Therapeutic Drug Monitoring Flashcards
What is therapeutic drug monitoring?
the measurement of drugs and/or their metabolites in body fluids-usually blood-to maintain therapeutic benefits
What is the definition of drugs (for the purpose of this class)?
medications that are prescribed by medical providers
What is the definition of therapeutic range (TR)?
the dose, or concentration, range of a drug within which the drug produces the desired therapeutic effect
What is the result if a drug is outside of the therapeutic range?
Inefficacy or toxicity
What are the two main purposes of TDM?
- Ensure correct drug dosages for the T.R.
- Identify drug-drug interactions if multiple drugs are taken together
When would TDM be appropriate for a drug?
- The drug has a narrow therapeutic range
- Marled pharmacokinetic variabilities
- Critical adverse effects
All of the following are what?
Age
Gender
Genetics
Diet
Co-administered drugs
Naturopathic agents
Factors that influence drug concentrations and efficacy
Define pharmacokinetics
Study of the movement of drugs in the body
What does pharmacokinetics tell us?
Provides a time-course of drug concentrations in the body as a function of absorption, distribution, metabolism, and excretion
What is bioavailability?
The fraction of the administered dose that eventually reaches its site of action
The following are all examples of what?
Oral—most common, least invasive
Intravenous (IV)—most direct & effective
Intramuscular (IM)
Subcutaneous (SC)
Aerosol
Transdermal patch
Rectal
Routes of administration
What are the three factors that effect the efficiency of absorption from GI tract?
- Dissociation from its administered form
- Solubility in GI fluids
- Diffusion across GI membranes
T/F:
In order for a drug to passively diffuse from the GI tract to the bloodstream, it must be in the hydrophilic state.
FALSE
The drug must be in the hydrophobic state (nonionized)
Drugs will be absorbed in the GI tract ____ in healthy people.
Predictably
Weak acids are efficiently absorbed by the __a__; weak bases are absorbed in the __b__
a) Stomach
b) intestine
Drug absorption is affected by what?
Changes in intestinal motility, pH, inflammation
T/F:
Absorption is not changed wen someone is getting older, becomes pregnant, or develops a pathological condition.
FALSE
What is the definition of drug distribution?
The movement of a drug between blood circulation and tissues and organs and the relative proportion of the drug in the tissues
____ ____ affects the ability of a drug to leave circulation
Lipid Solubility
What is a free fraction?
The portion of a drug that exerts a pharmacologic effect
Free fractions can diffuse out of the __a__ and into the __b__ and __c__ spaces.
a) vasculature
b) interstitial
c) intracellular
What is the formula for drug distribution?
The volume of distribution of a drug = (dose of the drug) / (concentration of the drug)
The following are characteristics of what protein?
Majority of plasma protein constituents
Major transporter of drugs
Changes in concentration affects free vs bound
Albumin
T/F:
Most drugs are subject to binding with serum protein constituents to form drug-protein complexes
TRUE
Only ________ fractions can interact with the site of action to result in a biologic response
Free/unbound
All drugs absorbed from the intestine (except rectum) enter what system?
Hepatic portal system
What is the first pass effect?
The phenomenon in which a drug is metabolized, results in a reduced concentration o the drug before reaching the circulatory system
What are the consequences of impaired liver function?
- Reduced ability to metabolize
- Effects ability to perform biotransformation to produce the therapeutically active metabolite of the drug
- May require dosing adjustments
What are xenobiotics?
Makes up the most drugs. They are exogenous substances capable of entering biochemical pathways that are meant for endogenous substances
_____ is the biochemical pathway responsible for a large portion of drug metabolism
Hepatic mixed function oxidase (MFO) systems
What are the two basic function of MFO?
- Involves taking hydrophobic substances & through a series of enzymatic reaction, converts them to water soluble products
- Products can then be transported into the bile or released into general circulation for elimination by renal filtration
Result of Phase 1 reactions in MFO
To produce reactive intermediates
Result of Phase 2 reactions in MFO
Conjugate functional groups to reactive sites in water-soluble products
T/F:
Drug elimination is dependent on the clearance mechanism
FALSE:
Independent of clearance mechanism, decreases in the plasma drug concentration most often occur as a first-order process
For drugs not secreted or reabsorbed, the elimination rate directly relates to ____
Glomerular Filtration Rate (GFR)
A decreased GFR results in increased half life and plasma concentration
Many drugs metabolized in the liver are excreted in ____
Bile
T/F:
When administering drugs on a schedule, you only want the peak blood drug concentration to be in the therapeutic range
FALSE
You want to have both peak and trough concentrations to be in the therapeutic range
How many doses are typically needed to reach a steady-state oscillation?
5-7 doses
What is the definition of pharmacodynamics?
