior hypothalamus

Preparation/Administration:
Available in 3 synthetic analogues: (all clear, colourless liquids)
- Argipressin in 20IU/mL (SC/IV or IM) - draw up into 20U/20mL
- terlipressin
- desmopressin in oral, IV, IN

(Note - analogues L2)

Answer 166

A

Management of catecholamine-refractory shock: Argipression is 0.6-2.4IU/hr
Cranial diabetes insipidus & Management of polyuria/polydipsia post hypophysectomy: 100mic TDS desmopressin, adjusted to response
Bleeding oesophageal varices: terli: 0.5mg/hr for 48/24
Perioperative/trauma management of people with haemophilia and VW disease

Answer 167

A

Absorption: desmopressin - 0.08-0.16% of dose is absorbed via PO route; 10% via IN route

Distribution: Argi: Vd = 0.14L/kg, not protein bound. Largest is terlipressin: 0.5l/kg

Answer 168

A

Metabolism: Endogenous vasopressin metabolised by vasopressinases (endothelial peptidases). Argi = 35% metabolised, desmo - minimal, terli - completely metabolised

Excretion: Endogenous vaso has a half life of 10-35 minutes; argi is shorter (10-20), terli is longer (50-70), desmo is 2-3hrs. 65% of argi and desmo is unchanged in urine

Answer 169

A

Act on GPCR vasopressin receptor
- V1 = GqPCR - act via PLC –> IP3 + DAG –> increase IC Ca
- V2 = GsPCR - activated AC –> cAMP –> increase IC Ca
Onset 1-2min
Duration up to 20min

Answer 170

A

CVS: V1 receptors in smooth muscle - activation causes vasoconstriction (via increased intracellular calcium) - increases MAP + SVR. At very low doses, causes vasodilation of pulmonary artery
GU: reduction in urine output and resolution of polydipsia in DI (V2 in DCT + CDs), activation leads to aquaporin-2 trafficking from intracellular vesicle membranes within renal epithelial cells into apical cell membrane –> water resorption
Endo: release of ACTH from pituitary

Answer 171

A

Class: Ionotrope
Chemistry: Bypyridine molecule
Preparation/Administration: Clear, colourless solution for injection in 10-20mL glass ampoules (1mg/mL)

Answer 172

A

Severe treatment-resistance congestive cardiac failure
Low cardiac output states following cardiac surgery (loading dose 50mic/kg over 10min; infusion between 0.375-0.75mic/kg/min titrated to response)

Answer 173

A

Absorption: -
Distribution: Vd = 0.3-0.4L/kg; 70-80% protein bound

Answer 174

A

Metabolism: 12% glucuronidated in liver; Mostly cleared renally - unchanged
Excretion: Mostly cleared renally - unchanged; half life 2.3hrs in patients with heart failure, longer in renal dysfunction

Answer 175

A

Mechanism of action: Selective inhibition of type III cAMP PDE in cardiac + vascular muscle (PDE responsible for cAMP catabolism) –> increased intracellular Ca –> increased contractility in cardiac; decreased vascular contraction

Answer 176

A

CVS: positive ionotropic effect –> CI increases by 25-30%, decreased SVR + MAP. May increase AV nodal conductance (may lead to increase in ventricular response in pts with atrial flutter or AF)
Renal: u/o + GFR may increase due to increased CO

Other
- Decrease infusion rate in renal failure

Answer 177

A

(mnemonic: DR SVC)
- Diuretics (see renal)
- RAAS antagonists
- ACE inhibitors
- ARBs
- Direct renin inhibitors- eg.Aliskiren
- Sympatholytics
- B-blockers
- A-blockers
- Mixed A + B
- Centrally acting (eg clonidine)
- Vasodilators
- Arterial
- Arterial + venous
- Ca- Channel antagonists

Answer 178

A

Indications: Hypertension, HFrEF, Post MI, diabetic nephropathy
Examples:
- Captopril (dose range 6.25mg-max 150mg/24hrs. Usually 12.5mg BD for HTN),
- perindopril (2.5mg arginine = 2mg erbumine. Usually 4-5mg (max 8-10mg daily)),
- ramipril dosing same as perindopril arginine

Answer 179

A

ACEIs: Blocks ACE which catalyses conversion of angiotensin I–> angiotensin II

ARBs: Block AT1 receptor (10000-fold more selective for AT1 than AT2). Inhibits biological effects of AngII, similar to ACEIs

Answer 180

A

Organ effects:
- CVS: ↓vasoconstriction & ↓hypertrophic remodelling (less ATII) & ↑ bradykinin levels (decrease breakdown) –> stimulates PGs –> vasodilation
- Renal: ↑ natriuresis

Adverse effects:
- Hypotension,
- cough (accumulation of lung bradykinin),
- hyperkalaemia (in pts taking K+ sparing diuretics)
- Note: ARBs: ARF, less cough

Contraindicated in pregnancy (teratogenesis, fetal hypotension, anuria, renal failure)

Answer 181

A

Hypertension, some ACEs approved for diabetic nephropathy, valsartan for HF

Dose:
- Irbesartan (150mg daily - max 300mg)
- candesartan (4mg daily to max 32mg)
- telmisartan (40mg - max80mg)

Answer 182

A

Alter ion permeability - act on ligand gated ion channels (membrane spanning complexes that can form a transmembrane channel for ions). Types:
– Pentameric -> 5 membrane spanning units (eg, nicotinic Ach receptor at NMJ - Na+ flux, GABA A receptor - Cl- flux)  
– Ionotropic glutamate -> NMDA, AMPA and kainate iontropic ligand gated ion channels. They form Na, K and (NMDA only) Ca channels when glutamate binds   
– Purinergic receptors -> activated by purines such as adenosine & ATP. Permeable to Na, K and Ca
Produce intermediate messengers - act on membrane bound systems which transduce signal from an extracellular ligand to an intracellular signal transmitted by intermediate messengers. Eg:
○ G proteins (most common) - eg, Nad and Adr   
○ Tyrosine kinase - eg, insulin   
○ Guanylyl cyclase
- Membrane bound - eg. atrial natriuretic peptide on its receptors
- Soluble - eg. NO 
Regulate gene transcription 
○ Steroids & thyroid hormones act on intracellular receptors to alter the expression of DNA and RNA

Answer 183

A

Physiochemical properties
○ Antacids - neutralise gastric acid   
○ Chelating agents (eg, resonium - on gut K)   
Enzymes
○ Concentration of the substrate normally metabolized by the enzyme is increased, and product of reaction is decreased   
○ Eg, ACE inhibitors (captopril, enalapril) prevent the conversion of ACEI to ACEII & bradykinin into its breakdown fragments   
Voltage gated Ion channels
○ Involved in the conduction of action potentials in excitable tissues   
○ Eg, local anaesthetics (eg, lignocaine) block Na channels, calcium channel blockers (eg, diltiazem) acts on vascular smooth muscle ion channels  
Alteration on transport proteins - eg. Frusemide on NKCC2  
Prodrugs
○ Require conversion to activated form by a metabolic pathway
Eg. Levodopa –> dopamine

Answer 184

A

Class: Organic nitrate
Chemistry: Ester of nitric acid

Answer 185

A

Stable, unstable, variant angina
Dose: 0.3mg s/l; 0.4-0.8mg s/l buccal spray; 5-10mg/24 transdermal;
LV failure secondary to MI
Perioperative control of BP
Start 5-10mic/min. Increase up to 200microg/min IV infusion (sometimes up to 400mic/min)

