Therapeutic Drug Monitoring

• Therapeutic drug monitoring (TDM)


  Monitoring the circulating drug concentrations in serum, plasma, and whole blood specimens
• Standard dosage


  Dose of a drug that will give its therapeutic benefits
• Bioavailability


  Fraction of the administered dose that eventually reaches its site of action
• Therapeutic Index


  Ratio between minimum toxic level and maximum therapeutic serum concentration
• Half life


  Time required to reduce drug level to half of its initial value
• Peak Concentration


  Highest concentration of a drug obtained in the dosing interval
• Trough Concentration


  Lowest concentration of drug obtained in the dosing interval
• Therapeutic Range


  Difference between highest and lowest effective dosage
• Pharmacokinetics


  Activity of a drug in the body as influenced by Absorption, Distribution, Metabolism, and Excretion
• Pharmacodynamics


  Actions of drugs on the body
• Contents


  • Part I: Therapeutic Drug Monitoring
  • Part II: Drugs of Abuse
• Digoxin


  A cardiac glycoside used in the treatment of congestive heart failure, inhibits Na, K, ATPase which causes a decrease in intracellular potassium, resulting in increased intracellular calcium in cardiac myocytes
• Digoxin Route, Absorption and Elimination


  Orally administered, absorption varies due to dietary factors, gastrointestinal motility, and formulation, eliminated by renal filtration, half-life of plasma digoxin - 38 hours in an average adult
• Hyperthyroid patients


  Display a resistance to digoxin actions
• Hypothyroidism patients


  Are more sensitive to digoxin
• Immunoassay


  Used to measure total digoxin concentration in serum
• Digoxin peak serum level

  8 hours after an oral dose
• Digoxin half-life


  38 hours (average adult)
• Digoxin toxic level


  Greater than 2ng/mL
• Digoxin toxic effects


  Nausea, vomiting, visual disturbances, premature ventricular contractions and atrioventricular node blockage
• Quinidine


  Earliest known antiarrhythmic agent, a naturally occurring drug, 2 most common formulations: quinidine sulfate and gluconate
• Quinidine Route, Absorption and Elimination

  Orally administered, gastrointestinal absorption is complete and rapid for the sulfate, peak serum concentration reached about 2 hours after an oral dose for sulfate and 4-5 hours for gluconate, 70-80% of absorbed quinidine bound to serum proteins, eliminated by hepatic metabolism
• Quinidine therapeutic range


  2.3 - 5 ug/mL
• Quinidine toxic range


  Greater than 5 ug/mL
• Quinidine toxic effects


  Nausea, vomiting, abdominal discomfort, cardiovascular toxicity (PVCs)
• Procainamide (Pronestyl)


  Used to treat cardiac arrhythmia
• Procainamide Route, Absorption and Elimination


  Orally administered, gastrointestinal absorption is rapid and complete, peak plasma concentration 1 hour, 20% of absorbed procainamide bound to plasma proteins, eliminated by a combination of renal filtration and hepatic metabolism
• Procainamide therapeutic range


  1. 8 ug/ml
• Procainamide toxic effects


  Reversible lupus-like syndrome, nephritic syndrome, urticaria
• Disopyramide


  Used to treat cardiac arrhythmias, used as a quinidine substitute
• Disopyramide Route, Absorption and Elimination

  Orally administered, peak serum concentration 1-2 hours, binds to several plasma proteins, eliminated by renal filtration and to a lesser extent by hepatic metabolism
• Disopyramide therapeutic range


  1. 5 ug/mL
• Disopyramide toxic range


  10 ug/mL
• Disopyramide toxic effects


  Bradycardia and atrioventricular node blockage
• Lidocaine (xylocaine)


  Used to correct ventricular arrhythmia and to prevent ventricular fibrillation
• Lidocaine Route, Absorption and Elimination

  Administered by continuous IV infusion after a loading dose, cannot be administered orally, eliminated by hepatic metabolism, primary product of hepatic metabolism is monoethylglycinexylidide
• Lidocaine therapeutic range


  1.5 - 4.0 ug/ml
• Lidocaine toxicity range


  Greater than 4.0 ug/mL
• Lidocaine CNS depression


  Greater than 4-8 ug/mL
• Lidocaine seizure and decrease BP and cardiac output


  Greater than 8ug/mL