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Metabolism of drugs

Created: 28/7/2004

 
Metabolism in the liver into inactive compounds which are inactive and more ionised and therefore excreted by the kidney.

Other sites

  • suxamethonium and mivacurium: plasma cholinesterases
  • esmolol: erythrocyte esterases
  • dopamine: kidney
  • prilocaine: lungs

Active Metabolites

Morphine

morphine-6-glucuronide

Pethidine

nor-pethidine

Diazepam

desmethyldiazepam/temazepam/oxazepam

Atracurium

laudanosine

Pancuronium

3-hydroxypancuronium

Prodrugs: inactive form administered which is converted into an active metabolite

Methyl-dopa

methyl-noradrenaline

Prednisone

prednisolone

Midazolam

water soluble at acid pH in ampule, becomes more lipid soluble after injection

Phase I and Phase II Reactions

Phase I: reduction, hydrolysis and oxidation

  • oxidation: occurs at the smooth endoplasmic reticulum by cytochrome p450
  • oxidation: can also perform reduction reactions
  • hydrolysis: important in metabolism of ester and amide drugs

Phase II: conjugation of the drug or metabolite with an endogeous substrate

  • conjugation with glucuronic acid, sulphate and glycine
  • acetylation
  • methylation

Induction and inhibition

Some drugs can induce the activity of enzyme systems, particularly cytochrome p450 and glucuronyl transferase.

Some drugs can inhibit the action of enzymes e.g. etomidate; inhibits the synthesis of cortisol and aldosterone (increased mortality seen with infusions)


ArticleDate:20040728
SiteSection: Article
 
   
    
                                            
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