Organic Medicinal Chemistry Flashcards

1
Q

• The biotransformation of drugs in the body
• Important in the elimination of drugs from the body
• Converts drugs to hydrophilic, inactive and nontoxic
• Has 2 Phases: Functionalization & Conjugation

A

Metabolism

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

• Introduce a polar functional group (OH, COOH, NH2, SH) by:
- Direct introduction
- Modifying/Unmasking existing functionalities
• Produce a handle on the molecule for Phase II
• Reactions: Oxidation, Reduction, Hydrolysis

A

Phase 1 (Functionalization)

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

What are the 3 Reactions in Phase 1 Functionalization in Metabolism

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

What Reactions in Phase I stated below?

• Most common Phase 1 reaction
• Undergone by Olefins, Alcohols, Aldehydes & Aromatic moieties

A

Oxidation

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

What Reactions in Phase I stated below?

• Carbonyl compounds → Alcohol derivatives
• Nitro and Azo compounds → Amine derivatives

A

Reduction

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

What Reactions in Phase I stated below?

• Commonly undergone by lactams, esters and amides
• ex. Aspirin → Salicylic acid + Acetic acid

A

Hydrolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
  • Attach small, Ionizable, endogenous compounds to the functional handles
  • Reactions: Glucuronidation, Sulfation, Glycine & Glutamine conjugation, Glutathione, Acetylation, Methylation
A

Phase II (Conjugation)

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

What Reactions in Phase II stated below?

Coenzyme: Uridine-5’-diphospho-α-D-glucuronic acid (UDPGA)
• Transferase enzyme (TE): Glucuronyltransferase
• Most common
• Readily available supply of D-glucuronic acid
• Not yet developed in neonates

A

Glucoronidation

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

What Reactions in Phase II stated below?

Coenzyme: 3-phosphoadenosine-5-phosphosulfate(PAPS)
• TE: Sulfotransferase
• Conjugate endogenouscompounds such as steroids, heparin, chondroitin, catecholamines,thyroxine
• In neonates, it is the major process.

A

Sulfation

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

What Reactions in Phase II stated below?

  • Conjugate Carboxylic acid, particularly aromatic acids & arylalkyl acid
  • Glycine – common to mammals
  • Glutamine – humans & other primates
  • Minor pathway
A

Glazine and Glutamine Conjugation

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

What Reactions in Phase II stated below?

The first mammalian metabolite discovered from glycine conjugation

A

Benzoic acid → Hippuric acid

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

What Reactions in Phase II stated below?

• For detoxifying chemically reactive Electrophilic compounds

A

Glutathione

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

Glutathione is composed of 3 amino acids: [CGG]

A
  1. Cysteine - (-SH) is responsible for detoxification
  2. Glycine
  3. Glutamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What Reactions in Phase II stated below?

• For termination of activity & detoxification
• Important route of primary amino groups
• Acetyl group supplier: Acetyl-CoA
• TE: N-acetyltransferase

A

Acetylation

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

Slow acetylators (Low dose)

[EEC]

A

Europeans
Egyptians
Caucasians

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

Fast acetylators (High dose)

[EA]

A

Eskimos
Asians

17
Q

What Reactions in Phase II stated below?

• Coenzyme: S-Adenosylmethionine (SAM)
• TE: Methyl transferase
• Minor pathway that leads to non-polar & inactivated compounds
• Biosynthesis of epinephrine, melatonin
• Inactivation of norepinephrine, dopamine, serotonin, histamine

A

Methylation

18
Q

When orally administered drugs are extensively metabolized before reaching the systemic circulation

A

First-Pass Metabolism / Pre-systemic metabolism