Div: Describe calculations of loading dose & maintenance dose for IV infusion. What factors may affect these values in critically ill?
Calculations
- Maintenance dose (mg/hr) = DESIRED SS [ ] (mg/L) x CLEARANCE (L/hr)
- Loading dose (mg) = DESIRED SS [ ] (mg/L) x VD (L)
Steady State Concentration
- SS = administered rate equals rate of elimination
Maintenance Dose Continuous Infusion
- Maintenance dose (mg/hr) = desired SS [ ] x Clearance
- SS occurs when dose rate = clearance rate
- Takes 3 – 5 half lives
Maintenance Dose Regular Dosing
- Achieves SS in steps
- But again, in 5 half lives
This is ok if drug is going to have some long T effect, but for pain/AF you need immediate drug action & ∴ a LOADING DOSE
Loading Dose
- LD rapidly achieves SS sooner
LD = DESIRED SS [ ] x Vd
In an infusion SS & therapeutic effect achieved quicker
→ Same effect, but takes longer without load
NB: giving drug PO → all loading/maintenance dose need to be divided by OBA unless OBA is 100%
Effect of Critical Illness on Ld/Maintenance Dose
Factor
VD
Effect CI
↑VD (fluid overload)
↓VD (hypovolaemia)
Impact LD/Maintenance
↑LD
↑Maintenance dose/dose rate
Factor
Clearance
Effect CI
↓renal clearance
↑renal clearance
↓hepatic clearance
↑hepatic clearance
Impact LD/Maintenance
↓maint dose/dose rate
Loading dose no change
↑maint dose/dose rate
No change LD
↓maint dose/dose rate
↓LD PO because less 1st pass
No change LD IV
↑maint dose/dose rate
IV load no change
PO load ↑ because ↑1st pass
Factor
Bioavailability
Effect CI
↓PPB/competition for PPB
↓gut absorption
Impact LD/Maintenance
↑free drug
↑clearance
Give IV unreliable
Drug Examples
- Theophylline – 300mg tabs = 37.5mg/hr = infusion rate
- Phenobarbitone – huge VD → ↑LD for this VD would be lethal
- Morphine – poor OBA → not given orally
- Gentamicin – rapid renal clearance
- ↓renal function =
- No ∆ LD
- ↓dose/interval of maintenance dose
- ↓renal function =