Pharmacokinetics

Question 1

Most drugs exhibit ‘first-order’ elimination kinetics. What does this mean?

Answer 1

the rate of drug elimination is proportional to drug concentration

i.e. more drug ingested = more drug excreted

Question 2

Explain ‘zero-order’ kinetics

Answer 2

rate of excretion is constant despite changes in plasma concentration (graph plateaus)

Question 3

Give examples of drugs which exhibit zero-order elimination kinetics

Answer 3

phenytoin
salicylates (e.g. aspirin)
Ethanol

Question 4

Drug metabolism usually involves phase I and phase II reactions. Describe what happens in each

Answer 4

Phase I reactions:
- oxidation, reduction, hydrolysis
- usually P450 enzymes (some exceptions)

Phase II reactions:
- conjugation
- Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

Question 5

Where do most Phase I + II metabolism reactions take place?

Answer 5

Liver

Question 6

Are products of Phase I or Phase II metabolic reactions usually active and potentially toxic?

Answer 6

Phase I

In Phase II the products are often inactive and excreted in urine/bile

Question 7

What is meant by First Pass Metabolism?

Answer 7

concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism

=> larger oral doses needed than if given by other routes

*due to saturation of the metabolic process

Question 8

Give examples of drugs which exhibit first pass metabolism.

Answer 8

aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone

Question 9

Describe zero-order kinetics

Answer 9

Metabolism not proportional to concentration of drug. I.e. graph plateaus once metabolic process to eliminate that drug is saturated

Therefore constant amount of drug eliminated per unit time

Question 10

Give examples of drugs which exhibit “zero-order” kinetics

Answer 10

phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol