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32 Cards in this Set
- Front
- Back
Define: metabolism
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Reduce the duration of action of drugs - inactive form of less active metabolite
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Define: excretion
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Urine, feces, expired air, saliva, sweat, breast milk
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How does codeine become morphine?
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Lipophilic drugs gets transformed to more polar drugs (CYP2D6)
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What organs is most important in first-pass effect?
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liver
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What happens in phase I reaction?
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Enhance POLARITY by introducing/unmasking a functional group (OH, NH2, SH); IRREVERSIBLE reaction; Metabolite = inactivated or enhanced; If polar enough can be readily excreted
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What happens in a Phase II reaction
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Phase I conjugation that reacts with (glucuronic acid, sulfuric acid, acetic acid, amino acid); REVERSIBLE; products become highly polar -> easily excreted
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What are the reactions in Phase I? Phase II?
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Phase I = Oxidation, reduction, deamination, hydrolyses, Phase II = conjugation
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What is the MOA for metabolism of Isoniazid?
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Phase II (acetylation)-> Phase I (hydrolysisi)
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Mixed function oxidases
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Aka mono-oxygenases in the smooth ER; able to do oxidation-reduction reaction; requires P450 to do its job
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What is the output of cytochrome P450?
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Activated oxygen (potent oxidizer); Function = low substrate specificity + highly lipid soluble
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What CYPs are the major Cytochrome P450?
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1. CYP3A4, 2. CYP2C9, 3. CYP1A2, 4. CYP2D6
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What is induction?
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↑ ability of an enzyme - occurs b/c 1. could b on two different drugs -> thus ↑ number of metabolites in system and not enough drug -> could lead to drug tolerance
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What is a problem of induction?
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May lead to tolerance, results in ↓ pharacological action of inducer and co-administered drugs, reactive metabolites may exacerbate metabolite-induced toxicity
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For omeprazole and smoking what CYP450 system does it induce? What drugs have a built up tolerance?
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CYP450 = 1A2, Tolerance = Acetaminophen, Tamoxifen
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For barbiturates (nembutal) what CYP450 system does it induce? What drugs have a built up tolerance?
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CYP450 = 2C9; tolerance = celecoxib, Losartan
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For macrolides and stJohns wort what CYP450 system does it induce? What drugs have a built up tolerance?
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CYP450 = 3A4; Tolearance = Diazepam, spironolactone
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Define: inhibition
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Ceertain durgs inhibit P450 - reducing metabolism of the inhibitor or other substrates
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Fluvoxamine inhibits what CYP450? What drugs have a decreased metabolism?
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CYP = 1A2, ↓ metabolism = Acetaminophen + tamoxifen (receives longer response)
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Paroxetine inhibits what CYP450? What drugs have a ↓ metabolism?
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CYP = 2D6, ↓ metabolism = codeine + metoprolol (receives longer response)
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Erythromycin + grapefruit juice inhibits what CYP450? What drugs have a ↓ metabolism?
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CYP = 3A4, ↓ metabolism = diazepam + spironolactone (receives longer response)
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What are the Phase I enzymes?
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1. Flavin monooxygenase, 2. amine oxidases, 3. dehydrogenations (alcohol dehydrogenase)
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What is the location of Phase II reactions
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Microsomes or cytosol
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What is the name of transferase needed for Phase II glucuronidation reaction? Example of a drug that uses this?
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Transferase = UGTs (microsomes); Drug Example = Digoxin
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What is the name of transferase needed for Phase II ACETYLATION reaction? Example of a drug that uses this?
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Transferase = NATs(cytosol); Drug example = Isoniazid
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What is the name of transferase needed for Phase II GLUTATHIONE reaction? Example of a drug that uses this?
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Transferase = GST (Cytosol, microsomes); Drug example = Acetaminophen
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What is the name of transferase needed for Phase II GLYCINE reaction? Example of a drug that uses this?
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Transferase = Acyl-CoA glycinetransferase (mitochondria); Drug Example = Nicotinic acid
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What is the name of transferase needed for Phase II SULFATION reaction? Example of a drug that uses this?
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Transferase = SULTs (cytosol); Drug example = acetaminophen
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What is the name of transferase needed for Phase II METHYLATION reaction? Example of a drug that uses this?
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Transferase = TMTs (cytosol); Drug example = Dopamine
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What drug is given to prevent toxic metabolites from acetominophen?
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N-acetylcysteine = prevents acetaminophen to under go P450-dependent GSH-conjugation pathway (toxic metabolites)
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What are some factors the influence drug metabolism?
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1. Age, 2. gender, 3. liver function (cirrhosis, hepatitis), 4. cardiovascular (limited blood flow), 5. cruciferous veggies (broccoli/cabbage), 5. charcoal-broiled food, cigarette smoke, pesticides
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What are some genetic factors that influence drug metabolism?
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1. Fast vs slow acetylators (isoniazid), 2. ultra-rapid metabolizers (CYP2D6 is too good thus need more drug for same response), 3. poor metabolizers - side effect occur more readily (d/t impaired drug clearance)
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Metabolism of acetaminophen
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1. Glucuronidation + sulfination (95%- normal safe metabolism), 2. P450-depenent GSH conjugation pathway (5% - generates ROS -> liver cell death)
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