Answer 186

A

Absorption: Rapid + efficient s/l (40%). POBA 3%
Distribution: PB 60% Vd ~2L/kg

Answer 187

A

Metabolism: by liver + RBCs to mono- & di-nitrates + nitrites - all have lower activity than parent
Excretion: 80% urine. T1/2 1-3min

Answer 188

A

Metabolised to NO –> stimulates guanylate cyclase in vascular smooth muscle –> increased cGMP–> phosphorylation cascade–> relaxation

Onset: 1-3min s/l or ~100s IV
Duration:15-30min s/l or 3-5min IV

Answer 189

A

CVS: at low doses, venodilation –> veno + arterial at higher doses. Decreases afterload, decreases myocardial O2 demand, increases myocardial oxygen supply. Reflex tachycardia in normal individuals
CNS: ICP may increase due to cerebral vasodilation

Other:
40-80% of IV GTN adsorbed onto plastic giving-sets (needs non-PVC)

Answer 190

A

Class: Inorganic nitrate
Chemistry: Central Fe atom with 5 cyanide groups + 1x NO

Answer 191

A

Absorption: -
Distribution: Vd up to 0.2L/kg (EC space)

Answer 192

A

IV infusion 0.5-6microg/kg/min
- Hypertensive crisis
- Aortic dissection prior to surgery
- LV failure

Answer 193

A

Metabolism:
* Rapid non-enzymatic hydrolysis in RBCs –> 5x cyanide ions per molecule of SNP
* –> 1x cyanide reacts with methaemoglobin –> cyanomethaemoglobin
* –> 4x cyanides enter plasma –> 80% react with thiosulfate –> thiocyanate (catalysed by hepatic rhodanese). Remainder of cyanide reacts with hydroxycobalamin to form cyanocobalamin

Excretion: Metabolites excreted unchanged in urine. T1/2 2 min (thiocyanate 2 days)

Answer 194

A

Interacts with sulfhydryl groups on smooth muscle membrane –> releases NO –> vasodilation

Onset: 1-2min
Duration: 3-7min IV

Answer 195

A

CVS: decreases SBP, CO well maintained. Decrease Myocardial O2 consumption. Causes both veno - and arterio dilation
Resp: attenuates HPV in lungs
CNS: cerebral vasodilation, increased ICP. Shifts autoregulation to left

Other
Can be removed by haemodialysis
Needs to be protected from light
Can get cyanide toxicity

Answer 196

A

Antihypertensive
Pthalazine derivative

Answer 197

A

acute severe hypertension
Pre-eclampsia
IV 5-10mg, administered slowly. May repeat 20-30min later. IVI initially 200-300microg/min, maintenance 50-150microg/min
chronic moderate to severe hypertension - PO 50-200mg daily in divided doses

Answer 198

A

Activates ATP sensitive K+ channels –> inhibits opening of voltage gated Ca channels by hyperpolarising membrane –> electromechanical decoupling + inhibition of contraction

Onset: 5-20min when given IV
Duration: 2-6hrs

Answer 199

A

CVS: predominately arteriolar vasodilation –> decreases SVR. Compensatory tachycardia
CNS: CBF increases
Metabolic: increases plasma renin

Other:
Additive hypotensive effects with volatiles

Answer 200

A

Antihypertensive

Aniline derivative

Answer 201

A

0.05-0.6mg PO (max 900microg/day), IV 0.15-0.3mg
- Hypertension
- Migraine
- Chronic pain, opiate and alcohol withdrawal
- premedication in anaesthesia

Answer 202

A

Stimulates alpha 2 (200:1 ratio alpha 2:alpha1 affinity) receptors (pre-synaptic) –> decreases NAd release –> decreased sympathetic tone. GiPCR–> decrease cAMP –> dec Ca2+ influx & Ca-mediated NAd release
Analgesic effect - activation of alpha 2 R in dorsal horn of spinal cord (inhibits neurotransmission)

Onset: Within 5min IV
Duration: 3-7hrs when given IV

Answer 203

A

CVS: transient increase in BP (stimulation of alpha1), then sustained decrease. SVR decreased with long term treatment

CNS: Decreases cerebral blood flow + IOP. Depressant effect on spontaneous sympathetic outflow & afferent A delta- & C-fibre mediated somatosympathetic reflexes
Sedation
Analgesia

Answer 204

A

0.5mg -1mg BD or TDS initially. Maintenance 3-20mg in divided doses
- Hypertension
- CCF
- Raynauds (1-2mg BD)
- BPH

Answer 205

A

Inhibits post synaptic alpha1 receptors –> GqPCR –> inhibits PLC –> decreased IP3 + DAG –> decreased intracellular {Ca2+]

Onset: 30-90minutes
Duration: 10-24hrs

Answer 206

A

CVS: decrease in SVR without reflex tachycardia
Genitourinary: Improvement in urinary flow

Adverse: orthostatic hypotension, rarely tachycardia

Answer 207

A

β1 receptors:
* Distribution: mostly cardiac
* Effects:
○ CVS
§ ↑ SA node firing rate, ↑ HR
§ ↑ contractility
§ ↑ conduction velocity
§ ↑ AV node automaticity
○ Renal
§ ↑ renin secretion by the kidney
○ GI
§ ↓motility and tone of the stomach

Answer 208

A

β2 receptors:
* Distribution: Smooth muscle
* Effects:
○ Resp:
§ Bronchodilation
○ CVS:
§ Vasodilation of vascular beds (coronary arteries, arteries of abdo viscera, renal arteries)
§ Mild cardiac effects – β2 receptors make up 25% of total cardiac β receptor population
○ GI:
§ ↓motility + tone of stomach, intestine
§ Gallbladder relaxation
○ Skeletal muscle effects:
§ Increased K+ uptake
§ Glycogenolysis à Hyperlactataemia
○ Metabolic/endocrine
§ ↑glycogenolysis & gluconeogenesis in liver, insulin secretion, lipolysis, thermogenesis

Answer 209

A

β3 receptors:
* Bladder (detrusor) relaxation
* ↑ water & solute resorption at the kidney
* ↑ lipolysis and thermogenesis at the adipocyte
* Modulation of cardiac contractility
* Relaxation of uterine contractions

Answer 210

A

A - no available or inactivated PO (brush border COMT)
D - 0.1-0.2L/kg (Except aramine & ephedrine 4L/kg
M - COMT & MAO (aramine & ephedrine not metabolised)
E - urine

Answer 211

A

D - V (0.14) <M (0.4); PB V(0)<M (70)
M - V(liver + kidney)>M (liver - not much)
E - Urine

Answer 212

A

non selective
–> Prop + Sot
β-1 selective
–> Bisop, Esmo, Aten, Metop, Nebiv
combined α+β
–> Carvi + labet

Answer 213

A

PMN
- prop
- metop
- nebiv

Answer 214

A

labet
acebut
pindo

Answer 215

A

B-blocker/ antihypertensive
Racemic mixture of 4 stereoisomers

Answer 216

A

Dose: 100-800mg PO BD; 5-20mg bolus IV or titratable infusion 20-160mg/hr
- Hypertensive emergencies
- All grades of hypertension

Answer 217

A

A: Rapidly absorbed but extensive FPM. BA 10-90%
D: 50% PB; Vd up to 15L/kg

Answer 218

A

M: Metabolized by the liver via CYP3A4 and CYP2D6 – inactive compounds
E: Elimination half-life of 5-8 hours. Excreted in the urine and feces.

