Unit 5.2: Pharmacokinetics and Pharmacodynamics

• Topic 01

  Absorption, Distribution, Metabolism, Excretion (ADME)

  45 questions
• Topic 02

  Drug Receptor Theory

  45 questions
• Topic 03

  Therapeutic Index, Half-Life, and Steady State

  45 questions
• Topic 04

  Factors Affecting Drug Response

  45 questions

A few questions from this unit, with the answer and a full explanation. The complete bank is available when you start practising.

1. What is a receptor in pharmacological terms?

   • A
     A site on the kidney tubule where drugs are excreted into urine
   • B
     A channel in the cell membrane that allows drugs to enter cells passively
   • C
     A macromolecule, usually a protein, that specifically binds a chemical messenger or drug and transduces a biological response
     Correct answer
   • D
     An enzyme in the liver that metabolises drugs to active or inactive compounds
   Explanation

   In pharmacology, a receptor is a macromolecule (most commonly a protein) located on cell membranes, within cells, or in the nucleus.

   It recognises and binds specific chemical messengers (endogenous ligands such as neurotransmitters or hormones, or exogenous drugs) with high selectivity, and transduces this binding event into a biological response via a signalling cascade.

   Receptors are distinct from transport proteins, enzymes, and ion channels, although the latter can themselves act as receptors when they are the direct targets of drug action.

2. A patient is given an oral tablet that contains 500 mg of a drug. Only 150 mg reaches the systemic circulation unchanged. What is the bioavailability of this drug?

   • A
     50%
   • B
     30%
     Correct answer
   • C
     15%
   • D
     100%
   Explanation

   Bioavailability is calculated as (amount reaching systemic circulation / dose administered) × 100. Here, 150 mg / 500 mg × 100 = 30%. The remaining 70% was lost to incomplete absorption and/or first-pass hepatic metabolism before reaching the systemic circulation. A common error is to confuse the proportion absorbed with the proportion lost.

3. A student asks why phenoxybenzamine (an irreversible alpha-adrenoceptor blocker used before phaeochromocytoma surgery) produces a different dose-response curve pattern than a reversible alpha-blocker like phentolamine. Which explanation MOST accurately describes the difference?

   • A
     Phenoxybenzamine covalently and irreversibly binds to alpha-adrenoceptors, permanently inactivating each bound receptor; the maximum pressor response to adrenaline is reduced and cannot be restored by increasing the adrenaline dose — a non-competitive pattern
     Correct answer
   • B
     Phenoxybenzamine binds the same site as adrenaline but with higher affinity, producing competitive antagonism that requires very high adrenaline doses to overcome
   • C
     Both drugs produce identical dose-response shifts; the difference is only in duration, not the shape of the curve
   • D
     Phenoxybenzamine acts at a different receptor type from adrenaline, so it cannot shift the adrenaline dose-response curve at all
   Explanation

   Phenoxybenzamine is an irreversible (covalent) alkylating agent that permanently inactivates alpha-adrenoceptors it binds. Once a receptor is bound by phenoxybenzamine, it cannot respond to adrenaline regardless of agonist concentration.

   This is non-competitive antagonism: the number of functional alpha-receptors is progressively reduced, lowering Emax. No amount of added agonist can restore the response because the inactivated receptors are permanently lost until new receptors are synthesised.

   In contrast, phentolamine is a reversible competitive alpha-antagonist: it competes for the same orthosteric site, shifts the dose-response curve rightward (higher EC50), but allows the same Emax if enough adrenaline is given.

   In phaeochromocytoma surgery, phenoxybenzamine's irreversible blockade provides reliable, non-overridable alpha-blockade to control hypertensive crises from catecholamine surges during tumour manipulation.