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[MT 6314] Pharmacology & Toxicology > Drug Biotransformation > Flashcards

Drug Biotransformation Flashcards

1
Q

Foreign substances absorbed across the lungs or skin or by
ingestion (either unintentionally or deliberately absorbed)

A

Xenobiotics

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2
Q

T/F: Exposure to environmental xenobiotics may be inadvertent and accidental or inescapable

A

T

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3
Q

T/F: All xenobiotics are innocuous.

A

F; Some

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4
Q

T/F: The mammalian drug biotransformation systems are thought to have first evolved from the need to detoxify and eliminate
plant and bacterial bioproducts and toxins, which later extended to drugs and other environmental xenobiotics

A

T

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5
Q

Plays a pivotal role in terminating the biologic
activity of some drugs, particularly those that have small molecular volumes, possess polar characteristics, and functional groups that are fully ionized at physiologic pH

A

Renal Excretion

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6
Q

Most drugs would have a prolonged duration of action if termination of their action depended solely on _______ _______.

A

Renal Excretion

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6
Q

T/F: Many drugs do not possess such physicochemical
properties

A

T

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7
Q

Is an alternative process that can lead to the termination or alteration of biologic activity

A

Metabolism

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8
Q

Are often less pharmacodynamically active than the parent drug and may even be inactive

A

Metabolic Products

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9
Q

T/F: Some biotransformation products have enhanced activity or toxic properties

A

T

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10
Q

Have been exploited in the design of pharmacologically inactive prodrugs that are converted to active molecules in the body.

A

Drug-metabolizing enzymes

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11
Q

The principal organ of drug metabolism

A

Liver

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11
Q

Give the 4 endogenous substrates.

The synthesis of endogenous substrates such as __________ involves many pathways catalyzed by enzymes associated with the metabolism of xenobiotics

A

1) Steroid Hormones
2) Cholesterol
3) Active Vitamin D Congeners
4) Bile Acids

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12
Q

Other tissues where biotransformations can occur

A

1) Gastrointestinal Tract
2) Lungs
3) Skin
4) Kidneys
5) Brain

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12
Q

After oral administration, many drugs are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism.

A

First-pass effect

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13
Q

May be metabolized by Gastric acid

A

Penicillin

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13
Q

Give orally administered drugs that are more extensively metabolized in the intestine than in the liver

A

1) Clonazepam
2) Chlorpromazine
3) Cyclosporine

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14
Q

Harbors intestinal microorganisms that are capable of many biotransformation reactions.

A

Lower Gut

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14
Q

Can contribute to the overall first-pass effect, and individuals with compromised liver function may rely increasingly on such this type of metabolism for drug elimination.

A

Intestinal Metabolism

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15
Q

May be metabolized by gastric digestive enzymes

A

Polypeptides such as insulin

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15
Q

Must be given 2 hours before the meals if given through the oral route

A

Penicillin

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15
Q

May be metabolized by enzymes in the wall of the intestine

A

Sympathomimetic Catecholamines

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16
Q

Drugs metabolized by intestinal wall enzymes

A

Epinephrine

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17
Q

Can occur by spontaneous and non catalyzed chemical reactions, but mostly catalyzed by specific cellular enzyme

A

Drug biotransformation in vivo

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18
Q

Drug Biotransformation In Vivo: At subcellular level, enzymes are located in

A

1) Endoplasmic Reticulum
2) Mitochondria
3) Cytosol
a. Lysosomesnuclear envelope
b. Plasma membrane

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19
Q

Many drug metabolizing enzymes are located in the

A

Lipophilic endoplasmic reticulum of the liver & other tissues

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20
Q

Through homogenization and fractionation of the cell

A

Isolation of Lamellar Membranes

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21
Q

Are reformed into microsomes (vesicles)

A

Lamellar Membranes

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22
Q

Retain most of the morphologic and functional
characteristics of the intact membranes such as Rough and smooth surface features of the rough (ribosome-studded) and smooth (no ribosomes) endoplasmic reticulum