Answer 219

A

Non selective B-blocker with α1 blockade. Has some intrinsic sympathomimetic activity.
Alpha:beta 1:3 PO or 1:7 IV

Onset: IV – 5-30min
Duration: IV – 50min

Answer 220

A

CVS: beta-1 & beta-2 blockade in cardiac tissue à decreased HR & contractility
Alpha-1 block à vasodilation à
20% decrease BP
Decreases HR + CO by ~10%

Renal: decreased renal VC à increased RBF à GFR unchanged

Answer 221

A

Hypertension - PO initial 12.5mg daily –> 25mg (max 50mg)
Chronic heart failure with reduced ejection fraction - initial 3.125mg BD to max 25mg BD

Answer 222

A

Non selective B-blocker with α1 blockade, No ISA.

Onset: 30-60min
Duration: Long (t1/2 = 7-10hrs)

Answer 223

A

CVS: ↓CO, ↓HR, ↓ reflex orthostatic tachycardia, vasodilation, ↓PVR, ↑ANP
Renal: ↓renal VC, ↓ plasma renin

Answer 224

A

Pulmonary arteries can be classified:
○ Elastic (large, contain elastin)
○ Transitional (increasing amounts of circumferential muscle fibres)
○ Muscular (enough muscle to allow vasoreactivity)
○ Non-muscular (small endothelial vessels)
○ Capillaries (form a vascular sheet)
Pulmonary veins - thinner walled, contain more collagen + less elastin
Pulmonary arteries and veins travel with bronchi (+ nerves + lymphatics) in bronchovascular bundles (à peribronchial cuffing)

Answer 225

A

PA systolic pressure = 18-25mmHg
PA diastolic pressure = 8-15mmHg

Answer 226

A

Pulmonary capillary pressure = 4-12mmHg
Pulmonary venous pressure = 6-12mmHg

Answer 227

A

A volume of blood that needs to be added to pulmonary end capillary blood to explain the observed difference between pulmonary end capillary oxygen content and arterial oxygen content

Answer 228

A

Normal shunt fraction/venous admixture is 3%

Answer 229

A

Shunt fraction –> ratio of venous admixture to total cardiac output
○ Q_s/Q_t = ((Cc_(O_2 ) −Ca_(O_2 )))/((Cc_(O_2 )− Cv_(O_2 )))Where:
§ Q_s= shunt blood flow
§ Q_t = cardiac output (so Qs/Qt = shunt fraction)
§ Cc_(O_2 ) = pulmonary end-capillary blood O2 content
§ Ca_(O_2 ) = arterial O2 content
§ Cv_(O_2 ) = mixed venous blood O2 content

Answer 230

A

Iodinated benzofuran derivative (Class 3 antiarrhythmic)
PO tablets 100mg or 200mg; IV 30 or 50mg/ml amiodarone hydrochloride

Answer 231

A

tachydysrhythmias resistant to other treatment + related to WPW syndrome

Initial loading dose 5mg/kg in 250mL 5% dextrose. Maintenance 15mg/kg/day. PO dose initially 200mg TDS, which is reduced to 100-200mg daily after 1/52

cardiac arrest: shockable rhythm. 300mg IV every 3 cycles

Answer 232

A

Absorption: bioavailability of 22-86% (Smith) or 35-65% (Katzung)
Distribution: 96-98% protein-bound in plasma; VD is 1.3-65.8L/kg, according to dose

Answer 233

A

Metabolism: largely in liver, to desethyl-amiodarone (has anti-arrhythmic properties and is cumulative)
Excretion: 1-5% in urine, mostly in bile + faeces
T1/2 variable - up to 60days

Answer 234

A

prolongs cardiac action potential & delays refractory period.
- partial antagonism of alpha- and beta- agonists by reducing number of receptors or by inhibiting the coupling of receptors to the regulatory subunit of the adenylate cyclase system
- Delays K+ efflux, depresses Na+ influx & depresses Ca2+ influx

Onset: within 1hr IV, PO 2-3days-weeks
Duration after discontinuation can be weeks to months. Half-life (elimination half-life has slow (3-10days) and rapid (weeks) components)

Answer 235

A

CVS - marked prolongation of the action potential duration (and QT interval on the ECG) by blockade of intracellular K.
○ Sinus rhythm is slowed secondary to reduction in the slow diastolic depolarisation in nodal cells. Automaticity is depressed and AV nodal conduction is slowed by 25%

Other: Contraindicated in porphyria

Answer 236

A

○ Hypotension - Vasodilation w ↓ SVR (due to polysorbate 80)
○ ↓ CO - Decreased cardiac contractility
○ May get bradycardia/complete HB resistant to atropine, Ad & NAd

Answer 237

A

○ Pulmonary fibrosis
§ Tends to occur during chronic therapy
§ May be rapidly progressive and fatal
§ Risk factors: underlying lung disease, high doses, recent pulmonary insults (e.g. pneumonia)
§ Rx: Withdrawal of drug; high dose glucocorticoids [MIMS]

Answer 238

A

○ Peripheral:
- Peripheral neuropathy [MIMS]
□ Typically exposure-dependent (long term; high dosage)
□ Sensory > motor neuropathy (glove and stocking paraesthesia; disequilibrium)
□ Incomplete resolution on drug withdrawal

○ Central effects:
§ Tremor
§ Dizziness
§ Vertigo

Ocular:
○ Corneal microdeposits (almost ubiquitous, but usually asymptomatic) [Katzung, Goodman and Gilman’s]
§ Occasional visual changes (e.g. halos in peripheral visual fields) [Katzung, Goodman and Gilman’s]
○ Optic neuritis w blindness [Katzung, Goodman and Gilman’s]

Answer 239

A

Musculoskeletal system:
○ Proximal myopathy [MIMS]
Cutaneous:
○ Photodermatitis (photosensitivity) [Katzung]
○ Grey-blue discolouration in sun-exposed areas [Katzung]
Thrombophlebitis

Answer 240

A

Endocrine effects:
○ Blocks peripheral de-iodination of T4 to T3 [Katzung]
○ Hyperthyroidism
○ Hypothyroidism (Wolf-Chaikoff effect)
○ Amiodarone-induced thyroiditis (types 1 and 2)

Answer 241

A

Pharmacokinetic interactions:
§ Enzyme inhibition:
□ CYP3A4
□ CYP2C9
§ Efflux pump inhibition (PGP):
Pharmacodynamic interactions:
§ Negative chronotropes/dromotropes: risk of bradyarrhythmias
§ Synergistic QTc prolongation with other agents

Answer 242

A

○ Nausea and vomiting
○ Hepatic:
○ Drug-induced liver injury
§ Δ AST, ALT, ALP
§ Rarely, acute liver failure
○ Hypersensitivity hepatitis [Katzung]

Answer 243

A

Mechanism
Effect on (ventricular myocyte) AP:
- Moderate ↓ in phase 0 slope, ↑ APD, ↑ ERP
Effect on ECG:
- ↑ QRS + QT interval

Example
Quinidine
Procainamide

Na channel blockers (moderate)

Answer 244

A

Mechanism
Effect on (ventricular myocyte) AP:
- Small ↓ in phase 0 slope, ↓ APD, ↓ ERP.
Effect on ECG:
- minimal
Preferentially affects ischaemic or depolarised Purkinje and ventricular tissue

