Drug metabolism Drug metabolism and eliminationand elimination

MetabolismMetabolism

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

Metabolism/Metabolism/BiotransformationBiotransformation

Biologic transformation of a drug into:Biologic transformation of a drug into: An inactive metaboliteAn inactive metabolite A more soluble compoundA more soluble compound A more potent metabolite-rarelyA more potent metabolite-rarely

BiotransformationBiotransformation Generates more polar (water soluble), Generates more polar (water soluble),

inactive metabolitesinactive metabolites Readily excreted from bodyReadily excreted from body Metabolites may still have potent Metabolites may still have potent

biological activity (or may have toxic biological activity (or may have toxic properties)properties)

Phase I and Phase II Phase I and Phase II MetabolismMetabolism

Phase I Phase I functionalization reactionsfunctionalization reactions

Phase II Phase II conjugation reactionsconjugation reactions

Phase I Phase I Converts the parent drug to a more polar Converts the parent drug to a more polar

metabolite metabolite Usually results in loss of pharmacological Usually results in loss of pharmacological

activityactivity

Phase II (conjugation Phase II (conjugation reactions)reactions) Subsequent reaction in which a Subsequent reaction in which a

covalent linkage is formed between a covalent linkage is formed between a Phase I metabolite and an endogenous Phase I metabolite and an endogenous substrate such as glucuronic acid or an substrate such as glucuronic acid or an amino acidamino acid

Highly polar – rapidly excreted in urine Highly polar – rapidly excreted in urine and fecesand feces

Metabolism/Metabolism/Biotransformation Biotransformation (cont'd)(cont'd)

Enzymatic in nature Enzymatic in nature Happen in Organs or body tissuesHappen in Organs or body tissues Liver (main)Liver (main) Skeletal muscleSkeletal muscle KidneysKidneys Lungs Lungs PlasmaPlasma Intestinal mucosaIntestinal mucosa

Cytochrome P450 Cytochrome P450 Monooxygenase SystemMonooxygenase System

heme containing enzyme systemheme containing enzyme system Involved in metabolism of endogenous Involved in metabolism of endogenous

and exogenous compoundsand exogenous compounds DrugsDrugs Environmental chemicalsEnvironmental chemicals

In liver mainly In liver mainly

Metabolism/Metabolism/Biotransformation Biotransformation (cont'd)(cont'd)

Factors that decrease metabolismFactors that decrease metabolism Cardiovascular dysfunctionCardiovascular dysfunction Renal insufficiencyRenal insufficiency StarvationStarvation Obstructive jaundiceObstructive jaundice Erythromycin or ketoconazole drug Erythromycin or ketoconazole drug

therapytherapy

Metabolism/Metabolism/Biotransformation Biotransformation (cont'd)(cont'd)

Factors that increase metabolismFactors that increase metabolism BarbituratesBarbiturates Rifampin therapyRifampin therapy

Metabolism/Metabolism/Biotransformation Biotransformation (cont'd)(cont'd)

Delayed drug metabolism results in:Delayed drug metabolism results in: Accumulation of drugsAccumulation of drugs Prolonged action of the drugsProlonged action of the drugs

Stimulating drug metabolism causes:Stimulating drug metabolism causes: Diminished pharmacologic effectsDiminished pharmacologic effects

ExcretionExcretion

The elimination of drugs from the bodyThe elimination of drugs from the body Kidneys (main organ)Kidneys (main organ) LiverLiver BowelBowel

Biliary excretionBiliary excretion Enterohepatic circulationEnterohepatic 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-lifeHalf-life

The time it takes for one half of the original The time it takes for one half of the original amount of a drug in the body to be removedamount of a drug in the body to be removed

A measure of the rate at which drugs are A measure of the rate at which drugs are removed from the bodyremoved from the body

The drug A has a half life of 2 hours while The drug A has a half life of 2 hours while drug B has a half life of 10 hours. drug B has a half life of 10 hours.

-explain in your words what is meant by -explain in your words what is meant by half life of a drughalf life of a drug

-which drug of the two have to be given in -which drug of the two have to be given in more dosage frequency. Give reasons for more dosage frequency. Give reasons for your answer.your answer.

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

Onset, Peak, and Onset, Peak, and DurationDurationOnsetOnset The time it takes for the drug to elicit a The time it takes for the drug to elicit a

therapeutic responsetherapeutic response

PeakPeak The time it takes for a drug to reach its The time it takes for a drug to reach its

maximum therapeutic response maximum therapeutic response

DurationDuration The time a drug concentration is sufficient to The time a drug concentration is sufficient to

elicit a therapeutic responseelicit a therapeutic response

Comment on the graph.Comment on the graph.

Questions….Questions….