Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology > 4) Biotransformations > Flashcards

4) Biotransformations Flashcards

1
Q

Primary purpose of drug metabolism

A
  • Render lipid soluble and non-polar compounds to water soluble and polar compounds for easy excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Only water-soluble substances undergo

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

Lipid-soluble substances are

A
  • Passively reabsorbed into the blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Primary site of drug metabolism

A
  • Liver

- It is enriched with a variety of enzymes

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

Extra-hepatic metabolism (kidney, lungs, skin) takes place to a smaller extent due to

A
  • Presence of

lower level of enzymes

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

Not all drugs are bioavailable, in which this led to the development of

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

Phase I metabolism (biotransformaiton)

A
  • Makes xenobiotics more polar

- Oxidation, reduction, and hydrolysis

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

Phase II metabolism (conjugation)

A
  • To further increase polarity by
    conjugation
  • Addition of a new group (acetyl, sulfate, glucuronic acid, amino acid etc.) to the phase I metabolite
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

A drug has no absolute requirement to undergo

A
  • Both Phase I and Phase II transformations
  • In some instances Phase II transformations are enough to provide adequate water solubility for elimination without the need for Phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Active metabolite may retain

A
  • The activity of the parent drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Inactive metabolite has no

A
  • Pharmacological activity (unlike the parent drug)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Biotransformation

A
  • When the metabolite is active, and the parent drug is not

- We call the parent drug a prodrug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Phase I metabolism consists of three types of biotransformations

A
  • Oxidation
  • Reduction
  • Hydrolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Oxidation in phase I occurs via

A
  • Mainly Cytochrome P450s (for carbons)

- Flavin-containing monooxygenases (non- carbon) in the liver

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

Miscellaneous oxidases involved in phase I metabolism

A
  • Alcohol dehydrogenase, aldehyde dehydrogenase

- Monoamine oxidase (deamination of catecholamines)

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

Reduction in phase I occurs via

A
  • Reductase enzymes (e.g. disulfide bond)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hydrolysis in phase I occurs via

A
  • Esterases

- Peptidases (hydrolysis of esters and amides)

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

From a chemical perspective, oxidation refers to

A
  • Loss of electrons

- Increase in the oxidation state of an atom/molecule

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

The oxidation of a functional group on a drug molecule will result in one or more of the following:

A
  • Gain in oxygen
  • Loss of hydrogen
  • Loss of an alkyl group and/or a loss of a heteroatom
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Unsubstituted phenyl rings are primarily hydroxylated at

A
  • Para position due to a lack of steric hindrance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Steric hindrance is also present in _____ and _____ position gets hydroxylated.

A
  • Diazepam

- Para

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

Alkene oxidation can produce

A
  • Epoxides
  • Diols
  • Peroxides (as shown with protriptyline)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

At least one _____ on one of the two alkene carbon atoms is required for this type of oxidation to occur.

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

The _____ present within the structure of tamoxifen cannot undergo oxidation.

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

A benzylic carbon atom is an _____ carbon atom that is directly attached to an _____.

A
  • Aliphatic

- Aromatic ring

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

Benzylic oxidation only occurs at the

A
  • Least sterically hindered position
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

An allylic carbon atom is an _____ carbon atom that is directly attached to an _____.

A
  • Aliphatic
  • Alkene
  • Directly adjacent to a non-aromatic double bond
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Spironolactone has two allylic carbon atoms; however, only one of these can undergo allylic oxidation because

A
  • The other does not have a hydrogen atom attached to it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Aliphatic carbon chains can undergo oxidation at either the _____ in the chain or at the
_____ carbon atom in the chain

A
  • Terminal methyl group (omega/ω)

- Penultimate/next to last (omega-1/ω-1)

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

Oxidative de-amination mainly occurs with

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

In order for oxidative deamination to occur

A
  • The α-carbon (i.e., the carbon atom directly adjacent to the nitrogen atom) must be attached to at least one hydrogen atom
  • The carbon atom that is α to the amine undergoes oxidation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Carbinolamines are _____ and will undergo further reaction to generate either

A
  • Unstable intermediates

- An aldehyde or ketone (depending upon the nature of the R1 and R2 groups)

33
Q

Oxidative N-dealkylation can occur with

A
  • Secondary or tertiary amines or amides
34
Q

N-Dealkylation of tertiary amines will produce

A
  • Secondary amines
35
Q

N-dealkylation of secondary amines will produce

A
  • Primary amines
36
Q

N-oxidation involves a direct oxidation of the _____ as opposed to an adjacent carbon atom

A
  • Nitrogen atom
37
Q

Primary amines that are attached to a carbon atom that lacks a hydrogen atom can be oxidized to

A
  • Hydroxylamines

- Nitroso groups

38
Q

ADH enzymes catalyze the oxidation of primary and secondary hydroxyl groups to

A
  • Aldehydes and

ketones, respectively

39
Q

ALDH enzymes catalyze the oxidation of aldehydes to

A
  • Carboxylic acids
40
Q

Oxidation of functional groups with carbon-oxygen bonds

A
  • ADH: primary/secondary hydroxyl groups to aldehydes and ketones
  • ALDH: aldehydes to carboxylic acids
41
Q

Oxidative dehalogenation can remove halogens from _____ and _____ but NOT from ______.

A
  • Aliphatic chains
  • Aliphatic rings
  • Aromatic rings
42
Q

Summary for oxidation

A
  • Aromatic hydroxylation
  • Alkene oxidation
  • Oxidation of benzylic carbon
  • Oxidation of allylic carbon
  • Oxidation of aliphatic and alicyclic carbon
  • N-oxidation
  • Oxidative dehalogenation
  • Oxidative dealkylation
  • Oxidative deamination
43
Q

Reduction involves

A
  • Gain of electrons
  • Decrease in the oxidation state of an atom or molecule
  • Least common phase I metabolic pathway
44
Q

Some of the functional groups that are only present on a very limited number of drug molecules

A
  • Azo group

- Nitro group

45
Q

Hydrolysis (phase I)

A
  • Addition of a molecule of water across a C—X bond

- Subsequent cleavage of that bond

46
Q

C—X bond in hydrolysis reactions

A
  • X is an oxygen or nitrogen atom

- For some functional groups, the carbon atom is replaced by a sulfur or phosphorous atom

47
Q

Hydrolysis readily occurs with

A
  • Esters
  • Amides, and their cyclic analogs
  • Lactones
  • Lactams
48
Q

The hydrolysis of esmolol produces _____, while the hydrolysis of simvastatin converts this prodrug to its _____.

A
  • Inactive metabolites

- Active metabolite

49
Q

Amides and lactams are hydrolyzed at a slower rate than are

A
  • Esters and lactones
50
Q

Due to rapid ester hydrolysis, procaine has a half-life of

A
  • Less than 1 minute
  • Cannot be administered orally
  • Used parenterally as a local anesthetic
51
Q

The amide ester of procainamide is hydrolyzed

A
  • Much slower than procaine
52
Q

Phase II metabolism (cojugation)

A
  • Small polar endogenous molecules (such as glucuronic acid, sulfate, or glycine) are
    covalently attached to the functional groups of drug molecules to form water-soluble compounds
53
Q

Most conjugation reactions are catalyzed by

A
  • Transferases
54
Q

Glutathione conjugation endogenous compound

A
  • Glutathione (GSH)
55
Q

Acetylation endogenous compound

A
  • Acetyl CoA
56
Q

Methylation endogenous compound

A
  • Methionine
57
Q

Glucoronic acid conjugation endogenous compound

A
  • Glucose-1-phosphate
58
Q

Sulfate conjugation endogenous compound

A
  • Sulfate
59
Q

Amino acid conjugation endogenous compound

A
  • Glycine & glutamine (major)

- Serine, aspartic acid (minor)

60
Q

Most common phase II reaction

A
  • Glucuronic acid conjugation
61
Q

Glucuronidation substrates

A
  • Phenols
  • Alcohols
  • Carboxylic acids
  • Hydroxylamines
62
Q

Resulting conjugates of glucuronidation are excreted in the urine, or bile if

A
  • MW > 300
63
Q

In phase II glucuronidation, N-or S-glucuronides can be formed from

A
  • Sulfonamides
  • Amides
  • Amines
  • Thiols
64
Q

Compounds than can undergo sulfate conjugation reactions

A
  • Phenols
  • Alcohols
  • Arylamines
  • N-hydroxy
65
Q

Sulfate conjugation reactions are catalyzed by

A
  • Sulfotransferases
66
Q

Drugs with carboxylic acid groups can become conjugated to

A
  • Amino acids (glycine mostly)
67
Q

Carboxylic acid is first activated through formation of a _____, then linked to an amino acid (peptide bond forms)

A
  • Coenzyme A thioester
68
Q

Glutathione is the major antioxidant and called

A
  • The true detoxifying agent
69
Q

Glutathione is present in virtually all mammalian tissues and protects the body from potentially harmful _____.

A
  • Electrophiles (electron pair acceptor)
70
Q

Electrophiles are either initially present within the structure of an _____ or that arise as a product of _____.

A
  • Endogenous or exogenous compound

- Metabolic processes

71
Q

Acetylation conjugation involves

A
  • Transfer of acetyl groups to a primary amine group, (aliphatic and aromatic amines)
  • Amino acids
  • Sulfonamides
  • Hydrazines and hydrazides
72
Q

The function of acetylation

A
  • Deactivate the drug
73
Q

Methylation conjugation is a minor pathway important in the BIOSYNTHESIS of

A
  • Epinephrine

- Melatonin

74
Q

Methylation conjugation is a minor pathway important in the CATABOLISM of

A
  • Norepinephrine
  • Dopamine
  • Serotonin
  • Histamine
75
Q

Methylation conjugation is a minor pathway important in MODULATING the activities of

A
  • Macromolecules (proteins and ncleic acids)
76
Q

Methylation conjugation is catalyzed by

A
  • Methyltransferase
77
Q

Methylation conjugation is a minor pathway important in the METHYLATION REACTIONS of

A
  • Amines
  • Thiols
  • Phenols
78
Q

Phase II summary

A
  • Glucuronidation
  • Sulfate conjugation
  • Amino acid conjugation
  • Glutathione conjugation
  • Acetylation conjugation
  • Methylation conjugation

Pharmacology (27 decks)

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