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72 Cards in this Set
- Front
- Back
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what organs are invovled in drug metabolism
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liver
kidney lungs intestinges |
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what are the phase I reactions
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oxidactive reductive
hydrolytic |
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what might the hydrolytic reactions cleave
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esters
amides epoxides |
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P450s are Phase __ enzymes
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I
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P450s require ____ and ____
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NADPH O2
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what are the five major cyps
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1A2
2C9 2C19 2D6 3A4 |
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what is the cyp responsible for the metabolism of nearly 50% of prescribed Rx
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Cyp3a4
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cyp P450s are found in the PM of the ______
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ER
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state the major transformations catalyzed by cyt P450s
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aliphatic and aromatic hydroxylation
alkene adn aromatic epoxidation NOS dealkylation Noxidation Nhydroxylation oxidative deamination and desulfuration S oxidation Oxidative dehalogenation |
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list other enzymes involved in phase I reactions
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FAD monoxygenase
monoamine and diamine oxidase alcohol dehydrogenase aldehyde dehydrogenase |
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name the five major phase II (conjugation) reactions
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SMANG
sulfation mercapturic acid formation acetylation nos methylation glucuronidation |
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what is the cofactor of glucurndation
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UGT which adds glucuronic acid to acceptor molecules
endogetnous substrates include bilirubin, bile acids, steroid hormones |
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what is the cofactor of sulfation
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sulfotransferases
attaches sulfate group to hydroxyl groups |
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_____ is a sulfate donate
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PAPS
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name the transferase of mercapturic acid formation
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glutathione S transferase
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what is an example of a methyl transferase
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PMNT
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what is the cofactor in acetylation
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arylamne N acetyltransferase
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name five cyp inducers
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PAHs (BBQ)
anticonvulsants glucocorticoids rifampin PPARS |
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name the GST inducers
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phenobarbital
3 methylcholanthrnee allyl siothiocyante |
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name the UGT inducers
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phenobarbital
3 methylcholanthrene carbazepine nicotine |
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how does protein deficiency affect cyp metabolism
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decreases it
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what are the two most improtant mechanisms of renal excretion for drugs
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passive tubular reabsorption
active secretion |
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how small must a drug be to be filtered at glom
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<70kd
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T or F. active transprot is very important for na+ cl- HCO3- and drugs
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FALSE not for xenobiotics!
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______ is important for proteins and pollypeps that are filtered
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endocytosis
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what is normal GFR
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120-130 ML/min
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the amoutn of drug entering the tubule lumen depends on what two things
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GFR
extend of binding to proteins |
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clearence is a function of renal ___
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pH
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how are drugs actively secreted
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ATP binding cassette transporters
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state the creatinine clearance equation (cockroft gault)
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140-age x body weight/
serum creatinine(mg/dL) x 72 |
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what is the normal creatinine clearance for males? females?
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97-137 mL/min
88-128 females multiple by .85 for females |
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what is in bile
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water
electrolytes organic molecules bile acids cholesterol phopholipids billirubin |
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what kind of tranpsort puts things into bile
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active transport
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define zero order
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rate of change is independent of drug concentration
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define first order
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rate of chagne is directly proportional to drug conc
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if the rate of elimination is proportional to concetnration then
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the equation is first order
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all drugs infused at the same arate and having the same clearance will
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reach the same plateau conc
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how do you achieve a platue
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rate of infusion = rate of elimination = CL x Css
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what determines maintenance dose rate
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elimination rate
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give two examples of drugs that is metabolized to an active metabolite
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imipramine --> desipramine
diazepam--> nordiazepam |
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give an example of a drug that is metabolized from inactive to an active state
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acyclovir --> acyclovir triphosphate
(needs virus to become activated!) |
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give an example of a drug whose metabolite is toxic
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acetaminophin --> liver toxicity
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name the reactions catalyzed by cyps
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aliphatic and aromatic hydroxylation
alkene and aromatic epoxidation NOS dealkylation Noxidation N hydroxylation oxidative deamination and desulfation s oxidatioin oxidative dehalogenation |
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name other phase I enzymes
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FAD
monoamine diamine oxidase alcohol dehydrogenase aldehyde dehyrdogenase xanthine oxidase |
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FAD monoxygenase is important in metabolizing ____
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nicotine
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what are the five basic reactions of phase II
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glucuronidation
sulfation mercapturic acid formation NOS methylation acetylation |
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phase ___ is reactions that usually couple polar groups to funcitonaized substrates
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phase II
aka they usually add a big molecular fragement onto a functionalized substrate |
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name some endogenous substrates of glucuronidation
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bilirubin
bile acids steroid hormones |
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what are some acceptor molecules of glucuronidation
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hydroxyls
carb as thiols amines |
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sulfotransferases attaches a sulfate group to a ____ group
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hydroxyl
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what is a good donor for sulfation
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PAPS
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what does GST add to an accpetor in mercapturic acid formation
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glutathione (gly cys glu)
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what follows the addition of glutathione to acceptor molecules
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hydrolysis of glutamate and glycine
then acetylation of the cysteine |
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where do you find GST
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liver
kidney lung intestine |
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where are NOS methylation transferases found
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liver
kidney lung brain |
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NOS methylation adds a methyl group from _____ to accpetor molecules
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S adenosyl methionine
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what do arylamine N acetyltransferases catalyze
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transfer of an acetyl group from acetyl Coa to various amines and hydrazine acceptor molecules
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name cyp inducers
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PAHs (polycyclic aromatic hydrocarbons ex from BBQ)
anticonvulsants (carbamazepine, phenobarbital, phenytoin) glucocorticoids peroxisome proliferator activated receptor alpha agonists clofibrate, fencofibrate, PPARS) rifampin |
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name GST inducers
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phenobarbital
3-methylchlolanthrene allyl isothiocyanate carvone |
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name things that induce UGT
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phenobarbital
3-methylcholanthrene carbamazepine nicotine |
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what might cause cofactor deplemtion
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salicylamindes decrease sulfate
diethylmaleate decreases glutathione |
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name some reversible competitive inhibtors
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gemifibrozil
zoles class antifungals ex ketoconazole HIV protease inhibitor ritonavir H2 antagonists cimetidine grapefruit juice |
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name drugs that provide covalent inhibition
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disulfram
polyhalogenated compounds olefinic and acetylenic drugs |
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what is a pseudoirrreversible inhibition
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metabolism results in intermediates which slowly dissociate (not a true irreversible)
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what are some common cyp polymorphisms
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2D6
2C19 2C9 |
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what does COMT deficiency cause
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decreased isoproterenol metabolism
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what does thioprine S methyltransferase deficiency lead to
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6 mercaptopurine toxicity
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what leads to succinylcholine sesntivity or resistance
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pseudocholinesterase activity
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are asians fast or slow acetylators
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fast
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are eskimos slow or fast acetylators
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50% are fast
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50-59% of whites are ___ aetylators.
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slow
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most northern europeans and egyptians are ___ acetylators
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slow
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