therapeutic drug monitoring Flashcards
define therapeutic drug monitoring
the measurement of drugs and/or their metabolites in the body fluids - usually blood - to maintain therapeutic benefits
list important considerations of TDM
- timing of collections
- accurate measurement of drug concentrations
- timely reporting of results
describe when TDM is used
- drug has a barrow TR
- marked pharmacokinetic variabilities
- critical adverse effects
describe the main purpose of TDM
- ensure correct dosages
- ID drug-drug interactions
define pharmacokinetics
study of movement of drugs in the body
what does pharmacokinetics relate concentration of drug to
- absorption
- dist
- metabolism
- excretion
list routes of administration and the most common/most direct
- oral - most common
- intravenous - most direct
- intramuscular
- subcutaneous
- aerosol
- transdermal patch
- rectal
what does oral absorption depend on
efficiency of GI absorption which depends on:
- dissociation
- solubility of GI
- diffusion
what form does a drug need to be in to be passively diffused
- hydrophobic and non ionized
define drug distribution
the movement of a drug between blood circulation, tissues, organs and the relative proportion of the drug in the tissues
what does a drugs ability to leave circulation depend on
lipid solubility of the drug
- highly hydrophobic can easily cross
- polar and don’t ionize can cross cell membrane but don’t enter lipid compartments
- ionized diffuse out of vasculature but slowly
what is the volume of drug distribution equation
Vd = dose/concentration
true or false
- hydrophobic drugs have a large Vd
- ionizes or primarily bound to proteins has small Vd
true and true
what form do drugs need to be in to interact with site of action
free/unbound to result in biological response (active fraction)
how does albumin relate to free fraction of drugs
changes in [albumin] affect free vs bound since it is a major transporter
describe drug metabolism
- all drugs enter hepatic portal system and get metabolized
define first pass effect in regards to drug metabolism
phenomenon in which a drug is metabolized, results in a reduced concentration of the drug before reaching the circulatory system
describe how impaired liver function effects drug metabolism
efficacy of a drug depends on a therapeutically active metabolite that occurs in the liver = biotransformation
true or false
most drugs are xenobiotics
true
- exogenous substances capable of entering biochemical pathways that are meant for endogenous substances
what system is responsible for a large part of drug metabolism
- hepatic mixed-function oxidase (MFO)
- turns hydrophobic to water sol to be transported
describe phases of drug metabolism
- phase 1: produce reactive intermediates
- phase 2: conjugate functional groups to reactive sites in water sol products
describe how the MFO system can be induced
seen as increase in synthesis and activity of the rate-limiting enzymes w/in pathway
- results in accelerated clearance of drug
how are free fractions eliminated
- subject to glomerular filtration and/pr renal secretion
how does elimination rate relate to GFR
direct relation
- decrease GFR results in increased half life
independent of clearance mechanism, decreases in the plasma drug concentration most often occur as a ______
first-order process
- change in drug/change in time
how many doses are typically needed to enter steady-state oscillation
5-7
define pharmacodynamics
the study of the biochemical and physiological effects of drugs and their mechanisms of action
- concentration at site and response
what is the single most important factor in regards to therapeutic drug monitoring specimen collection
accurate timing
when is peak oral dose drawn
1 hr after dose
when is peak IV dose drawn from EDTA whole blood
90 minutes after dose
true or false
drug peaks only after steady state is achieved
true
define pharmacogenomics
the study of variations and development of drug therapies to compensate for the genetic differences impacting therapy regimes
-effectiveness depends on pt response
define the prominent gene affecting drug metabolism and what it can be used for
CYP450
- encodes cytochrome P450
- to personalize drug dosages
what is the most common cardioactive drugs
digoxin
describe digoxin
- treats arrythmias and CHF
- inhibits Na/K ATPase to increase intracellular calcium to improve cardiac contractability
- plasma protein binding rate of 25%
- free form sequestered in muscle
- measure bound and free with immunoassays
describe quinidine
- cardioactive drug to treat arrythmias
