Tema 4. FARMACOCINÉTICA; Metabolismo.

4. Pharmacokinetics and Metabolism

Overview of Metabolism

• Metabolism, or biotransformation, often activates the original compound; however, some metabolites can be equally or more active than the original drug, potentially leading to prolonged effects.

• In certain cases, metabolism converts inactive substances into active ones, referred to as prodrugs.

Sites and Types of Metabolic Reactions

• The liver is the primary organ for metabolism but other organs like lungs and kidneys also contribute.

• Phase 1 reactions include oxidation, reduction, and hydrolysis aimed at making substances more polar and water-soluble; oxidation is the most common method used by drugs.

Cytochrome P450 System

• The cytochrome P450 system in the liver plays a crucial role in metabolizing numerous endogenous substances; there are 25 to 30 identified isoforms.

• Major families involved in drug metabolism include CYP1, CYP2, and CYP3 with CYP2D6 and CYP3A4 being the most utilized.

Phase 2 Reactions

• Phase 2 involves conjugation reactions where drugs from phase 1 attach to substrates for easier elimination; this process requires energy input.

Factors Affecting Metabolism

• Various factors influence metabolism including age—neonates have immature systems while elderly individuals may experience reduced hepatic flow leading to toxicity risks.

• Enzyme inducers increase metabolic activity primarily in the liver but can affect other systems too; they may lead to tolerance or altered drug efficacy.

Clinical Implications of Induction and Inhibition

• Induction can decrease drug effect duration if it leads to inactive metabolites or increase toxicity if active forms are produced.

• Environmental contaminants and dietary substances can act as significant enzyme inducers; alcohol is a notable example.

Enzyme Inhibition Effects