a) Outline the effect of critical illness on enteral drug absorption
b) List the reasons for altered drug clearance in the critically ill.
a) Outline the effect of critical illness on enteral drug absorption
• Multiple factors may alter gastrointestinal mucosal absorption including mucosal oedema, disordered gastrointestinal motility and disordered mucosal blood flow
• Gastric emptying / gut motility affected by drugs (opioids. Anticholinergics, antacids, inotropes), enteral nutrition, brain or spinal injury, diabetes
• Incomplete oral medication disintegration or dissolution
• Changes in pH
b) List the reasons for altered drug clearance in the critically ill.
Liver function
Reduced clearance
With hepatic dysfunction present in more than half the critically ill patients, drug clearance may be reduced because of :
a. Lower hepatic blood flow
b. Decreased hepatocellular enzyme activity c. Lower bile flow
d. Administration of other drugs competing for enzymes
Increased clearance
Hepatic enzyme induction by certain drugs may increase clearance of others
Renal function
Reduced clearance
Compromised kidney function may be secondary to reduced perfusion, intrinsic damage secondary to ischaemia or drug toxicity and immunologic injury
A decrease in GFR would increase the half-life of medications that are renally cleared and may result in drug or metabolite accumulation
Increased clearance
Increased cardiac output in early sepsis increases GFR and increased drug clearance Burns, use of diuretics and hypertonic saline also result in increased GFR and potentially increase clearance
Protein binding changes
Three major proteins affecting drug protein binding – albumin, alpha 1 acid glycoprotein and lipoproteins
Reduced clearance
Some proteins (eg alpha 1-acid glycoprotein binding morphine) are increased in critically ill resulting in reduced clearance
Increased clearance
Albumin is reduced so there will be a higher concentration of free drug for drugs normally bound to albumin resulting in increased clearance
Protein binding affected by other factors including accumulation of endogenous binding
inhibitors, qualitative changes on binding sites, competition for binding by other substances, pH changes
a) in short, critical illness decreases drug absorption by the following mechanisms:
b) critical illness may reduce drug clearance by the following mechanisms:
Boucher, Bradley A., G. Christopher Wood, and Joseph M. Swanson. "Pharmacokinetic changes in critical illness." Critical care clinics 22.2 (2006): 255-271.