THERAPEUTIC DRUG MONITORING AND CLINICAL TOXICOLOGY Flashcards
Clinical chemistry laboratory
– Provides information concerning the diagnosis and management of patients suspected to _______________
– Provides information in patients __________________
– Assessment of individuals _____________
have taken drug overdose
taking drugs for treatment of disease conditions
screened for drugs of abuse
Therapeutic Drug Monitoring
Involves the analysis, assessment and evaluation of ___________ in serum, plasma, or whole blood.
Purpose is to ensure the medication dose is __________ and not _____
circulating concentrations of drugs
at therapeutic range and not toxic.
TDM enables the assessment of the ______ and ______ of a particular medication in a variety of clinical settings.
efficacy and safety
The goal of TDM is to _______ therapeutic regimens for optimal patient benefit
individualize
Key points of therapeutic drug monitoring
Goal
-Ensure that a given drug dosage produces maximal ______ and Minimal ________
-Must have _______ at site of action that produces benefits
therapeutic benefit ; toxic adverse effects
an appropriate concentration
Key points of therapeutic drug monitoring
Standard dosages are derived from _______
Only the ______ fraction of drugs can interact with site of action, resulting in a biologic response
healthy population
free
THERAPEUTIC RANGE/ THERAPEUTIC WINDOW
The therapeutic range is the _____ of drug in plasma where the drug has been shown to be _____ without ________
concentration range
efficacious; causing toxic effects in most people.
TARGET CONCENTRATION AND THERAPEUTIC RANGE -Range introduces uncertainty into ___________ the desired dose
exactly how to prescribe
INDICATIONS FOR TDM
Drugs for which relationship between dose and plasma concentration is unpredictable, e.g _________
Drugs with a narrow therapeutic window:- will allow dosage alterations to produce optimal therapeutic effect or to avoid toxic effects. Ex: ____,_____ and _____
Drugs for which there is difficulty in measuring or interpreting the clinical evidence of therapeutic or toxic effects,e.g, Nausea & vomiting occur in both ______ toxicity & ______
Drug with poorly defined end point or difficult to clinically predict the response. Example: _______ drugs
Phenytoin
Lithium, phenytoin, and digoxin
digitalis; congestive heart failure
immunosuppressant
INDICATIONS FOR TDM
Drug interactions: When another drug alters the relationship between dose & plasma concentration e.g. plasma concentration of lithium is increased by _______
For diagnosis of suspected toxicity & determining drug abuse
To evaluate compliance of patient
Guiding withdrawal of therapy: _____,_____
thiazide
Antiepileptics, Cyclosporine.
DRUGS THAT ARE NOT SUITABLE FOR TDM
Drugs having (narrow or wide?) therapeutic index
Toxicity is not a realistic concern ( ____ )
Effects can be measured using laboratory tests (______)
Plasma concentration not predictably related to effects ( ______ )
Effect of the relationship remains undefined (________)
Wide; Penicillin
Anticoagulants
Anticoagulants
Antidepressants
The following are important considerations to ensure an optimum TDM service in any setting
-Measurement of ___________ taken at appropriate time after drug administration
-Knowledge of _______________________
-Knowledge of _________ like demographic data, clinical status, laboratory and other clinical investigations
-__________ after taking into consideration all of the above information and individualizing drug regimen according to the clinical needs of the patient.
patient’s serum or plasma drug concentration
pharmacological and pharmacokinetic profiles of the administered drugs
relevant patient’s profile
Interpretation of SDC
Pharmacokinetics’ Process assists in establishing or modifying a dosage regimen
T/F
T
Most drugs given as a single bolus or mass
T/F
F
Most drugs given on a scheduled basis not as a single bolus or mass
Goal of dosage regimens
Achieve troughs in _______ and peaks that _____
therapeutic range
are non-toxic
_______, which gives a measure of the unbound drug concentration, may be a useful alternative when blood samples are difficult to collect.
Saliva
Avoid serum-separator tubes because these may _______ due to the ________
lower drug concentrations
adsorption of drug into the matrix.
Storage of samples: __________ type tubes are acceptable for most assays
Plastic cryovial
GUIDELINES TO SPECIMEN COLLECTION
1) Blood specimens for drug monitoring can be taken at ______ times - during the _________ therapeutic concentration (‘peak’ level), or its _____ (‘trough’ level).
Occasionally called _____ levels, trough levels show _______ levels; whereas peak levels show ____
two different
drug ́s highest ; lowest
residual; sufficient therapeutic
toxicity
Peak and trough levels should fall within the therapeutic range.
T/F
T
For chronically administered oral medications the peak levels usually occur _____ after the dose and the trough serum concentration ________.
______ is one exception.
1-2 hours
shortly after the dose is administered
Digoxin
The serum level to determine peak activity should be drawn after the serum digoxin __________ i.e., ______ after the oral dose.
Drawing the trough level at _______ is usually sufficiently accurate.
has had time to equilibrate with the tissue
6-10 hours
the time the dose is given
Intravenous medications should be given time to equilibrate before the peak level is drawn.
T/F
T
Intravenous medications should be sampled _____ after administration.
For example, the peak serum level of Gentamicin should be drawn _________ after infusion of the drug ends and not ______________
1⁄2-1 hour
thirty minutes
immediately after the infusion.
Intramuscularly administered medications if injected in an area with good blood flow will achieve peak levels within a similar time frame as intravenous.
