Drugs And The Liver

Drugs and the liver

Effect of the liver on the drugs :• The liver transforms lipophylic to hydrophylic drugs to be excreted • The are two phases I and II • It occurs by cytochrome P450 enzyme system

Factors affecting biotransformation of drugs;-

1-Inducers (barbiturates, rifampicin, phenytion, phenylbutazone, griseofulvin, smoking ) and inhibitors (allopurinol, chloramphenicol, INH, cimitidine , ketoconazol, oral contraceptives ) of CYP 2- Hepatic blood flow: - N.B:- hepatic clearance = hepatic blood flow x extraction ratio 3- Malnutrition 4- Age :5- Sex :- more activity in males than females 6- liver diseases 7- genetic factors (idiosyncracy)

Pharmacokinetic and pharmacodynamic changes in drug disposition in hepatic impairment

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Absorption Protein binding Distribution Metabolism Excretion

Hepatic drug insult • General facts:1- phase I reactions are more affected than phase II reactions 2- enzyme induction aggravates toxicity An example to this is INH N-acetyl transferase Isonicotinic acid + acetylhydrazide * Thus enzyme inducers such as rifampicin increase the liver cell necrosis induced by INH. 3- Hepatic drug reactions are less in children than adults and more in females therefore paracetamol is safer in infants than adults.

• Drug induced liver diseases 1- hepatocyte toxicity 2- biliary tract toxicity 3- hepatic vascular affection