Example:
“I’d buy Liddy’s Mexican Tacos”
Lidocaine, mexiletine
Phenytoin

Na channel blockers (weak)

Answer 245

A

Mechanism
Effect on (ventricular myocyte) AP:
- Significantly ↓ Phase 0 slope; No effect on ERP or APD in Purkinje and ventricular tissue
Effect on ECG:
- Significant ↑ in QRS duration, therefore ↑ Qtc
- Significantly prolongs ERP in AV node + accessory bypass tracts, therefore ↑ PR interval

Example
“Can I have fries please”
Flecainide, propafenone

Na channel blockers (Strong)

Answer 246

A

Mechanism
Effect on (pacemaker) AP:
- ↓ SA & AV nodal activity (↓cAMP & Ca2+ currents)
- Suppress abnormal pacemakers - ↓ slope of phase 4
Effect on ECG:
- AV node particularly sensitive - ↑ PR interval

Example
Metoprolol

B-blockers

Answer 247

A

Mechanism
Effect on (ventricular myocyte) AP:
- ↑APD, ERP,
Effect on ECG:
- ↑QT interval

Example
Amiodarone
Sotalol

K channel blockers

Answer 248

A

Mechansim
Effect on (pacemaker) AP:
- ↓conduction velocity, ↑ERP
Effect on ECG:
- ↑PR interval

Example
Verapamil
Diltiazem

Ca channel blockers

Answer 249

A

Class/chemistry
Sodium channel blocker
Tertiary amine
pKa 7.9, ionisation 25%

Administration/preparation
- Multiple routes - IV, S/c, IT, epidural, topical
- 1-2% IV solution for injection, topical gel
- Combined formulations with adrenaline

Answer 250

A

Local anaesthetic (3mg/kg to max 200mg)
Class Ib antiarrhythmic - Rx for ventricular tachydysrhythmias - IV bolus 1mg/kg over 2 min, Inf 20-50mic/kg/min

Answer 251

A

Absorption
Absorption of LAs related to site of injection, dose, VCs (delay absorption)

Distribution
~ 70% PB (alpha-1 glycoprotein); VD = ~1L/kg

Answer 252

A

Metabolism
Liver with multiple metabolites. Some lower seizure threshold, some with antiarrhythmic properties

Elimination
Half life ~100min
<10% in urine

Answer 253

A

Diffuse into cells in unionised form, combine with H+ –> enters internal opening of Na+ channel and combines with receptor –> decreases Na+ conductance –> prevents depolarisation of cell membrane

Acts on Nav1.5 subunit of fast voltage gated Na channels

Onset: 1-5min local infiltration; rapid IV
Duration: ~1-2hrs local (increased with adrenaline); 10-20min IV

Answer 254

A

CVS: decreases rate of rise of phase 0 of ventricular AP, slows AP propagation + reduces automaticity. In toxicity, it decreases PVR & contractility –> hypotension + CV collapse

Resp: Bronchodilation. Resp depression in toxicity

CNS: biphasic effect - excitation then depression

Other
Not removed by dialysis

Answer 255

A

Class/chemistry
Antiarrhythmic Class 1c

Dose/indication:
PO 50-100mg BD (max 400mg daily)
IV 2mg/kg (max 150mg)
- SVT
- Suppression of irritable foci eg. ventricular tachycardia + ectopics
- In treatment of re-entry dysrhythmias eg WPW
- In treatment of pAF

Answer 256

A

Sodium channel blocker. Reduces maximum rate of depolarisation –> slows conduction. Has greatest effect on His-Purkinje system + ventricular myocardium

Answer 257

A

CVS: markedly slows phase 0 of action potential, but decreases ERP - may be proarrhythmogenic. Increases QRS duration, PR prolongation
CNS: may have visual disturbances

Adverse effects
May exacerbate heart failure, ventricular dysrrhythmias, increases non-fatal cardiac arrest

Answer 258

A

HTN, angina
2.5-5mg daily (max 10mg daily)

Answer 259

A

Class IV antiarrhythmic
Non-dihydropyridine/phenylalkylamine

Answer 260

A

240-480mg BD-TDS;
- Hypertension
- Angina
- pSVT, AF, flutter - 2.5-10mg IV

Answer 261

A

Competitive blockade of slow Ca2+ channels, leading to decrease Ca2+ influx into vascular smooth muscle and myocardium

Onset: PO 10-20min; IV 3-5min
Duration: PO 6-8hrs; IV 0.5-6hrs

Answer 262

A

CVS: decreases automaticity and conduction velocity, increases refractory period. Decreases SVR, potent coronary artery vasodilator
CNS: cerebral vasodilation

Adverse effects
Dizziness, flushing, nausea, first or second degree heart block

Other
Avoid co-administration with dantrolene

Answer 263

A

Ca2+ channel blocker - dihydropyridine

Answer 264

A

IV infusion and tablets (30mg)

D/I
- Prevention of cerebral vasospasm secondary to subarachnoid haemorrhage
- Dose: 60mg Q4H; IV 1mg/hr for first 2hrs –>2mg/hr 5-14 days
- Migraine
- Drug-resistant epilepsy

Answer 265

A

CNS: headache, cerebral vasodilation, increased CBF
CVS: hypotension, bradycardia
GI: nausea

Answer 266

A

Absorption
Rapidly and well absorbed, significant FPM - BA low (30%)

Distribution
Highly protein bound, large Vd (1-2L/kg)

Answer 267

A

Metabolism
Liver

Excretion
Urine
t1/2 up to 6hrs

Answer 268

A

Modulates opening of Ca2+ channels on vascular smooth muscle (?preferential action on cerebral vasculature) –> prevents Ca2+ influx –> vasodilation

Answer 269

A

B-blocker/antiarrhythmic

Answer 270

A

Usually ~80mg BD initially
- AF, maintenance of sinus rhythm
- SVT
Ventricular arrhythmias

Answer 271

A

Non-selective B-blocker - prolongation of atrial action potentials. K+ channel blocker - prolongs phase 3 of ventricular AP

Onset: 1-2hrs PO

Answer 272

A

CVS: slows heart rate, decreases AV nodal conduction, increased AV nodal refractoriness, prolongation of atrial and ventricular action potentials

Adverse effects
Bradycardia, chest pain, palpitations, dizziness, fatigue, headache, dyspnoea

Answer 273

A

Cardiac glycoside. Contains steroid nucleus

Answer 274

A

Doses - loading dose 250-500microg every 4-6hours to effect (max daily dose 1.5mg). Then maintenance at 125-250microg daily

Indication - use in AF + Flutter, heart failure, prevention of supraventricular dysrhythmias post thoracotomy

Answer 275

A

Direct action - binds to & inhibits Na+/K+ ATPase in sarcolemma cell membrane–> ↑ intracellular Na+ & ↓ intracellular K+. ↑Na/Ca exchange via INCX - ↑ intracellular Ca–>ionotropy. Decreased K+ leads to slowed AV conduction & ↓ pacemaker cell action
Indirectly modifies autonomic activity & ↑ efferent vagal activity

