PK calculations Flashcards
Digoxin mechanism of action and therapeutic range?
Increase CF, Decrease AV conduction (POSITIVE INOTROPE). Increases amount of calcium in cardiomyocytes.
target = 0.8-2microgram/L
toxicity > 2.5microgram/L
Theophylline Target
Clearance increased in?
10-20mg/L
Smoking
Theophylline Target neonates
50% metabolised to caffeine. 5-10microgram/L
Gentamicin info, side effects, therapeutic ranges
aminoglycoside. Low therapeutic index causing nephro + ototoxicity
Target peak = 5-8mg/L multiple or 20mg/L for once daily
Target trough < 1mg/L
PEAK =/ measured 1 hour post IV/IM should not exceed 12mg/L
TROUGH = immediately before dose should not exceed 2mg/L
If trough too high - increase dose interval
Lithium, how it works, target concentrations. Signs of toxicity
Substitute for sodium or potassium in the CNS
0.4-1mmol/L optimum prophylaxis
0.8-1.2mmol/L for acute mania
TOXICITY > 1.5mmol/L = N+D+V, CNS deficits, tremor
Lithium model , concentration measurements and drug interactions
2-compartment model. Before morning dose and ideally 12 hours after last evening dose. Steady state in 3-5 days.
ACE increase Lithium levels, thiazide increase levels through impact on sodium levels. Theophylline and caffeine decreases
Designing a Lithium dose regimen
- Estimate CrCL (ml/min)
- Estimate Lithium Clearance (L/h)
- Choose Lithium concentration within the range (e.g. 5mmol/L)
- DR (mg/h) = CL x Cssav / F.s.m
- Daily dose (mg) = CL x 0.5 (target conc) x 24 / F.s.m
s and m convert dose of lithium salt from mg to dose of Li in mmol
Checking a Lithium dose regimen
- Estimate CrCL (ml/min)
- Estimate Lithium Clearance (L/h)
- Predict average SS conc and compare with target
Predicted = DR/CL = F.s.m.Dose (mg)/Lithium Clearance x 24
Factors to consider when interpreting serum concentration
Poor control, toxicity
Is the time the sample is taken a valid comparison with target range?
Is the sample likely to represent steady state?
Has the patient adhered to regimen?
Beware of on admission samples
Is the result consistent with prescribed/reported dosage regimens
Designing a gentamicin dose regimen
- Target peak>12mg/L
trough < 0.5mg/L - How often?
dosage interval must be 4-5 intervals, choose practical 24, 36, 48 hourly - Dose (mg) = Target C (mg/L) x V (L)
- Confirm safety. Predict SS peak and trough then check these are within the target range.
Designing a vancomycin dose regimen
1. Loading dose Target Cpeak = 20mg/L Dose = Ctarget x V (round to nearest 250mg) 2. Maintenance Dose Css target = 20mg/L DR (mg/L) = Ctarget x CL (L/h) Daily dose (mg/day) = Ctarget x CL (L/h) x 24
vancomycin how to administer:
- Continuous infusion
- Intermittent infusion
- daily dose then either continuous or 2x 12hr infusions
- Daily dose into 1,2 or 3. Aim to maintain trough >10mg/L.
* EACH DOSE INFUSED AT 500mg/hr and NO FASTER*
vancomycin toxicity
> 20mg/L
7 days duration
rate >500mg/hr - red man syndrome caused by histamine release. Occurs 4-10mins after start of infusion
2 compartment model
e.g. digoxin/lithium
Compartment 1 - drug first diffuses into blood, liver, kidney
Compartment 2 - poorly perfused tissues
Distribution into 2nd compartment continues until the free conc in the 2nd compartment is equal to the free conc in the peripheral compartment.
diffuses back into compartment 1 for elimination
considerations for 2 compartment model when measuring concentrations
High C before distribution misleading (not actually dangerous). After IV digoxin, clinicians wait 4-6 hours before taking serum concentration.
Plasma samples obtained less than 6 hours after oral digoxin or 12 hours after oral IR lithium are of questionable value
