Pharmacodynamics/kinetics

Question 1

Define pharmacodynamics

Answer 1

Effects of a drug on the body
How and where a drug acts
Side effects

Question 2

Define pharmacokinetics

Answer 2

Effects of the body on a drug:

Absorption
Distribution
Metabolism
Excretion

Question 3

What is bioavailability?

Answer 3

The amount (%) of unchanged drug that reaches the systemic circulation after administration

Question 4

What is first-pass metabolism?

Answer 4

When a substantial proportion of a drug is metabolised in the GIT or liver before reaching the systemic circulation

Question 5

What are the 4 primary first-pass metabolism systems?

Answer 5

Enzymes of the gastrointestinal lumen
Gut wall enzymes
Bacterial enzymes
Hepatic enzymes

Question 6

What is volume of distribution? How is it related to drug concentrations in the body?

Answer 6

Describes the extent of drug distribution in body tissues/dilution of plasma concentrations.

Vd = total amount of drug in body/plasma concentration

Question 7

What clinically relevant value is volume of distribution used to calculate?

Answer 7

Loading dose

Loading dose = Vd x plasma concentration

Question 8

Name the major tissues where drugs may be metabolised

Answer 8

Liver
Kidneys
GIT
Lungs

Question 9

Phase 1 metabolism

Answer 9

Introduces or exposes a functional group on molecule (e.g. oxidation, hydrolysis)
Primes molecules for Phase 2
Some drugs are excreted straight after Phase 1

Question 10

Phase 2 metabolism

Answer 10

Polar conjugate is added to exposed group (commonly glucuronide)
Makes drug polar, hydrophilic, allows for easy excretion in urine

Question 11

Pro-drugs

Answer 11

Inactive compounds that are metabolised to become active drugs
Relatively uncommon

e.g. ACE inhibitors, prednisone

Question 12

First-order elimination

Answer 12

Rate of metabolism increases with plasma concentration of drug
Increased dose = linear increase in drug concentration
Metabolising enzymes aren’t saturated (clinical scenario)

Rate of elimination = clearance x plasma []
[Elimination = excretion +-metabolism]

Question 13

Zero-order elimination

Answer 13

Drugs are metabolised by rapidly-saturable enzyme system (occurs commonly in clinical practice)
Rate of metabolism is independent of drug concentration
Dose increase once enzymes saturated = exponential increase in drug concentrations

Rate of elimination = constant
e.g. Phenytoin, alcohol

Question 14

Apparent clearance

Answer 14

Relates drug concentration to elimination from the body

Clearance = rate of elimination/plasma concentration

Question 15

Enterohepatic circulation

Answer 15

Conjugated drug/metabolite excreted in bile
Bacteria in gut cleave conjugate
Metabolite/drug reabsorbed
Leads to prolonged drug effect

e.g. oral contraceptives, TCAs
[affected by Abx treatment]

Question 16

Kinetics of CYP450 inhibition and induction

Answer 16

Inhibition occurs and wanes rapidly - minutes to hours

Induction occurs and wanes - up to 2-4 weeks

Question 17

Potency vs efficacy vs effectiveness

Answer 17

Potency: Achieving same effect at lower dose/concentration
Efficacy: Ability to reach a certain therapeutic effect
Effectiveness: Efficacy in the practical setting i.e. actual patient, not theoretical therapeutic effect

Question 18

Mechanism of action of aspirin at different doses

Answer 18

Low dose: Irreversibly inhibits COX in platelets –> no Thromboxane A2 –> no platelet aggregation

Higher dose: Inhibits prostacyclin in vascular endothelium –> inhibits vasodilation and inhibits inhibition of platelet aggregation