Drug Metabolism and Excretion

Question 1

Describe first pass metabolism and its importance

Answer 1

Liver, and gut wall possess drug metabolising enzymes

For certain drugs extensive metabolism occurs before the drug reaches the systemic circulation
→ only a small proportion of the dose reaches the systemic circulation
→ larger oral dose is required // different route of administration
e.g. intravenous,
inhalational, sublingual

Examples of high FPM:
25% propanolol oral dose reaches systemic circulation

30-40% morphine oral dose reaches systemic circulation

Question 2

Define bioavailability

Answer 2

Bioavailability is defined as the proportion of a drug that passes into the systemic circulation after administration.

Question 3

bioavailability depends on

Answer 3

1. Absorption - gut motility, other drugs and foods etc

2. Metabolism - in the gut/liver = FPM. High FPM = low bioavailability

Question 4

Metabolism is a general term for chemical transformations that occur in the body and its processes change drugs in two major ways by:

Answer 4

Reducing lipid solubility

Altering biological activity

Question 5

Metabolism mechanisms:

1. Reducing lipid solubility

Answer 5

Most drugs are lipophilic (i.e. lipid soluble) - allows absorption of drugs across membranes to reach site of action

Lipophilic compounds are not eliminated efficiently by the kidney so they must be made more water soluble to allow them to be excreted in urine

Metabolism is the process that introduces hydrophilic components onto the drug to aid excretion
→ makes lipid soluble drugs water soluble

Hydrophilic (water soluble) drugs tend to be largely excreted unchanged i.e. as the parent drug