Biopharmaceutics & Pharmacokinetics Week 4 Quiz

Metabolism Overview

• Metabolism, also referred to as biotransformation, involves enzymatic or biochemical transformation of drugs into less toxic metabolites for easier elimination.
• Drug metabolism is a chemical process facilitated by the biological environment, aiming to supply energy, break down foreign compounds, and increase water solubility.

Liver Function and Structure

• The liver is the principal organ responsible for metabolism, acting as both a synthesizing and eliminating organ.
• Liver anatomy includes the liver lobule as the basic structural unit, hepatic artery for oxygen-rich blood, and hepatic portal vein for nutrient-rich blood.

Metabolizing Enzymes

• Drug metabolism occurs in various liver fractions, including soluble, mitochondrial, and microsomal.
• Some metabolism can also occur in the bloodstream due to enzyme leakage from cells.

Classes of Metabolites

• Inactive metabolites decrease pharmacological action (e.g., Procaine to p-aminobenzoic acid).
• Metabolites retaining similar activity continue to exert effects (e.g., Codeine to Morphine).
• Metabolites with altered activity (e.g., Iproniazid to isoniazid) may have different effects than the parent drug.
• Bioactivated metabolites are inactive until converted (e.g., Enalapril to Enalaprilat).
• Reactive metabolites can potentially be toxic (e.g., Acetaminophen to NAPQI).

Biotransformation Components

• Three major components involved in drug biotransformation are the reactant (the drug), the product (the metabolite), and the treatment provided.

Conjugation Pathways

• Sulfate Conjugation: Enzyme sulfotransferases in liver, kidney, and GI tract; limited capacity and easily saturated at high doses.
• Methylation: A minor pathway involving methyl transferase, significant for endogenous substances.
• Acetylation: Catalyzed by acetyl transferases; genetics influence speed of metabolism (slow vs. fast acetylators).
• Glutathione Conjugation: Detoxifies reactive oxygen species; critical in cellular protection.
• Amino Acid Conjugation: Glycine and Glutamine play roles in conjugation with organic acids.

Maturation of Metabolic Processes in Infants

• Metabolic capacity develops over time with significant processes emerging at various ages, such as sulfation at birth and glucuronidation around two months.

Enzyme Induction and Inhibition

• Enzyme Induction: Increased enzyme activity speeds metabolism; it is an adaptation to exogenous substances.
• Enzyme Inhibition: Results in decreased enzyme activity, leading to increased drug effects due to slower metabolism.

First Pass Effect

• Describes pre-systemic metabolism where drugs undergo transformation before systemic circulation, often reducing their bioavailability.

Excretion Mechanisms

• Excretion finalizes drug removal from the body through various routes including renal (urine), fecal, and respiratory pathways for volatile compounds.

Clearance

• Clearance reflects the rate of drug elimination from the body, measured in volume over time (mL/min or L/hr).
• The kidney plays a vital role, maintaining fluid balance and producing essential hormones like renin and erythropoietin.

Kidney Function

• Three main processes in kidney function include glomerular filtration (passive), active tubular secretion, and tubular reabsorption necessary for waste removal and electrolyte balance.