- absorption rapid through oral-GI
- eliminated through hepatic metabolism
- monitor trough, peak if toxic
describe disopyramide
- cardioactive drug
- sub for quinidine
- renal elimination
- binds several plasma proteins
describe procainamide and relation to N-acetylprocainamide
- oral and rapid absorption
- 20% bound to plasma proteins
- eliminated renal and hepatic
- N-acetylprocainamide (NAPA) is the hepatic metabolite of procainamide => skips liver
describe aminoglycosides
- broad category antibiotic
- treats GN and some GP infections
- inhibits bacterial protein synthesis
- nephrotoxicity and ototoxicity
- needs IV or IM
describe gentamicin
- aminoglycoside antibiotic
- treats GNR if life threatening
- can do higher dosing if good renal function
describe tobramycin
- aminoglycoside antibiotic
- treats GNR
- ototoxic and nephrotoxic
- baseline audiology testing
describe amikacin
- aminoglycoside antibiotic
- treats severe blood infections
- orally administered to lower intestinal flora
- excreted by kidneys
describe kanamycin
aminoglycoside antibiotic
describe vancomycin
- glycopeptide antibiotic
- against GPC and GPR
- poor GI abs = IV
- redman syndrome
- nephrotoxic and ototoxic
- only trough is measured
describe (general) antiepileptic drugs
- used to treat and suppress seizures
- only effective while drug metabolites are in the body
- measured w/ immunoassays or chromatography
describe primidone
- AED
- used for grand mal seizures if resistant to other AEDs
- converted to metabolites (phenobarbital and phenylethylmalonamide)
- reaches steady state quicker than phenobarbitol
describe phenobarbital
- slow acting oral AED
- eliminated hepatic w/ renal
- only troughs measured
describe phenytoin and free phenytoin
- AED
- common seizure and short term prophylactic in brain injury
- high protein bound portion 87-97%
- free fraction is biologically active form
- measure both free and bound for dosage adjustment
describe valproic acid (depakote)
- oral AED
- high protein bound
- hepatic elimination
- toxic at upper end TR
- hepatic dysfunction in some pt w/in TR
describe carbamazepine (tegretol)
- severe adverse events, only used if no other AEDs work
- oral
- toxicity diverse and variable but close to TR
describe Gabapentin (neurontin)
- common AED
- oral max bioavailability of 60%
- for for seizures and pain management
- does not bind proteins
- not metabolized in liver
- eliminated unchanged in liver
- used in pt w/ liver disease
describe lithium
- oral psychoactive mood altering drug
- doesn’t bind protein
- toxic at 1.5-2 ug/dL
describe tricyclic antidepressants (TCAs)
- treat depression, insomnia, extreme apathy, loss of libido
- oral
- high protein bound (85-95%)
- hepatic metabolism
- immunoassay screening NOT TDM due to cross reactivity
- chromatographic TDM
describe clozapine
- psychoactive drug for refractory schizophrenia
- 97% protein bound
- TDM used for adherence checks and toxicity
- metabolized in liver
describe olanzapine
- psychoactive drug for: schizophrenia, acute manic episodes, recurrence of bipolar disorders
- IM or oral (usually oral)
- 40% inactivated after first pass
- 93% bound to plasma proteins
- metabolized in liver
describe (general) immunosuppressive drugs
- TDM used to prevent organ rejection
- individual dosage regimens to minimize toxic
- chromatographic, liquid chromatography-tandem mass spec
describe cyclosporine
- immunosuppressive drug
- cyclic polypeptide
- suppress graft vs host rejection
- oral w/ low abs
- whole blood specimen
describe tacrolimus FK-506
- oral
- 100x more potent that cyclosporine
- 98% bound to plasma proteins
- whole blood sample
describe sirolimus
- immunosuppressive
- antifungal to prevent graft rejection in kidney transplants
- rapid oral abs
- co administered w/ cyclosporine or tacrolimus
- 92% bound to lipoproteins
describe everolimus
- derived from sirolimus
- more rapid steady state achievement
- whole blood specimen
describe mycophenolic acid (MPA)
- immunosuppressive
- prodrug converted in liver to active MPA
- oral but abs in neutral pH
- 95% protein bound
- renal elimination
describe antineoplastics
- immunosuppressant
- not aided by TDM
- rapidly metabolized or incorporated into cellular macromolecular structures
- delivered dose more important than circulating concentrations
describe methotrexate
- antineoplastic
- oral administration
- 50% bound to plasma protein
- extretated renal
- trough specimens preferred
describe bronchodilators
theophylline
- used to treat respiratory disorders
- for pt who can’t use inhaler
- 50-65% bound to plasma proteins
