08 - Drug Interactions

Question 0

27) Example of rare exceptions where two drugs chemically interact

Answer 0

thiopental + suxamethonium -> precipitation

Question 1

26) The definition of drug interactions

Answer 1

Change in magnitude or duration of pharmacological response to a drug due to presence of a second drug

Question 2

28) Pharmacodynamic considerations of a drug.

Answer 2

If drug’s therapeutic index is narrow:

- small reduction in drug's effect -> loss of efficacy
- small increase in drug's effect -> toxicity

Question 3

29) Pharmacokinetic considerations of a drug

Answer 3

If concentration-response for drug is steep:

- Small change in plasma conc. -> big change in effect

Question 4

30) Examples of risky drugs (serious consequences when drug effects change suddenly):

Answer 4

1. Anti-thrombotics
2. Anti-dysrhythmic
3. Anti-viral
4. Anti-epileptic

Question 5

31) How can drug interactions affect absorption process:

Answer 5

1. Gastrointestinal absorption:
   
   • Slowed by drugs inhibiting gastric emptying (opiates)
   • Accelerated by drugs hasten gastric emptying (metaclopramide)
2. Complex formation in GI tract:
   
   • Ca2+ and Fe2+ form insoluble complexes with tetracycline
   • Colestyramine binds warfarin and digoxin
3. Drug ioinisation:
   
   • Alkalinisation (sodium bicarbonate) or acidification (vit C) of
     urine increase excretion of certain drugs

Question 6

32) How can drug interactions affect distribution process?

Answer 6

1. Displacement of drug from plasma-binding protein:

- Administration of two drugs with high binding to plasma proteins -> increased free drug levels for both

Question 7

33) Example of drug interactions that affect distribution

Answer 7

Phenylbutazone displaces warfarin from albumin and inhibits warfarin metabolism -> increased prothrombin (coagulation) time and risk of bleeding

Question 8

34) How can drug interaction affect phase 1 metabolism process?

Answer 8

1. Enzyme induction:
   
   • Increase in enzyme activity caused by a foreign compound
   • Accelerated clearance, reduced action, increased formation of toxic metabolites
   • net effect is decreased pharmacological activity
   • Needs repeated/prolonged exposure
2. Enzyme inhibition:
   
   • Decrease in enzyme activity caused by a foreign compound
   • Needs only a single dose
   • Impaired clearance, prolonged action
3. Haemodynamic effects:
   
   • Reduced hepatic blood flow -> reduced metabolism

Question 9

35) Drugs whose metabolism is enhanced by Barbiturates (inducer)

Answer 9

1. Barbiturates
2. Estradiol
3. Phenytoin
4. Quinine

Question 10

36) Drugs whose metabolism is enhanced by Phenytoin

Answer 10

1. Dexamethasone
2. Digitoxin
3. Theophyline

Question 11

37) Drugs whose metabolism is enhanced by Rifampicin

Answer 11

1. Anticoagulants (warfarin)

2. Oral contraceptives

Question 12

38) Example of drugs whose metabolism is inhibited by Cimetidine

Answer 12

1. Diazepam

2. Warfarin

Question 13

39) Example of drugs whose metabolism is inhibited by Disulfiram

Answer 13

1. Antipyrine
2. Ethanol
3. Phenytoin
4. Warfarin

Question 14

40) Example of drug whose metabolism is inhibited by Ethanol

Answer 14

Methanol

Question 15

41) Grapefruit juice (inhibits a form of cytochrome P450) should not be taken in combination with..

Answer 15

1. Ca2+ channel blockers (nifedipine)

2. Cyclosporin

Question 16

42) Example of a non CYP enzyme inhibition:

Answer 16

Allopurinol inhibit Xanthine Oxidase activity which increase immunosuppressant side effects of mercaptopurine

Question 17

43) Example of drugs that have haemodynamic effects

Answer 17

1. Lidocaine

2. Propanolol (reduce cardiac output)

Question 18

44) What is the main mechanism of drug interaction to alter renal excretion of drugs?

Answer 18

1. Alter protein binding, hence filtration
2. Inhibit tubular secretion
   
   • eg. probenecid inhibits penicillin secretion
3. Alter urine flow and/or urine pH

Question 19

45) What is the definition of “contraindication”

Answer 19

A factor that renders the administration of a drug or the carrying out of a medical procedure inadvisable