Onset: PO 1-2hrs; IV 5-60min
Duration of action: 3-4 days; Half life: 36-48hrs

Answer 276

A

CVS - ↑ ionotropy. ↓ HR (depression of SA node discharge, AV node conduction), ↑ AV nodal refractory period & indirect vagal effect. Rapid IV administration may cause vasoconstriction, leading to HTN & ↓ CBF. ECG changes - prolonged PR, ST depression, T wave flattening & shortened QT
○ (toxicity) - any dysrhythmia - esp junctional brady, ventricular bigemini, 2nd/3rd degree HB. Reverse tick on ECG
Renal - mild intrinsic diuretic effect
GI - (toxicity): anorexia, nausea, vomiting, diarrhoea, abdo pain
Neuro - (toxicity): headache, drowsiness, confusion, visual disturbances, muscular weakness, coma

Answer 277

A

Toxicity - Therapeutic range is 0.6-1.0nmol/L (=0.25 ng/mL) digoxin-specific antibody fragments can treat toxicity. They form complexes with dig molecules then are excreted in urine.
○ Indications for treatment: life-threatening arrhythmia, cardiac arrest, K>5.0
○ Consider treatment when: end organ dysfunction, mod-severe GI symptoms, serum dig >12ng/mL (25nmol/L), significant features of dig toxicity with serum dig > 4nmol/L
○ Formulation - 40mg reconstituted in 4mL. Response in ~20min (0-60)

Other specifics
○ Increased risk of dysrhythmias with concurrent sux/pancuronium or B-agonists
○ Increased likelihood of toxicity with: low K, Hyper Na, Hyper Ca, Low Mg, acid-base disturbance, hypoxaemia and renal failure
○ Increased plasma dig levels with coadmin of verapamil, nifedipine, amiodarone, diazepam
○ Cannot be removed by dialysis

Answer 278

A

Naturally occurring nucleoside
Clear, colourless solution 3mg/mL

Answer 279

A

Diagnosis and treatment of paroxysmal SVT. Initially 3-6mg IV, followed by 12mg at 1-2min intervals until effect observed

Answer 280

A

Metabolism - absorbed from plasma into RBCs –> phosphorylated to AMP or deaminated to inosine. T1/2 <10sec

Answer 281

A

Direct agonist at A1 and A2 receptors. Adenosine activates acetylcholine sensitive K+ current in the atrium and sinus & AV nodes - shortens APD, hyperpolarisation + slowing of normal automaticity

Onset 10 seconds
Duration 10-20 seconds

Answer 282

A

CVS: depression of SA & AV nodal activity; coronary vasodilation - endothelial A2 receptors
Resp: increase in depth + rate of respiration. May induce bronchospasm
CNS: infusion results in increased CBF

Adverse effects:
Facial flushing, dyspnoea, chest discomfort

Answer 283

A

Mg2+ 2nd most abundant intra-cellular cation

Mg2+ oxide, chloride, sulphate
PO & IV
IV MgSO4 (50% Mg & inorganic sulphate, 40mmol/100ml), ampoule 10mmol/5ml

Answer 284

A

Dose: depends on Mg2+ level, 10-20mmol over 20/60
Eclampsia & pre-eclampsia
Premature labour
Low Mg2+
Ventricular dysrhythmias incl TDP
Asthma

Answer 285

A

Absorption:
BA: 25-65%

Distribution:
ECF: 1% (0.7-1mmol/L)
Bone: 60%
ICF: 39% (15-20mmol/L)

30% bound to albumin

Answer 286

A

Metabolism
Dissociates into active Mg2+
No metabolism
Bound to bone or filtered into kidneys

Elimination:
Renal
90% reabsorbed in TAL LOH

Answer 287

A

Same role of endogenous Mg2+
Multiple mechanisms
* Reduces membrane excitability e.g. muscle & nerve
* Reduces NT release cholinergic & adrenergic synapses
Ca2+ antagonist -> relax smooth muscle

Onset: immediate after IV

Answer 288

A

CVS: Direct vasodilator - ¯ SVR, ¯ BP, ¯ cardiac conduction & force of contraction, ¯ HR, ¯ catecholamine release
Resp: Bronchodilator
CNS: ¯ catecholamine from adrenal medulla & adrenergic nerve terminals, CNS depressant, Anti-convulsant, Cerebral vasodilator
GIT: Osmotic laxative -> diarrhoea
GU: Renal vasodilator, Diuretic
O&G: ¯ uterine tone & contractility

Answer 289

A

N&V, facial flushing, CNS depression, areflexia, respiratory depression. Reverse with Ca2+
Plasma level (mmol/L) Effect
<0.7 Arrhythmia
4-6 Nausea, ¯ reflexes, speech impaired
6-10 Muscle weakness, resp depression, ¯ HR
>10 Cardiac arrest

Answer 290

A

Class: Anticholinergic
Chemistry: Racemic mixture of D- and l-hyoscyamine (l- form is active)
Prep/admin: Clear, colourless solution for injection in 0.5/0.6mg/mL and 3mg in 10mL

Answer 291

A

Bradycardia with haemodynamic compromise - 0.5-1mg - repeat 3-5minutely
Counter the muscarinic effects of anticholinergic agents
During CPR
treatment of organophosphate poisoning, tetanus

Answer 292

A

A: Well absorbed IM
D: 50% PB; Vd = 2-4L/kg. Crosses BBB & placenta

Answer 293

A

M: Hydrolysed in liver and tissues to tropine + tropic acid
E: T1/2 = 2.5hrs, excreted in 24hrs in urine

Answer 294

A

Competitive antagonism of acetylcholine at muscarinic receptors (GPCR)
Onset: immediate

Answer 295

A

CVS: tachycardia, increased CO. Decreases AV nodal conduction time
Resp: Bronchodilation, secretions reduced, RR increases
CNS: CNS excitation or depression can occur
GI: antiemetic, decreases gastric motility
Metabolic: reduces sweating, BMR increases, suppresses ADH secretion

Answer 296

A

Class: sedative/anxiolytic
Chemistry: Imidazobenzodiazepine
Preparation: Vials 5mg/5ml
Administration: IV + IM

Answer 297

A

Induction of anaesthesia - 0.15-0.2mg/kg
Sedation in ICU- 0.03-0.2mg/kg/hr
Termination of seizures

Answer 298

A

A: Poor bioavailability 44%
D: 96% protein bound (albumin) with Vd = 0.8-1.5L/kg

Answer 299

A

M: Extensively hepatic (CYP3A4). Hydroxylated and forms many active metabolites

E: Renally excreted as hydroxylated metabolites
T1/2 = 2hrs; CSHT 70-80min post 8hr infusion

Answer 300

A

Targets (between α & γ subunits) GABA-A receptors in CNS – enhances inhibitory effect of GABA (increased permeability to Cl-) Different receptor subtypes are responsible for the nuances in effects of the different benzos
Onset: IV 1-5min; Duration: ~1hr for sedation

Answer 301

A

CNS: sedation, hypnosis, anterograde amnesia. CMRO2 & CBF decrease
CVS: decrease in SVR, decrease in BP with compensatory increase in HR
Resp: Can cause apnoea, impairs ventilatory response to hypercapnoea

Answer 302

A

Class: Anticonvulsant/Hydantoin.
Chemistry: Little difference in activity between isomers
Fosphenytoin is the water-soluble prodrug
pKa 8
**Admin/prep: **
PO - 25/50/100/300mg capsules, syrup of 6mg/ml
IV - clear, colourless solution 50mg/mL

