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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Define pharmacodynamics

What a drug does to the body 


Define pharmacokinetics

What the body does to a drug


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

They are usually less pharmacologically active, with a few exceptions


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 



Describe the characteristics of a pro-drug

Stable and relatively unreactive


What happens to pro-drugs in phase 1 metabolism? 

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


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


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

  • Oxidation
  • Reduction 
  • Hydrolysis



 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 


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 


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

Glucoronic acid 


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

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


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

  • Sulphate ions 
  • Glutathione 



What does phase II metabolism require? 

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


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

The enter the venous blood


Where does the venous blood from the ileum drain? 

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


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




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



What do the enzymes in the cytochrome P450 system contain? 



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

About 50, and polymorphisms in the human population 


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

CYP3 A4 


What % of drug metabolism is CYP3 A4 responsible for? 

About 55%


What is the CYP co-factor? 



What accounts for variation in drug metabolism in the population?

  • Genetic factors 
  • Environmental factors 



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 


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 



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

Suxamethonium, which is a muscle relaxant used during anasthesia


How can the environment effect drug metabolism? 

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


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

Enzyme induction or inhibition can occur 


Give three examples of enzyme inducers

  • Ethanol
  • Nicotine
  • Barbituates