Pharmacology: practice questions with explanations

1What pharmacology studies

Pharmacology is the study of how drugs act on the body. A drug is a chemical that changes a body function, such as a painkiller, an antibiotic or a blood pressure tablet.

The subject has two halves that are easy to tell apart:

• Pharmacokinetics is what the body does to the drug: how it is absorbed, spread, broken down and removed.
• Pharmacodynamics is what the drug does to the body: which target it binds to and what effect follows.

Every drug has a generic name (for example paracetamol) and often several brand names. Generic names usually show the drug class in their ending:

• “-olol” (atenolol, propranolol): beta blockers.
• “-pril” (ramipril): ACE inhibitors. “-sartan” (losartan): angiotensin II receptor blockers.
• “-statin” (simvastatin): statins, which lower cholesterol. “-prazole” (omeprazole): proton pump inhibitors, which reduce stomach acid.

2Pharmacokinetics: the journey of a drug

Remember the four stages with ADME:

1. Absorption: the drug enters the blood. An intravenous dose is 100% available. A tablet is often less, because the liver breaks part of it down before it reaches the circulation (first-pass metabolism).
2. Distribution: the drug spreads into the tissues. Many drugs bind to plasma proteins, mainly albumin; only the free drug acts. Fat-soluble drugs cross the blood–brain barrier more easily.
3. Metabolism: mostly in the liver, often by the cytochrome P450 (CYP) enzymes. An enzyme inhibitor raises the level of other drugs; an enzyme inducer lowers it.
4. Excretion: mostly by the kidneys. In kidney failure, drugs cleared by the kidney build up, so the dose is reduced or the interval made longer.

The half-life (t½) is the time for the plasma level to fall by half. Most drugs follow first-order elimination: the same fraction is removed in each half-life.

With regular doses, the level reaches a steady state after about 4–5 half-lives. A loading dose is a larger first dose that reaches the target level faster.

3Pharmacodynamics: receptors and responses

Most drugs act on a receptor, a protein that a natural messenger (such as adrenaline or acetylcholine) normally binds to. Others act on enzymes, ion channels or transporters.

• An agonist binds to the receptor and activates it. Salbutamol is a beta-2 agonist that widens the airways.
• An antagonist binds to the receptor without activating it and blocks the agonist. Naloxone blocks opioid receptors.
• A partial agonist activates the receptor only partly, even when every receptor is occupied.

A competitive antagonist shifts the dose–response curve to the right: more agonist is needed, but the same maximum can be reached. A non-competitive antagonist lowers the maximum response.

Potency is how much drug is needed for an effect. The dose that gives half the maximum effect is the EC50; a lower EC50 means a more potent drug. Efficacy is the maximum effect the drug can produce.

The therapeutic index is the ratio between the toxic dose and the effective dose. Drugs with a narrow index, such as warfarin, digoxin, lithium and gentamicin, need close monitoring.

4How to reason about a drug

You cannot memorise every drug, but you can reason from a few facts. Use these steps:

1. Name the class from the drug name or the question.
2. Recall the target and the mechanism: which receptor, enzyme or channel, and whether it is activated or blocked.
3. Predict the effects from the mechanism. Wanted effects and side effects often come from the same target in different organs.
4. Think about kinetics: which organ clears the drug, which interactions change its level, and which patients (old age, kidney or liver disease) need care.
5. Recall monitoring and reversal. For example vitamin K reverses warfarin, protamine reverses heparin and naloxone reverses opioids.

5A worked example

Reason from the mechanism. Try to predict the next step before you open it.

6Common mistakes

• Mixing up potency (how much drug is needed) and efficacy (how big the maximum effect is).
• Getting enzyme interactions the wrong way round. An inhibitor slows breakdown, so the other drug’s level rises; an inducer makes it fall.
• Thinking a drug is gone after two half-lives. Only 25% is left then; after about 5 half-lives roughly 3% remains.
• Swapping the antidotes: vitamin K for warfarin, protamine for heparin.
• Forgetting first-pass metabolism, which affects drugs taken by mouth but not intravenous ones.
• Treating a competitive antagonist as if it lowered the maximum effect. That is a non-competitive antagonist.

7How exam questions look

• Easy (key terms and facts): definitions and classic facts. What half-life means, what an antagonist is, which drug treats anaphylaxis (adrenaline) or an acute asthma attack (a short-acting beta-2 agonist).
• Medium (applying the concepts): mechanisms and kinetics. How a drug class works, how an interaction changes a level, how kidney failure changes a dose.
• Hard (cases and analysis): a patient case. You recognise a toxicity or a dangerous interaction, explain it from the mechanism, or work out a level from the half-life.

For hard questions, go back to the target. Most adverse effects and interactions follow from the mechanism or from the organ that clears the drug.