Clinical Chemistry: Therapeutic Drug Monitoring Flashcards
ensure that dose produces maximal therapeutic benefit with minimal toxic side effects
main purpose of therapeutic drug monitoring
standard dose
dosage that provides therapeutic effect based on stats from healthy people
identify non-compliance and optimize dosing regimen
two smaller purposes of therapeutic drug monitoring
GI absorption, distribution throughout body (biological response), circulating free drug (protein binding), and elimination, renal excretion, metabolism (production of metabolites)
4 factors that affect oral drugs
pharmacokinetics
quantitative study of drug disposition in the body-mathematical relationships used to predict dosage adjustments
pharmacodynamics
study of the biochemical and physiological effects of drugs and their mechanism of action
therapeutic range
relationship between desired clinical effect and concentration in the plasma
half-life
time required for the serum concentration of a drug to decline by 50%
steady state
drug input and output are equal
5 half-lives
usual timing to reach steady state
peak concentration
highest concentration reached after dosage
trough concentraiton
lowest concentration reached after dosage
drug absorption
dependent on drug's dissociation from dosing form, solubility in GI fluids, and diffusion across GI membranes into blood stream
bioavailability
fraction of drug absorbed into systemic circulation calculated by comparing IV and oral doses; depends on size, solubility, and ionization
passive diffusion
concentration on one side of the membrane if higher than the other; 95% of all drug absorption
active transport
drug binds to carrier molecules and uses energy to go into blood stream
facilitated transport
same as active, but follows concentration gradient
drug distribution
free vs bound (to albumin); active when free-able to cross cellular membranes and interact with receptors
acidic drugs
drugs that primarily bind to albumin
basic drugs
drugs that primarily bind to globulins
uremia
condition that causes increased levels of free drugs due to binding sites being taken up by hemoglobin
drug metabolism (biotransformation)
breakdown of drugs into polar metabolites; substances absorbed from the intestine enter the hepatic portal system before entering general circulation; important in efficacy since it is how the drug is generated into the active metabolite
first-pass metabolism
process occurring within the liver-hepatic uptake and metabolism during passage
hepatic mixed-function oxidase (MFO) system
biochemical pathway responsible for a large portion of drug metabolism
phase I biotransformation
chemical structure of drug is modified through oxidation, reduction, or hydrolysis in the liver
phase II biotransformation
intermediate is conjugated in the liver-soluble compound is formed
enzyme activity/inhibition, drug interactions, disease states, and GI motility
four factors affecting drug metabolism and biotransformation
drug elimination (excretion)
drugs removed through hepatic metabolism, renal filtration, or combination of both
kidney
major elimination route; glomerular filtration, tubular secretion and reabsorption
creatinine clearance
an effective monitor of drug clearance; gent, tobra, amikacin, dig, vanc, and cyclosporine
first order elimination equation
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accurate specimen collection timing
single most important factor in steady state levels
responders
patients benefitting from therapeutic and desired effects of drug
nonresponders
patients not benefitting from the therapeutic and desired effects of drug
therapeutic effectiveness
attributed to interindividual variation in genetic polymorphisms of drug metabolism pathways
cytochrome P-450
gene group family that affects drug metabolism, family of enzymes within MFO system
cardioactive drugs
glycosides and antiarrhythmics
digoxin (Lanoxin)
cardiac glycoside used to treat CHF by inhibiting membrane Na-K-ATPase; absorbed by GI motility, eliminated by renal filtration; half life 38 hours; immunoassay
Quinidine
cardiac arrhythmia treatment; GI absorbed, hepatic metabolized; half-life 6-8 hours; immunoassay
Procainamide
cardiac arrhythmia treatment; GI absorption; renal and hepatic elimination; 4 hour half-life; immunoassay
Disopyramide
cardiac arrhythmia treatment; GI absorption, hepatic metabolism elimination; half life 7 hours; immunoassay
aminoglycosides
treat gram-negative bacterial infections that are resistant to other less-toxic antibiotics; gent, tobra, amikacin, and kanamycin; most serious effects are nephrotoxicity and ototoxicity; IV or IM only-not for outpatients
Vancomycin
glycopeptide antibiotic effective against gram-positive cocci and bacilli infections; IV infusion; toxicities include red man syndrome, nephrotoxicity and ototoxicity
red man syndrome
flushing of extremities; sign of vanco toxicity
Phenobarbital and primidone
slow-acting barbituate that effectively controls several types of seizures
primidone
inactive form of phenobarbital; rapidly absorbed in GI tract and converted to phenobarbital; preferred when steady-state kinetics need to be established quickly
Phenytoin and Fosphenytoin
commonly used treatment for seizure disorders; used as short-term prophylactic agent in brain injury to prevent loss of functional tissue
fosphenytoin
injectable proform of phenytoin that is rapidly metabolized (75 minutes) to form the parent drug
Valproic acid or valproate
used as a monotherapy for treatment of petit mal and absence seizures
Carbamazepine
treatment for various seizure disorders; less frequently used due to toxic affects-rash, leukopenia, nausea, vertigo, febrile reactions
Ethosuximide
used to control petit mal seizures; toxicity: nausea, vomiting, anorexia, dizziness, and lethargy
Felbamate
treatment for severe epilepsy; oral administration-GI absorption; known for toxicity; primarily indicated in severe epilepsies such as Lennox-Gastaut syndrome (children) and refractory epilepsy (adults)
Gabapentin
may be indicated as monotherapy or in conjunction with other antiepileptic drugs in patients suffering from complex partial seizures with or without generalized seizures
Lamotrigine, Levetiracetam, Topiramate, and Zonisamide
treat patients with partial and generalized seizures (4)
Oxcarbazepine
a pro-drug that is almost immediately metabolized to licarbazepine; indicated for monotherapy of partial seizures and secondarily generalized tonic-clonic seizures
Tiagabine
used in treatment of partial seizures; Adverse central nervous system (CNS) side effects: confusion, difficulty in speaking clearly (stuttering), mild sedation, and a tingling sensation in the body’s extremities, or paresthesia, especially in the hands and fingers
lithium
psychoactive drug orally administered to treat manic depression
Tricyclic antidepressants
a class of drugs used to treat depression, insomnia, extreme apathy, and loss of libido
Clozapine
an atypical antipsychotic used to treat otherwise treatment-refractory schizophrenia
Olanzapine
a thienobenzodiazepine derivative that effectively treats schizophrenia, acute manic episodes, and recurrence of bipolar disorders
cyclosporine
primary clinical use is suppression of graft-vs-host rejection of heterotopic transplanted organs
tacrolimus
immunosuppressive 100 times more potent than cyclosporine
sirolimus
an antifungal agent with immunosuppressive activity; FDA approved for patients receiving kidney transplants
mycophenolic acid
a lymphocyte proliferation inhibitor; used most commonly as supplemental therapy with cyclosporine and tacrolimus in renal transplant patients
methotrexate
antineoplastic; one of few which TDM offers benefit to therapeutic regimen; inhibits DNA synthesis in all cell
leucovorin
reverses effects of methotrexate at certain point so normal cells can divide and replicate
theophylline
bronchodilator used in treatment of respiratory disorders such as asthma and stable COPD for those that cannot use inhaler or with nocturnal symptoms; effects include insomnia, tachycardia, seizures, arrhythmias, cardiorespiratory arrest