Answer 303

A

Prophylaxis and treatment of GTC + partial epilepsies
- Status: IV 15-20mg/kg with additional 5mg/kg post 12hrs if needed
- 4-5mg/kg (usually 200-500mg) in 1 or 2 doses in epilepsy
Arrhythmias (especially from dig toxicity) - 3-5mg/kg
Trigeminal neuralgia
Onset: 0.5-1hr IV; PO 2-24hrs

Answer 304

A

A: Absorption is slow via PO + IM routes. (Note IM may cause muscular damage) Bioavailability is 85-95%
D: 90-93% protein bound in plasm - Vd = 0.5-0.7l/kg
Crosses BBB + placenta

Answer 305

A

M: In liver. Large genetic variation in rate of metabolism.
- Hydroxylated derivative –> conjugated to glucuronide
- Exhibits zero order elimination just above therapeutic range

E: 70-80% renally excreted by active tubular secretion as the major metabolite, 5% unchanged
- t1/2 = 9-22hrs in the first-order kinetics range
- plasma concentration increases disproportionately with increased dosage

Answer 306

A

Blocks voltage and use dependent Na+ channels. Also delays outward K+ flux & Ca2+ flux
High affinity binding site for phenytoin in CNS, so likely endogenous binding site

Answer 307

A

CNS - stabilises the seizure threshold by preventing the speed of seizure activity, rather than abolish a primary discharging focus. Tonic phase can be abolished, but clonic seizure may be exaggerated/prolonged. Toxicity - nausea/vomiting, drowsiness, behavioural difference, tremor, ataxia, nystagmus, paradoxical seizures, peripheral neuropathy + cerebellar damage
CVS - class IB antiarrhythmic properties + enhances AV nodal conduction. Hypotension may complicate rapid IV administration of the drug; complete heart block, VF & asystole
Metabolic/other -Hyperglycaemia, hypocalcaemia + LFT derangement (suppresses ADH secretion)
Haem - megaloblastic anaemia (folate deficiency with chronic use)

Answer 308

A

Drug interactions
- Increase phenytoin toxicity: metronidazole + isoniazid
- Reduces effect of benzodiazepines, pethidine + warfarin. May also decrease the MAC of volatiles
- May enhance CNS toxicity of Las
Therapeutic drug monitoring
Limited correlation b/w therapeutic efficacy and plasma conc but may be useful to confirm toxicity or compliance

Answer 309

A

Single agent (or adjuvant) for seizures (myoclonic, partial, generalised epilepsy)
- 250mg BD, then increase to 500mg in 2/52 (titrate to max 1.5g BD)
- Loading dose in status 60mg/kg (to max 4.5g)

Answer 310

A

Not well understood
- interact with SV2A (synaptic vesicle protein) to decrease release of neurotransmitters

Peak effect ~ 5-30min IV

Answer 311

A

CNS: Sedation, anticonvulsant
Adverse effects:
- Ataxia, fatigue, dizziness, somnolence
- Psychiatric disturbances - aggression, paranoid

Other:
- Does not interact with CytP450
- Dose reduce in renal failure

Answer 312

A

Primary generalised seizures
- Initially 600mg daily in 2 doses. Maintenance 20-30mg/kg in 2 doses(max 2.5g daily)
Chronic pain of non-malignant origin
- 200-400mg BD for migraine prevention
Bipolar disorder. Dosing similar to epilepsy

Answer 313

A

Inhibits GABA transaminase + succinate semialdehyde dehydrogenase (enzyme that metabolise GABA)
Blocks voltage-gated ion (Na+, K+ & Ca2+) channels

Answer 314

A

CNS: anticonvulsant, minimal sedation
Metabolic: infrequently, hyperammonaemia

Toxicity: liver dysfunction, decreased GCS, thrombocytopaenia, coagulation dysfunction

Adverse effects: weight gain, oedema, coagulation dysfunction, hepatic impairment, pancreatitis

Answer 315

A

Partial and generalised seizures - initial 25mg –> 100-200mg/day

Answer 316

A

Inhibits voltage gated Na+ channel & reduce release of glutamate

Answer 317

A

CNS: Anticonvulsant

Adverse:
Headache, nausea, diplopia & tremor, rarely aseptic meningitis, HLH, SJS

Answer 318

A

Epilepsy
- PO 60-240mg daily nocte
Status epilepticus
- 10-20mg/kg (max 1g) infused at <60mg/min. Repeat after 6hrs if needed

Answer 319

A

Enhance the binding of GABA to GABAA receptors. Extends the amount of time the chloride ion channel is open by interacting with GABAA receptor subunits.

Answer 320

A

CVS: can cause bradycardia,hypotension, syncope
CNS: CNS depression, confusion, dizziness, drowsiness
GI: constipation, nausea, vomiting
Resp: can get apnoea (especially with rapid IV use), hypoventilation, respiratory depression

Other:
Concentration monitoring 10-40mg/L or 24-180micrmol/L
Previously used as anaesthetic - but now rare use due to haemodynamics

Answer 321

A

Class: Sedative/hypnotic
Chemistry: Alkylphenol derivative. 2,6-diisopropylphenol

Answer 322

A

Not well understood. Potentiates inhibitory neurotransmitters (GABA + glycine) - presumably GABA-A agonism

Answer 323

A

Opaque, white liquid. 1% liquid emulsion (1mg/mL). Excipients include:
- soy bean oil, Egg lethicin
- NaOH (to adjust pH)
- EDTA (disodium edetate), which retards bacterial growth
- glycerol
Administered IV

Answer 324

A

Induction + maintenance of general anaesthesia 1.5-3mg/kg bolus, followed by 4-12mg/kg/hr
- 50% dose increase for children, and dose reduce for elderly
Sedation in ventilated ICU patients - 1-3mg/kg/hr (max 4mg/kg/hr)
Intractable nausea + vomiting in chemotherapy patients
Termination of status epilepticus

Answer 325

A

A: 98% protein bound in plasma with VD = 4L/kg. Highly lipophilic. pKa ~11

D: Short distribution half life. Has initial effect (alpha phase) before distribution to tissues.

Answer 326

A

M: There are 2 metabolic pathways
- glucuronide metabolite (inactive) by liver
- hydroxylated metabolite (quinol) which is sulfated and glucuronidated by cyt P450
Extrahepatic metabolism (40%)
Inter-individual variability effects which pathway it is metabolised.

