Drug Biotransformation Flashcards
(214 cards)
1
Q
Foreign substances absorbed across the lungs or skin or by
ingestion (either unintentionally or deliberately absorbed)
A
Xenobiotics
2
Q
T/F: Exposure to environmental xenobiotics may be inadvertent and accidental or inescapable
A
T
3
Q
T/F: All xenobiotics are innocuous.
A
F; Some
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
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
6
Q
Most drugs would have a prolonged duration of action if termination of their action depended solely on _______ _______.
A
Renal Excretion
6
Q
T/F: Many drugs do not possess such physicochemical
properties
A
T
7
Q
Is an alternative process that can lead to the termination or alteration of biologic activity
A
Metabolism
8
Q
Are often less pharmacodynamically active than the parent drug and may even be inactive
A
Metabolic Products
9
Q
T/F: Some biotransformation products have enhanced activity or toxic properties
A
T
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
11
Q
The principal organ of drug metabolism
A
Liver
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
12
Q
Other tissues where biotransformations can occur
A
1) Gastrointestinal Tract
2) Lungs
3) Skin
4) Kidneys
5) Brain
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
13
Q
May be metabolized by Gastric acid
A
Penicillin
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
14
Q
Harbors intestinal microorganisms that are capable of many biotransformation reactions.
A
Lower Gut
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
15
Q
May be metabolized by gastric digestive enzymes
A
Polypeptides such as insulin
15
Q
Must be given 2 hours before the meals if given through the oral route
A
Penicillin
15
Q
May be metabolized by enzymes in the wall of the intestine
A
Sympathomimetic Catecholamines
16
Q
Drugs metabolized by intestinal wall enzymes
A
Epinephrine
17
Q
Can occur by spontaneous and non catalyzed chemical reactions, but mostly catalyzed by specific cellular enzyme
A
Drug biotransformation in vivo
18
Drug Biotransformation In Vivo: At subcellular level, enzymes are located in
1) Endoplasmic Reticulum
2) Mitochondria
3) Cytosol
a. Lysosomesnuclear envelope
b. Plasma membrane
19
Many drug metabolizing enzymes are located in the
Lipophilic endoplasmic reticulum of the liver & other tissues
20
Through homogenization and fractionation of the cell
Isolation of Lamellar Membranes
21
Are reformed into microsomes (vesicles)
Lamellar Membranes
22
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
Microsomes
23
Dedicated to protein synthesis
Rough microsomes
24
Relatively rich in enzymes responsible for oxidative
drug metabolism
Smooth microsomes
25
Contain the important class of enzymes known as the
mixed function oxidases (MFOs), or monooxygenases
Smooth microsomes
26
MFOs require
1) A reducing agent (nicotinamide adenine dinucleotide phosphate [NADPH])
2) A molecular oxygen (O2)
27
MFOs in a typical reaction
One molecule of oxygen is consumed/reduced per substrate molecule
28
Plays a key role in the oxidation-reduction process
Microsomal Enzymes
29
One mole of NADPH CPR
1) One mole of flavin mononucleotide (FMN)
2) One mole flavin adenine dinucleotide (FAD)
29
A flavoprotein
NADPH cytochrome P450 oxidoreductase / POR / CPR
30
A hemoprotein which serves as the terminal oxidase
Cytochrome P450 / P450 / CYP
31
Name is derived from the spectral properties of this hemoprotein
Cytochrome P450
32
Microsomal membrane harbors multiple forms of ____
P450
33
Is increased by repeated administration of or exposure to exogenous chemicals
Multiplicity
34
Binds to carbon monoxide to give a complex that absorbs light maximally at 450 nm
Reduced (ferrous) form
35
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.
T
36
Microsomal Drug Oxidations Require
1) P450
2) P450 reductase
3) NADPH
4) a molecular oxygen
37
In microsomal drug oxidations, __________ of this activated oxygen permit oxidation of a large number of substrates
Potent oxidizing properties
38
is very low for this enzyme complex (Microsomal Drug Oxidations)
Substrate specificity
39
Are remarkably sluggish catalysts and their drug biotransformation reactions are slow.
P450s
39
Is the only common structural feature of the wide variety of structurally unrelated drugs and chemicals that serve as substrates in this system
High lipid solubility
40
Mechanism by which the body terminates the action of some drugs
Drug Metabolism
41
3 possible pathways of drug metabolism
1) Active > Inactive (readily excreted by the kidneys)
2) Active > Active Metabolites
3) Inactive > Active (Prodrug)
42
T/F: Metabolism of drugs does not always lead to detoxification and elimination of compounds.
