Term
| What percent of the blood volume is filtered at the glomerulus? |
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Definition
|
|
Term
| What determines whether drugs are filtered at the glomerulus? |
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Definition
|
|
Term
| What is forced alkaline diuresis? |
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Definition
| used for individuals who OD on barbituates. Give Sodium bicarb to make the urine more alkalikne and to trap the acidic drug (barbituate) in the urine). Can do the same thing with forced acid diruesis |
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Term
| Name an example of a drug that is secreted into the renal tubules. |
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Definition
|
|
Term
| How do tubules secrete drugs into urine? |
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Definition
| 2 active transport systems for acidic and basic drugs that are not particularly specific and in some cases can remove protein bound drugs from the blood |
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Term
| How do drugs get into hepatocytes? |
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Definition
| passive diffusion and carrier mediated transport |
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Term
| By what mechanism does the hepatocyte transfer drugs/drug metabolites into bile canaliculi? |
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Definition
|
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Term
| What must happen for a drug to participate in enterohepatic cycling? |
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Definition
| must be lipid soluble and excreted by the liver |
|
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Term
| whats the clinical significance of enterohepatic cycling? |
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Definition
| prolongated effect of drug |
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Term
| Describe why certain drugs get excreted in milk and other's do not. |
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Definition
| milk has a pH of 6.5 while blood is 7.5 so weak bases will be trapped. Also the fat content of milk increases over time and lipid soluble drugs become more likely to be trapped in milk |
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Term
| Describe phase I metabolism. |
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Definition
| nonselective (oxidation, reduction, hydrolysis) |
|
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Term
| Describe phase II metabolism |
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Definition
| synthetic- conjugation (sugars, amino acids, sulfuric acid, acetic acid) |
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Term
| Name two molecules in the body that contain heme. |
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Definition
| hemoglobin and cytochrom p450 |
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Term
| Where in the cell is cytochrom p450 located? |
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Definition
| bound to the ER (part of e transport chain |
|
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Term
| What is the function of CPR? |
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Definition
| (cytochrom p450 reductase) takes an electron from NADPH (turning into NADP+) and then helps Cyt p450 convert S + O2 --> H2O and SOH |
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Term
| How does Cyt p450 help you excrete drugs? |
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Definition
| adds O2 to drugs to make them more water soluble |
|
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Term
| What other molecules are involved in reducing Cyt p450? |
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Definition
| NADPH P450 reductase, cyt b5, and NADH cyt b5 reductase |
|
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Term
|
Definition
| NADPH p450 reductase or NADH cyt b5 reductase |
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|
Term
| Name a few reactions cytochrome p450 catalyzes. |
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Definition
| aromatic hydroxylation, aliphatic hydroxylation, epoxidation, dealkylation |
|
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Term
| How does codeine have codeine have analgesic effects. |
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Definition
| 1% of codeine is converted to morphine via a dealkylation by cyt P450 |
|
|
Term
| What are the reasons for wide variations in foreign compound metabolism by P450? |
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Definition
| broad selectivity of the P450 active site, multiple forms of P450, enzyme induction, polymorphisms |
|
|
Term
| What are the different types of polymorphisms in cytochrome P450? |
|
Definition
| 1) expression (promoter region)2) structural gene (inthe protein sequence itself) 3) splicing polymorphism |
|
|
Term
| Describe the nomenclature of cytochrome p450. |
|
Definition
family= number dependent on 40% sequence similarity
subfamily= letter represents 59% similarity
individual number |
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Term
| What induces CYP1A and what does CYP1A metabolize? |
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Definition
| induced by and metabolizes polycyclic hydrocarbons (found in cigarette smoke) |
