MEDICAL PHYSIOLOGY

Detailed explanation-1: -The first pass effect is often associated with the liver, as this is a major site of drug metabolism . However, the first pass effect can also occur in the lungs, vasculature, gastrointestinal tract, and other metabolically active tissues in the body.

Detailed explanation-2: -Although a spectrum of drug biotransformations can occur during first-pass, the most common are oxidations catalyzed by cytochromes P450. It is the isozymes CYP2D6, CYP3A4, CYP1A2, CYP2C9 and CYP2C19 that are most often implicated in first-pass drug elimination.

Detailed explanation-3: -The first pass metabolism refers to the combined action of drug metabolism by the liver and the gut, because certain drugs are digested by microbes in the gut or digestive enzymes. Thus, before reaching systemic circulation, the drug will encounter organs with high quantities of biotransformation enzymes.

Detailed explanation-4: -The first-pass effect can occur in the gastrointestinal tract, the liver and lung. Although the liver is the main drug metabolizing organ in the body, the gut wall can play an important role in the first-pass metabolism of certain drugs.