T
43
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.
Redox Cycling
44
Identified by Gene arrays
P450 isoforms in liver
45
Identified by Immunoblotting analyses of microsomal preparations
P450 isoforms in liver
46
Identified by use of relatively selective functional markers and selective P450 inhibitors
P450 isoforms in liver
47
Most important P450 forms
§ CYP1A2 (15%)
§ CYP2A6 (4%)
§ CYP2B6 (1%)
§ CYP2C9 (20%)
§ CYP2D6 (5%)
§ CYP2E1 (10%)
§ CYP3A4 (30%)
§ Isoform (Approximate percentage in the total human
liver P450 content)
48
Responsible for the metabolism of over 50% of the prescription drugs metabolized by the liver.
CYP3A4
49
They are responsible for catalyzing the bulk of the hepatic drug and xenobiotic metabolism
P450 Forms
50
Selective functional markers
In vitro
51
Selective chemical P450 inhibitors
In vitro
52
P450 antibodies
In vitro
52
Relatively selective noninvasive marker
In vivo
53
Including breath tests or urinary analyses of specific metabolites after administration of a P450-selective substrate probe
In vivo
54
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
Enzyme Induction
55
Results in accelerated substrate metabolism and usually in a decrease in the pharmacologic action of the inducer and of co-administered drugs
Enzyme Induction
56
In cases of drugs metabolically transformed to reactive metabolites, ________ may exacerbate metabolite-mediated toxicity
Induction
57
Characteristics of various substrates induce P450 isoforms
1) Having different molecular masses
2) Exhibiting different substrate specificities and immunochemical and spectral characteristics.
58
Capable of inducing P450 enzymes
Environmental chemicals and pollutants
59
Examples of Environmental chemicals and pollutants
benzo[a]pyrene and other
polycyclic aromatic hydrocarbons, which are present in tobacco smoke, charcoal-broiled meat, and other organic pyrolysis products
60
A trace byproduct of the chemical synthesis of the
defoliant 2,4,5-T
2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD)
60
Used widely in industry as insulating materials and
plasticizers
Polychlorinated biphenyls (PCBs)
61
Increased P450 synthesis requires enhanced transcription, translation, and synthesis of _____, its prosthetic cofactor
Heme
62
Cytoplasmic receptor (AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified
CYP1A induction
63
Seen in cruciferous vegetables, and the proton pump inhibitor, omeprazole
CYP1A induction
64
Process of CYP1A Induction
1) Translocation
2) Ligand-induced Dimerization with Arnt
3) Subsequent activation of regulatory elements of CYP1A genes
4) CYP1A Induction
65
Relatively large and structurally diverse phenobarbital class of inducers of CYP2B6, CYP2C9, and CYP3A4.
Constitutive androstane receptor (CAR)
66
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
CYP3A induction
67
Nuclear receptor highly expressed in liver and kidneys
Peroxisome proliferator receptor α (PPAR-α)
68
Consistent with its major role in the regulation of fatty
acid metabolism
Peroxisome proliferator receptor α (PPAR-α)
68
Uses lipid-lowering drugs as ligands such as Fenofibrate & Gemfibrozil
Peroxisome proliferator receptor α (PPAR-α)
69
Responsible for the metabolism of fatty acids
Peroxisome proliferator receptor α (PPAR-α)
69
Mediates the induction of CYP4A enzymes
Peroxisome proliferator receptor α (PPAR-α)
70
PXR, CAR, and PPAR-α each form heterodimers with another nuclear receptor, the ________________.
retinoid X-receptor (RXR)
71
This heterodimer (retinoid X-receptor (RXR), in turn, binds to response elements within the promoter regions of specific P450 genes to
induce _________
Gene Expression
72
Effectively reduce the metabolism of (1) endogenous substrates (e.g., testosterone) & (2) other co-administered drugs through competitive inhibition
Imidazole-containing drugs
72
Certain drug substrates inhibit cytochrome P450 enzyme activity
Enzyme Inhibition
72
Bind tightly to the P450 heme iron
Imidazole-containing drugs
73
ketoconazole
Imidazole-containing drugs
73
cimetidine
Imidazole-containing drugs
74
troleandomycin
Macrolide antibiotics
75
erythromycin & derivatives
Macrolide antibiotics
76
Are metabolized, apparently by CYP3A, to metabolites
that complex the cytochrome P450 heme iron and render
it catalytically inactive
Macrolide antibiotics
77
Binds tightly to the heme iron and quasi-irreversibly
inactivates the enzyme, thereby inhibiting the metabolism of potential substrates.
