Div: Outline alterations to drug response due to critical illness
Absorption
PO
Delayed Absorption
- Delayed gastric emptying/ileus
- Multifactorial drugs, Sx
- ↓gut blood flow
- Intestinal wall oedema
Impaired Absorption
- Accelerated transit time 2° diarrhoea/drugs
- Bacterial overgrowth
- Brush border loss 2° ischaemia
- ↓gut SA 2° ischaemia/Sx
Impaired 1st Pass Metabolism
- ↓1st pass = ↑OBA
IM/SC
- Unreliable
- ↓peripheral perfusion
- Delayed absorption i.e. IM SUXAMETHONIUM
Inhaled
- ↓FRC, ↓V/Q MATCHING
- Commonly, drugs which affect PVR given via inhaled route in critically ill → direct delivery to effect site
Distribution
PPB
- ↓[protein] = ↑free drug (should be matched by ↑clearance, but not if concurrent renal F)
Vd
- Usually ↑due to fluid overload
- May ↓with hypervolaemic shock
- Significantly affecting loading dose, esp. for RSI i.e. PPF
Metabolism
Hepatic Metabolism
- ↑ = ↓t ½
- Fever → ↑metabolic rate
- Enzyme induction by other drugs
- ↓ = ↑t ½
- ↓hepatic BF
- Hepatic injury
- Hypothermia → ↓metabolic rate
Plasma Esterases
- ↓plasma esterases =↓metabolism sux, remifentanil
Hoffman Degradation
- ↓with hypothermia
Tissue Metabolism
- ↓2° ↓tissue BF
Elimination
Renal Clearance
- ↓renal clearance
- ↓RBF
- ↓GFR
- ↓ nephrons
- ↓active & passive transport
- ATN
NB: some ↑ clearance → young, multi-trauma
Biliary Clearance
- ↓biliary clearance
- Biliary stasis
- ↓gut transit & recirculation
Dynamics
- CVS – susceptible to cardiotoxicity; altered circulation time → delayed onset
- Renal – susceptible to impairment due to dehydration & ↓RBF
- Nervous system – susceptible to CNS toxicity due to encephalopathy
- Haem – susceptible to anticoagulation due to sepsis DIC, extracorporeal circuits