- 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.
- 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
- 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
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health, a Clinical Adjunct Associate Professor at Monash University, and the Chair of the Australian and New Zealand Intensive Care Society (ANZICS) Education Committee. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of LITFL.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of two amazing children.
On Twitter, he is @precordialthump.