Drug and Alcohol Metabolism Flashcards Preview

ESA 1 - Metabolism > Drug and Alcohol Metabolism > Flashcards

Flashcards in Drug and Alcohol Metabolism Deck (54)
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1

Define pharmacodynamics

What a drug does to the body 

2

Define pharmacokinetics

What the body does to a drug

3

How do the metabolites of a drug usually compare to the original form? 

They are usually less pharmacologically active, with a few exceptions

4

Give three exceptions to the rule that metabolites of drugs are less pharmacologically active than the original 

  • Primidone to phenobarbitone
  • Pethidine for norpethidine 
  • Codeine to morphine 

 

5

Describe the characteristics of a pro-drug

Stable and relatively unreactive

6

What happens to pro-drugs in phase 1 metabolism? 

A reactive group is exposed on the parent molecule, or added to the molecule 

7

What is the result of the exposure of a reactive group in phase I metabolism? 

It generates a reactive intermediate that can be conjuated in phase II with a water-soluble molecule to form a water soluble complex

8

What are the most common chemical reactions that occur in phase I metabolism? 

  • Oxidation
  • Reduction 
  • Hydrolysis

 

9

 What to the chemical reactions in phase I metabolism require? 

A complex enzyme system called the cytochrome P450 (CYP) system, and a high energy cofactor, NADPH 

10

What happens to the reactive intermediate from phase I in phase II metabolism? 

It is conjugated with a polar molecule to form a water soluble complex in a process called conjugation 

11

What is the most common conjugate used in phase II metabolism?

Glucoronic acid 

12

Why is glucaronic acid the most common conjugate used in phase II metabolism? 

Becasue it's an available by-product of cell metabolism 

13

Other than glucoronic acid, what else can drugs be conjugated with in phase II metabolism? 

  • Sulphate ions 
  • Glutathione 

 

14

What does phase II metabolism require? 

Specific enzymes and a high-energy cofactor- uridine diphosphate glucuronic acid 

15

What happens to substances absorbed from the lumen of the ileum? 

The enter the venous blood

16

Where does the venous blood from the ileum drain? 

Into the hepatic portal vein, which is then transported directly to the liver

17

What is the problem with venous blood from the ileum being transported directly to the liver? 

The liver is the main site of drug metabolism, as it contains all the necessary enzyme systems, and so any drug absorbed from the ileum may be extensively metabolised during the first pass through the liver - the first pass effect

 

 

18

What % of an oral dose of paracetamol is metabolised by the first pass effect? 

90%

19

What do the enzymes in the cytochrome P450 system contain? 

Haem 

20

How many different haem-containg enzymes are the in the cytochrome P450 system? 

About 50, and polymorphisms in the human population 

21

What is the most important isoform in the cytochrome P450 system? 

CYP3 A4 

22

What % of drug metabolism is CYP3 A4 responsible for? 

About 55%

23

What is the CYP co-factor? 

NADPH

24

What accounts for variation in drug metabolism in the population?

  • Genetic factors 
  • Environmental factors 

 

25

In terms of genetics, why can drug effects vary from person to person? 

We all differ slightly in the level of expression of metabolic enzymes 

26

Give three examples of a genetic difference that might have a big effect on drug metabolism? 

  • Some individuals may lack the gene that codes for a crucial enzyme such as CYP3 A4
  • Some people are described as slow acetylators, as they lack the main enzyme responsible for the acetylation reaction in phase II
  • Some people have relatively low levels of pseudocholinesterase enzymes in the plasma, which affects their ability to metabolise drugs containg an ester bone 

 

27

Give an example of a drug containing an ester bond, and what it does? 

Suxamethonium, which is a muscle relaxant used during anasthesia

28

How can the environment effect drug metabolism? 

If two drugs are given together, the metaboilsm of one drug may affect the metabolism of another

29

How can the metabolism of one drug affect the metabolism of another? 

Enzyme induction or inhibition can occur 

30

Give three examples of enzyme inducers

  • Ethanol
  • Nicotine
  • Barbituates