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NURS 572A-6
Drug interactions
| Question | Answer |
|---|---|
| drug interaction definition | interaction of drug with other substance, whether intended or not |
| 3 types of interaction consequences | *potentiative *inhibitory *unique response |
| Potentiative effect definition | *increased therapeutic effect (beneficial) *increased side effect (detrimental) *unique response (varies) |
| Example of increased therapeutic effect (beneficial) | amoxicillin + clavulanate |
| Example of increased side effect (detrimental) | warfarin + ASA |
| Example of decreased therapeutic effect (detrimental) | propranolol in asthmatic |
| Example of decreased side effects (beneficial) | naloxone in morphine OD |
| Example of unique response | disulfiram + ETOH |
| 4 Mechanisms of drug interaction | *direct/chemical/physical interactions (IV) *pharmacokinetic interactions (affect metab) *pharmacodynamic interactions *combined toxicity interactions |
| Direct chemical/physical interactions occur- | *mostly in vitro (incompatible IV components) *some in vivo (depending on circumstances) |
| Example of direct chemical/physical interaction | oral ciprofloxacin + oral iron --> Fe binds cipro (could also be kinetic-->decreased absorption |
| 4 mechanisms of pharmacokinetic interactions | *altered GI absorption *altered absorption of injected drugs by regional blood flow (epi in local anesthetics) *altered distribution *altered metabolism *altered excretion |
| 3 types of altered GI absorbption | *phys/chem binding adsorption *influence of pH on ionization *GI transit time (laxatives increase speed, decrease absorption) |
| 2 types of altered distribution | *competition for protein binding *alteration of regional pH (ion trapping) |
| example of pH partitioning concept | prevention of ASA reabsorption from renal CD by alkalinization of urine --> trapping ionized ASA in urine |
| example of altered metabolism | *usually involves CYP450 enzymes |
| effect of drugs that induce CYP450 enzymes | *increase their activity-->metabolism increases *inhibit their activity --> metabolism decreases |
| effect of drugs that increase/inhibit CYP450 enzymes | can increase/decrease rate of metabolism of 1+ drugs --> cause opposite change in serum levels/half-life --> affects intensity and/or side effects |
| effect of grapefruit juice | inhibits CYP450 system (CYP3A4), can't metabolize for 24H |
| effect of St. Johns Wort | CYP450 inducer |
| 3 examples of altered excretion | *glomerular filtration *reabsorption *tubular secretion |
| Mechanism of glomerular filtration | drug decreases blood flow/cardiac output, will decrease filtration of all drugs filtered |
| Mechanism of reabsorption | altering pH--> ion trapping (ASA & alkaline urine example) |
| Mechanism of tubular secretion | can be affected by 2 drugs competing for same active transport system |
| example of tubular secretion | *probenecid *many PCNs/cephalosporins |
| 2 types of pharmacodynamic interactions | *occurring at same receptor site *occurring a different receptor site |
| Example of same receptor site- pharmacodynamic | *usually inhibitory - 2 drugs try to bind same receptor *naloxone for morphine OD |
| Effect of interactions at different sites | can be potentiating, inhibitory or neutral |
| Example #1 interactions diff sites | BNZ + narcotic. 2 drugs with sedative properties bwo different mechanisms --> synergistic effect |
| Example #2 interaction at diff sites | 2 drugs with 1+ opposite effects may cancel/minimize side effect: *thiazide (K+ excreting diuretic) and spironolactone (K+ sparing diuretic) combined result in little net effect of serum K+ |
| Effect of combined toxicity interactions | *synergistic effects on -sedative effects -kidney toxicity -liver toxicity -K+ wasting |
| example of 2 drug interaction - kidney toxicity | aminoglycoside antibiotic + vancomycin |
| example of 2 drug interaction - liver toxicity | TB drugs INH + PZA |
| example of 2 drug interaction - K+ wasting | corticosteroids + thiazide diuretics |
| Drug-Food interactions (4) | *alters rate of absorption (Ca binding TCN) *alters metabolism (grapefruit juice, inhib CYP3A4) *alters MAOIs *alters timing of administration with respect to meals |
| Grapefruit juice effects (specifically) | CYP3A4 in GI mucosa |
| Foods that effect MAOIs | *tyramine *theophylline + caffeine *K+sparing diuretic + salt sub *Vitamin K rich foods + warfarin |
| Timing of admin with respect to foods | 1 hour before ac, 2 hours after pc meals |
| pitfalls in literature evaluation | *time course *extrapolation from normal subjects to patients *extrapolation from single drug to entire class *significance of individual cases to general population *sequence of administration *dosage *influence of underlying disease states |
| Demographic risk factors | *female gender *extremes of age *previous ADR *obesity *poor metabolizer (genetic) *chronic medical conditions/medications *narrow tx window drugs *infrequent/inadequate monitoring |
| Chronic disease risk factors | *seizure disorder *COPD *psychiatric diagnosis *infectious diseases, esp HIV *GI disease *connective tissue disease *CV/lipid disorder *endocrine disease (esp hypothyroidism) *liver/renal disease |
Created by:
lorrelaws
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