MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

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MLAB 2401 Clinical ChemistryKeri Brophy-Martinez

• Chapter 14 Therapeutic Drug Monitoring and
  Toxicology

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Therapeutic Drug Monitoring TDM

• Involves the analysis, assessment and evaluation
  of circulating concentrations of drugs in serum,
  plasma or whole blood
• Goal
• Ensure that a given drug dosage produces maximal
  therapeutic benefit
• Minimal toxic adverse effects
• Must have an appropriate concentration at site of
  action that produces benefits
• Standard dosages derived from health population
• Only free fraction drugs can interact with site
  of action, resulting in a biologic response

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Routes of Administration

• Routes
• Injections
• Circulation IV (intravenous)
• MusclesIM (intramuscular)
• Skin SC (subcutaneous)
• Epidermal
• Inhaled
• Absorbed through skin
• Rectal
• Oral (most common)

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Absorption

• Where It Occurs
• Absorption through intestine then enters the
  hepatic portal system.
• Many drugs have high hepatic uptake and
  metabolism( first-pass metabolism)

• Oral Administration
• Absorption depends on..
• formulation of drug( liquid/pill)
• Intestinal motility
• pH
• Inflammation
• Food
• Other drugs
• Patient age
• Pregnancy
• Pathologic Conditions

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Drug Distribution, Metabolism and Elimination

• Distribution
• Free fraction of circulating drugs can diffuse
  out of vasculature into interstitial and
  intracellular spaces
• Ability to leave circulation is dependent on
  lipid solubility of the drug
• Elimination
• Hepatic metabolism
• Hepatic mixed function oxidase (MFO)
• Function is to take hydrophobic substances and
  through enzymatic reactions covert then to
  water-soluble substances. These substances
  transported into the bile or released into
  general circulation to be eliminated by renal
  filtration.
• Renal filtration
• Combination of both
• Functional changes in organs can affect rate of
  elimination
• i.e. Hepatic disease with a loss of tissue
  result in slow rate of clearance wit ha longer
  half-life.

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Pharmacokinetics

• Mathematic modeling of drug concentration in the
  circulation
• Relationship of drug concentration to time
• Process assists in establishing or modifying a
  dosage regimen

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Pharmacokinetics

• Most drugs given on a scheduled basis not as a
  single bolus or mass
• Oscillation between a maximum(peak) and a minimum
  (trough)of serum concentration
• Steady-state(equilibrium) oscillation after 7
  doses
• Goal of multiple dosage regimens
• Achieve troughs in therapeutic range and peaks
  that are non-toxic

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Sample Collection

• Timing of TDM most important
• Trough right before next dose
• Peak one hour post administration of dose
  (Verify drug protocal)
• Specimen Type
• Serum no gel
• Plasma Heaprinized
• EDTA, Citrated, Oxalated not acceptable

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Drug Groups

• Cardioactive
• Antibiotics
• Antiepileptic
• Psychoactive
• Antiasthmatic
• Immunosuppressive
• Antineoplastics

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Drug Groups Cardioactive

• Digoxin
• Used to treat CHF( congestive heart failure)
• Peaks draw at 2 hours post dose
• Actions and toxicities influenced by electrolyte
  concentration and thyroid status
• Measured by immunoassay
• Quinidine
• Used to treat cardiac arrhythmic situations
• Measured by chromatography or immunoassay
• Procainamide
• Used to treat cardiac arrhythmic situations
• Often measured with NAPA(N-Acetyl procainamide)
• Measured by immunoassay

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Drug Groups Antibiotics

• Aminoglycosides
• Used to treat infections with gram-negative
  bacteria that are resistant to less toxic
  antibiotics
• Examples include gentamycin, tobramycin,
  amikacin and kanamycin
• Measured by chromatography and immunoassay
• Vancomycin
• Used to treat infections with gram-positive cocci
  and bacilli

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Drug Groups Antiepileptics AEDs

• Most first and second generation AEDs used to
  treat seizure disorders and epilepsy
• Measured by immunoassay or chromatography

First Generation
Phenobarbital BarbituratePrimidone is a proform
Phenytoin/ Dilantin
Valproic Acid/ Depakene
Carbamazepine/Tegretol
Second Generation
Felbamate
Gabapentin
Levetiracetam
Oxcarbazpine
Tigabine
Topiramate
Zonisamide
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Drug Groups Psychoactive

• Lithium
• Used to treat manic depression (bipolar disorder)
• Measured by ion-selective electrode, flame
  emission photometry, and AAS
• Tricyclic Antidepressants TCAs
• Used to treat depression, insomnia, loss of
  libido
• Measured by immunoassay and chromatography

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Drug Group Antiasthmatic

• Used to treat neonatal breathing disorders or
  respiratory disoders of adults or children, like
  asthma
• Examples include theophylline and theobromine
• Measured by immunoassay or HPLC

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Drug Group Immunosuppressive

• Monitoring of this group of drugs important to
  prevent organ rejection
• Cyclosporine
• Suppresses host-versus-graft rejection
• Whole blood is the specimen of choice, since it
  sesequesters in the RBC
• Tacrolimus (Prograf)
• Sirolimus

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Drug Group Antineoplastics

• Methotrexate
• Inhibits DNA synthesis