ELFH - Pharmacology Flashcards
Which of the following may alter drug response:
Select true or false for each of the following statements.
True
False
A. Tachyphylaxis
B. Changes in receptor number
C. Hypersensitivity reactions
D. Idiosyncratic drug responses
E. Tolerance
True. Tachyphylaxis is defined as a decreased response following a single administration of a drug.
True. Whether this affects drug response depends on the degree of change in receptor number, and whether the drug response involves spare receptors (i.e. a full response is obtained despite some receptors not being occupied).
True. See below
True. Such reactions are not related to known pharmacological properties of a drug (i.e. not a common side effect, they are dose independent). They include anaphylaxis and anaphylactoid reactions.
True. Tolerance is the decreased responsiveness following repeated drug adminsitration.
The following processes are mediated by cAMP:
Select true or false for each of the following statements.
True
False
A. Decreased heart rate
B. Liver carbohydrate metabolism
C. Increased contractility
D. Triglyceride breakdown
E. Smooth muscle relaxation
True. Both increases and decreases in heart rate are mediated via cAMP. Beta1-adrenoreceptors are G-protein coupled - their stimulation causes increased cAMP and subsequent tachycardia. Muscarinic M2 receptors are Gi type g-protein coupled receptors and when stimulated decrease cAMP and reduce heart rate via opening of potassium channels
True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent glycogenolysis (also increases insulin and glucagon secretion).
True. Beta1-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent increase in contractility.
True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent lipolysis (also increases insulin and glucagon secretion). Beta 3-adrenoreceptors are also G-protein coupled and increase cAMP - they help regulation lipid metabolism.
True. Beta2-adrenoreceptors are G-protein coupled, and their stimulation causes increased cAMP and subsequent smooth muscle relaxation.
Regarding chemical bond strength:
Select true or false for each of the following statements.
True
False
A. Van der Waals > Hydrogen > Ionic > Covalent
B. Covalent > Ionic > Hydrogen > Van der Waals
C. Covalent > Hydrogen > Ionic > Van der Waals
D. Ionic > Covalent > Hydrogen > Van der Waals
E. Van der Waals > Hydrogen > Covalent > Ionic
False.
False.
False.
True.
False.
Ionic bonds involve the electrostatic forces of attraction between oppositely charged ions after the complete loss or gain of electrons and are in general stronger than covalent bonds. Covalent bonds involve the sharing of electrons in order to gain full outer electron shells. Taken in isolation covalent bonds are generally weaker than an ionic lattice, however in complex molecules where there may be double or triple bonding they may become stronger than an ionic bond. For example a single covalently bonded carbon-oxygen required 350KJ/mol to break, but a triple-bonded carbon-oxygen requires 1080KJ/mol to break. A sodium-chloride ionic lattice requires 769KJ/mol to break.
Hydrogen bonding involves the forces of attraction between the postively charged nucleus of a hydrogen atom and an electronegative atom. Electron clouds have no definite shape, therefore at any moment one part of the cloud may be relatively more positively or negatively charged than the other - Van der Waals forces are the forces of attraction / repulsion between such areas.
Receptors:
Select true or false for each of the following statements.
True
False
A. Drug affinity depends on the attraction between receptors and drugs
B. Thyroid hormones bind to cell surface receptors
C. Acetylcholine receptors have 2 alpha and 2 beta subunits
D. Midazolam acts at GABAb receptors
E. Nicotinic hormones bind to intracellular receptors
True. Affinity is the ability of a ligand to bind to a specific receptor.
False. They bind to intracellular receptors.
False. The adult acetylcholine receptor has 2 alpha subunits (to which acetylcholine binds), a beta subunit, a delta subunit and an episilon subunit (this is replaced by a gamma subunit in the foetus).
False. It acts at GABAa receptors.
False. Nicotinic receptors are type 1 receptors according to Urquhart’s calssification - membrane bound ligand gated ion channels.
Regarding negative exponential processes:
Select true or false for each of the following statements.
True
False
A. The rate of decay varies with time
B. The time constant is longer than the half-life
C. The time constant is the natural logarithm of the half-life
D. Is converted into a straight line by a semi-log plot
E. The time constant is the time for the process to complete if the rate continued at its initial speed
True. In an exponential process the rate of change of a variable is proportional to the magnitude of the variable at that moment in time. In a negative exponential process, the rate of decay is decreasing with increasing time.
True. An exponential process is said to be complete after 3 time constants, as opposed to 5 half-lives.