Proadifen
78
T/F: Some substrates irreversibly inhibit P450s via covalent interaction of a metabolically generated reactive intermediate
T
79
Inhibitors of P450s may react with?
1) P450 Apoprotein
2) Heme Moiety
80
Inhibitors of P450s may cause?
Heme to fragment and irreversibly modify the apoprotein
81
Antibiotic and metabolized by CYP2B1 to a species - modifies the P450 protein & inactivates the enzyme
Chloramphenicol
82
Inactivators that attack the heme or the protein moiety
Suicide inhibitors
83
A barbiturate & inactivates CYP2B1 by modification of both its heme and protein moieties
Secobarbital
84
Other metabolically activated drugs whose P450 inactivation
mechanism is not fully elucidated
1) Mifepristone
2) Troglitazone
3) Raloxifene
4) Tamoxifen
85
Types of Metabolic Reactions
Non-synthetic reactions
Phase 1
86
Types of Metabolic Reactions
Converts the parent drug to a more polar conjugate (water
soluble) or more reactive product
Phase 1
87
Types of Metabolic Reactions
Done by introducing/ inserting/ unmasking a polar functional group (OH, SH, NH2)
Phase 1
88
Types of Metabolic Reactions
Oxidation
Phase 1
89
Types of Metabolic Reactions
Deamination
Phase 1
89
Types of Metabolic Reactions
Reduction
Phase 1
90
Types of Metabolic Reactions
Hydrolysis
Phase 1
91
T/F: In Phase 1, if metabolites are sufficiently polar, they may be readily excreted
T
92
T/F: If metabolites are not eliminated rapidly, they will undergo phase II
T
93
T/F: Metabolites in Phase 1 may be active, modified, or enhanced
F; inactive
94
Types of Metabolic Reactions
Used for synthetic reactions
Phase 2
95
Types of Metabolic Reactions
Endogenous substrate is added to the parent drug to make it more polar
Phase 2
96
Types of Metabolic Reactions
Glucuronidation- addition of glucoronic acid
Phase 2
97
Types of Metabolic Reactions
Acetylation-acetyl CoA
Phase 2
98
Types of Metabolic Reactions
Sulfation
Phase 2
99
Types of Metabolic Reactions
Methylation
Phase 2
100
Types of Metabolic Reactions
Glycine conjugation - glycine
Phase 2
101
Types of Metabolic Reactions
Glutathione conjugation
Phase 2
102
Types of Metabolic Reactions
H2O conjugation – addition of OH and H+ without hydrolysis
Phase 2
103
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
Glucuronidation
104
Type of Conjugation
Endogenous Reactant: Acetyl-CoA
Transferase (Location): N- Acetyltransferase (cytosol)
Types of Substrates: Amines
Examples: Sulfonamides, isoniazid, clonazepam, dapsone, mescaline
Acetylation
105
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
Glutathione conjugation
106
Type of Conjugation
Endogenous Reactant: Glycine
Transferase (Location): Acyl-CoA glycinetransferase (mitochondria)
Types of Substrates: Acyl-CoA derivatives of carboxylic acids
Examples: Salicylic acid, benzoic acid, nicotinic acid, cinnamic acid, cholic acid, deoxycholic acid
Glycine conjugation
107
Type of Conjugation: Sulfation
Endogenous Reactant: Phosphoadenosyl phosphosulfate (PAPS)
Transferase (Location): Sulfotransferase (cytosol)
Types of Substrates: ?
Examples: Estrone, aniline, phenol, 3-hydroxycoumarin, acetaminophen, methyldopa
Phenols, alcohols, aromatic amines
107
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
Epoxide hydrolase (microsomes)
108
Type of Conjugation: ?
Endogenous Reactant: Water
Transferase (Location): Cytosol
Types of Substrates: Alkene oxides, fatty acid, epoxides
Examples: Leukotriene A4
Water Conjugation
109
T/F: Phase II reactions are relatively faster than P450-catalyzed reactions, thus effectively accelerating drug biotransformation.
T
110
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.
F; Phase II
111
Are polar molecules that are readily excreted and often inactive.
Conjugates
112
involves:
o High-energy intermediates
o Specific transfer enzymes (Transferases) - located in
microsomes in the cytosol.
