Term
| What type of interaction is due to differences in mechanism of action? |
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Definition
| pharmacodynamic interactions |
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Term
| SSRI's and tramadol, triptans, meperidine, or litium; Warfarin and NSAIDs; Beta-blockers and diltiazem/verapamil all have what sort of combined effect? |
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Definition
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Term
| NSAIDs and ACE inhibitors/ARBs; Ibuprofen and aspirin; and Acetylcholinesterase inhbitors and anticholinergic agents have what sort of combined effect? |
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Definition
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Term
| The interactions of Fluroquinolones and metal cations (Al, Mg, Zn); and Antibiotics and digoxin, affect what dimension of pharmokinetics? |
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Definition
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Term
| The interaction of Amiodarone and digoxin affect what dimension of pharmacokinetics? |
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Definition
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Term
| The induction or inhibition of CYP450 enzymes affects what dimension of pharmacokinetics? |
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Definition
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Term
| The interaction of Probenecid and penicillins; and Litium and NSAIDs effect what dimension of pharmacokinetics? |
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Definition
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Term
| What 6 drugs were removed from market due to fatal drug interactions? |
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Definition
1. Terfenadine (Seldane) 1998
2. Mibefranil (Posicor) 1998
3. Astemizole (Hismanol) 1999
4. Cisapride (Propulcid) 2000
5. Cerivastatin (Baycol) 2001
6. Nefazodone (Serzone) 2004 |
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Term
| What is responsible for Phase 1 reactions, is in all living organisms, and is present mostly in the liver, but also in intestine, lung, brain, and placenta? |
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Definition
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Term
| What are the 5 isozymes usually involved in drug metabolism and which 2 are over 80% of drugs metabolized by? |
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Definition
CYP's 1A2, 2C9, 2C19, 2D6, and 3A4
>80% metabolized by 2D6 and 3A4 |
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Term
Identify what each part of the cytochrome nomenclature for this name means:
CYP1A2 |
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Definition
CYP - Cytochrome P450 enzyme
1 - family
A - sub family
2 - individual enzyme (isozyme) |
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Term
| What is the definition of a CYP450 substrate? |
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Definition
| a drug or substance metabolized by the CYP450 enzyme |
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Term
| Why are cisapride, codeine, metoprolol, and nifedipine more signficantly affected as substrates? |
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Definition
| because they each rely on one specific enzyme to be metabolized, so if you knock out that enzyme, you completely halt metabolism of these substrates |
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Term
| Why are fluoxitene, theophyiline, warfarin, and imipramine less affected from the inhibition of their enzymes? |
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Definition
| because they rely on multiple enzymes to be metabolized so if you halt one, they can still be metabolized by another (although may be less effective) |
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Term
| What is the definition of a CYP450 inducer? |
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Definition
drug that increases CYP450 enzyme activity leading to increase in metabolism of substrate
- onset of effect usually delayed and depends on inducer T1/2 |
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Term
| What is the definition of a CYP450 inhibitor? |
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Definition
| drug that decreases CYP450 enzyme activity leading to decrease in metabolism of substrate. Decreases clearance and increases concentration and T1/2 of substrate |
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Term
Name the enzyme:
- no genetic polymorphism
- important substrates: caffeine, theophylline, proparanolol, TCA's, R-warfarin, clozapine
- important inhibitors: ciprofloxacin, cimetidine, fluvoxamine
- important inducers: cig smoke, charbroiled foods, omeprazole, phenobarbital, rifampin |
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Definition
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Term
| What drug interaction inhibits CYP1A2 mediated 1 and 3-demethylations, and 8-hydroxylation of theorphilline? |
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Definition
Theophylline-Ciprofloxacin
- if cipro dose >250mg BID, recommend a non-interacting quinolone OR cut dose of theo by ~25-50% |
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Term
Name the enzyme:
- 3% caucasions poor metabolizers
- Important substrates: S-warfarin, NSAIDs, sulfonylureas, angiotensin receptor blockers, phenytoin, diazepam, carvedilol
- Important inhibitors: amiodarone, fluconazole, fluoxetine, metronidazole, paroxetine, sulfonamides
- Important inducers: carbamazepine, phenobarbital, rifampin |
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Definition
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Term
Which drug is this?
