Week 3 - Therapeutic Drug Monitoring Flashcards
Therapeutic Drug Monitoring is the clinical practice of measuring the ______ levels of specific drugs to ______ individual dosage regimens
plasma, optimize
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
TDM will be useful if the following criteria are met:
• Drug has a________ ________ range
• ________ _______ can not be readily assessed by the clinical observation
• A direct relationship between the drug levels in _______ and the _____ effects
• Availability of _____-effective drug _______
narrow,therapeutic,Therapeutic,effect,plasma,toxic,cost,assay
Special Populations where TDM 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
mdr1 defect; can not give drug that you normally use
Advantages of TDM
• Maximizing drug ______
• Avoiding ______
• Identifying Therapeutic ______
• ____ effective
efficacy, toxicity, Failure, Cost
What information is required for TDM?
•_____ of drug administration
• Present and previous (if applicable) ______ drug concentrations
•______ status of the patient
•_______ of sampling
•______ data
•________ drug therapy
History,plasma,Clinical,Time,Physiological,Concurrent
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)
Three PK variables:
• Absorption, clearance, volume of distribution
Two PD variables:
______ ______ in the target tissue
________
Maximum efficacy, Potency
What is TDM’s relationship with Absorption?
Compliance failure (over- or under-dosage): Can be detected by drug measurements
What is TDM’s relationship with Clearance?
• _______ is the single most important factor determining drug fate
• Factors influencing clearance are:?
Clearance, Dose and intrinsic function of liver and kidneys
Describe TDM’s relationship with Volume of Distribution
• Increase Vd, _____ binding
• Decrease Vd, _____ ______ binding
• Older patients: Decreased _____ ______ mass, ___ binding, a ____ Vd
• Accumulation of ___ (?) markedly ______ Vd of ____ drugs
(e.g., gentamicin) that normally have a small Vd.
tissue, plasma protein, skeletal muscle, less, lower, fluid, edema, ascites, increases, hydrophilic
What is TDM’s relationship with Half life?
• Determines the ____ taken to reach a _____ _____ level
• Decreased Drug clearance causes _______ half-life
• TDM usually involves measurement of drug levels at _____ ____ (the rate of drug _______ is balanced by the drug of ______)
time, steady state, increased, steady state, administration, elimination
What is TDM’s relationship with Efficacy?
• When drug concentrations are»_space; EC50, all pharmacological responses are _____
• Avoid administration of further, _____ (and possibly ____) doses of drug
saturated, ineffective, toxic
What is TDM’s relationship with Potency?
• Diminished potency/sensitivity
• Measuring drug in a patient who is not _____ but who is receiving _____ dosage
improving, normal
Define the target concentration strategy
A multi-step process for _______ dosage in an individual on the basis of ___ and ___ and pharmacogenetics properties
optimizing, PK, PD
What are the steps of the target concentration strategy
The steps are:
1. Chose _____ ________ (?)
2. Predict __ and __ from standard population values
3. Measure patient’s ______ and drug ________
4. Revise ___ and/or ___ based on measured drug concentration
target concentration, TC, Vd, CL, response, concentration, Vd, CL
How do you measure the target concentration?
If a patient has drug concentrations outside the therapeutic range, the dose should be ?
modified to change the drug concentrations into the therapeutic range by a proportional adjustment
E.g. of dosage adjustment formula (dose)
E.g. dosage adjustment formula (interval)
What drugs would be good candidates for TDM?
• Drugs with ____ therapeutic index
• Drugs with _____ variability in their PK properties
• Drugs used in patients who are at ___ risk of toxicity
low, great, high
