Diii: Describe the effects of obesity on drug pharmacology and give examples of drugs to illustrate
Definitions
- Obesity = BMI ≥ 30 kg/m2
- Drug administration based on TBW
- Obese: TBW >> LBW > IBW
- Also, morbidly obese excluded from clinical trials ∴limited appropriate dosing data
Absorption
- ↑gastric emptying rate = ↑absorption
- Difficult IV access
- Difficult IM administration = unreliable absorption
- ↓subcutaneous blood supply = ↓subcutaneous absorption
- ↓FRC = ↑uptake volatiles
Distribution
- ↑body fat = ↑Vd lipophilic drugs
- Dose lipid soluble (midaz) on actual BW
- Dose polar drugs (roc) on IBW
- = ↑accumulation esp with prolonged infusions in ICU
- ↑blood vol & CO → requires ↑loading dose for therapeutic effect
- PPB → by ↑lipid content → ↑lipid binding to protein
- ∴ drugs with high PPB (warfarin, phenytoin) affected/displaced
- ↑TBW = ↑Vd hydrophilic drugs (gentamicin)
Metabolism
- ↑plasma + tissue esterases → ↑clearance (remi)
- ↑pseudocholinesterase → ↑clearance (sux)
*** Sux requires TBW dosing for good/fast effect
- Fatty liver → ↓metabolism (haloperidol)
- ↑HBF 2° ↑CO = ↑clearance of HER drugs (i.e. PPF)
- ↑Ph II enzyme activity = ↑clearance (paracetamol)
Elimination
- ↑Vd lipophilic drugs = ↑t ½
- ↑CO = ↑GFR = ↑renal clearance of drugs in patients with normal kidney function
- ↓renal function → requires dose adjustment g. diabetic nephropathy
- ↓biliary clearance 2° bile stasis
Overall
- Difficult to calculate LBM/fat body mass
- Dosing challenging → easy to over/under dose
- Monitoring of drug levels & kidney function v. important