MLAB 2401: Clinical Chemistry
Keri Brophy-Martinez
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring= TDM
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Goal
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Ensure that a given drug dosage produces
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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
Routes of Administration
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Routes
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Injections
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Circulation= IV (intravenous)
Muscles=IM (intramuscular)
Skin= SC (subcutaneous)
Epidermal
Inhaled
Absorbed through skin
Rectal
Oral (most common)
Pharmacokinetics
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Involves the dynamics associated with the movement of
drugs across cell membranes
Includes biological events:
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Absorption
Distribution
Metabolism/Biotransformation
Excretion
Relationship of drug concentration to time
Process assists in establishing or modifying a dosage
regimen
Absorption
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Rate at which drug leaves the site of administration and
the extent to which this happens
Mechanism
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Passive diffusion
Active transport
Absorption: Limiting Factors
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Oral Administration
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Absorption depends on..
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Formulation of drug
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liquid/pill
Intestinal motility
pH
Inflammation
Food
Presence of other drugs
Patient age
Pregnancy
Concurrent Pathologic Conditions
Distribution
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Dependent on
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Blood flow
Capillary permeability
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Binding of drugs to proteins/Availability of free fractions
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pH gradients
Lipid solubility of the drug
Free vs. bound drug
Tissue volume
Metabolism
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Primarily occurs in the liver
Biotransformation of the parent drug molecule into one
or more metabolites
Metabolites are:
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water soluble
easily excreted by kidney or liver
Pharmacologically active or inactive
First-Pass Metabolism
Elimination
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Elimination Routes
 Hepatic metabolism
 Renal filtration
 Other: skin, lungs, mammary glands and salivary glands
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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.
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Elimination half-life
 The time required to reduce the blood level concentration to one-half
after equilibrium is obtained.
Pharmacokinetics
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Most drugs given on a
scheduled basis not as a
single bolus or mass
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Oscillation between a
maximum(peak) and a
minimum (trough)of serum
concentration
Goal of dosage regimens
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Achieve troughs in
therapeutic range and peaks
that are non-toxic
Sample Collection
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Timing of TDM most important
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Collaborate with nursing & phlebotomy staff for appropriate
timing
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Trough: right before next dose
Peak: one hour post administration of dose (Verify drug protocol)
Random
Specimen Type
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Serum: no gel
Plasma: Heparinized
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EDTA, Citrated, Oxalated not acceptable
Whole Blood
Saliva
Drug Groups
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Cardioactive
Antibiotics
Antiepileptic
Psychotherapeutic
Antiasthmatic
Immunosuppressive
Antineoplastic
Antihypertensive
Drug Groups: Cardioactive
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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
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Lidocaine
 Used to treat premature ventricular contractions
 Affects the timing of cardiac contraction
Drug Groups: Cardioactive (2)
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Quinidine
 Used to treat cardiac arrhythmic problems
 Inhibits sodium and potassium channels
 Prevents arrhythmias, atrial flutter and fibrillation
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Procainamide
 Used to treat cardiac arrhythmic situations
 Blocks sodium channels
 Affects cardiac muscle contraction
 Often measured with NAPA(N-Acetyl procainamide)
Drug Groups: Antibiotics
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Aminoglycosides
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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
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Used to treat infections with more-resistant gram-positive
cocci and bacilli
Inhibits cell wall synthesis
Drug Groups: Antiepileptics “AEDs”
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Most first and second generation AEDs used to treat seizure disorders and
epilepsy
First Generation
Phenobarbital
•Barbiturate Primidone is a
proform
Second Generation
Felbamate
Gabapentin
Levetiracetam
Phenytoin=Dilantin
Oxcarbazpine
Tigabine
Valproic Acid= Depakene
Topiramate
Zonisamide
Carbamazepine=Tegretol
Drug Groups: Psychotherapeutic
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Used to treat manic depression (bipolar disorder)
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Lithium
Tricyclic Antidepressants “TCAs”
Clozapine
Drug Group: Antiasthmatic
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Used to treat neonatal breathing disorders or respiratory
disoders of adults or children, like asthma
Examples include theophylline and theobromine
Drug Group: Immunosuppressive
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Monitoring of this group of drugs important to prevent
organ rejection (host-versus-graft)
Used to treat autoimmune disease
Examples
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Cyclosporine
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Whole blood is the specimen of choice, since it sequesters in the
RBC
Tacrolimus (Prograf)
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Prevents rejection of liver and kidney transplants
Drug Group: Antineoplastics
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Inhibit RNA or DNA synthesis of tumor cells, leading to
cell death
Methotrexate
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Inhibits DNA synthesis
Drug Group: Antihypertensive
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Used in treatment of high blood pressure
Dilate blood vessels
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Sodium nitroprusside
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Used for short-term control of hypertension
Techniques for Measurement of TDM
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Immunoassays
Gas chromatography
Liquid chromatography
Mass spectrometry
References
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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 .