E: Metabolites are renally excreted. Quinol metabolite can cause green discolouration of urine + hair.
Maximal CSHT ~20min

Answer 327

A

CVS: Bradycardia, decreases cardiac output by 20% (decreases systemic vascular resistance due to production and release of NO & blunts baroreceptor reflex)
CNS: Causes hypnosis/sedation. Some people may have initial jerking movements (? Imbalance in subcortical inhibitory/excitatory centres), anticonvulsant, decreases CBF, ICP, CMRO2, antiemetic
Resp: Causes decrease in tidal volume, apnoea, decreased response to hypercarbia + hypoxia, decreases laryngeal reflexes

Other:
Toxicity - propofol infusion syndrome - rhabdo, renal failure, multi-organ failure

Answer 328

A

**Class: **Sedative
**Chemistry: **Phencyclidine derivative. Racemic mixture (S-enantiomer more potent). Soluble in water
**Preparation/ Administration: **
50, 100mg/ml
IV, IM, IN, Oral (lozenges)

Answer 329

A

**Induction: **1-2mg/kg
**Procedural sedation: **0.2-0.5mg/kg every 5-10minutes
Analgesia: 0.25-0.5mg/kg bolus, then 0.05-0.25mg/kg/hr

Answer 330

A

A: BA (oral 25%), nasal (50%), IM (93%)
D: 20% PB, Vd = 3L/kg

Answer 331

A

M: CYP450 - Norketamine (25% activity of parent)
E: Elim half life 2hr; 90% in urine

Answer 332

A

NMDAR non-competitive antagonist at NMDAR
Inhibition of glutamate

Onset: 1min; Duration 10-15min

Answer 333

A

**CVS: **Stimulates SNS, increases HR, CO, BP - however is a direct myocardial depressant. S-ketamine - less myocardial depressant effect
**CNS: **Dissociative anaesthesia, analgesia. May increase CMRO2
**Resp: **Bronchodilation, respiratory rate. Airway reflexes intact
**AS: **increases salivation
**GI: **causes nausea + vomiting

Answer 334

A

Class: Sedative
Chemistry: Imidazole derivative
IV formulation. Nil additives

Answer 335

A

Dose 0.2-1mic/kg/hr
- Procedural sedation
- Sedative in ICU

Answer 336

A

-

94% PB; VD = 1.3L/kg

Answer 337

A

M: Hepatic via CYP & glucuronidation, inactive metabolites

E: Urine;
t1/2 - large variation in CSHT (~4min after 10min infusion - 2-3H post 8 hr infusion)
T1/2 elimination = 2hrs

Answer 338

A

Selective alpha2 adrenoceptor agonist
Sedative actions primarily post synaptic alpha2 adrenoceptors
Inhibition of NAd release in locus ceruleus

Answer 339

A

CNS - sedation, easily roused. Decreases cerebral VO2, blood flow, ICP
CVS - Higher doses cause peripheral alpha2 effects - decreased sympathetic output

Answer 340

A

Class: sedative/anxiolytic
Chemistry: Benzodiazepine
Preparation/administration: Tablets - 2mg, 5mg, oral liquid 1mg/mL
IV solution 5mg/mL (2mL)

Answer 341

A

Short term treatment of anxiety - 2-5mg
Alcohol withdrawal - individualised
Muscle spasm in tetanus or other spastic conditions

Answer 342

A

A: Rapidly absorbed. BA 86-100%
D: 99% protein bound; Vd = 1L/kg

Answer 343

A

M: Liver. Major active metabolite = desmethyldiazepam (t1/2~100hrs). Other active metabolites - oxazepam + temazepam -formed by oxidation & further undergo glucuronidation. Low HER
E: T1/2 20-40hrs

Answer 344

A

Targets (between α & γ subunits) GABA-A receptors in CNS – enhances inhibitory effect of GABA (increased permeability to Cl-)

**Onset: **IV 4-5min; **duration: **hours

Answer 345

A

CVS: Transient decrease in BP + CO
Resp: respiratory depression in large doses
CNS: anxiolysis, sedation, hypnosis, anticonvulsant properties, anterograde amnesia

Answer 346

A

Class: Sedative
Chemistry: Thiobarbituate. pKa 7.6, 61% unionised at pH 7.4
High lipid solubility
Preparation/administration: (hygroscopic) yellow powder, stored under atmosphere of nitrogen. Reconstituted with water which is stable in solution for 24-48hrs

Answer 347

A

Induction of anaesthesia: 2-6mg/kg
Management of status epilepticus
Neuroprotection (raised ICP): 1.5-3.5mg/kg intermittent bolus dose

Answer 348

A

A: Is absorbed PO and PR
D: PB 80%, Vd = 2L/kg

Answer 349

A

M: Liver - oxidation to pentobarbital & cleavage to urea + 3-C fragments. 15% dose metabolised/hr
E: Elim half life - 3-22hrs. CSHT variable

Answer 350

A

Prolong GABAA receptor opening duration, direct activation at higher doses
Primarily act at synapses by depressing post-synaptic sensitivity to NTs and impairs pre-synaptic NT release
- Multisynaptic pathways depressed preferentially (eg. Reticular System)
Membrane stabilising effects - ↓s Na+ + K+ conductance

Answer 351

A

CNS: anaesthesia, CBF, ICP, IOP ↓. Anticonvulsant
CVS: negative ionotrope, ↓ CO, SVR
Resp: Potent respiratory depressant, ↓ in ventilatory response to hypercapnoea. Laryngeal spasm occasionally seen, may get bronchoconstriction

Other: contraindicated in porphyria

Answer 352

A

Class/chemistry: Typical antipsychotic/1st generation antipsychotic/ Butyrophenone

Preparation/ Administration: PO tablets, capsules, syrup,, solution for injection, depot

Answer 353

A

IV 1-5mg; Po dose 1-15mg
- Schizophrenia/psychoses
- Nausea + vomiting
- Acute confusional states + delirium
- Premedication
- Palliative care

Answer 354

A

Central dopaminergic (D2) blockage –> increased threshold for vomiting at CTZ
Post synaptic GABA antagonism

Answer 355

A

CVS: some alpha2 antagonism - may have hypotension
CNS: Neurolepsis, raises seizure threshold
Metabolic: may cause hyperprolactinaemia

Other: May produce extrapyramidal symptoms, including NMS

Answer 356

A

Class/chemistry: 2nd generation/atypical antipsychotic/ thienodiazepine

PO, IM

Answer 357

A

Varies 5-10mg
- Agitation/aggression (organic + psychiatric causes)
- Delusional disorders
- Schizophrenia
- Huntington associated chorea

Answer 358

A

Potent antagonism of 5HT2A +2C, D1-4, H1, alpha1-adrenergic receptors

Answer 359

A

CVS: orthostatic hypotension
GI: constipation
Metabolic: increased cholesterol

Answer 360

A

2nd generation/atypical antipsychotic/ dibenzothiazepine

PO

Answer 361

A

Varies 25-100mg
- Agitation/aggression (organic + psychiatric causes)
- Delusional disorders
- Schizophrenia
- GAD

Answer 362

A

5HT2 + D2 antagonism with H1 + alpha effects
Nil cholinergic/benzo effects

Answer 363

A

CVS: increased BP, tachycardia
Metabolic: cholesterol
CNS: may cause EPS

Answer 364

A

Chemistry
- 3-ring central structure plus side chain. Most have pKa ~8.5
§ Tertiary amines have 2 methyl groups at the end of the side chain. They are generally more potent in blocking 5-HT over NE (amitriptyline, doxepin, imipramine)
§ Secondary amines have one methyl group at the end of the side chain. They are more potent in blocking NE (nortryptiline, desipramine)

Preparation: most available in oral forms only

Dose/Indication
- Major depression. Dose is started at 25-75mg for all, with titration ever 2-3 days to 75-150mg
- Clomipramine used in OCDs + cataplexy with narcolepsy
- Imipramine can also be used for nocturnal enuresis

Answer 365

A

Inhibit both NE + serotonin uptake
Also block cholinergic, histaminergic, alpha1-adrenergic and (inhibit fast Na channels in His-Purkinje system & myocardium –> similar to Class 1A antiarrhythmics)

Answer 366

A

CVS - alpha1 blockade can cause orthostatic hypotension, QT prolongation, and other conduction delays
CNS - can lower seizure threshold
Anticholinergic - blurred vision, constipation, dry mouth, urinary retention
Antihistaminic - Increase appetite, cause sedation

