Toxicology and Therapeutic Drug Monitoring

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Toxicology and Therapeutic Drug Monitoring
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Therapeutic Drug Monitoring

• Measurement of serum concentration of medications
  to obtain optimal concentration and benefit to
  patient
• For most drugs, therapeutic drug monitoring not
  necessary.
• Important if drug has narrow effective range or
  if narrow therapeutic/toxic index

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Reasons for TDM

• After initiation of new therapy
• In neonates/infants- renal and hepatic function
  changes rapidly during development
• In elderly- impaired renal or hepatic function
• During illness
• Medication suddenly ineffective
• New drug added to regimen

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Drugs commonly measured

• Cardiac medications (digoxin)
• Anti-seizure drugs (dilantin, Tegretol, Depakane,
  phenobarbital)
• Antibiotics (amikacin, gentamicin, vancomycin)
• Anti-cancer drugs
• Immunosuppressants
• Antidepressants (tricyclic antidepressants)
• Lithium (bipolar disorder)

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Pharmacokinetics

• Study and characterization of time course in body
• Pharmacokinetic parameters affecting TDM
• Bioavailability amount of drug absorbed. For IV
  drugs bioavailability 1.
• Volume of distribution determines serum conc.
  after a loading dose
• Distibution phase time to distribute from plasma
  to tissues
• Clearance
• Half-life depends of volume of distribution and
  clearance

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Timing of Specimen Collection

• Usually draw at peak or trough
• Peak for drugs given intravenously or if patient
  has signs of toxicity shortly after dose
• Majority drawn as trough
• If lengthy distribution phase- need to wait until
  equilibrium reached
• Important to know if circadian rhythms affect
  distribution

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Proteins and Drug Levels

• Some drugs highly protein bound (only the unbound
  fraction is active)
• Changes in serum protein levels can alter amount
  of free drug
• May be necessary to measure free drug
  concentration rather than the total

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• Example Dilantin 90 bound (Active drug is only
  10 of total). If albumin levels are decreased so
  that only 80 of a dose is bound

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Testing for Drugs of Abuse

• Employment
• Department of Transportation regulations
• Forensic
• compliance

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DOT mandated drug testing

• Gross vehicle weight gt13 tons
• Hauling hazardous materials
• Transporting 16 passengers (including driver)

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• Test for marijuana, cocaine, opiates,
  amphetamines, phencyclidine
• Testing done
• Before employment
• Random
• Reasonable suspicion
• Post-accident

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Components to testing

• Specimen collection
• Laboratory analysis
• Medical review of results by MRO

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Certification of labs

• Chain of custody protocol
• Screen by immunoassay (EMIT or RIA) and confirm
  postives by GC-MS
• Specific lab rules (no false ceilings,
  restricted access, video camera monitoring,etc.)
• PT every 2 months
• Inspection every 6 months

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Specimen collection

• Direct or indirect observation
• Properly ID patient
• All articles, bulky clothing outside restroom
• Wash hands before entering restroom
• Bluing agent in toilet
• Restrict water in collection area
• No cleaning supplies
• Record temperature
• Split sample collection