Drug Metabolism/Excretion

Annotations:

• Acid drugs are found in acid environment, basic drugs are also found in the basic environment. Drugs are broken down and excreted.

1. Biotransformation and excetion

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   • Phase 1: Is in the endoplasmic reticulum Phase II: Relates to the enzymes in the cytosol, to produce a conjugation reaction. Both phases act on broad range of chemically unrelated substances. Phase III: Process by a drug which it is pumped out.
2. Site of drug metabolism

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   • Liver: 70% Lung: 14% Kidney: *% Intestine: 6% Placenta: 5% Adrenal: 2% Dominant organ in drug metabolism is the liver. Ocular metabolism may be significant after application of drugs to eye.
3. 1st Pass Metabolism

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   • Portion of the drug that was inactivated by liver via normal circulation. Oral drugs will pass thru liver before entering systemic circulation. It was then divided into 2 phases Phase 1: enzymes act on lipophilic drugs and use  molecular oxygen. It also known as Cytochrome P450 system.
   1. P450

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      • CHange in CYP450 system will determine drug metabolism. Examples subclass are CYP3M5 or CYP2E1 (to increase alcohol metabolism) CYP205
   2. Phase II

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      • Conjugation reactions.
      1. Paracetamol

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         • One example is paracetamol, by which Phase II will turn it into Glucuronide or sulfate. However, in the Phase I metabolism it gives a reactive intermediate.
4. Factors affecting Drug metabolism

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   • Age Gender Genetic Variations Nutrition Induction/inhinition metabolic enzymes Drug/Drug interactions Diseases