Term
| what is the major organ of drug metabolism? |
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Definition
|
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Term
| what is the major organ of drug exretion? |
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Definition
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Term
| what is biotransformation? |
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Definition
| a process that transforms drug molecules into inactive, less toxic and polar metabolites so they can be excreted. |
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Term
| Orans that can metabolize drugs? |
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Definition
| liver, GI, lungs, brain, skin, testes and kidneys |
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Term
| What occurs during a phase 1 biotransformational reaction? |
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Definition
mainly oxidation, reduction, deamination, and hydrolysis.
These introduce functional groups that were ingrained into the lipophilic structure. this renders the structure more hydrophilic. |
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Term
| Where do most phase 1 reactions occur? |
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Definition
| microsomal enzyme oxidizing system in live, which is located in the membrance of the smooth ER. |
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Term
| What family of enzymes is part of the MEOS ? |
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Definition
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Term
| What percent 1 of phase oxidations occur by CYP450? % of all drugs metabolized by CYP450? |
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Definition
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Term
| What is required for a phase 1 reaction to occue by CYP450? |
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Definition
| NADPH, O2, CYP450 reductase, and CYP450 heme-protein. |
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Term
| What are some important substrates for the CYP 1A2 isoform? |
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Definition
| theophylline and warfarin, tylenol |
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Term
| What inducers(increases) activity of CYP1A2? |
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Definition
| tabacco smoke (benzo[a]pyrene) |
|
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Term
| what isoform do barbiturates inducer? |
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Definition
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Term
| What are some important substrates of CYP 3A4? |
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Definition
| acetaminophen (tylenol), lovastatin, HIV protease inhibitors |
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Term
| What are some inducers of CYP 3A4? |
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Definition
| barbiturates, rifampin, and phenytoin |
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Term
| What are some inhibitors of CYP3A4? |
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Definition
| ERTHRYOMYCIN, GRAPEFRUIT juice, clarithromycin, ritonavir, fluconAZOLE, itraconAZOLE |
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Term
| How does erythromycin inhibit CYP3A4? |
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Definition
|
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Term
| what are "suicide inhibitors"? |
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Definition
| metabolites of a drug that irreversibly inhibit enzymes that meatbolize them. |
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Term
| What are some examples of phase 1 non-CYP450 oxidations? |
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Definition
Alcohol and acetylaldehyde dehydrogenase
monoamine oxidase-oxidize catecholamine
decarboxylation of levodopa |
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Term
| what is the most abundant CYP isoform? |
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Definition
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Term
| what is involved in a phase II reaction? |
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Definition
| invovled in synthesis by addition or conjugation of endogenous polar substrates onto functional groups. |
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Term
| Phase II reactions require |
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Definition
| transfer enzymes known as transferase and high energy intermediates. |
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Term
| Where are phase II transferases found? |
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Definition
| in the cytosol or microsomes. |
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Term
| What is an example of the drug that skips phase I and goes directly to phase II? |
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Definition
| isoniazid (INH)is aceytlated to N-acetyl INH which inactivates the drugand increases its solubility for renal excretion. |
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Term
| what is N-acetyl INH hyrolyzed to, one of which is hepatotoxic. |
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Definition
| acetylhydrazine(toxic) and isonictinic acid |
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Term
|
Definition
| the variation is pharmacodynamics and kinetics due to genes expression. age, gender, pregnancy. |
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Term
| what 3 processes are involved in drug elimination? |
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Definition
metabolism
exretion
clearance |
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Term
| what is an example of an efflux pump? |
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Definition
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Term
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Definition
| liver, kidney, GI and BBB. |
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Term
| What is the funxtion of an efflux pump? |
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Definition
| to remove the active form of a drug from the body, thus, reducing its bioavailiablity |
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Term
|
Definition
renal (main)
biliary
and fecal |
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Term
| How are weak acid and base removed? |
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Definition
| many are secreted at the proximal tubules by special carriers that use active transport |
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Term
|
Definition
| organic anionic transporters. secrete weakly acidic drugs in proximal tubule |
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Term
|
Definition
| organic cationic transporteres. secrete weakly basic drugs in prox. tubule |
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Term
| What happens to the non-ionized forms of weak acids and bases in the distal tubule? |
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Definition
| they are passively reabsorbed into the blood. |
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Term
| how can u prevent paassive transport of the drugs out of the nephron? |
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Definition
| by altering the environment. increase or decrease its pH |
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Term
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Definition
| drugs that are metabolized and secreted in the bile can be reabsorbed in the gut. this helps prolong action of many drugs. |
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Term
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Definition
| volume of plasma containing drug that is completely cleared by the kidneys per unit time. |
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Term
| What is renal clearance dependent on? |
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Definition
|
|
Term
| what is clinically used to estimate GFR? |
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Definition
|
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Term
| Why is creatinine used to measure GFR? |
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Definition
1. it is a beakdown of creatine, which is turned over constantly in muscle.
2. It is filtered solely by kidney, so any change in GFR will be seen as a change creatinine conc in serum |
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