OIA1013 DRUG METABOLISM

Overview of Drug METABOLISM

Definition and Importance of Drug Elimination

Drug elimination refers to the irreversible removal of drugs from the body through various routes.

It is crucial for maintaining drug levels within therapeutic ranges and preventing toxicity.

Understanding drug elimination helps in optimizing drug dosing regimens.

Processes of Drug Elimination

Excretion: The removal of the intact drug from the body, primarily through urine, bile, and sweat.

Biotransformation: The chemical conversion of drugs into metabolites, which may be active, inactive, or toxic.

Biotransformation and Drug Metabolism

Mechanisms of Biotransformation

Biotransformation primarily occurs in the liver, with enzymes facilitating the conversion of hydrophobic drugs to hydrophilic metabolites for easier excretion.

The 'first-pass effect' significantly reduces the bioavailability of certain drugs by metabolizing them before they reach systemic circulation.

Phase I and Phase II Reactions

Phase I Reactions: Involve oxidation, reduction, or hydrolysis, resulting in more polar metabolites. Commonly catalyzed by cytochrome P450 enzymes.

Phase II Reactions: Involve conjugation with endogenous substances, leading to inactive and water-soluble metabolites for excretion.

Cytochrome P450 Enzymes

Cytochrome P450 enzymes are crucial for drug metabolism, with over 50 isoforms identified, including CYP1A2, CYP2C9, CYP2D6, and CYP3A4, which metabolize 90% of drugs.

These enzymes are inducible and can be affected by various factors, including drugs and diet.

Clinical Relevance of Drug Metabolism

Effects of Drug Metabolism on Pharmacokinetics

Drug metabolism can convert active drugs into inactive metabolites, terminating their action, or into active metabolites, prolonging their effects.

Understanding metabolism is essential for predicting drug interactions and adverse effects.

Factors Affecting Drug Metabolism

Enzyme Induction: Certain drugs can increase the activity of P450 enzymes, leading to enhanced metabolism and reduced drug effects (e.g., phenobarbital and warfarin).

Enzyme Inhibition: Some substances can inhibit P450 enzymes, decreasing metabolism and increasing drug effects, potentially leading to toxicity (e.g., grapefruit juice and statins).

Routes of Drug Excretion

Major Routes of Excretion

Renal Excretion: The primary route for drug elimination, involving filtration, secretion, and reabsorption processes in the kidneys.

Biliary Excretion: Involves the secretion of drugs into bile, which can be reabsorbed or eliminated in feces.

Factors Influencing Renal Excretion

Factors such as urine pH, drug solubility, and renal function significantly affect the excretion of drugs.

Alterations in renal function can lead to accumulation of drugs and increased risk of toxicity.

Discussion questions

1/6

What are the two primary processes involved in drug elimination, and how do they differ from each other?

Difficulty: Easy

2/6

Discuss the significance of cytochrome P450 enzymes in drug metabolism and their impact on pharmacokinetics.

Difficulty: Medium

3/6

How does the first-pass effect influence drug bioavailability, and what are its clinical implications?

Difficulty: Medium

4/6

Explain the differences between phase I and phase II metabolic reactions in drug metabolism.

Difficulty: Hard

5/6

What factors can influence drug metabolism, and how do they affect drug efficacy and safety?

Difficulty: Hard

6/6

Describe the role of renal excretion in drug elimination and the factors that can affect this process.

Difficulty: Medium