A

Microsomes

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23
Q

Dedicated to protein synthesis

A

Rough microsomes

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24
Q

Relatively rich in enzymes responsible for oxidative
drug metabolism

A

Smooth microsomes

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25
Q

Contain the important class of enzymes known as the
mixed function oxidases (MFOs), or monooxygenases

A

Smooth microsomes

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26
Q

MFOs require

A

1) A reducing agent (nicotinamide adenine dinucleotide phosphate [NADPH])
2) A molecular oxygen (O2)

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27
Q

MFOs in a typical reaction

A

One molecule of oxygen is consumed/reduced per substrate molecule

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28
Q

Plays a key role in the oxidation-reduction process

A

Microsomal Enzymes

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29
Q

One mole of NADPH CPR

A

1) One mole of flavin mononucleotide (FMN)
2) One mole flavin adenine dinucleotide (FAD)

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29
Q

A flavoprotein

A

NADPH cytochrome P450 oxidoreductase / POR / CPR

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30
Q

A hemoprotein which serves as the terminal oxidase

A

Cytochrome P450 / P450 / CYP

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31
Q

Name is derived from the spectral properties of this hemoprotein

A

Cytochrome P450

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32
Q

Microsomal membrane harbors multiple forms of ____

A

P450

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33
Q

Is increased by repeated administration of or exposure to exogenous chemicals

A

Multiplicity

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34
Q

Binds to carbon monoxide to give a complex that absorbs light maximally at 450 nm

A

Reduced (ferrous) form

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35
Q

T/F: Relative abundance of P450s compared with that of the reductase in liver contributes to making P450 heme reduction a rate-limiting step in hepatic drug oxidations.

A

T

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36
Q

Microsomal Drug Oxidations Require

A

1) P450
2) P450 reductase
3) NADPH
4) a molecular oxygen

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37
Q

In microsomal drug oxidations, __________ of this activated oxygen permit oxidation of a large number of substrates

A

Potent oxidizing properties

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38
Q

is very low for this enzyme complex (Microsomal Drug Oxidations)

A

Substrate specificity

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39
Q

Are remarkably sluggish catalysts and their drug biotransformation reactions are slow.

A

P450s

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39
Q

Is the only common structural feature of the wide variety of structurally unrelated drugs and chemicals that serve as substrates in this system

A

High lipid solubility

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40
Q

Mechanism by which the body terminates the action of some drugs

A

Drug Metabolism

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41
Q

3 possible pathways of drug metabolism

A

1) Active > Inactive (readily excreted by the kidneys)
2) Active > Active Metabolites
3) Inactive > Active (Prodrug)

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42
Q

T/F: Metabolism of drugs does not always lead to detoxification and elimination of compounds.

A

T

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43
Q

May also occur in the metabolism of drugs to toxic products, thereby generating reactive O2 species (ROS) and consequent oxidative stress that greatly enhance acetaminophen-induced hepatotoxicity.

A

Redox Cycling

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44
Q

Identified by Gene arrays

A

P450 isoforms in liver

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45
Q

Identified by Immunoblotting analyses of microsomal preparations

A

P450 isoforms in liver

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46
Q

Identified by use of relatively selective functional markers and selective P450 inhibitors

A

P450 isoforms in liver

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47
Q

Most important P450 forms

A

§ CYP1A2 (15%)
§ CYP2A6 (4%)
§ CYP2B6 (1%)
§ CYP2C9 (20%)
§ CYP2D6 (5%)
§ CYP2E1 (10%)
§ CYP3A4 (30%)
§ Isoform (Approximate percentage in the total human
liver P450 content)

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48
Q

Responsible for the metabolism of over 50% of the prescription drugs metabolized by the liver.

