Therapeutic Drug Monitoring & Toxicology

• First-Pass Metabolism


  All substances including drugs absorbed from the intestine enter the hepatic portal system. All the blood from the GI tract is routed through the liver before it enters general circulation. Certain drugs are subject to significant Hepatic Metabolism during this passage.
• Half-life


  The time needed for the body to reduce the drug concentration by one-half from the peak level
• Heparinized plasma is suitable for most drug analysis and not EDTA, citrate or oxalate
• Intravenous (IV)


  The most immediate route for drug delivery and has 100% bioavailability
• The locations where the drugs are effective are in the body tissue, not generally in the blood
• Half-life


  Time required for a 50% decrease in serum drug concentration after absorption and distribution
• Measurement of Drugs

  1. Peak levels - Can detect toxicity levels of the drug at a certain time after administration to allow for absorption

  2. Trough levels - Immediately prior to next dose
• Routes of Administration

  • Intravenous (IV)
  • Intramuscular (IM)
  • Oral
  • Rectal
  • Inhalation
  • Transdermal
• LD50

  Median lethal dose, a measure of toxicity of the drug
• ED50


  Median effective dose, a measure of effectiveness of the drug
• Pharmacokinetics


  • Action of the body on the drug; how the body handles the drug (absorption, distribution, metabolism, excretion)
• Pharmacodynamics


  • Action of the drug on the host body; Relationship between drug concentration at reception site and response of tissue to the drug
• Pharmacotherapeutic


  • Treatment of a disorder using a drug
• Peak Levels


  • Oral - 1 to 5 hours after dose
  • IV - 30 minutes after infusion has stopped
  • IM - 60 minutes after IM injection
• ED50


  median effective dose, a measure of effectiveness of the drug
• LD50


  dose of the drug required to kill 50% of the population
• ED50


  dose of the drug required to produce a specified effect in 50% of the population
• TD50


  dose that would be predicted to produce a toxic reaction in 50% of the population
• Therapeutic Index


  • ratio of LD50 to ED50
  • a statement of how selective the drug in producing desired effects
• Effective dose can overlap toxic dose
• Effective dose can't overlap lethal dose
• Intravenous


  • most rapid onset
  • 100% bioavailability
• Intramuscular


  • large volume
  • maybe painful
• Oral


  • most convenient
  • first-pass effect maybe significant
• Rectal


  • less first pass effect
  • for vomiting or unconscious patients
• Inhalation


  • often very rapid due to large surface area of respiratory tract
• Transdermal

  • usually very slow absorption
  • used for lack of first pass effect
• Spectrophotometry


  for tentative identification of drugs
• Barbiturate


  depends on its shift of absorption spectrum (double beam UV)
• Nitroprusside


  can be monitored indirectly by spectrophotometry of its metabolite, thiocyanate
• Salicylates


  mixed first with ferric ions to produce a purple color
• Quinidine


  uses fluorescence spectrophotometry
• Thin Layer Chromatography


  • used extensively for toxicologic screening of blood and urine
  • not used for quantitation of substances
  • efficient, rapid, economical
• Gas Chromatography


  • used for the quantitation of many drugs that are volatile or that can be chemically derivatized into volatile form
  • Alcohols are resolved separately by GC, as their metabolites
  • Barbiturates can also be separately resolved according to their solubility properties
• High-Performance Liquid Chromatography


  can be highly quantitative, but the procedure takes a long time for analysis and requires expensive equipment with a great deal of maintenance
• Mass Spectrometer


  • can be added onto the effluent end of GC, enhancing its capability
• GC-MS is considered the ULTIMATE for confirmation of drug identity
• East Avenue Medical Center


  Reference laboratory for drugs
• Immunochromatography


  1. Toxi Lab A - Basic Dyes
  2. Toxi Lab B - Acidic Dyes
• Flame Photometry or Ion Selective Electrode (ISE)


  Lithium