12)Drug interactions

Question 1

Drug interaction

Answer 1

Occurs when the effects of one drug are modified by administration of another drug/same drug

May arise from

• Alteration in absoprtion
• Distribution
• Bio transformation
• Combination of effects

Question 2

Classification of drug-drug interactions - DDI

Answer 2

• Summation ⇢ combined effects = sum of individual effect
• Additive ⇢ combined effects = expected effects of drugs acting by same mechanisms
• Synergism ⇢ combined effects > effect of active component alone eg narcotic analgesics
• Antagonism ⇢ combined effects < effect of active component alone (chemical, competitive, irreversible, non-competetive)

Question 3

Pharmacokinetic DDI

Answer 3

A DDI due to interference w/absorption/distribution/metabolism/excretion ⇢ results in change of drug conc = pharmacokinetic interactions

Include:

• Absorption
• Metabolism
• Excretion + transporter proteins

Question 4

Absorption

Answer 4

• Quinolones should not be administered w/cations at thr same time
• Only separate by at least a 2 hr period

Question 5

Metabolism

Answer 5

• Concentrations of a substrate (eg drug metabolised by cytochrome P450) ⇢ may be affected by inhibitor/inductor
• Drug biotransformation occurs via ⇢ phase I reactions (ox/red/hyd) + phase II reactions (conjugation)
• Resulting metabolite is highly polar + more easily eliminated

Question 6

Excretion + Transporter proteins

Answer 6

Excretion

• DDI during excretion = most prevalent type of interaction
• Reduction of G.F = mechanism of DDI’s for aminoglycosides + digoxin

Drug transporters

• P-glycoportein (PGP) ⇢ ATP dependant drug transporter
• Pumps drugs across through membranes in SI, kidneys, liver, BBB etc
• ⇣ drug absorption, ⇡ drug removal, ⇣ drug entry

Question 7

Pharmacodynamic DDI

Answer 7

May occur due to overlapping pharmacologic effects

Warfarin + NSAID use

• Inhibit platelet function
• Cause development of gastric erosions

May also cause additive or antagonistic effects

NSAIDS

• Hypertensive effect ⇢ ⇣ anti-hypertensive effect of ACEI’s

Nitrates + sildenafil

• Should be avoided due to risk of myocardial infarction + death

ACEI + Diuretics

• Risk of renal failure

Question 8

Minimising risk of DDI

Answer 8

Clinician should use computer software/compendia/other references when making assessment of DDI risk

Knowledge is key for identification + management of DDIs

Practical recommendations:

• Use 1 pharmacy to fill all patient’s prescriptions
• Read all drug labels
• Learn about warning of patient’s meds
• Keep complete record of patients meds