2 - mechanisms of drug action

Question 1

define ‘drug’

Answer 1

a chemical substance that interacts with a biological system to produce a physiological effect

Question 2

State the four types of drug antagonism.

Answer 2

Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmacokinetic antagonism

Question 3

What is receptor blockade? (type 1 drug antagonism)

Answer 3

antagonist binding to receptor and preventing binding of agonist

Question 4

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

Answer 4

(refers to ion channel blockers)
The more the tissue/cell on which a drug is acting is being used (i.e. the more active they are), the more effective the blocker will be
(binding sites are inside the ion channel -so the more it is open/active, the more drug can bind)

Question 5

Give an example of receptor blockade

Answer 5

local anaesthetics

Question 6

What is physiological antagonism? (type 2 drug antagonism)

Answer 6

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

Question 7

Give an example of physiological antagonism

Answer 7

NA (vasoconstriction of vasculature) and histamine (vasodilation)

Question 8

What is chemical antagonism? (type 3 drug antagonism)

Answer 8

Interactions of drugs in solution

Question 9

Give an example of chemical antagonism

Answer 9

dimercaprol (chelating agent) forms heavy metal complexes, which are more rapidly excreted by the kidneys

Question 10

What is pharmacokinetic antagonism? (type 4 drug antagonism)

Answer 10

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 11

Give an example of pharmacokinetic antagonism

Answer 11

repeated administration of barbiturates increases production of microsomal enzymes. Drugs metabolised by these enzymes will be metabolised faster and will exert less of an effect

Question 12

Define drug tolerance.

Answer 12

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

Question 13

What are the five main mechanisms of drug tolerance?

Answer 13

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

Question 14

Describe the mechanism of pharmacokinetic factors on drug tolerance
Give an example

Answer 14

metabolism of the drug is increased after repeated use

e.g. alcohol and barbiturates

Question 15

Describe the mechanism of loss of receptors on drug tolerance
Give an example of receptors what are susceptible to this

Answer 15

overstimulation can lead to endocytosis of receptors so there are fewer receptors available on the cell membrane
(receptor down regulation`0
e.g. beta adrenoreceptors

Question 16

Describe the mechanism of change of receptors on drug tolerance

Answer 16

conformational change in the receptors so that they are desensitized, so a proportion of the receptors are no longer effective

Question 17

Describe the mechanism of exhaustion of mediator stores on drug tolerance using an example

Answer 17

(happens with amphetamines)
amphetamines 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 18

Describe the mechanism of physiological adaptation of receptors on drug tolerance

Answer 18

like a homeostatic response to maintain a stable internal environment

Question 19

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

Answer 19

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 20

Give an example of each type of the 4 receptor families

Answer 20

Type 1 – nicotinic AChr and GABA-A
Type 2 – (beta-1) adrenoreceptors in the heart
Type 3 – insulin receptor and growth factor receptors
Type 4 –steroid/thyroid hormone receptors

Question 21

Describe the structure of type 1 receptors.

Answer 21

Consists of 4 or 5 subunits with transmembrane alpha helices

Question 22

Describe the structure of type 2 receptors.

Answer 22

Consists of 1 big subunit but with 7 transmembrane domains

Question 23

Describe the structure of type 3 receptors.

Answer 23

Single protein with 1 transmembrane domain and an intracellular domain
When the agonist stimulates the receptor it activates the catalyst

Question 24

Describe the structure of type 4 receptors.

Answer 24

These are steroid receptors that are found in the nucleus

Question 25

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

Answer 25

Zinc fingers