Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Drug Metabolism > Flashcards

Drug Metabolism Flashcards

1
Q

What is the main purpose of drug metabolism?

A

detoxification
inactivation
activating prodrugs
providing active/more active metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the best way to eliminate the drug?

A

increase water solubility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the reactions of phase 1 metabolism?

A

oxidation
reduction
hydrolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Phase 2 metabolism reactions?

A

glucuronic acid conjugation
sulfate conjugation
amino acid conjugation
glutathione conjugation
methylation and acetylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Methylation and acetylation generally terminate drug action but do not increase?

A

water solubility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Are drugs lipid or water soluble?

A

lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The liver, intestines, and other metabolic sites will perform how many transformation to eliminate a drug?

A

the minimum number

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Functional groups are more likely to undergo metabolic transformation if they are?

A

easily accessible and are not sterically hindered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Most oxidative transformations are catalyzed by what kind of enzymes?

A

CYP450
flavin monooxygenase
alcohol dehydrogenase
aldehyde dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Oxidation

A

loss of electrons, hydrogen, alkyl group, or a heteroatom
gain of oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

in CYP450 oxidation the carbon atom that is oxidized must contain what?

A

a hydrogen atom that can be abstracted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CYP450 mechanism

A
  1. drug attaches to Fe^3+
  2. complex is reduced
  3. oxygen is added
  4. auto oxidation forms a radical
  5. complex is reduced
  6. loss of water
  7. hydrogen abstraction and carbon radical formed
  8. radicals combine to form oxidized drug and release iron
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 6 major cyp enzymes that are required for metabolism of endogenous substances?

A

CYP7
CYP11
CYP17
CYP19
CYP21
CYP27

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

If a drug induces a CYP enzyme, it leads to an increase in ?

A

drug metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

If a drug inhibits a CYP enzyme, it leads to a decrease in?

A

[drug]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What major CYP enzymes are involved in xenobiotic metabolism?

A

CYP1
CYP2
CYP3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Flavin monooxygenase enzymes

A

directly oxidize N and S
do not require an H atom on the N or S

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Where are unsubstituted phenyl rings primarily oxidized and why?

A

para position
lack of steric hinderance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which enhances aromatic hydroxylation: EWG or EDG?

A

EDG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Alkene oxidation produces ?

A

epoxides, trans diols, and peroxides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Alkene oxidation needs at least one of which atom?

A

H

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Benzylic oxidation

A

oxidation occurs at the least sterically hindered site
benzylic carbon atom directly attached to an aromatic ring
does not usually occur with C-hydroxyl/ether bonds
can sometimes make toxic isomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Allylic oxidation

A

carbon atom must have a hydrogen attached to it
occurs at carbon attached to an alkene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where does oxidation of aliphatic and alicyclic carbon atoms occur?

A

at the terminal methyl group in the chain or the penultimate carbon atom in the chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the 3 major oxidative transformations for amines and amides?

A

oxidative deamination
oxidative N-dealkylation
N-oxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Quaternary nitrogen atoms can undergo?

A

only N-dealkylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Oxidative deamination

A

complex is oxidized to form a carbinolamine
carbinolamine is then delaminated o form a ketone and amine
primarily occurs with primary amines, sometimes secondary amines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Oxidative N-dealkylation

A

secondary or tertiary amine is oxidized into a carbinolamine
this is deaminated into a primary amine and a ketone or aldehyde
NOT for t-butyl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

N-oxidation

A

direct oxidation of the nitrogen atom
primary route of oxidative metabolism for aromatic nitrogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Primary amines can be directly oxidized to form?

A

hydroxylamines, imines, oximines, ,aldehydes, and carboxylic acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Secondary amines can be directly oxidized to form?

A

hydroxylamines, imines, nitrogen, aldehydes, and carboxylic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Tertiary amines and heterocyclic amines can be directly oxidized to form?

A

N-oxides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Which functional group is most likely to undergo N-oxidation into N-oxides?

A

Heterocyclic Amines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Alcohol Dehydrogenase

A

enzymes that catalyze the oxidation of primary and secondary hydroxyl groups to aldehydes and ketones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Aldehyde Dehydrogenase

A

enzymes that catalyze the oxidation of aldehydes to carboxylic acids

36
Q

What is the intermediate in oxygen dealkylation? Is it stable?

A

hemiacetal or hemiketal
no

37
Q

Thioesters can undergo direct S-oxidation with FMO to produce?

A

sulfoxides
sulfones

38
Q

Desulfuration

A

thiocarbonyl -> carbonyl
oxidation

39
Q

Can oxidative dehalogenation remove halogens from aromatic rings?

A

no, need a hydrogen atom

40
Q

reduction

A

gain of hydrogen
least common pathway

41
Q

Aldehydes are primarily oxidized to?

A

carboxylic acids

42
Q

When ketones are reduced what sometimes forms?

A

a chiral center

43
Q

Azo groups can be reduced to ?

A

2 aromatic amines

44
Q

Nitro groups can be reduced to ?

A

primary amines

45
Q

Sulfoxides are normally oxidized to sulfones but can sometimes be reduced to ?

