Drug Metabolism Reactions Flashcards by Lindsey Herrera

Drug-metabolizing enzymes have _____ substrates and play role in normal metabolism.

endogenous

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Nonresponse to antidepressants has been reported in ______ UMs.

CYP2D6

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______ is a detoxifying process involving formation of readily excreted metabolites that are pharmacologically inactive.

Drug metabolism

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Individual patients can vary in enzyme activity and can be classified at the extremes as ______ or ______ with total absence of enzyme.

ultra-rapid (UM) metabolizers; poor metabolizers (PM)

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______ has been reported in CYP2D6 UMs.

Nonresponse to antidepressants

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_____ are generally converted to more water-soluble (more polar) compounds that are then more readily excreted.

Lipid-soluble compounds

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Insufficient analgesia with codeine is seen in CYP2D6 _____ due to failure to metabolize to the active metabolite, morphine.

PMs

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Drug metabolism is a ______ involving formation of readily excreted metabolites that are pharmacologically inactive.

detoxifying process

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Hydrolysis of some _______ by intestinal bacterial enzymes (β-glucuronidase) results in the formation of _____.

glucuronides; free drug

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What is N-Acetylation?

amide bond formation via N-acetyltransferases

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_____ enzymes are present in plasma, liver, and other tissues.

Esterases

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______ are microsomal enzymes present in liver, kidney, GI tract.

Glucuronyl transferases

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Glucuronyl transferases are microsomal enzymes present in the ____, _____, and _____.

liver, kidney, GI tract

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Glutathione-S-transferases have a limited role in drug metabolism but are extremely important in detoxification of _____, ______, and _______.

carcinogens; pollutants; toxic metabolites

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Oxidation is a _____ metabolic reaction.

phase I

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Sulfate conjugation results in formation of strong acids with a pKa of _____.

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What is the product of a conjugation reaction?

a highly water-soluble, readily excreted product

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In N-acetylation, the acetyl group is donated by _____.

acetyl CoA

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______ of PPIs for peptic ulcers is seen in CYP2C19 PMs.

Decreased efficacy

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Where are amidases found?

liver and gut flora

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Name a drug that, when metabolized, can create a toxic metabolite.

acetaminophen (to N-Acetyl-benzoquinoneimine)

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Increased ______ is seen in patients with CYP2D6 activity PMs.

antipsychotic drug toxicity

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_____ hydrolyze esters to corresponding alcohol and acid.

Esterases

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In _____, an amide bond is formed via N-acetyltransferases.

N-acetylation

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\_\_\_\_\_\_ have endogenous substrates and play role in normal metabolism.

Drug-metabolizing enzymes

What 2 isozymes account for 25% of drug metabolism?

CYP2D6 and CYP2C19

\_\_\_\_\_\_ of some glucuronides by ______ (β-glucuronidase) results in the formation of free drug.

Hydrolysis; intestinal bacterial enzymes

Which phase I reduction can produce toxic intermediates?

nitro reduction

Give 2 examples of drugs that, when metabolized, are more active.

1) codeine (to morphine) 2) hydrocodone (to hydromorphone)

Codeine intoxication is seen in _____ UMs due to rapid metabolism to morphine.

CYP2D6

What is the postnatal development of the cytochrome P-450-dependent oxidation?

variable; usu neonates are 50-75% of adult levels, but some drugs are metabolized faster

Most drugs undergo ______ after administration to the patient.

enzyme-catalyzed chemical structure transformation

Increased antipsychotic drug toxicity in patients with CYP2D6 activity \_\_\_\_\_\_.

PMs

Increased antipsychotic drug toxicity is seen in patients with _____ activity PMs.

CYP2D6

What is Enterohepatic recirculation?

when the drug is secreted by the liver into bile as a drug-conjugate and then reabsorbed via the GI tract as a free drug

Which reactions do phase I transformations include?

oxidation, reduction, hydrolysis

What do CYP450 enzymes do?

catalyze oxidation in the smooth ER

The coenzyme donor of sulfate is \_\_\_\_\_.