False. The time constant is the reciprocal of the rate constant.
True. This is true of other exponential processes also. It allows for easier interpretation.
True. It can also be defined as the time taken for an exponential process to fall to 37% or 1/e of its previous value.
The following antagonists have agonist properties:
Select true or false for each of the following statements.
True
False
A. Ranitidine
B. Prazosin
C. Pindolol
D. Naltrexone
E. Xameterol
False. It is an H2-receptor antagonist.
False. It is a selective alpha1-adrenoreceptor blocker.
True. It is a non-selective Beta-blocker with partial beta-agonist activity. It also has partial agonist / antagonist activity at the 5-HT1A receptor.
False. It is an opioid receptor antagonist.
True. It is a mixed beta-agonist/antagonist.
Mixed agonist-antagonists are drugs that can exert both agonistic and antagonistic properties. Such drugs include: Opioids (Pentazocine, Nalbuphine and Buprenorphine), Mirtazepine, Pindolol and Xameterol.
Receptors and 2nd messengers:
Select true or false for each of the following statements.
True
False
A. G-protein receptors have alpha, beta and delta subunits
B. Insulin receptors are G-protein coupled
C. Opioid receptors are G-protein coupled
D. cAMP is a hydrophobic molecule
E. Nitric oxide acts via cAMP
False. G-proteins consist of alpha, beta and gamma subunits.
False. The Insulin receptor utilises tyrosine kinase.
True.
False. It is hydrophilic.
False. It acts via cGMP.
Regarding the log dose-response curve:
Select true or false for each of the following statements.
True
False
A. The ED50 is the drug concentration that induces a response halfway between zero and maximum
B. Therapeutic index = Lethal Dose 50 / Effective Dose 50
C. Drugs with a narrow therapeutic window do not require monitoring
D. It is shifted to the left with the addition of a competitive antagonist
E. Potency is represented by the height of the curve
False. ED50 refers to the dose of drug - this question defines the Effective Concentration 50.
True.
False. Drugs with a narrow therapeutic window often require close monitoring as the risk of reaching toxic levels is greater.
False. The curve is shifted to the right as a higher dose of agonist is required to produce an equivalent response.
False. It is represented by the position of ED50, much like the position of P50 on the oxy-Hb dissociation curve.
Antagonists:
Select true or false for each of the following statements.
True
False
A. Have intrinsic activity, but lack affinity
B. Competitive antagonism reduces Emax
C. Competitive antagonists bind to a site distal to the receptor involved
D. Non-competitive antagonism is overcome by increasing agonist dose
E. May also act as agonists
False. They have affinity, but an intrinsic activity of zero.
False. Maximum efficacy (Emax) remains the same, but the dose-response curve is shifted to the right. Non-competitive antagonism reduces Emax
False. Competitive antagonists compete for a receptor with agonists. Non-competitive antagonists bind to a distal site, and induce a change at the receptor.
False. This is competetive antagonism.
True. Mixed agonists-antagonists can act as agonists at some receptors and antagonists at others e.g. pentazocine.
Partial agonists:
Select true or false for each of the following statements.
True
False
A. Act as both agonists and antagonists
B. Have similar intrinsic activity to full agonists
C. Include buprenorphine
D. Include pentazocine
E. Include clozapine
True. Partial agonists act as agonists in isolation, but can act antagonistically when given in combination with a full agonist.
False. Full agonists have an intrinsic activity of 1, whereas a partial agonists have an intrinsic activity of <1.
True.
False. Pentazocine is a mixed agonist-antagonist.
True. Clozapine is a partial agonist at D2 receptors.
The following are true regarding Volume of Distribution (Vd):
Select true or false for each of the following statements.
True
False
A. It is the amount of drug that distributes following administration
B. Can be greater than total body water
C. Is measured in kg/L
D. Is a constant for a given drug
E. Is equal to Clearance divided by Time Constant
False. It is the volume that a drug distributes into following administration.
True. TBW = 42L whilst Vd can be up to 1000L.
False. It is measured in L/Kg.
True.
False. Vd = Clearance x Time Constant.
Context sensitive half-time:
Select true or false for each of the following statements.
True
False
A. Is a decrement time
B. Shares a constant relationship with elimination half-life
C. Varies with duration of drug infusion
D. Is reliably used to describe time for recovery
E. Reflects the combined effects of absorption and distribution
True. Decrement time = the time taken of the plasma level for a drug to fall to a specified value (Context-Sensitive Half-Time is 50%).
False. There is no such relation.
True. This is the ‘context’.
