Pharmacokinetics, receptors & pharmacogenetics — MRCP Part 1 flashcards

Question 1

Phase 1 drug metabolism (oxidation, reduction, hydrolysis) is mainly done by ______ enzymes; phase 2 metabolism is conjugation (e.g. glucuronidation, acetylation, methylation).

Accepted Answer

cytochrome P450 — Phase 1 makes a drug more polar (and sometimes active or toxic). Phase 2 adds a polar group, usually inactivating it so it can be excreted in bile or urine.

Question 2

Phase 1 drug metabolism (oxidation, reduction, hydrolysis) is mainly done by cytochrome P450 enzymes; phase 2 metabolism is ______ (e.g. glucuronidation, acetylation, methylation).

Accepted Answer

conjugation — Phase 1 makes a drug more polar (and sometimes active or toxic). Phase 2 adds a polar group, usually inactivating it so it can be excreted in bile or urine.

Question 3

In zero-order elimination, what happens to the half-life as plasma concentration rises?

Accepted Answer

It is not constant: it lengthens, because a fixed amount (not a fixed fraction) is removed per unit time once the enzymes are saturated. — In first-order kinetics a constant fraction is removed, so half-life is constant. Zero-order kinetics means the elimination pathway is saturated.

Question 4

Apart from phenytoin and ethanol, name two drugs that show zero-order (saturable) kinetics at high doses.

Accepted Answer

High-dose aspirin (salicylates) and theophylline (tolbutamide is also classically listed). — These drugs saturate their metabolising enzymes at higher concentrations, so elimination becomes a fixed amount per hour.

Question 5

Which hepatic enzyme is deficient in 'slow acetylators'?

Accepted Answer

N-acetyltransferase (NAT2). — Slow acetylators clear acetylated drugs more slowly, so levels rise and dose-related toxicity is more likely.

Question 6

Name three drugs whose toxicity is increased in slow acetylators.

Accepted Answer

Any three: sulphonamides, hydralazine, isoniazid, procainamide, dapsone. — All are cleared by acetylation, so slow acetylators accumulate them (e.g. isoniazid neuropathy, hydralazine/procainamide lupus).

Question 7

A 45-year-old man on standard quadruple therapy for pulmonary TB develops numbness and burning in both feet. He is known to be a slow acetylator. Which vitamin should have been co-prescribed to prevent this?

Accepted Answer

Pyridoxine (vitamin B6). — Isoniazid causes pyridoxine deficiency and a peripheral neuropathy; slow acetylators have higher isoniazid levels and greater risk.

Question 8

Name three drugs with extensive first-pass hepatic metabolism.

Accepted Answer

Any three: glyceryl trinitrate, isosorbide dinitrate, lidocaine, propranolol, verapamil, aspirin, hydrocortisone, testosterone. — After oral absorption, the portal circulation takes these drugs to the liver, which removes much of the dose before it reaches the systemic circulation.

Question 9

The maximum response a drug can produce once bound to its receptor is its ______ (Emax); the concentration needed to produce an effect is its potency (EC50).

Accepted Answer

efficacy — A drug can be very potent (works at low concentration) but have low efficacy (small maximal effect), and vice versa.

Question 10

The maximum response a drug can produce once bound to its receptor is its efficacy (Emax); the concentration needed to produce an effect is its ______ (EC50).

Accepted Answer

potency — A drug can be very potent (works at low concentration) but have low efficacy (small maximal effect), and vice versa.

Question 11

What is the therapeutic index of a drug?

Accepted Answer

The ratio of the dose that causes toxicity (undesired effect) to the dose that produces the desired effect. — A narrow therapeutic index (e.g. gentamicin, lithium, digoxin) means toxic and therapeutic doses are close, so levels are monitored.

Question 12

Through which type of receptor do insulin and IGF-1 act?

Accepted Answer

Receptor tyrosine kinase (enzyme-linked receptor). — Ligand binding activates the receptor's own intracellular tyrosine kinase domain, which phosphorylates downstream signalling proteins.

Question 13

Which signalling pathway do the receptors for GH, prolactin, EPO, G-CSF and IL-2/IL-6 use?

Accepted Answer

Cytokine receptors without intrinsic kinase activity that signal via associated JAK kinases (JAK–STAT pathway). — These receptors have no kinase domain of their own; they recruit Janus kinases, which phosphorylate STAT transcription factors.

Question 14

Which second messenger mediates the effects of ANP and BNP?

Accepted Answer

cGMP, generated by membrane guanylate cyclase. — Natriuretic peptide receptors are guanylate cyclases; raised cGMP causes vasodilatation and natriuresis.

Question 15

Where are the receptors for glucocorticoids and thyroid hormone located?

Accepted Answer

Inside the cell (intracellular/nuclear receptors) — they bind DNA and regulate gene transcription. — These lipid-soluble hormones cross the cell membrane, so their effects take hours to days (new protein synthesis).

Question 16

Which HLA allele should be tested for before starting carbamazepine in patients of Han Chinese or Thai origin?

Accepted Answer

HLA-B*15:02. — Carriers have a much higher risk of carbamazepine-induced Stevens–Johnson syndrome / toxic epidermal necrolysis.

Question 17

Deficiency of which enzyme causes severe, sometimes fatal, toxicity with fluorouracil or capecitabine, so it is tested before treatment?

Accepted Answer

Dihydropyrimidine dehydrogenase (DPD). — DPD breaks down fluoropyrimidines; patients with low activity accumulate the drug and develop severe mucositis, diarrhoea and myelosuppression.

Question 18

For a drug with first-order kinetics given at a regular dose, after about how many half-lives is steady state reached?

Accepted Answer

About 4–5 half-lives. — Each half-life closes half of the remaining gap to steady state (50%, 75%, 87.5%, 94%, 97%). The same 4–5 half-lives are needed to clear a drug after it is stopped.

Question 19

Which pharmacokinetic parameter mainly determines the size of a loading dose?

Accepted Answer

The volume of distribution (loading dose = target plasma concentration × Vd ÷ bioavailability). — The loading dose has to fill the whole volume the drug distributes into. The maintenance dose depends on clearance (rate of elimination), not Vd.

Pharmacokinetics, receptors & pharmacogenetics flashcards

More Clinical Pharmacology & Toxicology topics