Drug metabolism and elimination Metabolism The metabolism of

Drug metabolism and elimination

Metabolism § The metabolism of drugs and into more hydrophilic metabolites is essential for the elimination of these compounds from the body and termination of their biological activity.

Metabolism/Biotransformation • Biologic transformation of a drug into: – An inactive metabolite – A more soluble compound – A more potent metabolite-rarely

Biotransformation § Generates more polar (water soluble), inactive metabolites § Readily excreted from body § Metabolites may still have potent biological activity (or may have toxic properties)

Phase I and Phase II Metabolism § Phase I § functionalization reactions § Phase II § conjugation reactions

Phase I § Converts the parent drug to a more polar metabolite § Usually results in loss of pharmacological activity

Phase II (conjugation reactions) § Subsequent reaction in which a covalent linkage is formed between a Phase I metabolite and an endogenous substrate such as glucuronic acid or an amino acid § Highly polar – rapidly excreted in urine and feces

Metabolism/Biotransformation (cont'd) – Enzymatic in nature – Happen in Organs or body tissues – – – Liver (main) Skeletal muscle Kidneys Lungs Plasma Intestinal mucosa

Cytochrome P 450 Monooxygenase System § § heme containing enzyme system Involved in metabolism of endogenous and exogenous compounds § Drugs § Environmental chemicals In liver mainly

Metabolism/Biotransformation (cont'd) Factors that decrease metabolism • • • Cardiovascular dysfunction Renal insufficiency Starvation Obstructive jaundice Erythromycin or ketoconazole drug therapy

Metabolism/Biotransformation (cont'd) Factors that increase metabolism • Barbiturates • Rifampin therapy

Metabolism/Biotransformation (cont'd) Delayed drug metabolism results in: • Accumulation of drugs • Prolonged action of the drugs Stimulating drug metabolism causes: • Diminished pharmacologic effects

Excretion The elimination of drugs from the body • Kidneys (main organ) • Liver • Bowel – Biliary excretion – Enterohepatic circulation

Figure 2 -5 Renal drug excretion. The primary processes involved in drug excretion and the approximate location that these processes take place in the kidney are illustrated. Mosby items and derived items © 2005, 2002 by Mosby, Inc.

Half-life • The time it takes for one half of the original amount of a drug in the body to be removed • A measure of the rate at which drugs are removed from the body

§ The drug A has a half life of 2 hours while drug B has a half life of 10 hours. -explain in your words what is meant by half life of a drug -which drug of the two have to be given in more dosage frequency. Give reasons for your answer.

Name one disease condition that can increase the half life of a drug in the body.

Onset, Peak, and Duration Onset • The time it takes for the drug to elicit a therapeutic response Peak • The time it takes for a drug to reach its maximum therapeutic response Duration • The time a drug concentration is sufficient to elicit a therapeutic response

Comment on the graph.

Questions….