A

CYP3A4

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49
Q

They are responsible for catalyzing the bulk of the hepatic drug and xenobiotic metabolism

A

P450 Forms

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50
Q

Selective functional markers

A

In vitro

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51
Q

Selective chemical P450 inhibitors

A

In vitro

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52
Q

P450 antibodies

A

In vitro

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52
Q

Relatively selective noninvasive marker

A

In vivo

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53
Q

Including breath tests or urinary analyses of specific metabolites after administration of a P450-selective substrate probe

A

In vivo

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54
Q

Repeated administration of some of the chemically dissimilar P450 substrate drugs induce P450 expression by (1) enhancing the rate of its synthesis & (2) reducing its rate of degradation

A

Enzyme Induction

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55
Q

Results in accelerated substrate metabolism and usually in a decrease in the pharmacologic action of the inducer and of co-administered drugs

A

Enzyme Induction

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56
Q

In cases of drugs metabolically transformed to reactive metabolites, ________ may exacerbate metabolite-mediated toxicity

A

Induction

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57
Q

Characteristics of various substrates induce P450 isoforms

A

1) Having different molecular masses
2) Exhibiting different substrate specificities and immunochemical and spectral characteristics.

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58
Q

Capable of inducing P450 enzymes

A

Environmental chemicals and pollutants

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59
Q

Examples of Environmental chemicals and pollutants

A

benzo[a]pyrene and other
polycyclic aromatic hydrocarbons, which are present in tobacco smoke, charcoal-broiled meat, and other organic pyrolysis products

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60
Q

A trace byproduct of the chemical synthesis of the
defoliant 2,4,5-T

A

2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD)

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60
Q

Used widely in industry as insulating materials and
plasticizers

A

Polychlorinated biphenyls (PCBs)

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61
Q

Increased P450 synthesis requires enhanced transcription, translation, and synthesis of _____, its prosthetic cofactor

A

Heme

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62
Q

Cytoplasmic receptor (AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified

A

CYP1A induction

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63
Q

Seen in cruciferous vegetables, and the proton pump inhibitor, omeprazole

A

CYP1A induction

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64
Q

Process of CYP1A Induction

A

1) Translocation
2) Ligand-induced Dimerization with Arnt
3) Subsequent activation of regulatory elements of CYP1A genes
4) CYP1A Induction

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65
Q

Relatively large and structurally diverse phenobarbital class of inducers of CYP2B6, CYP2C9, and CYP3A4.

A

Constitutive androstane receptor (CAR)

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66
Q

Mediated by a pregnane X receptor (PXR), a member of the steroid-retinoid-thyroid hormone receptor family by various chemicals in the liver and intestinal mucosa

A

CYP3A induction

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67
Q

Nuclear receptor highly expressed in liver and kidneys

A

Peroxisome proliferator receptor α (PPAR-α)

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68
Q

Consistent with its major role in the regulation of fatty
acid metabolism

A

Peroxisome proliferator receptor α (PPAR-α)

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68
Q

Uses lipid-lowering drugs as ligands such as Fenofibrate & Gemfibrozil

A

Peroxisome proliferator receptor α (PPAR-α)

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69
Q

Responsible for the metabolism of fatty acids

A

Peroxisome proliferator receptor α (PPAR-α)

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69
Q

Mediates the induction of CYP4A enzymes

A

Peroxisome proliferator receptor α (PPAR-α)

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70
Q

PXR, CAR, and PPAR-α each form heterodimers with another nuclear receptor, the ________________.

A

retinoid X-receptor (RXR)

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71
Q

This heterodimer (retinoid X-receptor (RXR), in turn, binds to response elements within the promoter regions of specific P450 genes to
induce _________

A

Gene Expression

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72
Q

Effectively reduce the metabolism of (1) endogenous substrates (e.g., testosterone) & (2) other co-administered drugs through competitive inhibition

A

Imidazole-containing drugs

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72
Q

Certain drug substrates inhibit cytochrome P450 enzyme activity

A

Enzyme Inhibition

72
Q

Bind tightly to the P450 heme iron

A

Imidazole-containing drugs

73
Q

ketoconazole

A

Imidazole-containing drugs

73
Q

cimetidine

A

Imidazole-containing drugs

74
Q

troleandomycin

A

Macrolide antibiotics

75
Q

erythromycin & derivatives

A

Macrolide antibiotics

76
Q

Are metabolized, apparently by CYP3A, to metabolites
that complex the cytochrome P450 heme iron and render
it catalytically inactive

A

Macrolide antibiotics

77
Q

Binds tightly to the heme iron and quasi-irreversibly
inactivates the enzyme, thereby inhibiting the metabolism of potential substrates.

