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
A nurse realises that a patient has been given the wrong dose of a medicine. What is the first action?
AComplete the incident report before anything else
BCorrect the chart so it shows the right dose
CAssess the patient for effects of the error
DWait to see whether the patient notices
2.PharmacologyHard
A patient develops a dry cough on an ACE inhibitor and is switched to losartan. Why is losartan less likely to cause cough?
AIt does not block the breakdown of bradykinin
BIt also acts as a bronchodilator
CIt blocks histamine receptors in the airways
DIt is excreted faster by the kidney
3.Dosage calculationsMedium
A dose of 80 mg is needed from a 2% (w/v) solution. What volume V contains this dose?
80 mg2% w/v
V = mL
4.Dosage calculationsHard
You must prepare 1000 mL of a 0.5% (w/v) solution from a 10% (w/v) stock solution. How much water W must be added to the stock?
C₁ = 10%C₂ = 0.5%V₂ = 1000 mL
W = mL
5.Clinical pharmacokineticsMedium
Practice exercise (made-up values, not clinical guidance). A 74 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.
74 kgVd = 0.7 L/kgC = 20 mg/LS = 0.92
LD = mg
6.Clinical pharmacokineticsHard
Practice exercise (made-up values, not clinical guidance). A patient's gentamicin half-life is 3.5 h. The target is a peak of 6 mg/L and a trough of 1 mg/L. Assuming rapid IV doses and first-order elimination, what dosing interval τ lets the level fall from the peak to the trough? Round to one decimal place.
t½ = 3.5 hCpeak = 6 mg/LCtrough = 1 mg/L
τ = h
3Solutions
1.Pharmacology
Answer: C · Assess the patient for effects of the error
Why this is the answer
The first priority is to assess and monitor the patient, then inform the prescriber so treatment can be given if needed. The error is documented factually and reported through the incident system.
Answer
C · Assess the patient for effects of the error
2.Pharmacology
Answer: A · It does not block the breakdown of bradykinin
Why this is the answer
ACE (kininase II) breaks down bradykinin, so ACE inhibitors raise bradykinin, which can cause cough and angioedema. ARBs block the angiotensin II receptor without affecting bradykinin breakdown.
Answer
A · It does not block the breakdown of bradykinin
3.Dosage calculations
Answer: V = 4 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.
Concentration
2% = 20 mg/mL
Volume
V = 80/20 = 4 mL
Answer
V = 4 mL
4.Dosage calculations
Answer: W = 950 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.
Volume of stock
V₁ = 0.5·1000/10 = 50 mL
Water to add
W = 1000 − 50 = 950 mL
Answer
W = 950 mL
5.Clinical pharmacokinetics
Answer: LD = 1126 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 = 0.7·74 = 51.8 L
Amount of active drug needed
Vd·C = 51.8·20 = 1036 mg
Loading dose
LD = 1036/(0.92·1) = 1126 mg
Answer
LD = 1126 mg
In practice the dose is rounded to a convenient amount.
6.Clinical pharmacokinetics
Answer: τ = 9 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.
Rate constant
k = 0.693/3.5 = 0.198 h⁻¹
Dosing interval
τ = ln(6/1)/0.198 = 1.792/0.198 = 9.047 ≈ 9 h
Answer
τ = 9 h
In practice the interval is rounded to a convenient value such as 8, 12, 24 or 36 h, and the levels are checked again.