MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

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MLAB 2401 Clinical ChemistryKeri Brophy-Martinez

• Therapeutic Drug Monitoring

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Therapeutic Drug Monitoring TDM

• 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 healthy population
• Only the free fraction of 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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Pharmacokinetics

• Involves the dynamics associated with the
  movement of drugs across cell membranes
• Includes biological events
• Absorption
• Distribution
• Metabolism/Biotransformation
• Excretion
• Relationship of drug concentration to time
• Process assists in establishing or modifying a
  dosage regimen

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Absorption

• Rate at which drug leaves the site of
  administration and the extent to which this
  happens
• Mechanism
• Passive diffusion
• Active transport

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Absorption Limiting Factors

• Oral Administration
• Absorption depends on..
• Formulation of drug
• liquid/pill
• Intestinal motility
• pH
• Inflammation
• Food
• Presence of other drugs
• Patient age
• Pregnancy
• Concurrent Pathologic Conditions

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Distribution

• Dependent on
• Blood flow
• Capillary permeability
• pH gradients
• Lipid solubility of the drug
• Binding of drugs to proteins/Availability of free
  fractions
• Free vs. bound drug
• Tissue volume

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Metabolism

• Primarily occurs in the liver
• Biotransformation of the parent drug molecule
  into one or more metabolites
• Metabolites are
• water soluble
• easily excreted by kidney or liver
• Pharmacologically active or inactive

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First-Pass Metabolism
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Elimination

• Elimination Routes
• Hepatic metabolism
• Renal filtration
• Other skin, lungs, mammary glands and salivary
  glands
• Functional changes in organs can affect rate of
  elimination
• i.e. Hepatic disease with a loss of tissue
  result in slow rate of clearance with a longer
  half-life.
• Elimination half-life
• The time required to reduce the blood level
  concentration to one-half after equilibrium is
  obtained.

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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
• Goal of dosage regimens
• Achieve troughs in therapeutic range and peaks
  that are non-toxic

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Sample Collection

• Timing of TDM most important
• Collaborate with nursing phlebotomy staff for
  appropriate timing
• Trough right before next dose
• Peak one hour post administration of dose
  (Verify drug protocol)
• Random
• Specimen Type
• Serum no gel
• Plasma Heparinized
• EDTA, Citrated, Oxalated not acceptable
• Whole Blood
• Saliva

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Drug Groups

• Cardioactive
• Antibiotics
• Antiepileptic
• Psychotherapeutic
• Antiasthmatic
• Immunosuppressive
• Antineoplastic
• Antihypertensive

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Drug Groups Cardioactive

• Digoxin
• Used to treat CHF( congestive heart failure)
• Peaks draw at 2 hours post dose
• Inhibits sodium and potassium transport within
  the heart
• Allows for better cardiac muscle contraction and
  rhythm
• Lidocaine
• Used to treat premature ventricular contractions
• Affects the timing of cardiac contraction

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Drug Groups Cardioactive (2)

• Quinidine
• Used to treat cardiac arrhythmic problems
• Inhibits sodium and potassium channels
• Prevents arrhythmias, atrial flutter and
  fibrillation
• Procainamide
• Used to treat cardiac arrhythmic situations
• Blocks sodium channels
• Affects cardiac muscle contraction
• Often measured with NAPA(N-Acetyl procainamide)

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Drug Groups Antibiotics

• Aminoglycosides
• Used to treat infections with gram-negative
  bacteria that are resistant to less toxic
  antibiotics
• Inhibits protein synthesis of the micro-organism
• Examples include gentamycin, tobramycin,
  amikacin and kanamycin
• Vancomycin
• Used to treat infections with more-resistant
  gram-positive cocci and bacilli
• Inhibits cell wall synthesis

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Drug Groups Antiepileptics AEDs

• Most first and second generation AEDs used to
  treat seizure disorders and epilepsy

First Generation
Phenobarbital Barbiturate Primidone is a proform
PhenytoinDilantin
Valproic Acid Depakene
CarbamazepineTegretol
Second Generation
Felbamate
Gabapentin
Levetiracetam
Oxcarbazpine
Tigabine
Topiramate
Zonisamide
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Drug Groups Psychotherapeutic

• Used to treat manic depression (bipolar disorder)
• Lithium
• Tricyclic Antidepressants TCAs
• Clozapine

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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

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Drug Group Immunosuppressive

• Monitoring of this group of drugs important to
  prevent organ rejection (host-versus-graft)
• Used to treat autoimmune disease
• Examples
• Cyclosporine
• Whole blood is the specimen of choice, since it
  sequesters in the RBC
• Tacrolimus (Prograf)
• Prevents rejection of liver and kidney
  transplants

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Drug Group Antineoplastics

• Inhibit RNA or DNA synthesis of tumor cells,
  leading to cell death
• Methotrexate
• Inhibits DNA synthesis

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Drug Group Antihypertensive

• Used in treatment of high blood pressure
• Dilate blood vessels
• Sodium nitroprusside
• Used for short-term control of hypertension

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Techniques for Measurement of TDM

• Immunoassays
• Gas chromatography
• Liquid chromatography
• Mass spectrometry

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References

• Arneson, W., Brickell, J. (2007). Clinical
  Chemistry A Laboratory Perspective .
  Philadelphia, PA F.A. Davis Company.
• Bishop, M., Fody, E., Schoeff, l. (2010).
  Clinical Chemistry Techniques, principles,
  Correlations. Baltimore Wolters Kluwer
  Lippincott Williams Wilkins.
• Sunheimer, R., Graves, L. (2010). Clinical
  Laboratory Chemistry. Upper Saddle River Pearson
  .