Pharmacokinetics

This section presents the key aspects of pharmacokinetics in TDM, including therapeutic and toxic states, and the processes of metabolism and excretion

Pharmacokinetics in Therapeutic Drug Monitoring (TDM)

• Definition: The study of how the body affects a drug after administration, including absorption, distribution, metabolism, and excretion (ADME)
• Importance in TDM: Understanding pharmacokinetics is essential for optimizing drug therapy by maintaining drug concentrations within a specific therapeutic range

Therapeutic States

• Therapeutic Range: The range of drug concentrations associated with a high probability of desired therapeutic effect and a low probability of adverse effects
• Subtherapeutic State
  • Definition: Drug concentration is below the therapeutic range, resulting in inadequate therapeutic effect
  • Causes: Inadequate dose, poor adherence, drug interactions, rapid metabolism, increased clearance, malabsorption
  • Management: Increase the dose, improve adherence, adjust dosing interval, avoid/manage drug interactions, use an alternative drug
• Therapeutic State
  • Definition: Drug concentration is within the therapeutic range, achieving the desired therapeutic effect with minimal adverse effects
  • Goal of TDM: To maintain drug concentrations within the therapeutic range
  • Management: Monitor drug concentrations regularly, adjust dose as needed, monitor for adverse effects, educate the patient
• Toxic State
  • Definition: Drug concentration is above the therapeutic range, increasing the risk of adverse effects
  • Causes: Excessive dose, decreased clearance, drug interactions, overdose
  • Consequences: Adverse effects, organ damage, life-threatening conditions
  • Management: Reduce dose, discontinue drug, administer antidote, provide supportive care
• Supratherapeutic State
  • Definition: Drug concentration is above the therapeutic range but may be intentional in certain situations
  • Management: Monitor patients closely for adverse effects and adjust the dose accordingly

Toxic States

• Causes of Toxic States
  • Excessive dosage
  • Impaired Elimination: Renal or hepatic impairment
  • Drug Interactions: Enzyme inhibition or induction
  • Patient-Specific Factors: Age, genetics, disease states
• Commonly Monitored Drugs and Toxic Effects
  • Digoxin, Lithium, Theophylline, Aminoglycosides, Vancomycin, Phenytoin, Valproic Acid, Methotrexate, Cyclosporine/Tacrolimus, Tricyclic Antidepressants, Salicylates, Acetaminophen
• Symptoms and Clinical Presentation
  • Gastrointestinal, Neurological, Cardiovascular, Renal, Hepatic, Hematological, Dermatological
• Laboratory Tests for Monitoring Toxicity
  • Therapeutic Drug Monitoring (TDM), Renal Function Tests, Hepatic Function Tests, Electrolyte Monitoring, Cardiac Monitoring, Hematological Tests
• Management
  • Discontinue the drug, provide supportive care, consider decontamination, enhance elimination, administer antidotes
• Prevention
  • Appropriate Prescribing, Patient Education, Therapeutic Drug Monitoring, Medication Reconciliation, Electronic Prescribing, Pharmacist Involvement

Metabolism and Excretion

• Drug Metabolism
  • Definition: The process by which the body chemically alters a drug
  • Primary Site: Liver
  • Purpose: Convert drugs to more water-soluble forms for elimination, inactivate drugs, or activate prodrugs
  • Phases of Metabolism: Phase I (oxidation, reduction, hydrolysis), Phase II (conjugation)
  • Cytochrome P450 (CYP) Enzymes: Key enzymes involved in drug metabolism
  • Factors Affecting Drug Metabolism: Genetic factors, age, disease states, drug interactions, diet
• Drug Excretion
  • Definition: The process by which the body eliminates a drug or its metabolites
  • Primary Routes: Kidneys (urine), Liver (bile)
  • Renal Excretion: Glomerular filtration, tubular secretion, tubular reabsorption
  • Biliary Excretion: Excretion into the bile and eliminated in the feces
  • Clearance (CL): Measure of the body’s efficiency in eliminating a drug
• Clinical Significance
  • Drug-Drug Interactions (DDIs): Knowledge of metabolic pathways is crucial
  • Pharmacogenomics: Genetic testing for personalized dosing
  • Dosage Adjustments: Adjustments in patients with renal/hepatic impairment
  • Therapeutic Drug Monitoring (TDM): Monitoring to optimize drug therapy