Mechanisms of drug action

Question 1

State the four types of drug antagonism

Answer 1

Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmacokinetic antagonism

Question 2

State what is meant by “use-dependency” of ion-channel blockers

Answer 2

The more active a tissue is, the more effective the blocker acting on that tissue will be (e.g. local anaesthetics acting on rapidly firing nociceptive neurones)

Question 3

What is “physiological antagonism”?

Answer 3

It describes the ability of an agonist to inhibit the response to a second agonist via activation of different receptors that are physically separate. The receptors for the two agonists are linked to the same cellular response components but affect them differently, or are linked to different cellular response components that give rise to opposite tissue responses.

Question 4

What is chemical antagonism?

Answer 4

Interactions of drugs in solution (e.g. dimercaprol is a chelating agent that forms heavy metal complexes which are more easily excreted by the kidneys)

Question 5

What is pharmacokinetic antagonism?

Answer 5

When one drug reduces the concentration of another drug at the site of its action by reducing its absorption, increasing its metabolism, or increasing its excretion (e.g. barbiturates)

Question 6

Define drug tolerance

Answer 6

Gradual decrease in responsiveness to a drug with repeated administration

Question 7

State and briefly describe the five main mechanisms of drug tolerance

Answer 7

Pharmacokinetic factors - increased rate of drug metabolism

Loss of receptors - membrane endocytosis leads to receptor “down-regulation”

Change in receptors - conformational change resulting in desensitisation

Exhaustion of mediator stores

Physiological adaption - homeostatic responses may counteract the therapeutic/side effects of a drug