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What is the purpose of therapeutic drug monitoring?
To establish maximum benefits with minimal toxic effects for drugs whose correlation with dosage, effect, or toxicity is not clear
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Name the most common routes of drug administration
- Oral
- IV
- IM
- SC (subcutaneous)
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What is the term for the drug concentration that produces benefits?
Therapuetic range
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What happens in to all drugs that are absorbed from the GI tract?
All drugs must go through the liver before entering the general circulation
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How do most drugs circulate in the blood?
Bound to plasma proteins
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What do acidic drugs primarily bind to?
Albumin
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What do basic drugs primarily bind to?
Alpha1-acid glycoprotein (AAG)
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Which drugs can interact with target sites and produce a response?
Only free drugs
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In most TDM assays, what is quantified, the free or total drug concentration?
Quantification of the total drug
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In general, how are drugs eliminated from the circulation?
Through hepatic metabolic processes and renal filtration
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Approximately how many doses need to be given before a steady state of a peak and trough levels can be assessed?
Approximately 7 doses
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What is the function of digoxin?
Cardiac glycoside used to treat congestive heart failure
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What is the therapeutic range of digoxin?
0.8-2.0 ng/mL
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What is the function of lidocaine?
Antiarrhythmic drug used to treat ventricular arrhythmia and prevent ventricular fibrillation
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What is the therapeutic range of lidocaine?
1.5-4.0 micro-gram/mL
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What happens when toxicity of lidocaine occurs?
- 4-8: CNS depression
- >8: seizures and severe hypotension
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What is the function of quinidine?
Antiarrhythmic drug used to treat cardiac arrhythmia
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What is the therapeutic range of quinidine?
2-5 micro-gram/mL
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What is the function of procainamide?
Antiarrhythmic drug used to treat cardiac arrhythmia
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What is the therapeutic range of procainamide?
4-8 micro-gram/mL
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What is the function of aminoglycosides?
Used to treat infections caused by gram negative bacteria
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What is included in the aminoglycosides?
- Gentamicin
- Tobramycin
- Kanamycin
- Amikacin
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What is associated with the toxicity of aminoglycosides?
- Nephrotoxicity
- Ototoxicity
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What is the function of vancomycin?
Used to treat infections caused by gram positive bacteria
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What is associated with the toxicity of vancomycin?
- Nephrotoxicity
- Ototoxicity
- "Red-man syndrome" (erythemic flushing of extremities
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What is the function of phenobarbital?
Slow acting barbituate used to control seizures
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What is associated with toxicity of phenobarbital?
- Drowsiness
- Depression
- Fatigue
- Altered mental ability
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What is the therapeutic range of phenobarbital?
15-40 micro-gram/mL
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What is the function of phenytoin?
Used to control seizures and to keep the brain from swelling and injuring tissue during brain traumas
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What is associated with toxicity of phenytoin?
Seizures
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What is the therapeutic range of the total and free serum levels of phenytoin?
- Total serum level: 10-20 micro-gram/mL
- Free serum level: 1-2 micro-gram/mL
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What is the function of valproic acid?
Used to control seizures
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What is the therapeutic range of valproic acid?
50-100 micro-gram/mL
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What is the function of carbamazepine?
Used to control seizures
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What is the therapeutic range of carbamazepine?
4-12 micro-gram/mL
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What is the function of lithium?
Used to treat manic depression
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What is the therapeutic range of lithium?
1.0-1.2 mmol/L
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What is the function of tricyclic antidepressants (TCAs)?
Used in cases of depression, insomnia, extreme apathy, and loss of libido?
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What is included in tricyclic antidepressants (TCAs)?
- Amitriptyline
- Imipramine
- Doxepin
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What is the the therapeutic range of amitriptyline?
120-150 ng/mL
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What is the therapeutic range of imipramine?
150-300 ng/mL
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What is the therapeutic range of nortriptyline?
50-150 ng/mL
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What is the therapeutic range of desipramine?
150-300 ng/mL
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What is the function of theophylline?
Used to treat asthma and other chronic obstructive pulmonary disorders (COPD)
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What is the therapeutic range of theophylline?
10-20 micro-gram/mL
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What is the function of cyclosporine?
Used to suppress transplant rejections and graft-versus-host disease
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What is the therapeutic range of cyclosporine?
- Range differs depending on the organ being transplanted
- Liver, pancreas, and heart: 200-350 ng/mL
- Renal: 100-300 ng/mL
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What is the function of tacrolimus (prograf)?
- Used to suppress transplant rejections and graft-versus-host disease
- Potency far exceeds cyclosporine by a factor of 100
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Which drug is preferred for the use to suppress transplant rejections and graft-versus-host disease?
- Tacrolimus (prograf)
- Because potency far exceed cyclosporine by a factor of 100
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What is the therapeutic range of tacrolimus (prograf)?
10-15 ng/mL
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What is the function of sirolimus (rapamune)?
Used to suppress transplant rejections and graft-versus-host disease
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What is the therapeutic range of sirolimus (rapamune)?
4-12 ng/mL
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What is the function of methotrexate?
Used to destroy neoplastic cells
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What refers to the administration of leucovorin to offset the effect of methotrexate in an attempt to prevent cytotoxicity of normal cells?
Leucovorin rescue
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What is the therapeutic monitoring of of methotrexate?
- High dose therapy generally exceeds 50 mg/m2
- Serum levels are monitored at 24, 48, and 72 hrs after drug administration
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Name some antibiotics that are monitored for therapeutic levels
- Amikacin
- Chloramphenicol
- Dibekacin
- Gentamicin
- Kanamycin
- Netilmicin
- Streptomycin
- Tobramycin
- Vancomycin
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Name some antineoplastics that are monitored for therapeutic levels
Methotrexate
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Name some cardiac glycosides that are monitored for therapeutic levels
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Name some anticonvulsants that are monitored for therapeutic levels
- Carbamezepine (Tegretol)
- Ethosuximide
- Phenobarbital
- Phenytoin (Dilantin)
- Primidone
- Valproic Acid
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Name some antiarrhythmics that are monitored for therapeutic levels
- Disopyramide
- Flecainide
- Lidocaine
- Procainamide
- N-Acetylprocainamide
- Propanolol
- Tocainide
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