False. It is the time for the plasma levels to fall to 50% of the value when the infusion is stopped.
False. It reflects the combined effects of distribution and metabolism.
The following influence Volume of Distribution (Vd):
Select true or false for each of the following statements.
True
False
A. Regional blood flow
B. Lipid solubility
C. Degree of tissue protein binding
D. Degree of plasma protein binding
E. Degree of ionisation
True.
True.
True.
True.
True.
Infusion kinetics:
Select true or false for each of the following statements.
True
False
A. It takes 5 half-times to reach steady state concentration
B. Steady state volume of distribution is dependent on lipid solubility and molecular weight
C. Loading Dose = Vd x Desired Plasma Concentration
D. Maintenance Dose = Steady State Vd x Clearance
E. Clearance = Input (mg/min) x Plasma Concentration (mg/ml)
False. It takes 5 Half-lives to reach steady state concentration.
False. Steady state volume of distribution is dependent on lipid solubility and clearance.
True.
False. Maintenance Dose = Steady State Concentration x Clearance.
False. In infusion kinetics at steady state Input = Elimination
Input (mg/min) is therefore equal to Clearance (ml/min) x Plasma Concentration (mg/min). Therefore:
Clearance = Input (mg/min) / Plasma Concentration (mg/ml)
The following statements are true of Cytochrome P450 enzyme isoforms:
Select true or false for each of the following statements.
True
False
A. CYP2E1 is involved in metabolism of paracetamol
B. CYP3A4 is involved in metabolism of phenytoin
C. Are only found in the liver
D. Account for most phase 2 reactions
E. CYP2E1 is involved in the metabolism of chloride containing volatile agents
True.
False. CYP3A4 is important in the metabolism of both midazolam and alfentanil.
False. CYP2E1 is found in the kidneys.
False. Account for most phase 1 reactions.
False. CYP2E1 is involved in the metabolism of fluoride containing volatile agents.
The following are enzyme inducers:
Select true or false for each of the following statements.
True
False
A. Rifampicin
B. Metronidazole
C. Acute alcohol use
D. Carbamazepine
E. Chloramphenicol
True.
False. It is an enzyme inhibitor.
False. Acute alcohol use inhibits whilst chronic use induces.
True.
False. It is an enzyme inhibitor.
Phase 2 reactions include:
Select true or false for each of the following statements.
True
False
A. Oxidation
B. Acetylation
C. Sulphation
D. Hydrolysis
E. Glucuronidation
False. This is a Phase I reaction.
True.
True.
False. This is a Phase I reaction.
True.
Elimination:
Select true or false for each of the following statements.
True
False
A. Can only be by either distribution or metabolism
B. In 1st order kinetics, half-life is constant
C. In 1st order kinetics, a constant amount of drug is eliminated per unit time
D. Zero order kinetics is a linear process
E. In zero order kinetics, half-life increases with dose administered
False. Can also be by excretion.
True.
False. A constant proportion is eliminated per unit time.
False. Zero order kinetics is also known as non-linear kinetics.
True.
Hepatic clearance:
Select true or false for each of the following statements.
True
False
A. A drug with a high extraction ratio is not affected by protein binding
B. Lignocaine is an example of an enzyme limited drug
C. High extraction ratio implies significant 1st pass metabolism
D. Enzyme induction / inhibition can profoundly affect the clearance of drugs with a low extraction ratio
E. Warfarin is an example of an enzyme limited drug
True. It is not affected by enzyme level either.
False. Lignocaine has a high extraction ratio (>0.7) and is therefore flow / perfusion limited (as opposed to enzyme / capacity limited).
True. Most of the drug is extracted on the first pass through the liver, hence why changes in hepatic blood flow can drastically affect clearance.
True. Drugs with a low extraction ratio are enzyme / capacity limited drugs.
True. As are phenytoin, theophylline and most benzodiazepines and barbituates.
Bioavailability:
Select true or false for each of the following statements.
True
False
A. Of drugs administered via the IV route can be as high as 90%
B. Is the fraction of administered drug that reaches systemic circulaiton
C. Glycopyrrolate has >80% bioavailability
D. Is influenced by genetics
E. Is influenced by circadian rhythm
False. IV drug administration provides 100% bioavailability.
True.
False. Glycopyrrolates bioavailability is < 5%.
True. There are phenotypic variations in bioavailability.
True.
Isoflurane:
Select true or false for each of the following statements.