Answer 367

A

-Delayed Absorption (dec. gut motility - anticholinergic); acidaemia- dec glycoprotein binding (incr free drug)

Signs/symptoms
- CNS - mental state changes (agitation, delirium), decreased GCS, seizures (? GABAA antag)
- CVS - Hypotension (peripheral vasodilation - alpha1 blockage). Tachycardia (vagolysis) + reflex tachy. Can have arrhythmias.
–> ECG: widened QRS (>100ms), QT prolongation
- Anticholinergic (hyperthermia, flushing, dilated pupils)

Management
- Decontamination, Supportive care
- Antidote: NaHCO3 - cardiac toxicity (QRS >100msec)
–> Plasma alkalinsation (improves protein binding)
–> Intracellular alkalosis (increases the unbinding rate of TCAs from Na+ channel receptor + favours the non-ionised state of the TCA)
–> Sodium load

Answer 368

A

Chemistry: Hydrazine + non-hydrazine compounds
Preparation: Mostly oral formulations
Dose/Indication: (moclobemide 150mg starting dose)
○ Major depression (third line)
○ Some anxiety disorders/panic disorder

Answer 369

A

Inhibit MAO-A & MAO-B (located in the mitochondria and metabolise monoamines). MAO-A metabolises dopamine, NE, serotonin; MAO-B metabolises dopamine. Both enzymes exist in the brain + are distributed differently throughout the body

Answer 370

A

CNS: increased NTs (5-HT, NE)–> improves postsynaptic NT binding. Supratherapeutically: seizures, mania, serotonin syndrome, restlessness, agitation, nausea, insomnia
CVS: MAO-A + B metabolise dietary tyramine –> inhibition of metabolism –> release of tyramine into general circulation –> triggers release of NE. May precipitate hypertensive crisis
Hepatic: can cause hepatotoxicity, hypoglycaemia

Other specifics
- Irreversible MAOIs will bind for the life of the MAOs (~2/52)

Answer 371

A

SSRI: initially block reuptake of 5-HT via SERT & result in increased length of time that serotonin is available in synapse, increasing postsynaptic receptor occupancy
- They are 10x more selective for SERT than NET
- Initial increase in synaptic serotonin eventually leads to increased production of neuroprotective proteins such as BDNF + Bc1-2

SNRI: inhibit SERT & NET

Answer 372

A

Class: Opioid analgesic
Chemistry: Naturally occurring phenanthrene derivative. Weak base (pKa 8). 23% ionised at pH 7.4
Preparation/administration:
- PO formulations various strengths
- 5/30mg suppositories
- IV 10/15/30mg/mL of morphine sulfate
- Preservative free formulation needed for epidural/spinal injection . Routes: PO, IV, IM, S/c

Answer 373

A

Dose generally titrated to effect. Initial dose 0.1-0.2mg/kg s/c or 0.05-0.1mg/kg IV
- Pre-mediation
- Pain relief in terminal care
- Treatment of ACS/LV failure

Answer 374

A

A: BA 30% (extensive FPM)
D: 20-40% PB; VD ~ 4L/kg

Answer 375

A

M: Liver - Morphine-3glucuronide(60%-arousal), morphine-6-glucuronide (5-10% analgesic-13x more potent than parent), normorphine

E: Urine, small percentage of metabolites in faeces. Half-life ~4hrs, accumulation of M6G in renal failure. Maximal CSHT 20min (regardless of duration of infusion)

Answer 376

A

Agonist at MOP & KOP.
At pre-synaptic MOP: GiPCR –> inhibition of adenylate cyclase –> decreased cAMP –> decreased Ca2+ influx –> decreased Ca2+ mediated NT release
- Post synaptic MOP: increases K+ conductance and hyperpolarisation of excitable cell membranes
Onset: 5-10min, 30min PO; Peak: 20min
Duration: 3-5hrs IV

Answer 377

A

CVS: may cause some histamine release - decreases SVR, may cause orthostatic hypotension
Resp: respiratory depression, may cause bronchoconstriction in high doses
CNS: potent analgesic. Euphoria
GI: decreases GI motility, increases CBD pressure (spasm of sphincter of Oddi). N/v/constipation
Renal: increases tone of ureters, bladder - retention
Endo: morphine increases ADH

Caution in hepatic/renal failure. Dependence is an issue
pruritis may occur from eipdural/spinal admin

Answer 378

A

2-5% of VO2 or 3ml/min (<2% of BMR)

Answer 379

A

Class/chemistry: Opioid analgesic. Tertiary amine (synthetic phenylpiperidine derivative)
pKa 8.4, 9% unionised at pH7.4.

Preparation: Available PO, IV, S/L, IN, TD, IM. 15 & 50microg/mL

Answer 380

A

Dose titrated to effect.
- analgesia during GA - 50-100microg IV
- premedication
- Palliative care
Epidural (50-100mic), Spinal (up to 25mic)

Answer 381

A

A: BA 33%
D: 90% PB; VD ~4L/kg. Octanol:water partition coefficient 717. High pulmonary uptake (partly due to active transport)

Answer 382

A

M: Liver - N-dealkylation –> norfentanyl, then further hydroxylation to hydroxypropionyl derivatives. CYP 3A4 plays predominant role in metabolism. Metabolites not pharmacologically active
E: 10% of drug excreted in urine. Elimination half-life ~2hrs. Maximum CSHT of 5hrs.

Answer 383

A

Highly selective MOP agonist (GiPCR) (pre-synaptic) –> inhibition of AC –> reduced cAMP, closure of voltage-gated Ca channels
Onset: <1-2min; Peak: 3-5min
Duration: 30-60min

Answer 384

A

Effects/Side effects

CVS: bradycardia (vagal); CO, MAP, SVR, PVR unaffected. Obtunds CV response to laryngoscopy and intubation
Resp: potent respiratory depressant - decreases RR & tidal volume. Decreased ventilatory response to hypoxia and hypercapnia. Chest wall rigidity
CNS: 50-80x more potent than morphine. Little hypnotic/sedative effect. Potent antitussive
GI: decreases GI motility & gastric acid secretion. Spasm of sphincter of Oddi

Other

Secondary peak in plasma fentanyl concentration due to elution from muscle

Answer 385

A

Class/chemistry: Opioid analgesia. Synthetic phenylpiperidine derivative. pKa 7.1; 68% unionised at pH7.4

Admin/prep: White lyophilised powder to be reconstituted. 1/2/5mg vials. IV only

Answer 386

A

Titrated to response. 0.0125-1mic/kg/min infusion or 1mic/kg bolus dose over 30s
- Analgesia in GA
- Analgesia during labour
- Analgesia/sedation during ‘awake’ fibreoptic

Answer 387

A

A: Given IV only
D: 70% PB. VD (ss)= 0.3L/kg

Answer 388

A

M: Rapidly hydrolysed by non-specific plasma and tissue esterases –> remifentanil acid (4600x less potent)

E: CSHT - fixed 4-5min. Elimination half life 10min

Answer 389

A

Pure MOP agonist (pre-synaptic Gi)
Peak effect 1-3min
Duration ~4min

Answer 390

A

CVS: decreases MAP + HR
Resp: Potent respiratory depressant. May get chest wall rigidity similar to fentanyl
CNS: analgesic potency similar to fentanyl. Centrally mediated vagal activity, miosis (EW nucleus)
GI: decreased GI motility. Relatively low n+v