Mechanisms of Drug Action

Question 1

Name 4 types of receptor antagonsim

Answer 1

1. Receptor Blockade
2. Physiological antagonism
3. Chemical antagonism
4. Pharmacokinetic antagonsim

Question 2

receptor blockade

Answer 2

See ‘PT1’ lecture
-> competitive
-> irreversible
[“Use-dependency” of ion channel blockers
e.g. Local anaesthetics]

Question 3

Physiological Antagonism

Answer 3

Different receptors -> opposite effects in same tissue

e.g. NA + histamine on B.P.

Question 4

Chemical Antagonism

Answer 4

Interaction in solution

Example : dimercaprol  heavy metal complexes (chelating agent)

Question 5

Pharmacokinetic antagonism

Answer 5

Antagonist decreases concentration of active drug at site of action
decreased absorption
increased metabolism
increased excretion

e. g. barbiturates
- >Clinically important interaction

Question 6

Drug Tolerance

Answer 6

Gradual decrease in responsiveness to drug with repeated admin. (days/weeks)

e.g. benzodiazepines

Question 7

What are the factors that cause drug tolerance?

Answer 7

1. Pharmacokinetic factors
2. loss of receptors
3. Change in receptors
4. Exhaustion of mediator stores
5. Physiological adaption

Question 8

Drug tolerance - pharmacokinetic factors

Answer 8

increased rate of metabolism

barbiturates; alcohol

Question 9

Drug tolerance - loss of receptors

Answer 9

By membrane endocytosis
Receptor “down-regulation”
beta-adrenoceptors

Note also: receptor “up-regulation”
(denervation supersensitivity)

Question 10

Drug tolerance - change in receptors

Answer 10

Receptor desensitization
 conformational change

nAChR at NMJ

Question 11

Drug tolerance - Exhaustion im mediator stores

Answer 11

Amphetamine

Question 12

Drug tolerance - physiological adaption

Answer 12

Homeostatic responses

Tolerance to drug side effects

Question 13

Receptors. List the four main families of receptors.

Answer 13

1. Ion Channel linked Receptors
2. GCPR
3. Tyrosine linked receptors
4. Intracellular steroid type receptors

Question 14

What distinguishes receptor types?

Answer 14

• Molecular structure

- Signal transduction systems

Question 15

Ion channel-linked receptors

Answer 15

• Fast responses (m secs)

- nAChR; GABAA

Question 16

GPCR

Answer 16

• Slower responses (secs)

- beta1-adrenoceptors (heart)

Question 17

Kinase linked receptors

Answer 17

• insulin/growth factors (mins)

Question 18

Intracellular Steroid receptors

Answer 18

• steroids/thyroid hormones (hrs)

- regulate DNA transcription