True
False
A. Is a stereoisomer of enflurane
B. Causes vasodilatation without reflex tachycardia
C. Has a saturated vapour pressure of 23.3 kPa at 20 degrees Celcius
D. 0.2% of isoflurane undergoes hepatic metabolism
E. The chloride group is attached to the chiral centre
False. It is a structural isomer.
False. A reflex tachycardia suggests that baroreceptor function remains intact with isoflurane use. The main cause of isoflurane induced hypotension is a reduction in systemic vascular resistance. Myocardial function and cardiac output see only a small decrease.
False. This is the SVP of enflurane. The SVP of isoflurane is 32 kPa.
True. Hepatic cytochrome P450 metabloizes the C - F bond. Renal toxicity is rare due to the low levels of fluoride ions produced.
True.
Factors that increase Minimum Alveolar Concentration:
Select true or false for each of the following statements.
True
False
A. Alpha-2 agonists
B. Hypernatraemia
C. Chronic alcohol intake
D. Acute alcohol intake
E. The premature neonatal period
False. These decrease MAC.
True.
True.
False. Acute alcohol intake decreases MAC.
False. The MAC is low in preterm neonates. For most agents MAC value peaks at 1-6 months.
Sevoflurane:
Select true or false for each of the following statements.
True
False
A. Has a chiral centre
B. Produces hydrofluoric acid if stored in glass
C. Has a blood:gas coefficient of 1.4
D. Causes coronary steal syndrome
E. Is metabolised by cytochrome isoform CYP3A4
False. It is achiral
True. This is highly toxic. Lewis acids degrade the ether and halogen bonds if sevoflurane is stored in water at concentrations less than 100ppm. The highly toxic hydrofluoric acid corrodes glass, driving Lewis acid production.
False. This is the blood:gas coefficient of isoflurane. 0.7 is the correct answer.
False. This is a side effect of isoflurane use.
False. This cytochrome isoform is responsible for the metabolism of opiates and benzodiazepines. CYP2E1 is responsible for sevoflurane / isoflurane / halothane metabolism.
Sevoflurane:
Select true or false for each of the following statements.
True
False
A. Is methyl-ethyl ether
B. Inhibits pulmonary vasoconstriction
C. Undergoes renal metabolism to produce inorganic fluoride ions
D. Compound A production is more likely in the presence of dry potassium hydroxide
E. Has a molecular weight higher than halothane
False. It is a polyfluorinated methyl isopropyl ether.
True.
False. This was a feature of methoxyflurane. 3.5% of sevoflurane undergoes hepatic metabolism to produce hexafluroisopropanol and fluoride ions.
True. The suggested nephrotxoic threshold for compound A is 150-200ppm. These are levels that far exceed what is seen in clinical practice.
True. Sevoflurane 200.1, Halothane 197, Isoflurane / Enflurane 184.5, Desflurane 168, Xenon 131 and N2O 44.
Minimum alveolar concentration:
Select true or false for each of the following statements.
True
False
A. Is above 6% for desflurane
B. Is above normal atmospheric pressure for nitrous oxide
C. May be as low as 0.7 for sevoflurane in 70% nitrous oxide
D. Is 0.95 for Halothane
E. Is lower for enflurane than it is for isoflurane
True.
True.
True.
False. MAC of halothane is 0.75
False. Isoflurane 1.17, Enflurane 1.68
Halothane:
Select true or false for each of the following statements.
True
False
A. Is an halogenated ether
B. Has a SVP at 20 degrees celcius, similar to isoflurane
C. May be given safely with adrenaline infiltration at doses of 100 micrograms per minute
D. Its C-Br bonds are metabolised with greater ease than its C-F bonds
E. Is metabolised under hypoxic conditions to produce trifluoroacetyl chloride which is implicated in halothane hepatitis
False. Halothane is a halogenated hydrocarbon. There is no ether ‘link’.
True. Halothane 32.3 kPa, Isoflurane 33.2 kPa.
False. This dose of adrenaline should be administered over a 10 minute period. Halothane sensitises the heart to catecholamines, which may lead to arrhythmias - particularly ventricular tachycardias and bradyarrhythmias.
True. C-F bonds are the most stable carbon-halogen bond.
False. This metabolite is produced under oxidative conditions. In a hypoxic state reduced metabolites are produced e.g. inorganic fluoride.
Desflurane:
Select true or false for each of the following statements.
True
False
A. Has a boiling point of 39 degrees celcius
B. Is administered via the Tec 5 vaporiser
C. Induces tachycardia and hypertensions at MAC values greater than 1
D. Produces carbon monoxide on contact with soda lime
E. Has a blood gas coefficient higher than nitrous oxide
False. Its boiling point is 23.5 degrees celcius.
