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Part 1 - dosing considerations -
“All drugs are controlled poisons”.
“Drugs don’t have dosages… ……patients have dosages….”.
Goldilocks Principle
Goldilocks principle states that something must fall
within certain margins, as opposed to reaching
extremes. When the effects of the principle are observed, it
is known as the Goldilocks effect.
Dosing objective: Hit the therapeutic window
> Too much = toxicity.> Right dose: eradicate the bacteria without injuring the patient.> Too little = ineffective.
Dosing our pts is problematicLack of experience/practice on part
of prescribers, nursing staff and pharmacists in dosing aminoglycosides & vancomycin.
Patients difficult to assess, remote to both prescriber & pharmacy staff.
Delay in lab results. We’re not 24/7.Inherently difficult population to
dose (elderly, bedridden, other potentially nephrotoxic medications).
The dose?Dosage based predominantly on:
Size of patientSite of infection
Severity of infectionResistance of organism
Hydration status of patient…and 163 other variables…
The interval?
Dosing interval based on:Clearance – the speed at
which the body eliminates the drug (predominantly
renal, with a small amount of clearance from the liver)
Younger patients who are otherwise healthy?
Think shorter dosing intervals (more frequent dosing,i.e., Q4H,Q6H, Q8H).
Elderly patients and patients with renal insufficiency?
Think longer dosing intervals (less frequent dosing, i.e., q12h, q24h, q48h, q72h)…
Quick review of dosing concepts…..
Dose?
Big patients = big doses
Little patients = little doses
Interval?Younger and otherwise healthy patients = more frequent dosing.
Older, elderly patients and patients with renal insufficiency =less frequent dosing.
Serum Creatinine – it’s just a number.Before you put the numbers in the calculator
think about the pt.
If your patient: - has a stable renal function SCr/UOP AND - is within the age range (18-65 years) AND - is reasonably well nourished/hydrated AND - doesn’t have renal disease (i.e., not diabetic, no diuretics, good urine output, etc.) The calculated answer may be reasonably close to actual clearance.
CrCl: which equation??
Simplified 4-variable MDRD study formula?
CKD-EPI equation?
Cockcroft-Gault based on: CG - Total Body Weight? CG - Ideal Body Weight? CG - Adjusted Body Weight? – use this one….
Fudge factor(s)?
→ If the reported SCr is < 1 mg/dL and the patient is: Is older than 65 years of age and/or Is sedentary/bedridden, paralysis and/or Has poor nutritional status and/or Has poor urine output
Fudge factor(s)→ Consider using “1 mg/dL” in your calculations and/or
→“Lowballing” the dose, i.e., - if the recommended peak level for the condition is 8-10 mcg/ml, consider using 6-8 mcg/ml in your calculations. - if the recommended trough level for the condition is <1 mcg/ml, consider using 0.3-0.5 mcg/ml in your calculations.
Why fudge the numbers?For patients:
- who are elderly (>65 years). - who have diminished muscle mass (bedridden, paralysis, malnourished, who are on diuretics, who are volume overloaded, etc.), the calculated CrCl tend to overestimate the actual clearance.