A

Proadifen

78
Q

T/F: Some substrates irreversibly inhibit P450s via covalent interaction of a metabolically generated reactive intermediate

A

T

79
Q

Inhibitors of P450s may react with?

A

1) P450 Apoprotein
2) Heme Moiety

80
Q

Inhibitors of P450s may cause?

A

Heme to fragment and irreversibly modify the apoprotein

81
Q

Antibiotic and metabolized by CYP2B1 to a species - modifies the P450 protein & inactivates the enzyme

A

Chloramphenicol

82
Q

Inactivators that attack the heme or the protein moiety

A

Suicide inhibitors

83
Q

A barbiturate & inactivates CYP2B1 by modification of both its heme and protein moieties

A

Secobarbital

84
Q

Other metabolically activated drugs whose P450 inactivation
mechanism is not fully elucidated

A

1) Mifepristone
2) Troglitazone
3) Raloxifene
4) Tamoxifen

85
Q

Types of Metabolic Reactions

Non-synthetic reactions

A

Phase 1

86
Q

Types of Metabolic Reactions

Converts the parent drug to a more polar conjugate (water
soluble) or more reactive product

A

Phase 1

87
Q

Types of Metabolic Reactions

Done by introducing/ inserting/ unmasking a polar functional group (OH, SH, NH2)

A

Phase 1

88
Q

Types of Metabolic Reactions

Oxidation

A

Phase 1

89
Q

Types of Metabolic Reactions

Deamination

A

Phase 1

89
Q

Types of Metabolic Reactions

Reduction

A

Phase 1

90
Q

Types of Metabolic Reactions

Hydrolysis

A

Phase 1

91
Q

T/F: In Phase 1, if metabolites are sufficiently polar, they may be readily excreted

A

T

92
Q

T/F: If metabolites are not eliminated rapidly, they will undergo phase II

A

T

93
Q

T/F: Metabolites in Phase 1 may be active, modified, or enhanced

A

F; inactive

94
Q

Types of Metabolic Reactions

Used for synthetic reactions

A

Phase 2

95
Q

Types of Metabolic Reactions

Endogenous substrate is added to the parent drug to make it more polar

A

Phase 2

96
Q

Types of Metabolic Reactions

Glucuronidation- addition of glucoronic acid

A

Phase 2

97
Q

Types of Metabolic Reactions

Acetylation-acetyl CoA

A

Phase 2

98
Q

Types of Metabolic Reactions

Sulfation

A

Phase 2

99
Q

Types of Metabolic Reactions

Methylation

A

Phase 2

100
Q

Types of Metabolic Reactions

Glycine conjugation - glycine

A

Phase 2

101
Q

Types of Metabolic Reactions

Glutathione conjugation

A

Phase 2

102
Q

Types of Metabolic Reactions

H2O conjugation – addition of OH and H+ without hydrolysis

A

Phase 2

103
Q

Type of Conjugation

Endogenous Reactant: UDP glucuronic acid (UDPGA)

Transferase (Location): UDP glucuronosyl- transferase (microsomes)

Types of Substrates: Phenols, alcohols, carboxylic acids, hydroxylamines, sulfonamides

Examples: Nitrophenol, morphine, acetaminophen, diazepam, N-hydroxydapsone, sulfathiazole, meprobamate, digitoxin, digoxin

A

Glucuronidation

104
Q

Type of Conjugation

Endogenous Reactant: Acetyl-CoA

Transferase (Location): N- Acetyltransferase (cytosol)

Types of Substrates: Amines

Examples: Sulfonamides, isoniazid, clonazepam, dapsone, mescaline

A

Acetylation

105
Q

Type of Conjugation

Endogenous Reactant: Glutathione (GSH)

Transferase (Location): GSH-S-transferase (cytosol, microsomes)

Types of Substrates: Epoxides, arene oxides, nitro groups, hydroxylamines

Examples: Acetaminophen, ethacrynic acid, bromobenzene

A

Glutathione conjugation

106
Q

Type of Conjugation

Endogenous Reactant: Glycine

Transferase (Location): Acyl-CoA glycinetrans​ferase (mitochondria)

Types of Substrates: Acyl-CoA derivatives of carboxylic acids

Examples: Salicylic acid, benzoic acid, nicotinic acid, cinnamic acid, cholic acid, deoxycholic acid

A

Glycine conjugation

107
Q

Type of Conjugation: Sulfation

Endogenous Reactant: Phosphoadenosyl phosphosulfate (PAPS)

Transferase (Location): Sulfotransferase (cytosol)

Types of Substrates: ?

