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Biochem Lec > Drug Metabolism > Flashcards

Drug Metabolism Flashcards

1
Q

body’s mechanism for processing, using, inactivating, and
eventually eliminating foreign substances, including drugs.

A

Metabolism i

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2
Q

recognizes the drug as a
foreign substance can break down or alter the chemical structure of drugs,
making them less active, or inert.

A

liver,
the blood, the lymph fluid, or any body tissue

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3
Q

role of these enzymes is to
degrade or modify the foreign structure, such that it can be more
easily excreted.

A

metabolic enzymes

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4
Q

defined as any
foreign substances or exogenous chemicals which the body does not recognize such as drugs, pollutants, others

A

Xenobiotics

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5
Q

once in the bloodstream, these molecules can ———– through other membranes and be distributed
effectively to reach various target organs to exert their pharmacological actions.

A

diffuse passively

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6
Q

for excretion

A

water soluble

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7
Q

for metabolism

A

lipophilic

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8
Q

Consequences of Drug Metabolism

A

May yield inactive metabolites (“detoxification of the drug”)
May retain similar activity
May produce metabolites with altered activity
Production of bioactivated metabolites

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9
Q

Hydrolysis of procaine to p- aminobenzoic acid & diethylethanolamine

A

(loss of anesthetic activity)

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10
Q

Oxidation of 6- mercaptopurine to 6- mercapturic acid

A

(loss of anticancer activity

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11
Q

Imipramine is demethylated

A

equally active antidepressant, desipramine

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12
Q

Acetohexamide is reduced

A

more active hypoglycemic, I- hydroxyhexamide

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13
Q

Codeine is demethylated

A

more active analgesic, morphine

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14
Q

Hydroxyzine (an antihistamine) can be metabolized

A

Cetirizine

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15
Q

antidepressant, Iproniazid is dealkylated

A

antitubercular drug, Isoniazid

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16
Q

retinoic acid (Vitamin A) is isomerized

A

anti- acne agent, isoretinoic acid

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17
Q

parent compounds

A

prodrugs

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18
Q

prodrug enalapril is hydrolyzed

A

enalaprilat

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19
Q

prodrug sulindac, a sulfoxide, is reduced

A

active sulfide (antibacterial)

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20
Q

antiparkinsonian levodopa (L- dopa) is decarboxylated

A

active dopamine

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21
Q

Sites of Drug Metabolism

A

Liver
Extrahepatic Metabolism

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22
Q

primary site of drug metabolism, functions to detoxify and facilitate excretion of xenobiotics (foreign
drugs or chemicals) by enzymatically converting lipid-soluble compounds to more water-soluble compounds.

A

liver

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23
Q

protect the organism against an accumulation of lipidsoluble exogenous and endogenous compounds by converting them to water-soluble metabolites which can be
easily excreted by the kidney are enymes located in

A

endoplasmic reticulum of liver cells

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24
Q

present in the liver are responsible for much of drug
metabolism

A

Cytochrome P450 enzyme species

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25
Q

affect the rate of
metabolism of a person.

A

liver cirrhosis, liver cancer, fatty liver disease, hepatitis,

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26
Q

drug biotransformation/ metabolism that takes place in tissues other than the liver

A

Extrahepatic Metabolism

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27
Q

Extrahepatic Metabolism

A

Plasma
Intestinal mucosa
Intestinal bacterial flora
Stomach
Nasal mucosa

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28
Q

Contains esterase enzymes which are responsible primarily for the hydrolysis of esters

A

Plasma

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29
Q

can activate a variety of prodrugs

A

, plasma esterases

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30
Q

Lipid- soluble drug passes through the intestinal mucosa which contains enzymes such as CYP 34A

A

Intestinal mucosa

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31
Q

Drug can be metabolized even before entering the blood

A

first pass effect

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32
Q

examples of drugs that easily undergo first- pass effect

A

imipramine
lignocaine
beta blockers
morphine
testosterone
Salbutamol
Cimetidine
Diazepam
Morphine

