The evaluation and design of individualized dosage regimens which optimize the therapeutic response while minimizing the change of an adverse drug reaction
What patient factors are important when considering Therapeutic Drug Management?
Age, Gender, Pharmacogenomic influences, Co-morbid condition and Patient’s needs or disorders
What are common disease that are influenced by Therapeutic Drug Management?
Severe Infections, Epilepsy, immunosuppression, Cancer, Anticoagulation
Define the Therapeutic Index:
A ratio of Therapeutic and Toxic doses/effects TI = TD50/ED50
For what situations is Measuring drug concentrations most useful?
To monitor drugs with a narrow therapeutic index or to evaluate Efficacy, Toxicity and Adherence issues
What antibiotics commonly require Therapeutic Drug management?
Aminoglycosides and Vancomycin
What Anticonvulsants commonly require Therapeutic Drug Management?
Phenytoin, Phenobarbitol, Valproic acid and Carbamazepine
What Immunosuppressants commonly require Therapeutic Drug Management?
Cyclosporine, Tacrolimus, Sirolimus
What Cardiovascular drugs commonly require Therapeutic Drug Management?
Lidocaine, Digoxin, Procainamide, Quinidine
What major drug classes commonly require Therapeutic Drug Management?
The dose that produces 50% of the maximal adverse effects
A drug with a wide therapeutic index would have what numeral for TI?
Much greater than 1
What pharmacokinetic parameter of Valproic acid changes widely between age groups?
Elimination Half-life and Dosage
(True/False) Valproic acid has high renal excretion in its unchanged form?
False, low 1-5%
Describe the protein binding of Valproic acid?
Non-linear, free fraction changes based on concentration
Is blood concentration the most representative and important part of Drug therapy?
No, does not always represent the true therapeutic effect
Are Max/Min and Peak/Trough interchangeable?
No
What is the difference between a Max and Min and a Peak and Trough?
Peak occurs slightly after the max and trough occurs slightly before the Min, Peak/Trough are used clinically
Why evaluate Peak and Trough rather than Max and Min?
1.) To allow for drug distribution from the site of injection 2.) To avoid irregularities in distribution (Variability around the Max)
(True/False) Drug concentrations will be higher than the peak at some point?
True
(True/False) Drug concentrations will be lower than the trough at some point?
True
What is PK/PD correlation?
Pharamcokinetic/Pharmacodynamic correlations: allows principles to be used in drug regimen decisions
What type of pattern of activity do Aminoglycosides have?
Type 1
What type of pattern of activity does Vancomycin have?
Type III
What does it mean to have a Type I pattern of activity of an antibiotic?
Concentration dependent killing and prolonged persistent effects
What does it mean to have a Type II pattern of activity of an antibiotic?
Time dependent killing and minimal persistent effects
What does it mean to have a Type III pattern of activity of an antibiotic?
Time dependent killing and moderate prolonged persistent effects
What is MIC?
Minimum inhibitory concentrations. The minimum amount of antibiotic in media that inhibits bacterial growth
What is the relevant PK/PD parameter for Type I patterns of activity?
24h-AUC/MIC or Peak/MIC
What is the relevant PK/PD parameter for Type II patterns of activity?
T>MIC
What is the relevant PK/PD parameter for Type I patterns of activity?
24h-AUC/MIC
In a clinical situation, how would you optimize the therapy of an Antibiotic with a Type I (Aminoglycosides) pattern of activity?
Give as large a dose as possible to increase the peak (can also dose more often to increase 24h-AUC)
In a clinical situation, how would you optimize the therapy of an Antibiotic with a Type III (Vancomycin) pattern of activity?
More frequent dosing or prolonged therapy to maintain concentrations as high as possible
What is the reason we have Nomograms?
To estimate complex patient specific parameters based on more easily measured values
Why do Nomogram recommendations often fail?
Inadvertently did not follow, specific patient parameters do not align
When choosing between a High-Dose extended interval and Conventional dosing regimen for a patient on Aminoglycosides, what factors would help you make your decision?
