Introduction to TDM Flashcards
For drugs that need therapeutic drug monitoring, can empirical doses be given?
No, especially if an individual’s PK parameters are unknown
It is difficult to acheive therapeutic concentrations with empiric doses in drugs that need therapeutic drug monitoring
When adjusting dosing for a drug according to PK variation, what are some important considerations?
- Correct Diagnosis
- Nature and Severity of Disease
- Patient Monitoring
- Dosage Regimen
- Selected Drug
- Therapeutic Objective
- Patient Condition
What is therapeutic drug monitoring?
It involves PK monitoring (measurement of drug concentrations)
OR
PD monitoring (surrogate markers of drug effect, ex. changes in BP)
What is the process for therapeutic drug monitoring?
- Diagnosis is made
- Consider patient’s condition/complicating factors - Drug selected/therapeutic objective defined
- Select target Css or clinical response
- Use pop. PK to estimate patient PK - Drug is administered
- Clinical response assessed
- Css measured
When do pharmacists request a drug plasma concentrations?
- For TDM to individualize patient’s dosage regimen
- Screen for potential toxic compiund causing medical emergency
What is clinical pharmacokinetics?
Application of PK principles to the design of individualized dosage regimens that optimize therapeutic response and minimize chances of an adverse reaction
How are individual doses initiated?
- Initial dose (individual PK parameters are unknown, so use population mean PK parameters)
- Adjustment (Changes according to patient’s drug concentrations)
Do most drugs exhibit linear PK?
Yes, most drugs exhibit linear PK
What are some advantages of drugs that exhibit linear PK when it comes to dosing regimens?
Allows use of drug Cpss to do the following:
- Assess response
- Compute individualized dosage regimen
This quality is due to the predictability in the relationship between plasma concentration and drug dose seen in linear PK drugs
Do all patients benefit from drug when drug dose is within the therapeutic range?
No, only 60-70% of patients see optimal benefit from empiric dosing
The remainder of the patients are either under or overdosed. This is why TDM is important for getting these patients to get benefit from these same drugs
What is the goal of therapeutic drug monitoring?
- Css in therapeutic range
- Appropriate clinical response
What are some drug characteristics that make it applicable for therapeutic drug monitoring?
- Css is the intermediate endpoint (no therapeutic endpoint that can be feasibly measured without undue harm)
- Predictable Css vs. response relationship (linear PK)
- Narrow range of safe and effective
- Wide interpatient variation in PK parameters
- Toxicity/lack of effect puts patient at grave risk
- Drug effect persists for relatively long time
- Availability of validated drug analytical assay
- Population PK parameters and therapeutic range is known
What are some common drugs that need therapeutic drug monitoring?
- Antibiotics (aminoglycosides, chloramphenicol, vancomycin)
- Cardiac agents (digoxin, amiodarone, procainamide, lidocaine, quinidine)
- Anti-epileptics (phenytoin, valproic acid, carbamazepine, barbiturates)
- Psychotherapeutics (lithium, TCAs)
- Miscellaneous (cyclosporine, methotrexate, theophylline)
What situations warrant a request for a drug level from the clinical lab?
- Assess therapy following initiation or change in dosing regimen
- Symptom of toxicity = Symptom of disease stage (some drugs like digoxin)
- Potential drug interactions
- Change in clinical state of patient
- Lack of response
- Need to assess compliance (especially with psychotropic drugs)
- Toxicity suspected
What additional information is required to adequately interpret drug level data?
- History of drug admininstration
- Drug, dose, dosage form, route, time of admin - Time of blood sample relative to dose administraton (usually taken before next dose of drug)
- Previous Cp data
- Clinical status of patient
- weight, age, gender, sex, condition being treated - Laboratory data
- Renal and hepatic function, albumin - Population PK parameters
- Analytical assay (do not disount possible lab error)
- Concurrent drug therapy
- Drug interactions
- Analytical assay interference
What are the three steps for using TDM to design individualized dosage regimens?
- Compute initial dose (LD and MD)
- Take a blood sample from patient to determine drug concentration at steady state levels (Cssmin)
- Use patient Cssmin and clinical response to determine need for dosage adjustment
Review slides 24 to 32 for a worked out TDM example
How long does it take to achieve a steady-state concentration of a drug?
4-5 half-lives
Review slide 35 for what other information is required to make a good interpretation of Cssmin
What are the principal methods of individual patient physiological parameter estimation?
- Body Surface Area (BSA)
a. Dubois/Dubois (used in average and obese)
b. Mosteller Method (used in average weight patients ONLY) - Ideal Body Weight (IBW)
a. Devine Method (using actual body weight may not be appropriate in emaciated or obese patients) - Creatinine Clearance
a. CKD-EPI (eGFR)
b. Schwartz Equation (used in pediatrics)
Review slide 38 for BSA equations.
Review slide 38 for Ideal Body Weight and Dosing Body Weight for Aminoglycosides equations
When is body surface area used in pharmacy practice?
BSA is necessary for:
- Dosing of some drugs (cancer chemotherapy)
- Assessment of severity of burn injury
- Calculation of cardiac index and other indices of organ function
Do the two types of BSA equations result in the same result?
Not always
The Dubois/Dubois Method equation for BSA is designed to allow average and obese patients to get more accurate BSA estimates
So it is important that we choose the right equation
What is the average person’s BSA value?
1.73m^2
What are the components of renal clearance?
- Glomerular filtration rate (GFR)
- Tubular secretion
- Tubular reabsorption
What is the utility of creatinine clearance (Clcr) in estimating kidney function?
It estimates GFR, and hence Clgfr
Review slide 47 for review of creatinine clearance
Are increases in serum creatinine always linked to reduction in GFR?
Not always
If tubular secretion of creatinine is inhibited, then serum creatinine accumulates while GFR remains unchanged
Review slide 49 for the Cockroft-Gault equation for estimating kidney function
Why is there is a correction factor (smaller value for women) when using serum creatinine to estimate kidney function?
Women have lower muscle mass, therefore they naturally have lower SCr, so we adjust for this sex difference by using a different correction factor for women and men
Is the Cockroft-Gault equation used to estimate creatinine clearance in obese patients?
No, the Salazar-Corcoran equation is used in obese patients
What equation is used to estimate creatinine clearance in pediatric patients?
The Schwartz Equation
What is the reccomended equation for estimating eGFR in patients with CKD?
CKD-EPI
Review slide 55
What is the difference between indexed and non-indexed eGFR?
Indexed eGFR: standardized to a BSA of 1.73m^2 (CKD staging and progression is assessed with indexed eGFR)
Non-indexed eGFR: adjusted for patient’s own BSA (drug dosing decisions are based on non-indexed eGFR)
Review slide 56
