GI Drug Absorption in Critical Illness

OVERVIEW

  • multi-factorial determinants influence the bioavailability of drugs
  • governed by factors altering transport of substances across cell membranes (diffusion, active transport, ultrafiltration)
  • Fick’s Law of diffusion plays important role (net diffusion = change in pressure x area x solubility / distance x (square root of molecular weight))

(1) BLOOD FLOW

  • in critically ill patient blood is often shunted away from the GI tract (increased sympathetic tone) -> decreased absorption

(2) SURFACE AREA

  • may be decreased from resection post surgery

(3) PRESENCE OF BINDING OR CHELATING AGENTS

  • in the presence of overdose binding agents (activated charcoal) or chelating agents (desferrioxamine in iron overdose) may be used therapeutically to abate toxicity.

(4) pH

  • may become altered in critical illness -> increased secretion of gastric acid -> decreased absorption of drugs that become more ionized with a lower pH

(5) ALTERED GI MOTILITY

  • ileus, diarrhoea, nausea and vomiting -> decrease bioavailability of drugs

(6) PERMEABILITY

  • sepsis and SIRS can result in increased gastrointestinal permeability -> increased interstitial deposition -> ileus

(7) CONCENTRATION GRADIENT

(8) SOLUBILITY OF DRUG

  • may be influenced by pH

(9) DISTANCE TO DIFFUSE

  • may be increased with increased GI oedema

Introduction to ICU Series

CCC Pharmacology Series

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the  Clinician Educator Incubator programme, and a CICM First Part Examiner.

He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.

His one great achievement is being the father of three amazing children.

On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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