Drug Interactions Flashcards
Pharmacokinetic mechanisms
Absorption-> 2 drugs my interact to alter rate of uptake-> tretracycline and Fe salts or Ca
pH-> passive absorption of many drugs -> separate acid altering drugs from other drugs by several hours
Binding-> colestyramine
GI motility-> changes in motility/ gastric emptying may alter absorption-> motocloperamide accelerates absorption of other drugs
Interaction
Occurs when the effects of one drug are changed by the presence of another drug, food, drink or environmental chemical
-> increase toxicity
-> reduce activity
May be beneficial or adverse
Increased by poly pharmacy
Increased by conditions such as renal impairment
Problem in drugs with narrow therapeutic window
MDR1
Multiple drug resistance transporter
P glycoprotein = MDR1= ATP binding cassette
GI tract and other cells
May be induced eg Rifampicin
May be inhibited eg verapamil
Digoxin is a substrate and induction of MDR1 reduces it’s bioavailability -> digoxin taken up by cells is also pumped out by MDR1-> rate increased by Rifampicin -> decreased bioavailability and vice versa for verapamil
Failure of anti cancer drugs
Displacement
Many drugs protein bound-> only act in free forms
Many drugs compete for binding sits resulting in displacement -> transient rise in toxicity
Counteracted by increase elimination so not important
CYP mediated metabolism
Many drugs metabolised by multiple CYPs
Some only a single CYP-> mostly likely to face competition
-> inhibition of metabolism -> increased toxicity
-> induction of CYP-> increased metabolism -> barbituates, Rifampincin, St. John’s wart
May take a week or two for effect
Effects may persist on stopping inducers
May cause failure of contraception
CYP450 inhibitors
Cimetidine Anti fungal agents Erythromycin, clarithromycin Ciclosporin Psoralen-> increased DHPs and statins Rapid onset-> 1-2 days Often revert quickly on stopping
Renal elimination and interactions
Completion for transporters
Aspirin and methotrexate compete
NSAIDS reduce renal perfusion
Monitor for toxicity
Fluid and electrolyte interactions
Diuretics-> volume depletion when combine with an ACEi -> increased risk of first dose hypertension
-> take them at different times
Diuretics-> loops and thiazides cause hypokalaemia->increased toxicity of digoxin as it effects K/Na ATPase
Pharmacological interactions
Actions oppose or augment
B blockers and rate limiting Ca channel blockers
B blockers slow hr-> decrease force of contraction
Verapamil-> also decrease force of contra ion
-> together could stop heart
Use dihydropyrimadines instead
Warfarin
Narrow therapeutic window and many interactions
-> enzyme inducers lead to failure
-> enzyme inhibitors lead to bleeding
Important interactions with erythromycin and ciprofloxacin-> macrolides
Increased bleeding with aspirin and NSAIDS
Either change antibiotic or monitor very closely
Interactions with foods
Cranberry juice and warfarin-> prevents metabolism of warfarin
Grapefruit juice can inhibit simvostatin metabolism
Alcohol interactions
Labels 2 and 4
Likely to interact with CNS drugs
-> TCAs, sedating antihistamine, benzodiazepines
Metrondiazole
Gastric effects-> avoid aspirin and NSAIDS
Beneficial interactions
L-dopa and carbidopa
Thiazides/loop diuretics and k sparring
Combine anti hypertensives although increased risk of diabetes
Paracetamol and anti emetics
Alarm bells
Warfarin Lithium Digoxin Theophylline Methotrexate P450 inducers/inhibitors Herbals
