Extremistan
Weight-based drug dosing for hydrophilic medications may produce excessive serum concentrations in obese patients so alternatives to total or actual body weight are sometimes recommended. Please cite the equation for ideal body weight (for a man or a woman)
45.5 + 2.3(every inch over 60 inches) (women) or
50 + 2.3 (every inch over 60) (men)
A drug is said to have _____ pharmacokinetics if the rate of elimination is estimated by percent per unit of time
Linear (regardless of the concentration, a percent of remaining drug is eliminated, e.g. half lives)
If a patient's total serum concentration of a drug is 100 mg/L and their free concentration is 8 mg/L, how protein bound is this drug?
About 92% protein bound
4-5 half lives (some sources say 3, so I'll accept 3-4 or 3-5 as well)
Renal dose adjustments for medications are commonly made using creatinine clearance as an estimate for renal function. Please tell me (or write on the board) the Cockcroft-gault equation for estimating CrCL.
What is (((140-age) x wt)/ (72 x serum creatinine) ) x 0.85 if female)
A patient with obesity may have increased drug elimination due to ________.
Increase renal size
A drug with _____ kinetics, may exhibit psuedo first order (or linear kinetics) until enzymes responsible for metabolism are saturated.
What is zero order or nonlinear kinetics
A patient had a phenytoin serum level of 10 mg/L on his regimen of 300 mg daily. The physician wanted a target serum concentration closer to 20 mg/L and the daily dose was doubled. Why is this a correct or incorrect approach?
What is incorrect and what is phenytoin has zero-order kinetics
Cmax after an initial bolus dose can be estimated using this equation.
C = Dose/Vd
Extremes of weight, diet (excessive protein intake or poor diet), frail elderly patients, unstable renal function, drug interactions
Neonates often have altered clearance. Please explain at least one reason neonates have clearance rates that are different than adults
What is reduced renal function, what is higher volume of distribution, what is differences in bioavailability, what is differences in CYP enzyme activity
If a patient's phenobarbital level, drawn at steady-state) is 10 mg/L, and he is taking 90 mg BID. How much do you need to increase the total daily dose to reach a serum level of 20 mg/L?
How much is 180 mg BID (or 360 mg TDD is also acceptable)
Typical goal phenytoin serum levels are 10-20 mg/L with an estimated fraction unbound of 0.1, thus goal free-phenytoin levels are 1-2 mg/L. If a patient has a fraction unbound of 0.2 and a total serum level of 20 mg/L, what is his free phenytoin level?
4 mg/L
If a patient's serum level is 15 mg/L after a bolus of 1000 mg and our target serum level is 20 mg/L. What incremental load (or mini-load) can be given to rapidly achieve the therapeutic concentration? Assume first order kinetics
About 335 mg (may vary slightly depending on how you rounded your decimal points) or if you solved via proportion, 333 mg.
About 110 mg q 12 hours
Age 3 weeks, weight 4 kg, Vd. 0.9L/kg, CL 0.004 L/kg/hr
C = 22 mg/L
A patient received a loading dose of phenobarbital of 15 mg/kg (patient 50 kg) and the serum level returned at 15 mg/L. Assume S of 0.9, F of 1. What additional dose can be given to rapidly increase her serum level to 20 mg/L?
250 mg (first calculate her patient specific Vd, then use the incremental load or mini load equation (VD)(Cdesired-Cactual)/S X F
Patient is elderly and should be initiated on a low dose (remember start low, go slow!). Recommend 2.5 mg qday.
If a patient's serum concentration (peak) is less than expected after one bolus dose, what does this imply?
Because C = Dose/Vd, if C is less than expected, it implies Vd is increased. Alternatives included improperly collected serum level (drawn during absorption period), Initial peaks are rarely impacted by clearance, so less likely to be affected by clearance
If a drug has a molecular weight of 40,000 daltons, a Vd of 0.9 L/kg, and is the Fu is 10%, would you expect the drug to be removed by dialysis?
No, drugs with high molecular weights, high Vds, and highly protein bound are generally poorly removed by dialysis
A 65 year old 70 kg female is taking phenobarbital 64.8 mg BID for prevention of seizures. Her serum level returns at 30 mg/L. She's been on this regimen for 10 years. Her seizures are well managed but she reports increasing fatigue. What is her patient-specific clearance and how does this compare to population estimates for phenobarbital?
0.18 L/hr or 0.16 L/hr (normal adult estimated clearance is 0.004 L/kg/hr or 0.28 L/hr in her case) Reduced clearance is often seen in the elderly and typical maintenance doses are reduced to 1.5 mg/kg/day (can be solved using CL = Dose/tau/ (Css)
If a patient is taking phenytoin sodium 200 mg qday, and her serum concentration is 7 mg/L, what is the recommended dose increase to achieve a target serum level of 10-20 mg/L?
50 mg/day (slide 17), note phenytoin follows zero order kinetics and concentrations cannot be expected to increase proportionally to an increase in dose (like drugs with first-order kinetics)
What's considered a lethal concentration of phenobarbital (in mg/L)?
100 mg/L, though patients can survive higher concentrations
A patient requires tobramycin for a psuedomonal infection of the lung. The MIC of the psuedomonas strain is 1 mcg/mL. The team would like to target a Cpeak 10x the MIC. What is your recommended initial dose if the patient is 63 kg. Assume Vd is 0.3 L/kg. Assume S and F of 1
189 mg or rounded to the nearest 20 mg - 200 mg.
Is amiodarone removed by dialysis? Justify your answer.
No, it's Vd is so large it looks like a typo