Session 2

Question 1

What is the difference between an agonist and an antagonist?

Answer 1

Agonists = when it binds to receptor, it stabilises it in the active conformation. 
Antagonist = when bound to receptor, it stabilises it in the inactive conformation.

Question 2

What is the difference between affinity and efficacy?

Answer 2

Affinity = the tendency of the drug to bind to a specific receptor type. 
Efficacy = the maximal effect of a drug when bound to a receptor. Expressed in percentage terms of the response, when no increase in drug concentration brings about any further increase. Antagonists have zero efficacy.

Question 3

What is potency?

Answer 3

Agonist potency = the drug conc. at which 50% of the maximal response is obtained. EC50.
Antagonist potency = the conc. of the drug that reduces maximal activation of a receptor by 50%.

Question 4

What is the drug therapeutic window?

Answer 4

The concentration range at which the drug exerts a clinically useful effect, but without exerting significant toxic effects.

Question 5

Give examples of drugs that have narrow therapeutic windows.

Answer 5

Warfarin, aminophylline, digoxin and aminoglycosides.

Question 6

How do you calculate the therapeutic window?

Answer 6

Lethal dose to 50% of people / effective dose to 50% of people.

Question 7

What are the main mechanisms affecting drug excretion?

Answer 7

Changes in protein binding, inhibition of tubular secretion and changes in urine flow/pH.

Question 8

What results following induction and inhibition of the CYP450 system?

Answer 8

Induction: faster elimination (shorter half-life and increased clearance). Dosing may then have to be increased.
Inhibition: Increased half life and reduced clearance, hence causes adverse drug reactions.

Question 9

Why can a falling cardiac output affect drug clearance?

Answer 9

Reduces organ perfusion, resulting in both reduced hepatic blood flow and renal blood flow, hence reducing clearance of the drug.

Question 10

What are the two types of adverse drug reactions?

Answer 10

On target ADRs: exaggerated therapeutic effect of the drug. Often consist of effect on the same receptor, but in different tissues. E.g. drugs for hypertension resulting in hypotension.
Off target ADRs: interactions with other receptor types secondarily to the one intended for therapeutic effect.

Question 11

When are drug interactions most likely to occur?

Answer 11

Hospital patients on a cocktail of six or more drugs, taking the overall chance of an ADR to 80%.

Question 12

Name factors that affect bioavailability.

Answer 12

Drug formulation, age, food, vomiting, malabsorption, first pass metabolism.

Question 13

Give three sites that first-pass metabolism can take place.

Answer 13

The gut lumen - gastric acid, proteolytic enzymes etc.
The gut wall - p-glycoprotein efflux pumps drugs out back into the lumen.
The liver - enzyme metabolism.

Question 14

What is pharmacogenetics?

Answer 14

The effect of genetic variations on pharmacokinetics/dynamics.

Question 15

Why three criteria are important when assessing changes in drug distribution due to protein binding?

Answer 15

1) High protein binding
2) Low volume of distribution
3) Drug has a narrow therapeutic ratio

Question 16

Give four factors that affect protein binding.

Answer 16

1) Hypoalbuminaemia
2) Pregnancy
3) Renal failure
4) Displacement by other drugs

Question 17

Describe the two ways that a non-competitive antagonist can bind.

Answer 17

1) At the same site for the agonist binding irreversible or unbinding very slowly
2) At a separate site to the agonist either reversibly or irreversibly.

Question 18

Give five classes of drugs in which drug-drug interactions commonly arise

Answer 18

Anticonvulsants
Anticoagulants
Antidepressants
Antibiotics
Antiarrhythmics

Question 19

Give four groups of people that are prone to adverse drug effects

Answer 19

Pregnant women
Breast-feeding women
Elderly
Patients with genetic enzyme defects (e.g. glucose-6-phosphate dehydrogenase deficiency).