- The study of the biochemical and physiological effects of drugs and their mechanisms of action
- Describes the relationship between a drug’s concentration at its site of action and its pharmacological responses
What is the single most important factor of specimen collection?
Accurate timing of specimen collection
When is the trough typically drawn?
Right before the next dose or random
If on oral meds, when is the peak drawn?
1 hour post oral dose
If on V medication, when is the peak drawn?
90 min post IV dose
T/F:
You want to draw peaks only after that 5-7 dose steady oscillation is achieved
TRUE
What tube is preferred for medication testing?
Serum (RED)– NO GEL as it may interfere
What tube do you collect for immunosuppressive drug testing?
EDTA WB
What is the definition of pharmacogenomics?
The science of studying variations and developing drug therapies to compensate for the genetic differences impacting therapy regimens
What is the difference between a responder and a nonresponder?
Responders will have the benefits of the therapeutic/desired effects of a drug while Nonresponders do not.
What is the prominent gene that affects drug metabolism?
Cytochrome P450 (CYP450)
What does CYP450 tell us?
Indicates which drug would work best, predicts interactions, or if there would be a benefit
Digoxin
One of the most common cardioactive drugs.
It is a cardiac glycoside and treats arrythmias and CHF.
Inhibits membrane Na-K-ATPase
LONG half live as once it is in the tissues it stays
Quinidine
Cardioactive Drug
Natural from bark to treat arrythmias
Disopyramide
Cardioactive Drug
Substitute for Quinidine
Procainamide and N-Acetylprocainamide
Cardioactive Drug
What is NAPA?
Cardioactive Drug
The hepatic metabolite of procainamide that works similarly to parent drug
Aminoglycosides
Antibiotic
Treats gram neg and gram pos infections
Inhibits bacterial protein synthesis
Gentamicin
Antibiotic
Treats GNR - life threatening
T/F:
Nephrotoxicity is always reversible without compromising renal function
FALSE
Nephrotoxicity is USUALLY reversible but it CAN CAUSE renal failure
T/F:
Ototoxicity is irreversible
TRUE
Tobramycin
Antibiotic
Treats GNR
Ototoxic and nephrotxic
Amikacin
Antibiotic
Treats severe blood infections
Vancomycin
Antibiotic
Glycopeptide antibiotic
Against GPC and GPR
What are adverse effects of vancomycin?
- Redman syndrome (extremity flushing)
- Nephrotoxicity
- Ototoxicity
Antiepileptic Drugs (AEDs)
Treat and suppress seizures
Only effective while drug metabolites are in the body
TDM is critical
Primidone
AED
grand mal seizure– when resistance to other AEDs
Phenobarbitol
AED
Phenytoin and Free Phenytoin
AED
Common treatment for seizure disorder and short term prophylactic agent in brain injury
What percentage do we have bound and free form of phenytoin and free phenytoin in the body?
90% bound form
10% free form
We need both in the body with some individualism as every body is different
Carbamazepine (Tegretol)
AED
Severe adverse events (only use if nonresponsive to other AED)
Valproic Acid (Depakote)
AED
Gabapentin (Neurontin)
AED
Used for seizures and pain management
Lithium
Psychoactive drug
Mood altering and used to treat bipolar, depression, aggresive/self-mutilatin, cluster headache, migraines
NO LIHEP TUBES
Tricyclic Antidepressants (TCAs)
Psychoactive drug
Used to treat depression, insomnia, extreme apathy, loss of libido
Clozapine (Clozaril, FazaClo)
Psychoactive drug
Treats refractory schizophrenia
Olanzapine (Zyprexa)
Psychoactive drug
Treats schizophrenia, acute manic episodes, bipolar disorder
Immunosuppressive Drugs
TDM used to monitor Immunosuppressive Drugs to prevent organ rejection
Most require est. of individual dosage regimens
Clyclosporine
Immunosuppressive Drug
Suppress graft vs host rejection
Tacrolimus FK-506
Immunosuppressive Drug
Oral, 100x more potent than cyclosporine
Sirolimus
Immunosuppressive Drugs
Antifungal agent to prevent graft rejection in kidney transplants
Everolimus
Immunosuppressive Drug
Derived from Sirolimus
Short half live results in a more rapid achievement of steady state pharmacokinetics
WB
Mycophenolic Acid (MPA)
Immunosuppressive Drug
MPA is the active from of Mycophenolate mofetil which is a prodrug that rapidly converts to in the liver to MPA
Antineoplastics
Pharmacodynamics are hard to est. so TDM isn’t as useful
Many rapidly metabolized or incorporated into cellular macromolecular structures
Delivered dose more relevant than circulating concentrations
Methotrexate
Antineoplastic
TDM offers some benefits to est. therapeutic regimen
Theophylline
Bronchodilator
Used to treat respiratory disorder
