List briefly ways in which clinical illness can change the pharmacokinetics and pharmacodynamics of antibiotic therapy.
There are many reasons for variable antibiotic pharmacology in ICU patients. Critical illness affects drug absorption, distribution and clearance via changes in fluid compartments, organ · function and plasma protein concentrations.
The question specifically refers to the effects of critical illness, not genetic polymorphisms, drug interactions etc. The answer required a list. It should have been comprehensive but without too much detail.
a) Changed pharmacokinetics
i) Absorption - unpredictable oral bioavailability due to diarrhoea. ileus and potentially slowed IMI absorption due to impaired peripheral blood flow.
ii) Distribution - volume of distribution commonly increased by increased total body water. Decreased protein binding may lead to shortened T and increased free drug eg. ceftriaxone.
iii) Elimination: metabolism, biotransfonnation and excretion.
Metabolism - may be slowed by acute hepatic impainnent or reduced hepatic blood flow.
Excretion - Nonrenal clearance (eg. hepatic) affected by bilary obstruction, renal clearance impaired by renal failure and variably restored by dialysis (eg. some detail on the effects on aminoglycoside dosing were expected).
b) Pharmacodynarnics refers to the effects of the drug. Effects on organ systems may be both toxic and therapeutic. There is obviously a close interplay with kinetics. The ways that critical illness influences the pharmacodynamics of antibiotics therefore may include:
i) Antibacterial effect potentially reduced by increased Vo. impaired tissue
blood flow etc or increased by failure to excrete.
ii) Renal - more susceptible to renal failure because of impaired renal blood flow, dehydration (eg.aminoglycosides, amphotericin).
iii) Cardiovascular - more susceptible to cardiovascular toxicity eg. bradycardia with vancomycin bolus.
iv) CNS more susceptible to cerebral toxicity of high dose penicillins
The list provided above, through marvellously comprehensive, is difficult for a tired trainee to recall in a pinch. I will adjust it to include fewer words.
A more detailed answer is reproduced here from Question 10 from the second paper of 2015
Roberts, Jason A., and Jeffrey Lipman. "Pharmacokinetic issues for antibiotics in the critically ill patient." Critical care medicine 37.3 (2009): 840-851.
Mehrotra, Rina, Raffaele De Gaudio, and Mark Palazzo. "Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness." Intensive care medicine 30.12 (2004): 2145-2156.