Formula sheets, the key method steps for every topic and 6 practice problems, with full solutions at the back.
Macrolides such as clarithromycin act by:
A patient with severe chronic hyponatraemia receives hypertonic saline. Why is the rate of correction strictly limited?
A dose of 500 mg is needed from a 5% (w/v) solution. What volume V contains this dose?
The prescription is 4350 units of a drug that comes as 5000 units/mL. Draw up the dose in the 1 mL syringe: what volume V do you give?
Practice exercise (made-up values, not clinical guidance). A 70 kg patient is to be loaded intravenously with phenytoin sodium to reach a phenytoin level of 15 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.
Practice exercise (made-up values, not clinical guidance). A 55-year-old woman weighs 91 kg and has a serum creatinine of 3.3 mg/dL (292 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 gentamicin regimen is 80 mg every 8 h for a creatinine clearance of 120 mL/min. Keeping the dose, the interval is lengthened in proportion to the fall in clearance. Find the new dosing interval τ. Round to one decimal place.
Answer: D · Binding the 50S ribosomal subunit to inhibit protein synthesis
Macrolides bind the 50S subunit of the bacterial ribosome and block protein synthesis. Fluoroquinolones inhibit DNA gyrase and beta-lactams the cell wall.
Answer: C · Raising sodium too fast can cause osmotic demyelination in the brain
In chronic hyponatraemia the brain adapts to low osmolality. Correcting sodium too rapidly shrinks brain cells and can cause osmotic demyelination (central pontine myelinolysis), so sodium is checked often.
Answer: V = 10 mL
Solution strengths: a percentage strength is grams per 100 mL, so 1% = 1 g/100 mL = 10 mg/mL. A ratio strength 1:1000 means 1 g in 1000 mL = 1 mg/mL; 1:10 000 is 0.1 mg/mL. For a dilution the amount of drug stays the same: C₁·V₁ = C₂·V₂.
Answer: V = 0.87 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.
On this 1 mL syringe every small line is 0.01 mL.
Answer: LD = 798.9 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.
In practice the dose is rounded to a convenient amount.
Answer: τ = 34.7 h
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.
In practice the interval is rounded to a convenient value such as 12, 24, 36 or 48 h.
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