T/F
T
CLINICAL SIGNIFICANCE OF TDM
Maximizes _____
Avoids ______
Identifies ______
Facilitates the therapeutic effect of drug by achieving ———-
Identify poisoning, drug toxicity and drug abuse
efficacy; toxicity
therapeutic failure
target drug concentration
Digoxin is measured in serum using immunoassay.
T/F
T
Lidocaine
Used to correct _________ and prevent _________
Completely eliminated by the ____ if ____ given as monoethylglycinexylidide (MEGX).
Toxic effects include _____
ventricular arrhythmias
ventricular fibrillation.
liver; orally
CNS depression
Drug Groups: Cardioactive
Quinidine
-Used to treat _______ problems
-Inhibits _______ channels
-Prevents arrhythmias, atrial flutter and fibrillation
cardiac arrhythmic
sodium and potassium
Procainamide
-Used to treat _______ situations
-Blocks ______ channels
-Affects cardiac muscle contraction
-Often measured with _______
cardiac arrhythmic
sodium
NAPA(N-Acetyl procainamide)
Drug Groups: Antibiotics
Aminoglycosides
Used to treat infections with gram- ______ bacteria that are resistant to less toxic antibiotics
Inhibits protein synthesis of the micro-organism
Examples include: gentamycin, tobramycin, amikacin and kanamycin
Associated with nephro and ototoxicity
Negative
Vancomycin
Used to treat infections with more-resistant gram- _____ cocci and bacilli Inhibits cell wall synthesis
positive
Drug Groups: Psychotherapeutic
Used to treat manic depression (bipolar disorder)
–______
–__________
–_____
Lithium
Tricyclic Antidepressants “TCAs”
Clozapine
Drug Group: Antiasthmatic
Used to treat neonatal breathing disorders or respiratory disoders of adults or children, like asthma
Examples include _______ and ______
theophylline and theobromine
Drug Group: Immunosuppressive
Monitoring of this group of drugs important to prevent ________ (host-versus-graft)
Used to treat _______ disease
organ rejection
autoimmune
Drug Group: Immunosuppressive
Examples
– Cyclosporine
Whole blood is the specimen of choice, since it _______
– Tacrolimus (Prograf)
Prevents ________ and ___________
sequesters in the RBC
rejection of liver and kidney transplants
Methotrexate is an anti_______
Neoplastic
Methotrexate:
– The efficacy of therapy is dependent on _______, one that is ___________
– This is accomplished by the administration of _______, which ____________ at a specific time after methotrexate infusion.
– This is referred to as __________
a controlled period of inhibition
selectively detrimental to neoplastic cells.
leucovorin; reverses the actions of methotrexate
leucovorin rescue.
Methotrexate:
– Failure to stop methotrexate actions results in _____ effects to most cells.
– Evaluation of _______ concentration, after the ______ period has passed, is used to:
determine how much _____ is needed to counteract many of the toxic effects of methotrexate.
cytotoxic
serum methotrexate
inhibitory time
leucovorin
TECHNIQUES FOR MEASUREMENT IN TDM
1. HPLC: ___________: The separation of a substance depends on the relative distribution of mixture constituents between two phases, a ____ phase ( _______ ) and a ______ phase.
.
High Pressure Liquid Chromatography
mobile
carrying the mixture
stationary
TECHNIQUES FOR MEASUREMENT IN TDM
- LC/MS: _____________: All chromatography-based techniques work on the principle that different substances are absorbed differently in solution. Two “phases” or materials are used to separate the components of a solution. The mobile phase ___________________________________, which separates out the components in the sample.
Liquid Chromatography Mass Spectrometry
carries the sample along the stationary or solid phase
GC/MS:_________ is a separation method using _____ temperatures to cause sample vaporization.
In mass spectrophotometry the vaporized fractions are _________. The molecules can be separated on the basis of ______. The pattern of separation is unique to each drug and therefore establishes a “ _____ ” for identification.
Gas chromatography
very high
passed through an electrical field
molecular weight
fingerprint
TECHNIQUES FOR MEASUREMENT IN TDM
_________ is the gold standard method for the identification of drugs of abuse.
GC/MS
Management of poisoning include use of specific antidotes like _____ for paracetamol poisoning
N-acetylcystein
Paracetamol poisoning
Metabolites following poisoning are mostly soluble and excreted in urine as ______ and ______
However, ________ formed through the action of cytochrome p450 accumulates following exhaution of ______ and causes hepatotoxicity
glucoronides and sulphate
n-acetyl-p-benzoquinoneimine (NAPQI)
glutathione
Clinical features of paracetamol poisoning
Insidious onset with _______ in first 24 hr
_______ is maintained unless associated sedative
Then ________, abnormal ______, elevated _____ and _____
Encephalopathy, liver and renal failure may follow depending on severity
nausea and vomiting
Consciousness
abdominal pain; prothrombin time
liver enzymes and bilirubin
Treatment of paracetamol poisoning
Regular ______
__________ management
Acid base homeostasis, renal status
Use of specific antidote _____ given by ___
Oral ______ assist in ______ regeneration
blood level monitoring
Fluid and electrolyte
N-acetylcystein; IV
methionine; glutathione
Screening for drugs
________ may just suffice for screening and diagnosis especially for drugs of abuse
This may be key for patient brought into the emergency unit in _____ state
In suspected case of _____, identification of poison is vital and be carried out by qualified personnel in special labs using urine or blood
Qualitative
unconscious; homicide
_________ is the antidote for alcohol or methanol
_______ is the antidote for beta blockers
______ is the antidote for heparin
______ is the antidote for warfarin
_______ is the antidote for methotrexate
Fomepizol
Glucagon
Protamine sulphate
Vitamin K
Leucovorin
