Pharmacodynamics

Metabolism

Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions

• phase I reactions: oxidation, reduction, hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic
• phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile. Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

The majority of phase I and phase II reactions take place in the liver

First-pass metabolism

This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:

• aspirin
• isosorbide dinitrate
• glyceryl trinitrate
• lignocaine
• propranolol
• verapamil
• isoprenaline
• testosterone
• hydrocortisone

Questions concerning zero-order kinetics and acetylator status are also common in the exam