PAPS

Cytochrome P450 is part of an oxidation system that also includes the cofactor NADPH, the flavoprotein NADPH-cytochrome P450 reductase, and \_\_\_\_\_\_.

molecular O2

Name an important enzyme in neurotransmitter metabolism.

monoamine oxidase

What is vitamin K reductase (VKORC1)?

the enzyme target of warfarin

Decreased efficacy of PPIs for peptic ulcers is seen in CYP2C19 \_\_\_\_\_.

PMs

What other tissues, besides the liver, have enzymes capable of drug metabolism?

the intestine, lung, kidney, skin, placenta, and bacteria in the intestine

What is a phase II transformation?

the endogenous substrate binds with functional group to form highly polar conjugate that is readily excreted

Many transformations are catalyzed by membrane-bound enzymes of the ______ and some by soluble enzymes in the \_\_\_\_\_.

smooth endoplasmic reticulum; cytosol

What is CYP2C9?

the enzyme that metabolizes warfarin

\_\_\_\_\_\_ include esterases and amidases.

Phase I hydrolysis reactions

What enzyme does warfarin target?

vitamin K reductase [VKORC1]

Drug-metabolizing enzymes have endogenous substrates and play role in \_\_\_\_\_.

normal metabolism

What analyzes blood-derived DNA to detect genetic polymorphisms in the activity of CYP2D6 and CYP2C19?

Amplichip® CYP450 Test

\_\_\_\_ reach adult levels in first few months and are used to design pro-drugs.

Esterases

Name 4 outcomes of drug metabolism.

1) inactivate drug 2) increase drug activation 3) activate previously unactive druge 4) make toxic metabolite

In N-acetylation, an _____ bond is formed via N-acetyltransferases.

amide

In cytochrome P-450-dependent oxidation, the substrate must be \_\_\_\_\_\_.

lipid soluble

What is the most common pathway of chemical transformation in the body?

oxidation

Phase I hydrolysis reactions include ____ and \_\_\_\_.

esterases; amidases

What is the Amplichip® CYP450 Test?

test that analyzes blood-derived DNA to detect genetic polymorphisms in the activity of CYP2D6 and CYP2C19?

\_\_\_\_\_\_\_ results in formation of strong acids with a pKa of 1.

Sulfate conjugation

Cytochrome P450 is part of an oxidation system that also includes the cofactor NADPH, the flavoprotein \_\_\_\_\_\_\_, and molecular O2.

NADPH-cytochrome P450 reductase

Where is monoamine oxidase located?

in the outer mitochondrial membrane

Full adult activity of ____ is not reached for 5 years.

alcohol dehydrogenase

In N-acetylation, an amide bond is formed via \_\_\_\_\_.

N-acetyltransferases

The cytochrome P-450-dependent oxidation has both ____ and \_\_\_\_\_.

inducibility and inhibition

Insufficient analgesia with codeine is seen in _____ PMs due to failure to metabolize to the active metabolite, morphine.

CYP2D6

Recent evidence has suggested that individual differences in response to the anticoagulant effects of warfarin may be based on genetic variations to?

1) enzyme that warfarin targets (vitamin K reductase[VKORC1]) 2) enzyme that metabolizes warfarin (CYP2C9)

What is the most common outcome of drug metabolism??

detoxification- excretion of metabolites that are pharmacologically inactive

\_\_\_\_\_\_ is part of an oxidation system that also includes the cofactor NADPH, the flavoprotein NADPH-cytochrome P450 reductase, and molecular O2.

Cytochrome P450

What do amidases do?

Hydrolyze amides to acids and amines

Hydrolysis of some glucuronides by intestinal bacterial enzymes (\_\_\_\_\_\_) results in the formation of free drug.

