COX II Inhibitors

CLASS

  • Selective COX-2 inhibitors

Types

  • celecoxib
  • parecoxib
  • rofecoxib
  • valdecoxib
  • also known as coxibs

MECHANISM OF ACTION

  • developed to try and inhibit prostacyclin synthesis by the COX-2 isoenzyme induced at sites of inflammation without affecting the action of the constitutively active COX-1 isoenzyme found in gastic mucosa, platelets & kidney.
  • have fewer GI side effects
  • no impact on platelet function
  • COX-2 is constitutively active in kidneys -> still produce the renal toxicities

INDICATIONS

  1. anti-inflammatory – OA, RA, familial adenomatous polyposis, gout, ankylosing spondylitis
  2. anti-pyretic
  3. analgesic – dysmenorrhoea, acute musculoskeletal pain, post op pain

ADVERSE EFFECTS

  • no effect on platelet aggregation, bleeding time & post-op blood loss.
  • bone healing attenuated
  • interactions: aspirin -> increases GI haemorrhage, warfarin -> increases INR, K+ sparring diuretics -> increase K+
  • ? increase in CVA & IHD events
  • increase in incidence of CHF
  • hypertension
  • liver dysfunction can take place
  • same renal risks as non-selective NSAIDs

PHARMACOKINETICS

  • Absorption – highly lipophilic
  • Distribution
  • Metabolism – hepatic
  • Elimination –

EVIDENCE

  • -> COX 2 inhibitors and NSAIDS have similar effects on renal function
  • -> COX 2 inhibitors don’t produce bronchospasm in aspirin induced respiratory disease
  • -> COX 2 inhibitors -> no effect of platelet function
  • -> COX 2 inhibitors -> same peptic ulcer rate as placebo (decreased compared to NSAIDS)
  • -> COX 2 inhibitors -> don’t give in patients with lots of vascular risk factors
  • -> parocoxib & valdecoxib DO NOT increase risk of cardiovascular disease after non-cardiac surgery
  • -> COX 2 inhibitors and NSAIDS are associated with the same rates of adverse CVS effects (MI)
  • -> short-term use of COX 2 inhibitors do not affect bone healing after spinal fusion
  • -> VIGOR study looked @ rofecoxib vs naproxen and found significant increase in MI in rofecoxib group (patients on low-dose aspirin were excluded)

PROS AND CONS

Advantages

  • less GI side-effects (dyspepsia, ulcers and GI bleeding) – although this point has been challenged
  • NICE recommendation of COX 2 use in individuals with high risk of GIH (2000)
  • opioid sparing actions

Disadvantages

  • increase in vascular morbidity (CVA, MI, IHD) – rofecoxib (VIGOR study)
  • more expensive
  • same adverse effect on platelets
  • contra-indicated in peri-operative patient with the following: previous MI or CVA, cardiac or vascular surgery, patient at high risk of vascular disease undergoing major surgery (MEDSAFE statement, 2005)
  • Na+ and K+ retention (effect on renal PG synthesis)
  • nephrotoxic
  • increased risk of thrombosis (reduced platelet prostacyclin without change in thromboxane)
  • hypertension
  • pregnancy -> premature closure of ductus arteriosus -> intrauterine foetal death
  • interacts with warfarin (increased risk of bleeding and increased INR)

CCC 700 6

Critical Care

Compendium

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 and 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 two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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