False. Is administered via the Tec 6. This heats the volatile to 39 degrees celcius under a pressure of 2 atmospheres.
True.
True. Volatile agents that contain a -CHF2 molecule (isoflurane, enflurane, desflurane) may produce carbon monoxide upon reaction with dry soda lime.
False. Blood gas coefficient of desflurane is 0.42; nitrous oxide 0.47
Nitrous Oxide
Select true or false for each of the following statements.
True
False
A. Has a critical pressure of 72 bar
B. Is stored in cylinders with a pin index configuration of 2 and 5
C. Increases cerebral blood flow
D. Inhibits methionine synthetase by reducing the cobalt ion in vitamin B12
E. Reduces that MAC of isoflurane to 0.5 when used at 70%
True. In addition to this, the critical temperature is 36.5 degrees celcius.
False. This is the pin index of oxygen. The configuration for nitrous oxide is 3 and 5.
True. It may also increase intracranial pressure.
False. It oxidises this cobalt ion. It may also inhibit methionine synthetase directly. Nitrous oxide therefore inhibits methionine, thymidine, tetrahydrofolate and DNA synthesis.
True.
Halothane:
Select true or false for each of the following statements.
True
False
A. Increases cerebral blood flow less than enflurane
B. Has a sweet odour
C. Has two bromide atoms
D. Is prepared with 0.01% thymol to prevent combustion
E. Causes vagal stimulation
False. In descending order; halothane, enflurane, nitrous oxide, isoflurane
True.
False. 1 bromide, 1 chloride and 3 fluoride ions.
False. It is prepared with 0.01% thymol to prevent decomposition by light.
True. It may also cause bradycardia by inhibiting atrioventricular conduction / activity.
In reference to inhaled anaesthetic agents:
Select true or false for each of the following statements.
True
False
A. Isoflurane does not increase cerebral blood flow at concentrations below 1 MAC
B. Xenon is hepatically metabolised
C. Oxygen has a critical pressure of 50 bar
D. Entonox seperates into its constituent parts below 7 degrees celcius
E. 0.1% of nitrous oxide is metabolised
True.
False. All clearance is by lung elimination.
True.
False. This is likely to occur at temperatures below -7 degrees celcius (pseudo-critical temperature) at pressures of 117 bar.
False. Less than 0.01% of nitours oxide undergoes metabolism.
Propofol:
Select true or false for each of the following statements.
True
False
A. Is highly protein bound
B. Produces vasodilatation by nitric oxide production
C. Is only partly unionized at physiological pH
D. Has a hydroxyl group situated on its 4th carbon
E. Undergoes both phase 1 and phase 2 metabolism
True. 97% protein bound.
True. Propofol causes hypotension (reduction in sytsemic vascular resistance and cardiac output) without tachycardia. Bradycardia is common, especially with opiate co-administration.
False. The pka of propofol is 11, therefore at pH 7.4 it is almost entirely unionized.
False. The hydroxyl group is situated on the 1st carbon. Phase 1 metabolism into a quinol derivative involves hydroxylation of the 4th carbon.
True. Glucuronidation is the predominant metabolic pathway, hydroxylation by cytochrome P450 to a quinol derivative prior to conjugation is also an important pathway. The relative importance of each pathway varies amongst patients.
Propofol:
Select true or false for each of the following statements.
True
False
A. Is used at a dose of around 4 mg/kg for IV paediatric induction
B. Causes a reduction in cardiac output solely by reducing heart rate
C. Clearance is by hepatic metabolism alone
D. Acts as an anti-emetic by competitive antagonism of central serotonin receptors situated in the chemoreceptor trigger zone
E. Is a cause of hypertrigylcerideaemia
True. Approx double the typical adult dose.
False. Propofol also reduces myocardial contractility and sympathetic tone.
False. Extra-hepatic metabolism is significant, suggested by the fact that clearance is higher than hepatic bolod flow. Sites for extra-hepatic metabolism include the kidneys (responsible for about a third of extra-hepatic metabolism) and lungs (to 2, 6 - diisopropyl - 1, 4 - quinol).
False. The anti-emetic effect of propofol is probably mediated through dopamine receptor antagonism.
True. This may be a part of the metabolic syndrome seen in children after prologed infusion. Propofol infusions have been linked to organ fatty infiltration with severe bradycardias, metabolic acidosis and increased mortality.