Examples: Estrone, aniline, phenol, 3-hydroxycoumarin, acetaminophen, methyldopa

A

Phenols, alcohols, aromatic amines

107
Q

Type of Conjugation: Water conjugation

Endogenous Reactant: Water

Transferase (Location): ?

Types of Substrates: Arene oxides, cis- disubstituted and monosubstituted oxiranes

Examples: Benzopyrene 7,8-epoxide, styrene 1,2-oxide, carbamazepine epoxide

A

Epoxide hydrolase (microsomes)

108
Q

Type of Conjugation: ?

Endogenous Reactant: Water

Transferase (Location): Cytosol

Types of Substrates: Alkene oxides, fatty acid, epoxides

Examples: Leukotriene A4

A

Water Conjugation

109
Q

T/F: Phase II reactions are relatively faster than P450-catalyzed reactions, thus effectively accelerating drug biotransformation.

A

T

110
Q

T/F: Parent drugs or their phase II metabolites that contain suitable chemical groups often undergo coupling or conjugation reactions with an endogenous substance to yield drug conjugates.

A

F; Phase II

111
Q

Are polar molecules that are readily excreted and often inactive.

A

Conjugates

112
Q

involves:
o High-energy intermediates
o Specific transfer enzymes (Transferases) - located in
microsomes in the cytosol.

A

Conjugate Formation

113
Q

Is known to activate prodrug minoxidil and morphine-6-glucuronide.

A

Sulfation

114
Q

May lead to the formation of reactive species responsible for the toxicity of the drugs

A

Conjugation Reactions

115
Q

Other Conjugation Reactions

A

1) acyl-glucuronidation
2) O-sulfation
3) N-acetylation

115
Q

Phase _ > Phase _ is the most common pathway

A

Phase I > Phase II

116
Q

Pathway that most drug uses

A

Phase I → Phase II

117
Q

Pathway that other drug uses

A

Phase II → Phase I

118
Q

Are anti-tubercular drugs

A

Isoniazid

119
Q

What drug?

Acetylation (Phase 2) precedes hydrolysis (Phase 1)

A

Isoniazid

120
Q

Is known to form an N-acetyl conjugate in a phase II reaction. This conjugate is then a substrate for a phase I type reaction, namely, hydrolysis to isonicotinic acid

A

Hydrazide moiety of isoniazid

121
Q

Most important organ for drug metabolism

A

Liver

122
Q

Activity of these SER enzymes require:

A

1) NADPH (reducing agent)
2) Molecular form of oxygen

122
Q

Contains high concentration of Phase 1 enzymes

A

Smooth endoplasmic reticulum (SER) in the liver

123
Q

Rates of drug metabolism and elimination and is determined by

A

1) Genetic Factors
2) Nongenetic Variables
3) Nutritional and Environmental Factors

124
Q

Those that influence enzyme levels account for some of these differences, giving rise to genetic polymorphisms in drug metabolism

A

Genetic Factors

125
Q

Occurrence of a variant allele of a gene at a population frequency of ≥1%

A

True genetic polymorphism

126
Q

Ester that is metabolized by plasma choline esterase

A

Succinylcholine

126
Q

T/F: Genetic polymorphisms in both phase I and II drug-
metabolizing enzymes exist that result in altered efficacy of drug therapy or adverse drug reactions (ADRs)

A

T

127
Q

In most individuals, the process occurs rapidly (duration of action is 5 minutes; muscle relaxant)

A

Hydrolysis of Esters ; Succinylcholine

128
Q

Genetic Factor

Isoniazid (INH)

A

Acetylation of Amines

129
Q

Genetic Factor

hydralazine and procainamide

A

Acetylation of Amines

130
Q

T/F: Slow Acetylators cause individuals deficient in acetylating capacity and prolonged or toxic responses to normal doses of this drug

