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

What is meant by ‘use dependency’ in terms of receptor blockade?

Answer 2

This refers to ion channel blockers
The more the tissue on which a drug is acting is being used (i.e. the more active they are), the more effective the blocker will be

Question 3

What is physiological antagonism?

Answer 3

When two drugs act on different receptors in the same tissue and have opposite effects

Question 4

What is chemical antagonism?

Answer 4

Interactions of drugs in solution

Question 5

What is pharmacokinetic antagonism?

Answer 5

When one drug reduces the concentration of another drug at the site of its action
A drug may reduce the absorption, increase the metabolism or increase the excretion of the other drug

Question 6

Define drug tolerance.

Answer 6

Gradual decrease in responsiveness to a drug due to repeated administration of the drug

Question 7

What are the five main mechanisms of drug tolerance?

Answer 7

Loss of receptors 
Change in receptors
Pharmacokinetic factors  
Physiological adaptation  
Exhaustion of mediator stores

Question 8

Describe each of these drug tolerance mechanisms briefly.

Answer 8

Loss of receptors – overstimulation can lead to endocytosis of receptors so there are fewer receptors available on the cell membrane
Change in receptors – conformational change in the receptors so that they are desensitized, so a proportion of the receptors are no longer effective
Pharmacokinetic factors – metabolism of the drug is increased after repeated use (e.g. alcohol)
Physiological adaptation – sort of like a homeostatic response to maintain a stable internal environment
Exhaustion of mediator stores – this happens with amphetamines –they get into the central noradrenaline synthesis system and replaces noradrenaline in the vesicles so you get a big increase in the production of noradrenaline

Question 9

What are the four receptor families? Describe how their transmission varies.

Answer 9

Type 1 – ionotropic
Type 2 – metabotropic (G protein coupled)
Type 3 – tyrosine kinase linked
Type 4 – intracellular steroid type
They increase in transmission time from 1-4

Question 10

Describe the structure of type 1 receptors.

Answer 10

Consists of 4 or 5 subunits with transmembrane alpha helices

Question 11

Describe the structure of type 2 receptors.

Answer 11

Consists of 1 subunit but with 7 transmembrane domains

Question 12

Describe the structure of type 3 receptors.

Answer 12

Single protein with 1 transmembrane domain
Inside the cell there is an intracellular domain
When the agonist stimulates the receptor it activates the catalyst

Question 13

Describe the structure of type 4 receptors.

Answer 13

These are steroid receptors that are found in the nucleus

Question 14

What is another name for the DNA binding domain of the steroid-receptor complex?

Answer 14

Zinc fingers

Question 15

Example of chemical antagonism

Answer 15

Dimercaprol is a chelating agent that forms heavy metal complexes that are more easily excreted by the kidneys

Question 16

Use of chemical antagonism

Answer 16

Anti venom

Question 17

Example of physiological antagonism

Answer 17

Noradrenaline will bind to alpha-1 receptors and cause vasoconstriction, histamine will bind to histamine receptors and cause vasodilation

Question 18

Example of receptor blockade

Answer 18

Normal neurons fire at a relatively low rate so if you put local anaesthetic on them there’ll be fairly limited effects. Nociceptor neurons fire rapidly so their iron channels are open more often meaning that the local anaesthetic can get inside the iron channel and block it more easily.

Question 19

Example of each type of receptor

Answer 19

1- nAChR, GABAA
2- mAChR, adrenoceptors
3- insulin, GFR
4- steroid