Mechanisms Of Drug Action & Drug Interactions

Question 1

Outline the major receptor types in Pharmacology.

Answer 1

• Enzymes e.g acetylcholinesterase
• Transport proteins e.g Na,K ATPase
• Structural proteins e.g tubulin

Question 2

Define LD50.

Answer 2

Refers to the dose of a drug required to kill 50% of the the population.

Question 3

Distinguish between TD50 and ED50.

Answer 3

TD50 refers to the dose of drug that causes a toxic response in 50% of the population while ED50 refers to the dose of a drug that is therapeutically effective in 50% of the population.

Question 4

What is Therapeutic Index?

Answer 4

• Refers to the ratio of Lethal dose to effective dose ( LD50/ED50).
• A higher Therapeutic Index means the drug is safe for use since there is a large margin between the lethal dose and the effective dose.

Question 5

What is meant by the term Protective Index?

Answer 5

• Refers to the ratio of a drug that provides protection against side effects or toxicity to the dose that causes toxic effects.
  *PI = TD50/ED50

Question 6

List examples of hormones that act via Tyrosine Kinase receptors.

Answer 6

• Insulin
• Epidermal Growth Factor
• Platelet Derived Growth Factor
• Lymphokines like TGF - alpha

Question 7

List examples of hormones that act via the Cytokine Receptor mechanism.

Answer 7

• Growth Hormone
• Erythropoietin
• Interferons

Question 8

Examples of Drug mediated actions that do not use receptors?

Answer 8

• Neutralization e.g by antacids.
• Osmotic effects e.g mannitol.
• Acidification and alkalinization e.g NaHCO3 and NH4Cl.
• Bulk forming agents e.g laxatives such as MgSO4 used to increase intestinal peristalsis.
• Counterfeit incorporation mechanisms e.g purine and pyrimidine analogues.

Question 9

Give 3 examples of commonly used drugs that have a narrow therapeutic index.

Answer 9

*Digoxin
*Warfarin
– The narrow TI converts the therapeutic doses to toxic doses.

Question 10

List examples of drug interactions that may occur outside the body.

Answer 10

• Loss of drug activity e.g rxn between penicillin and amino glycosides can give rise to inactive complexes.
• Formation of precipitates e.g from rxn between calcium and ceftriaxone in the lungs and kidney.
• Development of toxic products.
  *Rxn between protamine zinc insulin and soluble insulin results in reduced efficacy of soluble insulin .

Question 11

List examples of drugs that can induce their own metabolism.

Answer 11

• Carbamazepine

Question 12

State one major contraindication of Phenytoin.

Answer 12

Contraindicated in women who are on oral contraceptives. This is because Phenytoin increases the metabolism of oral contraceptives leading to reduced levels in plasma and failed contraception.

Question 13

List 4 examples of important enzyme inducers.

Answer 13

• Carbamazepine
• Phenytoin
• Phenobarbital
• Rifampicin

Question 14

List 4 examples of important enzyme inhibitors.

Answer 14

• Cimetidine - reduces clearance of Theophylline.
• Erythromycin
• Quinolones - inhibit oxidative metabolism of Theophylline.
• Sodium valproate- displaces phenytoin from its binding sites on plasma albumin.

Question 15

List examples of drugs that cause altered renal clearance of other drugs.

Answer 15

• Hydralazine increases the renal clearance of Digoxin.
• Probenecid decreases tubular secretion of Penicillins.
• Sodium bicarbonate decreases reabsorption and increases excretion of salicylates.