Nonsteroidal anti-inflammatory drugs (NSAIDs)
- non-selective COX inhibitors
Types – weak organic acids
- Salicylic acids – aspirin
- Acetic acids – diclofenac, ketorolac, indomethacin
- Propionic acids – ibuprofen, naproxen
- Fenamates – mefenamic acid
- Oxicams – tenoxicam, piroxicam
- Pyrazolones – phenylbutazone
MECHANISM OF ACTION
- cyclooxygenase (COX) is an enzyme that catalyses the synthesis of prostaglandins from arachidonic acid.
- prostaglandins mediate a large number of body processes including:
- secretion of a protective gastri layer
- maintenance of renal perfusion
- platelet aggregation
- NSAIDs block the action of COX -> reducing production -> results:
- decreased gastric mucosa -> ulceration
- decreased renal perfusion
- inhibition of biosynthesis of prostaglandins
- inhibition of chemotaxis
- down regulation of interleukin-1 production
- interference with Ca2+ mediated intracellular events
- decrease sensitivity of vessels to bradykinin & histamine
- affect lymphokine production from T lymphocytes
- reverse vasodilation
- inhibit platelet aggregation
- GI ulceration, haemorrhage
- hepatic dysfunction -> transaminitis
- renal dysfunction from excretion of hypertonic metabolites -> papillary necrosis
- inhibition of platelet aggregation
- prolongation of bleeding time
- hyperglycaemia -> glycosuria
- Absorption – most are well absorbed, absorption not affected by food
- Distribution – highly protein bound (>98%), all are found in joints after repeated dosing
- Metabolism – hepatic
- Elimination – renal most important, biliary -> enterohepatic circulation
-> effective analgesics of similar efficacy for acute pain
-> NSAIDs + paracetamol = more analgesia
-> with careful selection of patients NSAID induced renal impairment is low
-> aspirin + some NSAIDs increase perioperative bleeding after tonsillectomy except in paediatrics
-> NSAIDs reduce opioid consumption
-> NSAIDs increase perioperative blood loss
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. 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 three amazing children.
On Twitter, he is @precordialthump.