Therapeutic Drug Monitoring Flashcards
Definition of therapeutic drug monitoring?
The measurement of drug concentrations in body fluids (plasma, serum, blood etc.)
Why is it important to monitor plasma drug concentrations?
Avoid toxicity
Optimize dose and/or therapeutic response
Detect changes in pharmacokinetics
Monitor compliance
ADME rates are based on?
Age, weight gender
Genetics
Co-morbid diseases
Which drugs are suitable for TDM?
High inter-patient variability in plasma concentrations
Narrow therapeutic range
When the pharmacological effect persists and is dependent on the plasma concentrations
Availability of cost-effective, accurate drug assays with rapid turn around time and a small blood volume requirement
Examples of wide therapeutic range drugs requiring TDM?
NSAIDS
Most antibiotics
Beta-blockers
Examples of narrow therapeutic range drugs requiring TDM?
Lithium Warfarin Neuroleptics (e.g. phenytoin, phenobarbital) Gentamcyin, vancomycin, amikacin Digoxin Immunosuppressives
What is the rationale for TDM?
A closer relationship exists between serum concentration of a drug and the effect compared to the dose of the drug and the effect
Indications for TDM?
Patient factors:
Lack of clinical response
Non/poor adherence
Suspected toxicity
Co-morbidities:
Drug-drug interactions
Renal/hepatic impairment
Malabsoprtion
Special populations:
Pregnancy
Paediatrics
Goals in therapy?
Provide constant concentrations
Achieve transient high concentrations without toxicity
Varying concentrations between individuals on same dose
How many half-lifes does it take to reach steady state?
5 half-lives
Definition of “steady-state”?
When renal intake and excretion are equal
What must one do if they want to reach the steady state quicker?
Administer a loading dose
MEC?
Minimal effective concentration - the concentration above which efficacy is expected in most patients
MTC?
Maximum total concentration - upper concentration above which the rate and severity of adverse effects becomes unacceptable
Things to consider when interpreting a drug concentration?
Time of sample collection
Time of last dose
Dosage regime
Indication for drug monitoring
Possible reasons for the drug concentration to be lower than expected?
Incorrect dose given
Patient non-compliance
Rapid elimination
Timing of sample
Possible reasons for the drug concentration to be higher than expected?
Error in dosage regime
Overdose
Decreased renal/hepatic function
Slow elimination
Definition of “saturable” metabolism?
If a certain concentration reached, the elimination will not increase, but there will be an increased risk of toxicity
“Non-saturable” metabolism?
If the dose increases, the elimination increases
Why TDM with phenytoin?
Concentration-time profile unpredictable in an individual (PK variable)
Saturable metabolism
Small dose increases can produce disproportionate rises in blood levels and toxicity
Why TDM with Theophylline?
Narrow therapeutic index
Increased metabolism if used with anticonvulsants, Rif, smokers
Decreased metabolism if used with cardiac failure, elderly, liver disease, drugs