- Cholestyramine decreases its absorption
- Phenytoin, diflunisal decrease protein binding
- inducers/inhibitors of 2C9 enzyme have a major effect on metab
- inducers/inhibitors of 1A2, 2C19, 3A4 have a minor effect on metab |
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Definition
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Term
| Which enzyme metabolizes S-warfarin? |
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Definition
| 2C9 enzyme (3-5 x more active than R) |
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Term
| Which enzymes metabolize R-warfarin? |
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Definition
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Term
Name the enzyme:
- 8% caucasians, 7% blacks poor metabolizers
- Important substrates: beta-blockers, antidepressants, antipsychotics, codeine analogs, donepezil
- Important inhibitors: amiobdarone, fluoxetine, paroxetine, sertraline, quinidine, buproprion, cimetidine, terbinafine
- NOT inducible |
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Definition
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Term
| 35% of pts on what type of drugs and 3 or more meds have potential for drug-drug interaction. |
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Definition
anti-depressants
- most new anti-depressants inhibit one or more CYP450 enzymes |
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Term
| Fluoxetine (Prozac) is a potent inhibitor of what isozyme? |
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Definition
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Term
| Paroxetine (Paxil) is a potent inhibitor of what isozyme? |
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Definition
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Term
| Fluvoxamine (Luvox) is a potent inhibitor of what isozyme? |
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Definition
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Term
| Nafazodone (Serzone) is a potentn inhibitor of what isozyme? |
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Definition
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Term
| What enzymes account for 30% of total hepatic CYP enzymes? |
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Definition
CYP3A4 and CYP3A5
- 50% of drugs substrates of CYP3A4/5 |
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Term
| Where is CYP3A4 enzyme found? |
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Definition
in intestinal wall and liver
- 3A4 substrates tend to have low and variable bioavailability |
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Term
| 70% of Caucasians, 50% of Blacks are poor metabolizers of what enzyme? |
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Definition
CYP3A5
- substrates have highest clearance and lowest bioavailability |
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Term
Name the enzyme:
- Important substrates: benzodiazepines, HIV antivirals, statins, steroids, cyclosporin, R-warfarin, sildenafil, zolpidem, CCBs
- Important inhibitors: macrolides, azole antifungals, verapamil, dilitazem, protease inhibitors, grapefruit juice
- Important inducers: carbamazepine, phenytoin, phenobarbital, riampin, garlic, St. John's wort |
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Definition
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Term
| Macrolide drug interactions inhibit what enzyme? |
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Definition
CYP3A4
erythromycin = clarithromycin = telithromycin > azithromycin |
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Term
| What drug increases cisapride concentration by 3-fold? |
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Definition
clarithromycin
Cisapride 10mg QID + Clarithromycin 500mg BID |
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Term
| What drug has a box warning of fatal arrhythmias and prolonged QT interval? |
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Definition
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Term
| Grapefruit juice is an irreversible inhibitor of what enzyme? |
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Definition
CYP3A4
CCBs: 100-200% increase plasma levels
Cyclosporine: increase AUC 55-300%
Terfenadine: 7-10 fold increase in measured terfenadine |
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Term
| Rifampin induces what enzyme involved in oral contraceptives? |
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Definition
| CYP3A4 - mean AUC of EEC decreases by 68% |
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Term
| Concentrations of simvistatin and metabolite are dramatically decreased following what drug administration? |
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Definition
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Term
| Itraconazole, voriconazole, tacrolimus, and sildenafil are substrates of what enzyme? |
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Definition
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