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MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

MLAB 2401: Clinical Chemistry Keri Brophy-Martinez. Chapter 14: Therapeutic Drug Monitoring and Toxicology. Therapeutic Drug Monitoring= TDM. Involves the analysis, assessment and evaluation of circulating concentrations of drugs in serum, plasma or whole blood Goal

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MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

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  1. MLAB 2401: Clinical ChemistryKeri Brophy-Martinez Chapter 14: Therapeutic Drug Monitoring and Toxicology

  2. 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

  3. Routes of Administration • Routes • Injections • Circulation= IV (intravenous) • Muscles=IM (intramuscular) • Skin= SC (subcutaneous) • Epidermal • Inhaled • Absorbed through skin • Rectal • Oral (most common)

  4. Absorption • Oral Administration • Absorption depends on.. • formulation of drug( liquid/pill) • Intestinal motility • pH • Inflammation • Food • Other drugs • Patient age • Pregnancy • Pathologic Conditions • Where It Occurs • Absorption through intestine then enters the hepatic portal system. • Many drugs have high hepatic uptake and metabolism( first-pass metabolism)

  5. 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.

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

  7. 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

  8. 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

  9. Drug Groups • Cardioactive • Antibiotics • Antiepileptic • Psychoactive • Antiasthmatic • Immunosuppressive • Antineoplastics

  10. 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

  11. 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

  12. Drug Groups: Antiepileptics “AEDs” • Most first and second generation AEDs used to treat seizure disorders and epilepsy • Measured by immunoassay or chromatography

  13. 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

  14. 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

  15. 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

  16. Drug Group: Antineoplastics • Methotrexate • Inhibits DNA synthesis

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