A

T

131
Q

Genetic Factor

Dextrometorphan, metoprolol and some tricyclic antidepressants

A

Oxidation

132
Q

Genetic Factor

Oxidation by P450 isoenzymes are genetically predetermined

A

Oxidation

133
Q

Often transmitted as autosomal recessive traits

A

Phase I Enzyme Polymorphisms

134
Q

May be expressed at any one of the multiple metabolic
transformations that a chemical might undergo

A

Phase I Enzyme Polymorphisms

135
Q

Occurs in 3-10% of Caucasians and inherited as an autosomal recessive trait

A

Debrisoquin-sparteine Oxidation Polymorphism

136
Q

Precise molecular basis for the defect: faulty expression
of the P450 protein

A

Debrisoquin-sparteine Oxidation Polymorphism

137
Q

Occurs due to the presence of CYP2D6 allelic variants with up to 13 gene copies in tandem

A

Ultrarapid Metabolism (UM)

137
Q

Stereoselective and is catalyzed by CYP2C19 and inherited as an autosomal recessive trait

A

Aromatic (4)-hydroxylation of the anticonvulsant mephenytoin

137
Q

Extensively hydroxylated by CYP2C19 at the 4 position of the phenyl ring before glucuronidation and rapid excretion in the urine

A

Normal extensive metabolizers (EM)

138
Q

Totally lack the stereospecific (S)-mephenytoin
hydroxylase activity and both (S)- and (R)-mephenytoin enantiomers are N-demethylated to nirvanol

A

Poor metabolizers (PM)

139
Q

Shows signs of profound sedation and ataxia after
doses of the drug that are well tolerated by normal
metabolizers

A

Poor metabolizers (PM)

140
Q

Associated with increased transcription and thus higher
CYP2C19 expression and even higher functional acitivity
that that of the wild type CYP2C19-carrying EMs

A

CYP2C19*17

141
Q

Encodes an Arg144Cys mutation and exhibits impaired functional interactions with POR

A

CYP2C9*2

142
Q

Encodes an Ile359Leu mutation and lowered affinity for many substrates

A

CYP2C9*3

143
Q

Contribution to the well-known interindividual variability in drug metabolism is limited

A

Allelic variants of CYP3A4

144
Q

Most polymorphic P450 genes

A

CYP2B6 Polymorphisms

145
Q

Results from a single nucleotide polymorphism (SNP) within intron 3

A

CYP3A5 Protein Polymorphism

146
Q

Defect in slow acetylators (of isoniazid and similar
amines)

A

Phase II Enzyme Polymorphisms

147
Q

Caused by the synthesis of less of the NAT2 enzyme rather than of an abnormal form of it

A

Phase II Enzyme Polymorphisms

148
Q

Results in a rapidly degraded mutant enzyme and
consequently deficient S-methylation of aromatic and heterocyclic sulfhydril compounds the anti-cancer thiopurine drugs 6-mercaptopurine, thioguanine, and azathioprine, required for their detoxification

A

TPMT (thiopurine S-methyltransferase) gene

148
Q

Increases risk of thiopurine drfug-induced fatal
hematopoietic toxicity

A

TPMT (thiopurine S-methyltransferase) gene

149
Q

Associated with hyperbilirubinemic diseases (Gilbert Syndrome)

A

UGT polymorphism (UGT1A1*28)

150
Q

Expression can lead to significant adverse effects and toxicities of drugs dependent on its GSH conjugation for elimination

A

Genetic polymorphisms (GSTM1) in GST (mu1 isoform)

151
Q

Could greatly enhance safe and efficacious clinical therapy through dose adjustment or alternative drug therapy, thereby curbing much of the rising ADR incidence and its associated costs.

