Therapeutic Drug Monitoring Overview

Therapeutic Drug Monitoring (TDM)

• TDM aims to maximize therapeutic benefits while minimizing side effects by maintaining constant serum drug levels.
• Most drugs have a half-life unaffected by their concentrations; the half-life is crucial for determining time to reach steady-state concentrations.
• Only the free fraction of drug is active, impacting therapeutic response.

Indications for TDM

• Serious consequences arise from either overdosing or underdosing.
• Small therapeutic window exists, meaning therapeutic and toxic doses are closely related.
• Poor correlation between drug dosage and blood concentrations; however, blood concentrations correlate well with therapeutic/toxic effects.
• Changes in patients' physiological states can unpredictably alter blood drug concentrations.
• Potential drug interactions may necessitate monitoring.
• TDM aids in assessing patient compliance with prescribed therapy.

Routes of Drug Administration

• The circulatory system efficiently delivers drugs to their target sites.
• Intravenous administration guarantees 100% bioavailability (full entry into the bloodstream).
• Orally administered drugs typically achieve around 70% bioavailability.

Pharmacological Parameters Determining Serum Drug Concentration

• Liberation: Release of the drug from its formulation.
• Absorption: Transport of the drug from administration site to bloodstream (LADME).
• Distribution: Delivery of the drug to tissues; can result in higher drug concentrations in tissues than in circulation.
• Metabolism: Chemical modification of the drug, primarily occurs via cytochrome P450 enzymes in the liver.
• Excretion: Elimination of drugs and their metabolites from the body.

Absorption Characteristics

• Drugs must be at appropriate concentrations to exert therapeutic effects; passive diffusion is the primary absorption method.
• Non-ionized, hydrophobic state enhances absorption.
• Drugs absorbed from the intestine enter the hepatic portal system and pass through the liver before entering general circulation.
• Liquid solutions absorb quickly; tablets and capsules require dissolution first.
• Weak acids absorb mainly in the stomach, while weak bases absorb primarily in the intestine.
• Absorption influenced by factors like intestinal motility, pH, inflammation, and concurrent food or medication intake.

Distribution of Drugs

• Effective drug concentrations generally occur in body tissues, not in blood.
• Drugs often reach higher tissue concentrations compared to blood, indicating a large distribution space.
• A large distribution space suggests significant movement of the drug into tissues from circulation.

Excretion of Drugs

• Drug clearance rates depend on drug type and patient metabolism/excretion capabilities.
• Drugs are excreted either unchanged or as metabolites; liver metabolizes parent drugs via cytochrome P450 enzymes.
• Some drugs are recirculated into the enterohepatic system and can be excreted in stool.

Causes of Drug Toxicity

• Elevated free drug concentration can lead to toxicity.
• Abnormal responses to drugs post-administration can signify toxicity.
• Active drug metabolites may contribute to adverse effects.

This quiz covers the fundamentals of Therapeutic Drug Monitoring (TDM), focusing on its importance in maximizing therapeutic benefits while minimizing side effects. It highlights key concepts such as drug half-lives, indications for TDM, and the implications of drug administration routes on patient care.