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33
Q

converts vitamin precursor to their active forms
convert certain substances to their toxic forms

A

Bacterial flora

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34
Q

enzyme that Intestinal flora produces which can also be responsible for metabolism

A

azoreductase

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35
Q

Intestinal bacterial flora secrete enzyme which can metabolize drugs

A

beta- glucuronidase

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36
Q

Has enzymes necessary for metabolism and has an acidic environment

A

Stomach

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37
Q

Provides a high level of CYP450 enzymes that can cause metabolism

A

Nasal mucosa

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38
Q

microsomal superfamily of
isoenzymes that catalyzes the oxidation of many drugs.

A

cytochrome P-450 (CYP450)

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39
Q

enzymes metabolize 90% of drugs.

A

CYP1A2 (2%), CYP2C9 (15%), CYP2C19 (15%), CYP2D6 (25%), CYP3A4
(60%), and CYP3A5 (2%)

40
Q

true or false :
Drugs may be metabolized by only one CYP450 enzyme (e.g., metoprolol by CYP2D6) or by multiple enzymes (e.g.,
warfarin [Coumadin] by CYP1A2, CYP2D6, and CYP3A4)

A

true

41
Q

With aging, the liver’s capacity for metabolism through the CYP450 enzyme system is reduced by ——-
because hepatic volume and blood flow are decreased.

A

≥ 30%

42
Q

commonly due to impairments in the state of the enzymatic systems.

A

Qualitative changes

43
Q

evolve in two directions:

A

Quantitative changes

44
Q

the stimulation of enzymatic activity

A

(enzyme induction

45
Q

the reverse, a reduction in enzyme activity

A

(enzyme inhibition

46
Q

drug that causes change

A

precipitant drug

47
Q

drug that undergoes change

A

object drug

48
Q

block the metabolic activity of one or more CYP450 enzymes.
The extent to which an inhibitor affects the metabolism of a drug depends upon factors such as the dose and the
ability of the inhibitor to bind to the enzyme.

A

Inhibitors

49
Q

increase CYP450 enzyme activity by increasing enzyme synthesis.
Unlike metabolic inhibition, there is usually a delay before enzyme activity increases, depending on the half-life of the
inducing drug

A

Inducers

50
Q

These will slow down substrate drug metabolism and increase drug effect.

A

Enzyme inhibitor

51
Q

These will speed up substrate drug metabolism and decrease drug effect.

A

Enzyme inducer

52
Q

Phase I Metabolic Reactions

A

(Functionalization Reaction Phase)

53
Q

Phase II Metabolic Reactions

A

(Conjugation Reaction Phase)

54
Q

phase I reactions

A

oxidative processes (aromatic hydroxylation; aliphatic hydroxylation; N—, O—,
and S-dealkylation; N-hydroxylation; N-oxidation;

sulfoxidation; deamination; and dehalogenation),

reductive
(azoreduction, nitroreduction)

hydrolytic reactions.

55
Q

purpose of these phase 1 metabolism reactions is to produce a compound with

A

increased polarity and
enhanced water solubility.

56
Q

reactions undergone depend on;

A

nature of the available enzymes,
ii. the hydrocarbon skeleton of the drug and
iii. the functional groups present.

57
Q

Phase I metabolic reactions are done by either of two ways:

A

Direct introduction of a functional polar group into the xenobiotic molecule; or
ii. Modifying or “unmasking” existing functionalities

58
Q

first step of drug metabolism.

A

Oxidation

59
Q

Conversion of a hydrogen to a hydroxyl group.

A

hydroxylation

60
Q

Conversion of a hydroxyl group to a carbonyl group

A

R-C-OH ⇒ R-C=O (dehydrogenation)

61
Q

Conversion of a carbonyl group to a carboxyl group.

A
  • R-C=O ⇒ R-COOH (carboxylation)
62
Q

R-C-NH2⇒R-C=O Conversion of an amino group to a carbonyl group

A

.(deamination)

63
Q

R-CH3⇒ R-H

A

(demethylation)

64
Q

enzymes of oxidation

A

mixed-function oxidases,
monoxygenases,
cytochrome P450 enzymes.

