Drug receptor interactions

Question 1

Types of drug antagonism

Answer 1

Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmacokinetic antagonism

Question 2

Receptor blockade

Answer 2

“Use-dependency” of ion channel blockers (e.g. local anaesthetics) - increase activity of tissue = work more quickly and effectively
Competitive
Irreversible

Question 3

Physiological antagonism

Answer 3

Different receptors —> opposite effects in same tissue

E.g. NA + histamine on BP

Question 4

Chemical antagonism

Answer 4

Interaction in solution

E.g. dimercaprol —> heavy metal complexes (chelating agent) - forms complexes with heavy metal ions, reducing toxicity

Question 5

Pharmacokinetic antagonism

Answer 5

Antagonist —> lower conc of active drug at site of action
Decrease absorption, increase metabolism, increase excretion, e.g. barbiturates (acts as CNS depressant)

NOTE: clinically important interaction

Question 6

Drug tolerance

Answer 6

Gradual decrease in responsiveness to drug with repeated administration (occurs over days/weeks)
E.g. benzodiazepines

Question 7

Drug tolerance: pharmocokinetic factors

Answer 7

Increase rate of metabolism

Barbiturates; alcohol

Question 8

Drug tolerance: loss of receptors

Answer 8

By membrane endocytosis
Receptor “down-regulation”
Beta-adrenoreceptors

NOTE: receptor “up-regulation” (denervation supersentivity)

Question 9

Drug tolerance: change in receptors

Answer 9

Receptor desensitisation => conformational change
nAChR at NMJ
Affinity but no efficacy

Question 10

Drug tolerance: exhaustion of mediator stores

Answer 10

Amphetamine (CNS stimulant) - causes release of NA

Question 11

Drug tolerance: physiological adaption

Answer 11

Homeostatic responses

Tolerance to drug side effects but therapeutic effects remain

Question 12

Receptor families. 4 types are based on…?

Answer 12

Molecular structure

Signal transduction systems

Question 13

4 types of receptor families

Answer 13

Type 1: ion channel-linked receptors
=> fast responses
=> nAChR; GABAA

Type 2: G-protein-coupled receptors
=> slower responses (secs)
=> Beta1- adrenoreceptors (heart)

Type 3: kinase-linked type
=> insulin growth factors (mins)

Type 4: intracellular steroid type receptors
=> steroids/thyroid hormones (hours)
=> regulate DNA transcription

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Question 14

A 4 year old girl is bitten by a Tiger snake whilst holidaying in Australia. An anti-venom(harvested antibodies) is administered. Which form of antagonism is utilised by the anti-venom?

1. Competitive receptor blockade
2. Physiological antagonism
3. Chemical antagonism
4. Pharmacokinetic antagonism
5. Irreversible receptor blockade

Answer 14

3

Question 15

Tolerance to the euphoric effects of drugs of abuse (e.g. heroin and cocaine) can occur after repeated use. Which form of tolerance would not involve any change in the cells that mediate the euphoric effects?

1. Receptor desensitisation
2. Receptor down-regulation
3. Exhaustion of mediator stores
4. Receptor up-regulation
5. Increased metabolic degradation

Answer 15

5