Mechanism Of Drug Action

Question 1

Describe the different types of drug antagonism

Answer 1

1. Receptor blockade: antagonist binds to receptor and prevents binding of an agonist (use dependency - the more used the tissue the more the drug) Eg LA on wounded area where there is more firing
2. Physiological antagonism - two drugs act at different receptors to have opposite effects in the same tissue Eg NA causes constriction whereas histamine causes dilation (but different receptors)
3. Chemical antagonism - interactions of drugs in solution Eg dimercaprol chelates lead ions in solution
4. Pharmacokinetics antagonism - when one drug reduces the concentration of the other drug at the site of its action through absorption, metabolism and excretion Eg barbiturates (enzyme medication by increasing microbial enzyme )

Question 2

Define drug tolerance and list it’s causes

Answer 2

Drug tolerance is the gradual reduction in responsiveness to drug with repeated administration (Eg benzodiazepam)

1. Pharmacokinetic factors: increased rate of metabolism (alcohol)
2. Loss of receptors: cells takes receptors off via membrane endocytosis, receptor down regulation (beta adrenoreceptors are susceptible to this)
3. Change in receptor: if repeatedly exposed, conformational change will occur, receptor desensitised so a proportion of receptors are no longer effective
4. Exhaustion of mediator supply (eg amphetamine exhausts NA in bbb)
5. Physiological adaptation: homeostatic adaptation to maintain stable internal environment

Question 3

Summarise the type of receptors based on molecular structure and signal transduction systems

Answer 3

1. Ion-channel: fast response > nAchR (excitatory) and GABAa (inhibitory)
2. G-protein: slow response > B1 adrenoreceptors (heart)
3. Kinase linked protein - phosphorylation of intracellular proteins (insulin)
4. Intracellular steroid hormones - activated by steroid and thyroid hormones - regulates DNA transcription. The drug has to pass through cell membrane and access nucleus

Question 4

Describe the structure of the different types of receptors

Answer 4

Ion-channel: 4 or 5 subunits, alpha helixes, external binding domains stimulate ion channel open

G-protein: metabotropic (subunit, 7 transmembrane domain alpah helixes)

Kinasexlinked : single protein, intracellular domain, agonist stimulate

Steroid receptors: found in nucleus, DNA binding domain - zinc fingers