65
Q

Reactions resulting in the addition of hydrogen and/or the removal of oxygen

A

Reduction

66
Q

R-OH ⇒ R-H

A

(de-hydroxylation)

67
Q
  • R-C=O ⇒ R-C-OH
A

(hydrogenation)

68
Q

(decarboxylation)

A

R-COOH ⇒ R-C=O

69
Q

R-NO2⇒ R-NH2

A

(amination)

70
Q

R-C-H ⇒ R-CH3

A

(methylation)

71
Q

Enzymes involved in reduction reactions

A

reductases

72
Q

In a reaction with water, a bond in the compound is broken, resulting in two compounds. At the same time the
water molecule splits in two, with a hydrogen transferring to one of the compounds and a hydroxide to the
other compound.

A

Hydrolysis

73
Q

R-COO-R’ + H2O

A

R-COOH + R’-OH

74
Q

R-CO-NH-R’ + H2O

A

R-CO-NH-R’ + H2O

75
Q

e enzymes of hydrolysis reactions

A

esterases, peptidases, and amidases.

76
Q

synthetic reactions where the product
or the metabolite from Phase I gets conjugated. This always produces a large, polar, metabolite that is readily excreted
from the body.

A

Conjugation reactions a

77
Q

Phase II reactions

A

glucuronidation,
sulfation,
amino acid conjugation,
acetylation,
methylation or
glutathione conjugation to facilitate
elimination

78
Q

Glucuronidation
Co- enzyme:
Transfer enzyme:

A

Co- enzyme: UDP-GA (Uridine diphosphateglucuronic acid)
Transfer enzyme: UDP (Uridine diphosphate) glucuronyl transferase

79
Q

Glucuronidation Most Susceptible Functional Groups

A

-OH, -COOH, -NH2, -SO2NH2

80
Q

Sulfation
Co-enzyme:
Trasnfer enzyme:

A

Co-enzyme: PAPS (3’-Phosphoadenosine-5’-
phosphosulfate)
Trasnfer enzyme: sulfotransferases

81
Q

Sulfation Most Susceptible Functional Groups

A

-OH, -NH2, -SO2NH2, -NHOH

82
Q

Glutathione Conjugation
Transfer enzyme

A

Transfer enzyme: Glutathione-S-transferase

83
Q

Amino acid Conjugation
Co-enzyme
Transfer enzyme

A

Co-enzyme: acyl-CoA synthetase
Transfer enzyme: N-acetyltransferase

84
Q

Acetylation
Co-enzyme
Transfer enzyme

A

Co-enzyme: acyl-CoA synthetase
Transfer enzyme: N-acetyltransferase

85
Q

Methylation
Transfer enzyme:

A

Transfer enzyme: methyltransferases

86
Q

Glutathione Most Susceptible Functional Groups

A

Alkyl halides, alkyl nitrates, epoxides,
lactones, electrophilic centers

87
Q

Amino acid Conjugation Most Susceptible Functional Groups

A

-COOH, -NH2

88
Q

Acetylation Co-enzyme Most Susceptible Functional Groups

A

-OH, -NH2, -SO2NH2, -NHOH, -NHNH2

89
Q

Methylation Most Susceptible Functional Groups

A

-OH, NH2, -SH

90
Q

Active metabolite of the prodrug simvastatin

A

B-hydroxy acid metabolite

91
Q

Active metabolite of the prodrug Capacitabine

A

Fluorouracil

92
Q

Active metabolite of the prodrug Ramipril

A

Ramiprilat

93
Q

Active metabolite of the prodrug of Terfenadine

A

Fexofenadine

94
Q

Allopurinol

A

Oxypurinol

95
Q

Active metabolite of the prodrug of Bambuterol

A

Terbutaline

96
Q

Nabumetone

A

6 methoxy-2-naphthylacetic acid

Biochem Lec (2 decks)

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