β-glucuronidase

What is another name for a phase II transformation?

conjugation

poor metabolizers

What is the significance of monoamine oxidase?

it's an important enzyme in neurotransmitter metabolism

What may be the source of drug interactions in antibiotics and oral contraceptives?

enterohepatic recirculation

Which enzymes in the smooth ER catalyze oxidation?

CYP450 enzymes

\_\_\_\_\_\_ with codeine is seen in CYP2D6 PMs due to failure to metabolize to the active metabolite, morphine.

Insufficient analgesia

Cytochrome P450 is part of an oxidation system that also includes the cofactor \_\_\_\_, the flavoprotein NADPH-cytochrome P450 reductase, and molecular O2.

NADPH

Name 4 conjugations.

1) Glucuronidation 2) N-Acetylation 3) Glutathione Conjugation 4) Sulfate Conjugation

\_\_\_\_\_ occur in cytochrome P-450-dependent oxidation, including CYP1, CYP2, and CYP3.

Many different isozymes

\_\_\_\_\_ are involved in the activation of certain sulfonamides.

Azo reductions

\_\_\_\_\_\_ can include the azo reduction, nitro reduction, or carbonyl reduction.

Phase I reductions

Why are CYP2D6 and CYP2C19 important?

they account for 25% of drug metabolism, including many antidepressants, antipsychotics, and opioid analgesics

\_\_\_\_\_ is seen in CYP2D6 UMs due to rapid metabolism to morphine.

Codeine intoxication

What is a phase I transformation?

an insertion or unmasking of a functional group to make the molecule more soluble

\_\_\_\_\_\_\_ have a limited role in drug metabolism but are extremely important in detoxification of carcinogens, pollutants, toxic metabolites.

Glutathione-S-transferases

Nonresponse to antidepressants has been reported in CYP2D6 \_\_\_\_.

UMs

The duration of action for most drugs would be extremely prolonged if terminated by ______ only.

renal excretion

What is the chemical transformation drugs undergo inside the patient called?

biotransformation or drug metabolism

Many different isozymes occur in cytochrome P-450-dependent oxidation, including \_\_\_\_, \_\_\_\_\_, and \_\_\_\_\_.

CYP1, CYP2, and CYP3

Cytochrome P450-independent oxidations include ______ and \_\_\_\_\_.

dehydrogenases; oxidases

Lipid-soluble compounds are generally converted to ______ that are then more readily excreted.

more water-soluble (more polar) compounds

What is the richest source of CYP450?

Liver smooth endoplasmic reticulum

Adult levels of _______ activity is reached by age 3-4 years.

Glucuronidation

Why are conjugations limited by supply and more easily saturable than phase I reactions?

the drug or drug metabolite is coupled to an endogenous biochemical unit (highly reactive) provided by a coenzyme

Phase I reductions can include \_\_\_\_\_, \_\_\_\_\_, and \_\_\_\_\_.

the azo reduction, nitro reduction, or carbonyl reduction

What hydrolyzes amides to acids and amines?

amidases

Drug metabolism is a detoxifying process involving formation of readily excreted metabolites that are \_\_\_\_\_.

pharmacologically inactive

Codeine intoxication is seen in CYP2D6 ____ due to rapid metabolism to morphine.

UMs

What enzyme metabolizes warfarin?

CYP2C9

Give 3 examples of drugs that begin as inactive compounds and are metabolized to create the active ingredient.

1) Omeprazole (to a Sulfenamide) 2) Enalapril (to Enalaprilat) 3) Valacyclovir (to Acyclovir)

Name 3 drugs that are metabolized faster in neonates than adults.

theophylline, phenytoin, phenobarbital

\_\_\_\_\_\_ include dehydrogenases and oxidases.

Cytochrome P450-independent oxidations

\_\_\_\_\_ can vary in enzyme activity and can be classified at the extremes as ultra-rapid (UM) metabolizers or poor metabolizers (PM) with total absence of enzyme.

Individual patients

Azo reductions are involved in the activation of \_\_\_\_\_.

certain sulfonamides

ultra-rapid