Term
| What are the five pharmacokinetic effects of drug interaction mechanisms? |
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Definition
| Absorption, protein binding, modified renal excretion, modified nonrenal excretion, changes in CYP450 |
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Term
| What are the three pharmacodynamics effects of drug interaction mechanisms? |
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Definition
| Antagonistic effects, synergistic side effects, indirect pharmacodynamics effects |
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Term
| What are some miscellaneous factors that affect metabolism? (six are listed) |
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Definition
| Dietary factors, underlying disease states, circadian rhythm, sex, genes, pregnancy |
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Term
| What happens to a drug if the rate of metabolism decreases? |
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Definition
| Increased intensity and duration of drug action, increased accumulation in the plasma may lead to increased probability of toxicity |
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Term
| What happens to a drug if the rate of metabolism increases? |
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Definition
| Decreased intensity and duration of drug action and efficacy, toxicity may increase if the metabolite is a toxic compound and continues to circulate |
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Term
| What are the nomenclature guidelines for CYP450 enzymes? |
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Definition
| CYP(cytochrome P450) #(genetic family) Letter(genetic subfamily) #(specific gene) |
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Term
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Definition
| Point mutations of one or more amino acids within the polypeptide |
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Term
| What is the primary method to eliminate drugs? |
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Definition
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Term
| Define pharmacogenetics factors. |
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Definition
| Gene polymorphisms that produced a large number of CYP enzymes |
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Term
| How do most CYP isoenzymes arise? |
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Definition
| Single nucleotide differences, or polymorphisms, (SNP) |
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Term
| How long does it take to detect CYP450 enzyme induction? |
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Definition
| Detectable within 2 days, maximal effect within a week. |
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Term
| How does CYP450 enzyme induction happen? |
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Definition
| Enzyme induction is an adaptive process by which the body perceives the overabundance of a lipid-soluble compound (a drug) that needs to be eliminated from the body, leading to a stimulation of the isoenzyme synthesis, increasing its amounts. |
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Term
| What are some compounds that enhance metabolism? (nine listed) |
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Definition
| Phenobarbital (and other barbituates), glutethimide, phenylbutazone, meprobamate, ethanol, phenytoin, rifampin, griseofulvin, carbamazepine |
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Term
| What are the two enzyme inducer categories? |
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Definition
| Phenobarbitol-like inducers (P450 enzymes) and polycyclic aromatic hydrocarbon-like inducers (P448 enzymes) |
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Term
| What are four mechanisms of enzyme inhibition? |
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Definition
| Substrate competition, interference with protein synthesis, interference with drug metabolizing enzymes, hepatotoxicity leading to decreased metabolism |
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Term
| What is competitive inhibition? |
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Definition
| The inhibitor acts as an alternate substrate for the isoenzyme |
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Term
| What is non-competitive inhibition? |
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Definition
| The inhibitor inactivates the enzyme, but substrate binding remains normal for the isoenzyme |
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Term
| What is a suicide substrate? |
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Definition
| A substrate that forms a covalent bond between the active site and the drug |
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Term
| How long does it take for CYP450 enzyme inhibition to occur? |
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Definition
| As soon as sufficient concentration of the inhibitor is present in the bloodstream (typically 24 hours) |
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Term
| What are three examples of families of drug or molecular transporters? |
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Definition
| ABC (ATP-binding cassette transporter), SLC (solute-linked carrier transporter), SLCO (solute-linked carrier organic anion transporter) |
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Term
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Definition
| A trans-membrane protein located in many tissues that “pumps” an assortment of structurally and mechanistically unrelated compounds OUT of cells |
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Term
| What does a high affinity of a drug for P-gp indicate? |
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Definition
| A smaller overall amount of drug will be absorbed into the cell and the drug is pumped out of the cell quickly following absorption |
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Term
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Definition
| ABCB1 (ATP-binding cassette 1) |
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Term
| What are some substrates for P-gp? (eight listed) |
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Definition
| Digoxin, fexofenadine, vincristine, indinavir, colchicine, topotecan, paclitaxel, loperamide |
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Term
| What are some inhibitors for P-gp? (nine listed) |
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Definition
| ritonavir, cyclosporine, verapamil, erythromycin, ketoconazole, itraconazole, quinidine, azithromycin, valspodar |
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Term
| What are some inducers for P-gp? (two listed) |
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Definition
| Rifampin, St. John’s wort |
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Term
| What are the two types of protein polymorphisms? |
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Definition
| SNP (altered amino acid sequence) and silent polymorphism (coding equivalent changes in mRNA, produces a protein with identical AA sequence but different shapes) |
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Term
| What does a silent polymorphism in MDR1 gene change? |
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Definition
| Substrate specificity by altering the pumps’ final tertiary structural shape (no change in AA sequence) |
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Term
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Definition
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Term
| What are some substrates for OCT? (three listed) |
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Definition
| Cimetidine, methotrexate, zidovudine |
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Term
| What are some inhibitors for OCT? (four listed) |
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Definition
| Probenecid, cefadroxil, cefamandole, cefazolin |
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