A

Genotype information

152
Q

Diet and Environmental Factors

Inhibits the effect of the drug

A

Charcoal

153
Q

Diet and Environmental Factors

Increases the amount
of drug in the body

A

Grapefruit Juice

154
Q

T/F: Drug metabolites do not differ in young and old

A

F; does differ

155
Q

T/F: Males metabolize drugs faster than females

A

T

156
Q

Age & Sex

T/F: Children and elderly metabolize drugs slower

A

T

157
Q

Disease affecting drug metabolism

A

Hyperthyroidism

158
Q

T/F: Thyroid hormone increases the metabolism

A

T

159
Q

Other Drugs

Increase rate of synthesis of the enzyme

A

Enzyme Induction

160
Q

Other Drugs

Reduce the rate of degradation of the enzyme

A

Enzyme Induction

161
Q

Other Drugs

May also induce self metabolism of the drug

A

Enzyme Induction

162
Q

Other Drugs

May also induce metabolism of other drugs and reduce its effects

A

Enzyme Induction

163
Q

T/F: Increase susceptibility to pharmacologic/toxic activity of drugs: very young and very old patients

A

T

164
Q

T/F: Slower metabolism could be due to reduced activity
of metabolic enzymes or reduced availability of
essential endogenous co-factors.

A

T

165
Q

6 acute or chronic diseases that affect liver architecture or function markedly affect hepatic metabolism of some drugs

A

1) alcoholic hepatitis
2) active/inactive alcoholic cirrhosis
3) hemochromatosis
4) chronic active hepatitis
5) biliary cirrhosis
6) acute viral/drug-induced hepatitis.

166
Q

Impaired hydrolysis
of procainamide and procaine

A

Chronic respiratory insufficiency

167
Q

Decreases the half-life of
antipyrine, digoxin, methimazole, and some β
blockers

A

Hyperthyroidism

167
Q

Increased half-life of antipyrine (a P450 functional probe)

A

Lung Cancer

168
Q

Increases the half-life of antipyrine, digoxin, methimazole, and some β blockers

A

Hypothyroidism

169
Q

↓ Therapeutic Window _ Toxicity

A

↑

170
Q

Enzyme inducers + drug =

A

Decreased Effects

171
Q

4 Enzyme Inducers

A

1) Phenobarbital
2) Carbamazepine
3) Phenytoin
4) Rifampicin

172
Q

Other Drugs

Metabolism of the drug is diminished

A

Enzyme Inhibition

173
Q

Other Drugs

Increase effect of the drug

A

Enzyme Inhibition

174
Q

Enzyme inhibitors + drug =

A

increased effect

175
Q

5 Enzyme Inhibitors

A

1) Amiodarone
2) Cimetidine
3) Ketoconazole
4) Ritonavir
5) Furanocoumarin

176
Q

Types of Drug Interaction Mechanism

Cholestyramine inhibits the effect of digoxin when combined with it

A

Altered absorption

177
Q

Types of Drug Interaction Mechanism

Affects drug action

A

Altered metabolism

178
Q

Types of Drug Interaction Mechanism

Plasma protein binding would diminish the amount of
drug that would reach the receptors

A

Altered plasma binding protein

179
Q

Types of Drug Interaction Mechanism

Probenecid inhibits the secretion of acids

A

Altered excretion

180
Q

Types of Drug Interaction Mechanism

Penicillin inhibits the excretion of probenecid

A

Altered excretion

181
Q

Drug Interaction

1+1=2
Response elicited by combined drugs is equal to the combined response of the individual drugs

A

Additive

182
Q

Drug Interaction

Sedative + Ethanol

A

Additive

183
Q

Drug Interaction

1+1=3 Response elicited by combined drugs is greater than the combined responses of each individual

A

Synergistic

184
Q

Drug Interaction

0+1=2 Drug which has no effect enhances the effect of the second drug

A

Potentiation

185
Q

Drug Interaction

Cimetidine + anticoagulant

A

Potentiation

186
Q

Drug Interaction

1+1=0 Drug inhibits the effect of another drug

A

Antagonism

187
Q

Drug Interaction

Heparin + protamine

A

Antagonism

187
Q

A sedative inducer of note, a popular over-the-counter herbal medicine ingested as treatment for mild to severe depression.

A

St. John’s wort

188
Q

T/F: Some drugs require conjugation with endogenous substrates such as GSH, glucuronic acid, or sulfate for their inactivation.

A

T

[MT 6314] Pharmacology & Toxicology (20 decks)

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