Drug-receptor interactions

Question 1

What are the 4 types of drug antagonism?

Explain what each are and give examples.

Answer 1

1. receptor blockade
   competitive and irreversible antagonists
   use-dependency where drugs more readily act on the cells which are more active: eg. LAs on nociceptors
2. physiological antagonism
   drugs interact with different receptors and give opposite response in the same tissue
   eg. NA on vasculature -> vasoconstriction via adrenoceptors
   with histamine -> vasodilation
3. chemical antagonism
   interaction in solution
   eg. dimercaprol: heavy metal poisoning - chelates to form metal complex which is more easily excreted by kidneys
4. pharmacokinetic antagonism
   one drug reducing active drug conc at a site of action
   eg. barbiturates: avoid drug using same micrsomal enzymes in metabolism

Question 2

What is drug tolerance?

Answer 2

gradual decrease in responsiveness to a drug with repeated administration

Question 3

What are the 5 causes of drug tolerance?

Explain.

Answer 3

1. pharmacokinetic factor
   metabolism rate increases
   eg. barbiturates, alcohol
2. receptor down-regulation
   via membrane endocytosis
   eg. beta adrenoceptors
3. change in receptor
   receptor desensitisation -> conformational change -> lower proportion of effective receptors
4. exhaustion of mediator stores
   eg. amphetamine: increase NA production -> exhaust in NA stores
5. physiological adaptation
   homeostatic response
   tolerance develops in side effects

Question 4

Based on what are receptor families grouped?

Answer 4

molecular structure

signal transduction systems

Question 5

What are the 4 receptor families?

Answer 5

type 1. ionotropic receptor
type 2. G protein coupled receptor
type 3. tyrosine kinase-linked type receptor
type 4. intracellular steroid type receptor

Question 6

Give properties of ionotropic receptor and examples.

Answer 6

• fast response (milli secs)
• 4 or 5 subunits
• transmembrane segments
• channel lining - alpha helices
• external binding domain
• eg. nicotinic ACh receptor
  GABAa receptor

Question 7

Give properties of G protein coupled receptor and examples.

Answer 7

• slower response (secs)
• several subunits
• 7 transmembrane segments
• intracellular G protein coupling domain
• eg. beta 1 adrenoceptors
  5 HT receptors

Question 8

Give properties of tyrosine kinase-linked type receptor and examples.

Answer 8

• response in mins
• 1 protein, no subunits
• 1 transmembrane segment
• intracellular catalytic domain: agonist -> catalyst activated -> kinase reaction stimulated -> phosphorylation of intracellular proteins
• eg. insulin/growth factors receptors

Question 9

Give properties of intracellular steroid type receptor and examples.

Answer 9

• activated by steroids/thyroid hormones
• response in hrs
• DNA binding domain = zinc fingers - allows attachment to DNA for transcription