Conjugate Formation
113
Is known to activate prodrug minoxidil and morphine-6-glucuronide.
Sulfation
114
May lead to the formation of reactive species responsible for the toxicity of the drugs
Conjugation Reactions
115
Other Conjugation Reactions
1) acyl-glucuronidation
2) O-sulfation
3) N-acetylation
115
Phase _ > Phase _ is the most common pathway
Phase I > Phase II
116
Pathway that most drug uses
Phase I → Phase II
117
Pathway that other drug uses
Phase II → Phase I
118
Are anti-tubercular drugs
Isoniazid
119
What drug?
Acetylation (Phase 2) precedes hydrolysis (Phase 1)
Isoniazid
120
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
Hydrazide moiety of isoniazid
121
Most important organ for drug metabolism
Liver
122
Activity of these SER enzymes require:
1) NADPH (reducing agent)
2) Molecular form of oxygen
122
Contains high concentration of Phase 1 enzymes
Smooth endoplasmic reticulum (SER) in the liver
123
Rates of drug metabolism and elimination and is determined by
1) Genetic Factors
2) Nongenetic Variables
3) Nutritional and Environmental Factors
124
Those that influence enzyme levels account for some of these differences, giving rise to genetic polymorphisms in drug metabolism
Genetic Factors
125
Occurrence of a variant allele of a gene at a population frequency of ≥1%
True genetic polymorphism
126
Ester that is metabolized by plasma choline esterase
Succinylcholine
126
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)
T
127
In most individuals, the process occurs rapidly (duration of action is 5 minutes; muscle relaxant)
Hydrolysis of Esters ; Succinylcholine
128
Genetic Factor
Isoniazid (INH)
Acetylation of Amines
129
Genetic Factor
hydralazine and procainamide
Acetylation of Amines
130
T/F: Slow Acetylators cause individuals deficient in acetylating capacity and prolonged or toxic responses to normal doses of this drug
T
131
Genetic Factor
Dextrometorphan, metoprolol and some tricyclic antidepressants
Oxidation
132
Genetic Factor
Oxidation by P450 isoenzymes are genetically predetermined
Oxidation
133
Often transmitted as autosomal recessive traits
Phase I Enzyme Polymorphisms
134
May be expressed at any one of the multiple metabolic
transformations that a chemical might undergo
Phase I Enzyme Polymorphisms
135
Occurs in 3-10% of Caucasians and inherited as an autosomal recessive trait
Debrisoquin-sparteine Oxidation Polymorphism
136
Precise molecular basis for the defect: faulty expression
of the P450 protein
Debrisoquin-sparteine Oxidation Polymorphism
137
Occurs due to the presence of CYP2D6 allelic variants with up to 13 gene copies in tandem
Ultrarapid Metabolism (UM)
137
Stereoselective and is catalyzed by CYP2C19 and inherited as an autosomal recessive trait
Aromatic (4)-hydroxylation of the anticonvulsant mephenytoin
137
Extensively hydroxylated by CYP2C19 at the 4 position of the phenyl ring before glucuronidation and rapid excretion in the urine
Normal extensive metabolizers (EM)
138
Totally lack the stereospecific (S)-mephenytoin
hydroxylase activity and both (S)- and (R)-mephenytoin enantiomers are N-demethylated to nirvanol
Poor metabolizers (PM)
139
Shows signs of profound sedation and ataxia after
doses of the drug that are well tolerated by normal
metabolizers
Poor metabolizers (PM)
140
Associated with increased transcription and thus higher
CYP2C19 expression and even higher functional acitivity
that that of the wild type CYP2C19-carrying EMs
CYP2C19*17
141
Encodes an Arg144Cys mutation and exhibits impaired functional interactions with POR
CYP2C9*2
142
Encodes an Ile359Leu mutation and lowered affinity for many substrates
CYP2C9*3
143
Contribution to the well-known interindividual variability in drug metabolism is limited
Allelic variants of CYP3A4
144
Most polymorphic P450 genes
CYP2B6 Polymorphisms
145
Results from a single nucleotide polymorphism (SNP) within intron 3
CYP3A5 Protein Polymorphism
146
Defect in slow acetylators (of isoniazid and similar
amines)
Phase II Enzyme Polymorphisms
147
Caused by the synthesis of less of the NAT2 enzyme rather than of an abnormal form of it
Phase II Enzyme Polymorphisms
148
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
TPMT (thiopurine S-methyltransferase) gene
148
Increases risk of thiopurine drfug-induced fatal
hematopoietic toxicity
TPMT (thiopurine S-methyltransferase) gene
149
Associated with hyperbilirubinemic diseases (Gilbert Syndrome)
UGT polymorphism (UGT1A1*28)
150
Expression can lead to significant adverse effects and toxicities of drugs dependent on its GSH conjugation for elimination
Genetic polymorphisms (GSTM1) in GST (mu1 isoform)
151
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.