|
|
Term
| What is the difference between CYP1A1 and CYP1A2? |
|
Definition
1A1 is inducible and extrahepatic
1A2 is constitutively expressed only in the liver but also inducible |
|
|
Term
| Describe the polymorphism of CYP1A |
|
Definition
| expression and structural (primarily in CYP1A1 |
|
|
Term
|
Definition
| cigarette smoke, broccoli, cauliflour and caffeine |
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|
Term
|
Definition
| Ah-aryl hydrocarbon receptor induces it. Normally CYP1a is bound to heat shock protein 90. When bound to dioxin, it also binds to ARNT (nuclear transferase) that cuases more 1A1 to be made |
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|
Term
| How can you detect CYP1A2 polymorphisms? |
|
Definition
| caffiene metabolism (3-demethylation product of paraxathine) |
|
|
Term
| What metabolizes caffiene? |
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Definition
|
|
Term
| T/F because CYP1A2 is expressed only in the liver it is associated only with liver cancer. |
|
Definition
| false; it is assocated with cancers at distal sites |
|
|
Term
| What CYP is hormonally regulated? |
|
Definition
|
|
Term
| What cyp is necessary to prevent fetal gloucoma? |
|
Definition
|
|
Term
| What induces CYP1B1 and what does it break down? |
|
Definition
| induced by AH receptor; breaks down retinoic and arachidonic acid (prevents fetal gloucoma) |
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|
Term
| Describe the CYP 2A enzymes. |
|
Definition
| includes 2A6 (polymorphic) and 2A13, responsible for nicotine metabolism |
|
|
Term
| What is the major form of CYP2B? |
|
Definition
| form humans it is CYP2B6 (1 and 2 in rats) |
|
|
Term
|
Definition
| doing drugs or smoking tobacco |
|
|
Term
| What CYP is hormonally regulated (thought to be growth hormone) in rats? |
|
Definition
|
|
Term
| What are the major forms of CYP2C in humans? |
|
Definition
|
|
Term
| What drugs do CYP2C's metabolize? |
|
Definition
| 30% of commonly used drugs (Omeprazole and diazepam) |
|
|
Term
| Name an in vivo substrate of CYP2C19? |
|
Definition
|
|
Term
| Name an in vivo substrate of CYP2C9? |
|
Definition
|
|
Term
| What drugs does CYP2D6 metabolize? |
|
Definition
| codeine, dextromethorphan, hydrocodone, hydromorphone, oxycontin, oxycodone |
|
|
Term
| Name the important CYP2D in humans? |
|
Definition
|
|
Term
| What types of polymorphisms are there in CYP2D6? |
|
Definition
| structural and gene duplication |
|
|
Term
| Why is CYP2A thought to be hormonally regulated? |
|
Definition
| 2A1 is increased in female and young male rats and 2A2 is not found in female rats |
|
|
Term
| Why is CYP2A6 polymorphism clinically relevant? |
|
Definition
| coumarin hydroxylation; significant ehtnic variability |
|
|
Term
|
Definition
|
|
Term
| What are the substrates and induces of 2B6? |
|
Definition
substrates: alfentanil and MDMA (ecstasy)
Inducible: rifampicin, phenobarbital, and phenytoin |
|
|
Term
| What drugs does CYP2C19 metabolize? |
|
Definition
| omeprazole, imipramine, propranolol, hexobarbital, diazepam, taxol |
|
|
Term
| Pt's with excessive metabolism by what CYP are at increase risk for cancer? |
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Definition
|
|
Term
| CYP2D6 has interactions with... |
|
Definition
|
|
Term
| What CYP is linked to oral opiate dependence? |
|
Definition
|
|
Term
| What CYP inactivates the active ingredient in cough syrup? |
|
Definition
|
|
Term
| Ultra rapid metabolizers is often d/t.. |
|
Definition
|
|
Term
| Expression and inducibility of CYP2E1: |
|
Definition
| constitutively expressed and inducible |
|
|
Term
| What are teh typical substrates of CYP2E1? |
|
Definition
| ethanol and small hydrocarbons (benzene and toluene) |
|
|
Term
| CYP2E1 forms reactive intermediates of which compounds... |
|
Definition
| nitrosamine carcinogens, and acetaminophen |
|
|
Term
| What converts acetominophen to a hepatotoxic metabolite NAPQI? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the clinical significance of CYP2E1 polymorphisms? |
|
Definition
| role in cancer and role in alcohol related liver dysfunction |
|
|
Term
| What is the invivo substrate of 2E1? |
|
Definition
|
|
Term
| What is the major P450 in humans? |
|
Definition
|
|
Term
| What accounts for the fact that CYP3A4/5 is inducible by numerous drugs and metabolizes over 50% of commonly used drugs? |
|
Definition
| CYP3A4 is polymorphic but much of the wide variation in activity is due to CYP3A5 |
|
|
Term
| What are the in vivo substrates of CYP3A4/5? |
|
Definition
| erythromycin, alfentanil, midazolam |
|
|
Term
| T/F CYP 3A4/5 are only found in the liver. |
|
Definition
| false, also in intestines |
|
|
Term
| IF CYP3A4 is high in intestines, then... |
|
Definition
|
|
Term
| What is the effect of CYP3A5 on CYP3A4? |
|
Definition
| there is higher metabolism but less CYP3A4 response to inducers |
|
|
Term
| What patient populations have higher CYP3A4? |
|
Definition
|
|
Term
|
Definition
cimetidine (tagamet) (which affects the way pts metabolize sildenafil/viagra)
and grapefruit juice |
|
|
Term
|
Definition
| rifampicin and phenobarbital (which interferes with action of OCs) |
|
|
Term
| Name the enzymes other than P450s that perform oxidation on drugs? |
|
Definition
| flavin monooxygenase, alcohol dehydrogenase, aldehyde dehydrogenase, xanthine oxidase, tyrosine hydroxylase, monoamine oxidase |
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