FACEM Pharmacology Fundamentals 3 — Questions and Answers
Question 1: The 'ceiling effect' of buprenorphine as an analgesic is best explained by its pharmacology as a:
- Full agonist at mu-opioid receptors
- Partial agonist at mu-opioid receptors with high receptor affinity (Correct answer)
- Pure antagonist at all opioid receptors
- Kappa-selective agonist
Correct answer: Partial agonist at mu-opioid receptors with high receptor affinity
Buprenorphine's partial agonist activity means increasing the dose beyond a ceiling provides no additional analgesia, and its high affinity makes displacement by naloxone difficult.
Question 2: Which ion channel mechanism explains the local anaesthetic action of lignocaine (lidocaine)?
- Blockade of potassium channels during repolarization
- Inhibition of voltage-gated sodium channels in the inactivated state (Correct answer)
- Activation of GABA-A chloride channels
- Blockade of calcium channels at the neuromuscular junction
Correct answer: Inhibition of voltage-gated sodium channels in the inactivated state
Local anaesthetics block voltage-gated sodium channels preferentially in the inactivated state, preventing action potential propagation in nerve fibres.
Question 3: A patient receives a drug with a volume of distribution (Vd) of 500 L. This large Vd most likely indicates:
- The drug is confined to the plasma compartment
- The drug is extensively distributed into peripheral tissues (Correct answer)
- The drug is 100% protein-bound in plasma
- The drug has poor lipid solubility
Correct answer: The drug is extensively distributed into peripheral tissues
A large Vd (much greater than total body water ~42L) indicates extensive drug distribution into peripheral tissues, often due to high lipid solubility or tissue binding.
Question 4: Ketamine's dissociative anaesthetic properties are primarily mediated through:
- GABA-A receptor potentiation
- NMDA receptor antagonism (Correct answer)
- Sigma opioid receptor agonism
- Alpha-2 adrenoceptor agonism
Correct answer: NMDA receptor antagonism
Ketamine acts primarily as a non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist, blocking glutamate-mediated excitatory neurotransmission.
Question 5: When two drugs are said to have a 'synergistic' interaction, this means:
- Each drug reduces the other's plasma concentration
- The combined effect is greater than the sum of individual effects (Correct answer)
- Both drugs compete for the same receptor
- One drug accelerates hepatic metabolism of the other
Correct answer: The combined effect is greater than the sum of individual effects
Synergism occurs when the combined effect exceeds simple additivity (effect > drug A + drug B alone), as seen with opioids combined with benzodiazepines for sedation.
Question 6: The primary mechanism by which probenecid increases serum urate levels when co-administered with penicillin is:
- Inhibition of renal tubular secretion of penicillin (Correct answer)
- Induction of CYP3A4 increasing penicillin metabolism
- Displacement of penicillin from plasma proteins
- Reduction of penicillin bioavailability
Correct answer: Inhibition of renal tubular secretion of penicillin
Probenecid inhibits the OAT (organic anion transporter) in renal tubules, blocking tubular secretion of penicillin and increasing its serum concentration.
Question 7: In the context of enzyme kinetics, 'Km' (Michaelis constant) represents:
- The maximum rate of enzymatic reaction
- The substrate concentration at which reaction velocity is half maximal (Correct answer)
- The total number of active enzyme molecules
- The equilibrium constant for enzyme-product dissociation
Correct answer: The substrate concentration at which reaction velocity is half maximal
Km is the substrate concentration at which reaction velocity equals half of Vmax; a low Km indicates high enzyme affinity for the substrate.
FACEM Pharmacology Fundamentals 3
The 'ceiling effect' of buprenorphine as an analgesic is best explained by its pharmacology as a: