Drug Interactions

Question 1

what are the two types of drug interactions?

Answer 1

Pharmacodynamic

and

Pharmacokinetic

Question 2

what is a pharmacodynamic interaction?

Answer 2

modification of the pharmacological effect of a drug without altering its concentraiton

examples)

• paracetamol and NSAIDS - improved analgesia
• Vasodilators and Beta Blockers- improved BP control
• Warfarin and Aspirin - bleeding

Question 3

what is the definition of pharmacokinetic Drug interactions?

Answer 3

modification of the pharmacological effect of a drug through alteration in its concentration either by

1) absorption
2) distribution
3) metabolism
4) excretion

Question 4

describe the ‘absorption’ pharmacokinetic interaction

Answer 4

GI absorption can be slowed or accelerated by drugs which alter gastric emptying -

example- if you take one drug, then take a laxative, it reduces your absorption of the drug you’ve just taken per oral

Question 5

Describe ‘distribution’ pharmacokinetic interactions

Answer 5

distribution/protein binding - displacement of a drug from binding sites in plasma increases concentration of free drug available

ex) NSAIDs displaces Warfarin from albumin binding and increased bleeding can result

Question 6

why does St. John’s Wort effect oral contreceptives?

Answer 6

Interaction of St. John’s Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.

Question 8

what sorts of drugs competitively inhibit cytochrome P450 activity?

Answer 8

Erythromycin

Ketoconazole

and Grapefruit juice

therefore they result in inhibition of metabolism of some other antibiotics etc.

Question 10

grapefruit’s effects on cytochrome P450 is an example of pharmacokinetic interactions or pharmacodynamic interactions?

Answer 10

pharmacokinetic interactions

Question 11

what sort of things are Cytochrome P450 enzyme inducers?

Answer 11

phenytoin, carbamazepine, rifampicin, barbiturates, alcohol and St.John’s Wort

• therefore they increase the metabolism of many drugs and reduce the plamsa concentrations as a result -

Question 12

how might an cytochrome P450 inhibitor actually result in ‘loss’ of activity of a drug?

Answer 12

Some drugs awork through an active metabolite of the initial compound - therefore when they are not metabolised, they are not made active - therefore a reduction in metabolism by P450 would result in less active drug present

Question 13

Describe ‘exrection/clearance’ pharmacokinetic interactions

Answer 13

altering urine flow and GFR can lead to more excretion or less excretion of a drug

ex) NSAIDS reduce renal blood flow and reduce lithium carbonate clearance (toxicity potential)

Question 14

who is most at risk of experiencing negative drug interactions?

Answer 14

• The elderly - little physiological reserve, altered pharmacokinetics
• severely ill patients - renal or liver disease leading to altered pharmacokinetics, difficulties in distinguishing a drug interaction from disease
• patients who take over the counter medicaiton such as st. john’s wort, alcohol or aspirin

Question 15

what is the difference between type A and type B adverse effects?

Answer 15

Type A= predictable = like bleeding from warfarin

Type B= bizarre effects like hypersensitivity reactions, teratogenicity, skin reactions etc. from Warfarin

Question 16

what are some contraindications for Warfarin?

Answer 16

• Liver disease - reduced synthesis of clotting factors
• poor diet - vitamin K deficiency - likely to bleed
• Cytochrome P450 polymorphism
• women of childbearing years - consider the risk of teratogenicity

Question 17

What is more suitable to prescribe to a man who is on warfarin and develops oral thrush? Miconazole or Nystatin? Why?

Answer 17

Give Nyststin

Systemic miconazole can potentiate the anticoagulant effect of warfarin, because it is a strong inhibitor of the P450 isoenzyme CYP2C9, one of the main enzymes involved in warfarin metabolism.1

Clinically significant increases in INR can occur when miconazole oral gel is given to patients taking warfarin because miconazole can be absorbed through the oral mucosa, or from the bowel after the gel has been swallowed.