Drug Interactions Flashcards
drug interaction
-
one drug alters effect of another
- not a side effect, an adverse reaction or a toxic effect
- incidence is proportional to number of drugs administered
- individual and species differences
- predictable or unpredictable
possible consequences of drug interactions
- none
- altered therapeutic efficacy
- altered duration of action
- altered intensity of side effects
- novel effects
categories of drug interactions
- incompatibilities
- pharmacokinetic interactions
- pharmacodynamic interactions
drug incompatibilities
-
physical
- separation
-
chemical
- precipitation
- chelation
- binding
consequences of incompatibilities
- damage from toxic compounds
- particulate emboli
- tissue irritation (pH changes)
- therapeutic failure
sulcralfate
- coats stomach and binds to compounds
- binds to tetracycline, fluorquinolones, cimetidine, phenytoin, phenobarbital, griseofulvin
pharmacokinetic interactions
- occurs when one drug alters another via change in:
- absorption
- distribution
- metabolism
- elimination
- most common type of drug interaction
omeprazole and ketoconazole interactions
- omeprazole increases gastric pH and decreases absorption of ketoconazole by 50%
- ketoconazole likes acidic pH
effects of gastric pH change on absorption
- antacids (increased pH) will decrease absorption of weak acids and increase absorption of weak bases
- infections (decreased pH) will increase absorption of weak acids and decrease absorption of weak bases
metoclopramide and digoxin
- metoclopramide increases gastric emptying (prokinetic) and decreases absorption of digoxin
protein binding (distribution)
- some drugs are protein bound with varying affinities
- bound <–> unbound (active)
- competition arises when two highly protein bound drugs are simultaneously administered
- erythromycin, doxycycline, NSAIDs, amphoteracin B, furosemides
pharmacokinetic interaction: metabolism
- metabolism or biotransformation
- intestines -> portal circulation -> liver -> modified
- oxidation, reduction, hydrolysis, inactivated
- most become water soluble
- tolerance: increase activity of microsomal enzymes to speed metabolism of drug
- inducers, inhibitors, metabolites
inducers
- decrease duration/potency of others
- phenobarbital, rifampin
inhibitors
- increase duration/potency of others (slow metabolism)
- cimetidine, chloramphenicol, ketoconazole
drugs with active metabolites
- diazepam, ketamine, morphine
pharmacokinetic interaction: elimination
-
renal
- competition for same renal tubular transport system
- alter urinary pH (ion trapping)
- alter renal BF
-
biliary
-
enterohepatic recirculation
- altered by abx
-
enterohepatic recirculation
- respiratory
drugs that compete for renal excretion
-
acidic drugs
- penicillins, cephalosporins, sulfonamides, furosemide, NSAIDs
-
basic drugs
- procainamide, dopamine, trimethoprim, opioids
pharmacodynamic interaction
- act on same receptor (pharmacological)
- act on different receptors that regulate a common process (physiological)
- elicit effects that are not receptor-mediated but have final common pathway
- synergistic vs antagonistic
synergistic pharmacodynamic drug interactions
- CNS depressants
- autonomic drugs
- ß-blockers and Ca2+ blockers (decrease HR)
- NSAIDs + steroids (ulcers)
- aminoglycosides + amphotericin B (kidneys)
antagonistic pharmacodynamic drug interactions
- alcohol + caffeine
- anticoagulants + phytonadione
- furosemide + digoxin
drug interactions and electrolyte changes
- diuretics w/ digitalis, antiarrhythmics, or muscle relaxants (decrease K)
- hypokalemia: increased digitalis binding to Na/K ATPase (toxicity)
- hyperkalemia: decreased digitalis binding to Na/K ATPase (decreased efficacy)
digoxin drug interactions
- quinidine competes and decreases renal clearance
- diuretics: hypokalemia increases affinity to bind to Na/K ATPase
- hypercalcemia enhances digitalis-induced increased IC calcium
- hypomagnesemia (arrhythmia)
- decreased absorption when given with metoclopramide
preventing drug interactions
- avoid polypharmacy
- assess and plan tx regimen
- compatibility assessment
- color code IV lines
- multilumen catheters
- in-line filters
levetiracetam drug interactions
anti-convulsant
dose needs to be increased if given with P450 inducer like phenobarb
phenobarbital drug interactions
- P450 inducer
- may need to increase dose of other drugs because increased clearance
cimetidine drug interactions
- P450 inhibitor
- decreases metabolism of other drugs and can lead to toxicity (metronidazole)
chloramphenicol drug interactions
- P450 inhibitor
- increases metabolism of other drugs, may lead to toxicity
ketoconazole drug interactions
- P450 inhibitor
- decreases metabolism of other drugs, can lead to toxicity
- can be used to an advantage to reduce dose of other drugs (cyclosporine)
- decreased absorption when administered with omeprazole
diazepam drug interactions
- active metabolites
- preciptiation with ketamine
potassium bromide drug interactions
affected by chloride intake (too much salt water)
