Therapeutic Drug Monitoring Flashcards
What is therapeutic drug monitoring? What is the main goal? What are the 2 reasons to undertake this?
Therapeutic Drug Monitoring (TDM)
Is the clinical practice of measuring the plasma levels of specific drugs to optimize individual dosage regimens
The main goal of therapeutic drug monitoring is to achieve the desired therapeutic effect while minimizing adverse effects in each individual patient
Two main reasons to undertake TDM
Avoid drug toxicity
Improve therapeutic efficacy
The main goal of therapeutic drug monitoring is to ?
achieve the desired therapeutic effect while minimizing adverse effects in each individual patient
When is therapeutic drug monitoring useful?
- Drug has a narrow therapeutic range
- Therapeutic effect can not be readily assessed by the clinical observation
- A direct relationship between the drug levels in plasma and the toxic effects
- Availability of cost-effective drug assay
What are the special populations where Therapeutic Drug Montioring is useful?
- Patients at the extremes of age
- Patients with dosing problems
- Patients taking multiple medications
- Patients who have unusual PK as a result of physiological, environmental, disease, or genetic factors
What are the advantages of therapeutic drug monitoring?
- Maximizing drug efficacy
- Avoiding toxicity
- Identifying Therapeutic Failure
- Cost effective
What information is required for TDM?
- History of drug administration
- Present and previous (if applicable) plasma drug concentrations
- Clinical status of the patient
- Time of sampling
- Physiological data
- Concurrent drug therapy
Once you have acquired the necessary information for TDM, what can you do?
From such observations, the patient’s current pharmacokinetic parameters can be estimated, and a new dosage regimen can be designed to more closely achieve the target value(s)
What are the 3 PK variables?
• Absorption, clearance, volume of distribution
What are the 2 PD variables?
• Maximum efficacy in the target tissue, Potency
What is Therapeutic Drug monitorings relationship with Absorption?
Compliance failure (over- or under-dosage): Can be detected by drug measurements
What is Therapeutic Drug monitorings relationship with Clearance?
- Clearance is the single most important factor determining drug fate
- Factors influencing clearance are: Dose and intrinsic function of liver and kidneys
What is Therapeutic Drug monitorings relationship with Volume of Distribution?
• Increase Vd, tissue binding
• Decrease Vd, plasma protein binding
• Older patients: Decreased skeletal muscle mass, less binding, a lower Vd
• Accumulation of fluid (edema, ascites) markedly increases Vd of hydrophilic drugs
(e.g., gentamicin) that normally have a small Vd
What is Therapeutic Drug monitoringsrelationship with Half life?
• Determines the time taken to reach a steady state level
• Decreased Drug clearance causes increased half-life
• TDM usually involves measurement of drug levels at steady state (the rate of drug
administration is balanced by the drug of elimination)
What is Therapeutic Drug monitorings relationship with Efficacy?
• When drug concentrations are >> EC50, all pharmacological responses are
saturated
• Avoid administration of further, ineffective (and possibly toxic) doses of drug
What is Therapeutic Drug monitorings relationship with Potency?
• Diminished potency/sensitivity
• Measuring drug in a patient who is not improving but who is receiving normal
dosage
What are the steps to target concentration strategy in laymens terms?
Estimate dose ( target dose, loading dose, maintenance dose) -> Begin therapy -> assess therapy ( patient response/ drug level) -> refine dose estimate -> adjust dose
What is the equation for the new dose?
What is the equation for the new interval?
How can you adjust your dose in your patient after finding the new dose?
A conservative approach is to increase the dose incrementally
First trying a dose of 400 mg/day then increasing the dose to 500 mg/day.
This way, if toxicity is experienced as a consequence of the dose increase, it may
manifest itself at the lower, less toxic dose
