Pick the relation: C = C₀·e−kt, LD = Vd·C/(S·F), maintenance rate = CL·Css/(S·F), τ = ln(Cpeak/Ctrough)/k.
For kidney function, estimate CrCl with Cockcroft–Gault first, then scale the dose or the interval.
Check the result: levels fall by half every half-life, and steady state takes about five half-lives.
2Practice problems
1.PharmacologyMedium
How should a topical corticosteroid cream usually be applied?
AAs a thin layer to the affected area only, as directed
BUnder a tight plastic dressing every night without advice
COn broken, infected skin to speed healing
DAs a thick layer over the whole body
2.PharmacologyHard
A patient on stable warfarin is prescribed a course of metronidazole. What is the likely effect, and what should the nurse expect?
AThe INR stays the same, as these drugs do not interact
BMetronidazole replaces warfarin, so warfarin is stopped
CThe INR rises, so closer INR monitoring is needed
DThe INR falls, so the risk of clotting increases
3.Dosage calculationsMedium
A patient weighing 135 kg has a body surface area of 2.2 m². The prescription is 100 mg/m². Find the dose D in mg.
135 kgBSA = 2.2 m²100 mg/m²
D = mg
4.Dosage calculationsHard
The prescription is 2120 micrograms. The ampoule contains 4 mg/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
2120 mcg4 mg/mL
V = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). An 84 kg patient is to be loaded intravenously with phenytoin sodium to reach a phenytoin level of 20 mg/L. The volume of distribution is 0.7 L/kg and the salt factor is S = 0.92. Find the loading dose LD of phenytoin sodium in mg.
84 kgVd = 0.7 L/kgC = 20 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A 59-year-old woman weighs 86 kg and has a serum creatinine of 2.1 mg/dL (186 µmol/L). Estimate the creatinine clearance with Cockcroft–Gault: CrCl (mL/min) = (140 − age) × weight (kg)/(72 × SCr in mg/dL), × 0.85 for women. The usual vancomycin dose is 1000 mg every 12 h for a creatinine clearance of 100 mL/min. Keeping the interval, the dose is reduced in proportion to the creatinine clearance. Find the adjusted dose D. Round to the nearest whole number.
Answer: A · As a thin layer to the affected area only, as directed
Why this is the answer
Thin application to affected skin limits systemic absorption and skin atrophy. Occlusive dressings increase absorption and are used only when prescribed.
Answer
A · As a thin layer to the affected area only, as directed
2.Pharmacology
Answer: C · The INR rises, so closer INR monitoring is needed
Why this is the answer
Metronidazole inhibits the metabolism of warfarin (mainly via CYP2C9), so warfarin levels and the INR rise. The bleeding risk increases, and the INR is checked more often during and after the course.
Answer
C · The INR rises, so closer INR monitoring is needed
3.Dosage calculations
Answer: D = 220 mg
Body-surface-area dosing: many cytotoxic and some paediatric doses are prescribed per square metre of body surface area: dose (mg) = dose per m² × BSA (m²). The Mosteller formula estimates BSA = √(height (cm) × weight (kg)/3600).
Dose
D = 100·2.2 = 220 mg
Answer
D = 220 mg
4.Dosage calculations
Answer: V = 0.53 mL
Drawing up a dose: volume = (prescribed dose/stock strength) × stock volume. Convert to the same units first, then check that the volume fits the syringe and lands on one of its graduations.
Same units
4 mg/mL = 4000 mcg/mL
Volume
V = 2120/4000 = 0.53 mL
Answer
V = 0.53 mL
5.Clinical pharmacokinetics
Answer: LD = 1278 mg
Clearance and volume: at steady state the dosing rate equals the elimination rate, so the maintenance rate = CL × Css. A loading dose is LD = Vd × C/(S × F), with S the salt factor (fraction of active drug in the salt) and F the bioavailability (1 for IV). From two levels, k = ln(C₁/C₂)/Δt; for an IV bolus Vd = dose/C₀ and CL = k × Vd. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Volume of distribution
Vd = 0.7·84 = 58.8 L
Amount of active drug needed
Vd·C = 58.8·20 = 1176 mg
Loading dose
LD = 1176/(0.92·1) = 1278 mg
Answer
LD = 1278 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: D = 392 mg
Designing a regimen: with rapid IV doses the level falls from peak to trough during the interval, so τ = ln(Cpeak/Ctrough)/k and the dose that restores the peak is Vd × (Cpeak − Ctrough). The average steady-state level is Css,avg = S·F·dose/(CL·τ). An infusion rises as C = (R/CL)(1 − e−kt). For a drug cleared by the kidneys, the dose is scaled with the creatinine clearance. The numbers are for practice only; at the bedside always follow local protocols and have high-risk doses double-checked.
Creatinine clearance (Cockcroft–Gault)
CrCl = (140 − 59)·86/(72·2.1)·0.85 = 39.16 mL/min
Adjusted dose
D = 1000·39.16/100 = 391.6 ≈ 392 mg
Answer
D = 392 mg
In practice the dose is rounded to a convenient amount and checked against the product information.