A

sulfides

46
Q

Hydrolysis

A

breaking water bonds
occurs with esters, amides, lactones, lactams, phosphate esters, sulfonylureas, carbamates, and glycosides
phase 1 metabolic transformation
way to activate prodrug

47
Q

prodrug

A

compound that is either inactive/ possess weak activity and requires in vivo metabolism to convert to the active metabolite
activated by hydrolysis

48
Q

Advantages of prodrugs

A

enhanced water solubility for concentrated IV/ ophthalmic solutions
enhanced lipid solubility
enhanced duration of action
decreased side effects
selective activation at site of actio n

49
Q

What does each conjugation pathway use?

A

transferase enzyme

50
Q

Conjugation with what enhances water solubility and generally results in inactive products?

A

glucuronic acid
sulfate
amino acid

51
Q

Glutathione

A

react is with highly electrophilic intermediates
detoxifies drug molecules
highly water soluble, readily excreted, non toxic

52
Q

Addition of which groups terminate pharmacological actions of drug molecules?

A

methyl and acetyl groups

53
Q

All phase 2 conjugation paths except for what require an initial activation process?

A

glutathione

54
Q

Which phase 2 reaction cannot be reversed?

A

glutathione

55
Q

Why are aromatic rings not hydroxylated?

A

halogens, EWGs deactivate hydroxylation

56
Q

Amides can undergo what 2 reactions?

A

N-dealkylation and N-oxidation

57
Q

S-dealkylation of a thioether makes?

A

a thiol and an aldehyde

58
Q

Oxidative Dehalogenation product possibilities

A

aldehyde
ketone
call halide
carboxylic acid

59
Q

Oxidation of Alicyclic amines

A
  1. N-dealkylation
  2. Ring opens
    3.Oxidation
  3. condensation
60
Q

Disulfide bonds can be reduced to?

A

Thiol metabolites

61
Q

Where are hydrolytic enzymes?

A

liver, GI tract, plasma, skin, lungs, and kidneys

62
Q

Which occurs faster: hydrolysis of of esters and lactose or amides and lactams?

A

esters and lactose

63
Q

Which transferase and deconjugating enzymes are used in glucuronic acid conjugation?

A

UDP-Glucuronyl Transferase (UGT)
Beta-glucuronidase

64
Q

Which transferase and deconjugating enzymes are used in sulfate conjugation?

A

Sulfotransferase (SULT)
Sulfatase

65
Q

Which transferase and deconjugating enzymes are used in amino acid conjugation?

A

N-Acyltransferase
Amidase

66
Q

Which transferase and deconjugating enzymes are used in glutathione conjugation?

A

Glutathione S-transferase
NO DECONJUGATION

67
Q

Which transferase and deconjugating enzymes are used in acetylation?

A

N-acetyltransferase (NAT)
Amidase

68
Q

Which transferase and deconjugating enzymes are used in methylation?

A

methyltransferase
CYP450 oxidative phosphorylation

69
Q

Why is glucuronic acid conjugation the most common Phase 2 transformation?

A

acid is readily available; is an oxidative metabolite of glucose
can conjugate a large number of functional groups

70
Q

Which functional groups can glucuronic acids conjugate?

A

hydroxyl groups— most common
phenols—most common
carboxylic acids
tetrazoles
amines
sulfonamides
hydrazines
carbamates
sulfhydryl groups

71
Q

Due to the stereochemistry of alpha-glucose 1-phosphate and the mechanism of the transferase reaction, glucuronic acid always forms a?

A

Beta glucuronic

72
Q

Adding glucuronic acid to a drug increases what kind of solubility?

A

water

73
Q

Sulfate conjugation occurs with which functional groups?

A

mainly: phenolic hydroxyl groups
minor: aliphatic hydroxyl groups, aromatic amines, and N-hydroxyl groups

74
Q

Which enzyme releases estrogen at its tissue?

A

sulfatase

75
Q

Sulfate conjugation make make minor products that are?

A

highly reactive and cytotoxic

76
Q

Amino acid conjugation adds what?

A

carboxylic acids

77
Q

Which amino acids are used in amino acid conjugation?

A

mainly: Gly and Gln
minor: Aspartic acid, Serine, and Taurine

78
Q

Amino acid conjugation is primarily linked to which functional groups?

A

aromatic carboxylic acids
aryl acetic carboxylic acids

79
Q

Is the carboxylic acid activated before or after amino acid conjugation?

A

before

80
Q

Adding Gly or Gln during amino acid conjugation enhances what kind of solubility?

A

water

81
Q

What does glutathione conjugation protect the body from?

A

potentially harmful electrophiles

82
Q

What is glutathione?

A

a tripeptide made of gamma-glutamate, cysteine, and glycine

83
Q

Glutathione conjugation process

A
  1. initial conjugation
  2. removal of gamma-Glu and Gly
  3. N-acetylation
84
Q

Acetylation

A

pathway that uses Acetyl CoA to acetylate primary aliphatic amines, primary aromatic amines, hydrazines, hydrazine’s, and unsubstituted sulfonamides

does NOT produce a more water soluble metabolite

85
Q

Methylation

A

helps make nuclei acids, proteins, phospholipids, neurotransmitters, and other amines
seen with catechols, phenolic hydroxyl groups, amines, and sulfhydryl groups

DOES NOT ENHANCE WATER SOLUBILITY
inactivates drug molecules

86
Q

Where does methylation of catechols normally occur?

A

meta position

87
Q

methyltransferase enzymes

A

catechol-O-methyltransferase
phenol-O-methyltransferase
N-methyltransferase
S-methyltransferase

Pharmacology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions