Metabolism Flashcards

1
Q
Examples of reactive metabolites:
Meperidine
Morphine
Acetaminophen 
Furosemide 
Sulfamethoxazole 
Cyclophosphamide
A
Meperidine➡️nor-meperidine
Morphine➡️morphine-6-glucuronide
Acetaminophen➡️benzoquinoneimine
Furosemide➡️furo epoxide
Sulfamethoxazole➡️nitroso sulfomethoxazole
Cyclophosphamide➡️acroleine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Examples of bioactivation (pro-drugs)

A

Cefuroxime auxetil, Methydopa
ACEi Enalapril Ramipril
Valacyclovir➡️vala triphosphate
Fancyclovir➡️pencyclovir

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

These are biochemical reactions that are catalyzed by enzymes. And examples.

A

yes Phase 1 and 2 metabolism

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

Phase II metabolism examples

A

Conjugation (ADDITION) metabolism

Glucuronidation, glutathione conjg. sulfonation, acetylation and methylation

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

Phase 1 metabolism examples

A

Functional grps: OH, NH2, COOH, SH etc
Oxidation reduction hydroxylation deamination dealkylations demethylation oxidative deamination
Cytochrome oxidations (CYP450), reductase, aminase and monoamine oxidase (MAO)

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

In phase 1, alcohol oxidations yield what?

A
1* alc oxidation➡️aldehyde➡️acid
2*➡️ketone
3*➡️no oxidation 
methanol➡️formaldehyde ➡️formic acid- causes blindness 
ethanol➡️acetaldehyde
Ethylene glycol➡️oxaldehyde➡️oxalic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Both mechanisms are to create a polar substrate to be excreted.
Bacteria resident in the GI tract are involved in this reduction reactions.

A

Oxidation and Reduction.

Azi and Nitro reductions

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

What drug undegoes Azoreduction?

A

Azoreduction bond (-N=N-)
Sulfasalazine (in gut)➡️ 5aminosalicylic acid (5ASA) + Sulfpyridine
5ASA - Mesalamine

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

In Nitro reduction, what group does this produces? Drug examples that undergo this nitro and carbonyl reduction.

A

= amine (NH2) group
Chloramphenicol and Clonazepam- Nitro red.
Acetohexamide- carbonyl red.

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

Two functional groups that undergo hydrolysis, also for fixed oils, give catalyzing enzyme and products.

A

Esters ➡️ by esterases =acid + alcohol
Amide➡️ by amidases= acid + amide
Fixed oils➡️ by ester hydrolysis= glycerol + fatty acids

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

ASA and Acetaminophen drug metabolisms

A

ASA and SA- glucuronidation, glycine congjn, hydrolysis (major), hydroxylation
Ace- glutathion and sulphate congjn, glucuronidation and phase 1 metabolism

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

Drug examples that undergo deamination and hydrolysis

A

Deam: Amphetamine and Dopamine
Hydrolysis: Valacyclovir➡️Acyclovir
Famcyclovir➡️Pencyclovir

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

What metabolism adds glucuronic acid, drugs: aceta, morphine, diazepam, sulfathiazole, digoxin and SA.
What catalyzing enzyme?

A

Glucuronidation by Uridenyl Diphosphate Glucuronyl Transferase (UDP GT)

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

Ethacrynic acid and acetaminophen (to reduce what toxicity?) undergoes which drug metabolism? By what enzyme?

A

Glutathione conjg by enzyme Glutathione S-transferase (GST)

-reduced hepatotoxicity

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

1* amines undergo what metabolism (add acetyl grp NH2, OH) by what enzyme and drug examples.

A

Sulfonamides, Isoniazid, Clonazepam and Dapsone

by enzyme N-acetyl transferase

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

The only amino acid conjugation by what enzyme and drug examples

A

Glycine conj by Acetyl transferase

SA (75% of SA is excreted aft metabolism), Nicotinic acid (Niacin), deoxycholic acid

17
Q

Sulfate conjugation is by what enzyme and what drug examples.

A

Sulfotransferase

Acetaminophen, Methyldopa and Estrone

18
Q

Merhylation is by what enzyme and what drug examples.

A

N-methyltransferase

E, NE, DOPA and Histamine

19
Q

Phase 2 metab. is referred to as what?, parent drug or its metabolite with natural contituents.

A

Conjugation reaction

Glucuronic acid, glutamine, sulfate and glutathione

20
Q

How nutritional status affects drug metabolism.
Low protein diet
Vit. C def
Vit. E def

A

Low protein diet- dec. Oxidative
Vit. C def- Dec. Oxidative pathways
Vit. E def- retards dealkylation and hydroxylation

21
Q

Most common drug metabolizing cytochrome enzyme, also large grp of monooxygenase enzymes resp for toxic hydrocarbons metabolism. Located where?
Give the coenzyme and susbtrate.

A

CYP450 located in ER, also mitochondria membrane and highly concentrated in liver and small intestine
NADPH- coenzyme
O2- substrate

22
Q

Most common enzyme that catalyze phase 1 oxidative reactions.
Most common cytochrome SUBTYPE enzyme is?

A

CYP3A

-CYP3A4

23
Q

This metabolism is for 1* and 2*

A

1*- Steroid and bile acid metabolism

2*- drug metabolism

24
Q

What drugs undergo halogenation?

A

Halothane, Chloramphenicol

25
Species differences between Phase 1 and 2 metabolism
1: Quantitative- presence of enzyme inducers and inhibitors 2: Qualitative
26
Physiological or disease states affecting drug metabolism.
Liver, renal disease, CHF, hypo hyperthyroidism, alteration of albumin production as in elderly
27
This drug undergoes deamination followed by oxidation and reduction of the ketone formed, N-oxi then N-dealkylation and so on.
Amphetamines
28
Oxidation and complete removal of substituents at Carbon 5. N-dealkylation at N1 and N3 So on
Barbiturates
29
In the side chain N10: | N-dealkylation and N-oxidation then scission
Phenothiazines
30
Acetylation at N4 amino group conjg with glucuronic acid: -or sulfate at N4 amino grp -or acetylation at N1 amino group
Sulfonamides
31
Hepatic microsomal enzymes Extra hepatic microsomal enzymes Hepatic non-microsomal enzymes
H: Cytochrome IN liver Extra H: Cyto OUT of the liver H non: Acetylation, sulfate, GSH, alcohol, dehydrogenase, hydrolysis
31
What enzyme catalyzes most conjugation reactions?
UDP GT
32
Most common metabolic reaction in the GI. Most common phase 1 metabolic reaction. Most common metabolic reaction in human.
Hydrolysis Oxidation Glucuronidation
33
Most common CYP3A4 inhibitors?
Eryth, Clarith, GFJ, Ketoconazole, Cimetidine, Protease inhibitors
34
Most common CYP3A4 substrates?
BZD, statins, Digoxin, Sildenafil
35
Most common CYP2D6 substrate and inhibitor?
Codeine and Fluoxetine
36
Most common CYP3A4 inducers.
Phenobarbitals, Phenytoin, Carbamazepine, Rifampin, St. John’s Wort
37
Acetaminophen hepatotoxicity can be reduced by?
Glutathione conjugation