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/Biotransformatio n  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/Biotransforma tion (cont'd)  Enzymatic in nature  Happen in Organs or body tissues  Liver (main)  Skeletal muscle  Kidneys  Lungs  Plasma  Intestinal mucosa

Cytochrome P450 Monooxygenase System  heme containing enzyme system  Involved in metabolism of endogenous and exogenous compounds  Drugs  Environmental chemicals In liver mainly

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

Metabolism/Biotransforma tion (cont'd) Factors that increase metabolism  Barbiturates  Rifampin therapy

Metabolism/Biotransforma tion (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

Mosby items and derived items © 2005, 2002 by Mosby, Inc. 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.

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….