Genotype information
152
Diet and Environmental Factors
Inhibits the effect of the drug
Charcoal
153
Diet and Environmental Factors
Increases the amount
of drug in the body
Grapefruit Juice
154
T/F: Drug metabolites do not differ in young and old
F; does differ
155
T/F: Males metabolize drugs faster than females
T
156
Age & Sex
T/F: Children and elderly metabolize drugs slower
T
157
Disease affecting drug metabolism
Hyperthyroidism
158
T/F: Thyroid hormone increases the metabolism
T
159
Other Drugs
Increase rate of synthesis of the enzyme
Enzyme Induction
160
Other Drugs
Reduce the rate of degradation of the enzyme
Enzyme Induction
161
Other Drugs
May also induce self metabolism of the drug
Enzyme Induction
162
Other Drugs
May also induce metabolism of other drugs and reduce its effects
Enzyme Induction
163
T/F: Increase susceptibility to pharmacologic/toxic activity of drugs: very young and very old patients
T
164
T/F: Slower metabolism could be due to reduced activity
of metabolic enzymes or reduced availability of
essential endogenous co-factors.
T
165
6 acute or chronic diseases that affect liver architecture or function markedly affect hepatic metabolism of some drugs
1) alcoholic hepatitis
2) active/inactive alcoholic cirrhosis
3) hemochromatosis
4) chronic active hepatitis
5) biliary cirrhosis
6) acute viral/drug-induced hepatitis.
166
Impaired hydrolysis
of procainamide and procaine
Chronic respiratory insufficiency
167
Decreases the half-life of
antipyrine, digoxin, methimazole, and some β
blockers
Hyperthyroidism
167
Increased half-life of antipyrine (a P450 functional probe)
Lung Cancer
168
Increases the half-life of antipyrine, digoxin, methimazole, and some β blockers
Hypothyroidism
169
↓ Therapeutic Window _ Toxicity
↑
170
Enzyme inducers + drug =
Decreased Effects
171
4 Enzyme Inducers
1) Phenobarbital
2) Carbamazepine
3) Phenytoin
4) Rifampicin
172
Other Drugs
Metabolism of the drug is diminished
Enzyme Inhibition
173
Other Drugs
Increase effect of the drug
Enzyme Inhibition
174
Enzyme inhibitors + drug =
increased effect
175
5 Enzyme Inhibitors
1) Amiodarone
2) Cimetidine
3) Ketoconazole
4) Ritonavir
5) Furanocoumarin
176
Types of Drug Interaction Mechanism
Cholestyramine inhibits the effect of digoxin when combined with it
Altered absorption
177
Types of Drug Interaction Mechanism
Affects drug action
Altered metabolism
178
Types of Drug Interaction Mechanism
Plasma protein binding would diminish the amount of
drug that would reach the receptors
Altered plasma binding protein
179
Types of Drug Interaction Mechanism
Probenecid inhibits the secretion of acids
Altered excretion
180
Types of Drug Interaction Mechanism
Penicillin inhibits the excretion of probenecid
Altered excretion
181
Drug Interaction
1+1=2
Response elicited by combined drugs is equal to the combined response of the individual drugs
Additive
182
Drug Interaction
Sedative + Ethanol
Additive
183
Drug Interaction
1+1=3 Response elicited by combined drugs is greater than the combined responses of each individual
Synergistic
184
Drug Interaction
0+1=2 Drug which has no effect enhances the effect of the second drug
Potentiation
185
Drug Interaction
Cimetidine + anticoagulant
Potentiation
186
Drug Interaction
1+1=0 Drug inhibits the effect of another drug
Antagonism
187
Drug Interaction
Heparin + protamine
Antagonism
187
A sedative inducer of note, a popular over-the-counter herbal medicine ingested as treatment for mild to severe depression.
St. John’s wort
188
T/F: Some drugs require conjugation with endogenous substrates such as GSH, glucuronic acid, or sulfate for their inactivation.
T
