| Adverse effects of nonsteroidal anti-inflammatory drugs |
Introduction
Information regarding toxicity associated with NSAIDs is evolving, and remains somewhat unclear. None of the NSAIDs are risk-free, and this should be discussed with the patient. Generally, the toxicity profile for selective COX-2 inhibitors is similar to that of preferentially selective and nonselective NSAIDs. The main exception is gastrointestinal toxicity (see below); however, all NSAIDs can cause serious ulcers. The elderly are more at risk of NSAID-related adverse effects and the need for NSAID therapy should be assessed carefully.
For a summary of adverse effects of NSAIDs, see Table 13.2
.
Gastrointestinal toxicity
In the stomach, prostaglandins generated by both COX-1 and COX-2 may play a role in protection against, and healing of, ulcers. Prostaglandin E2 and prostacyclin are particularly important in this regard. NSAIDs increase the incidence of gastric erosions and the risk of upper gastrointestinal complications (bleeds, perforation). The relative risk of a serious gastrointestinal adverse event varies between NSAIDs and is also dose-related. Highly selective COX-2 inhibitors reduce, but do not eliminate, gastrointestinal toxicity. There is less convincing evidence of benefit in terms of reduced serious upper gastrointestinal complications with the preferentially selective COX-2 inhibitors (eg celecoxib, meloxicam) over nonselective NSAIDs (eg ibuprofen). The concomitant use of low-dose aspirin eliminates the upper gastrointestinal safety advantage of selective COX-2 inhibitors.
NSAIDs with shorter plasma half-lives (eg ibuprofen) appear to be less gastrotoxic than those with long half-lives (eg piroxicam)
Patient risk factors for increased gastrointestinal toxicity include age over 65 years, history of peptic ulcer, concomitant use of corticosteroids, antiplatelet drugs or anticoagulants, cigarette smoking, alcoholism and prolonged use of high-dose NSAIDs. Helicobacter pylori infection combined with NSAID use increases the risk of ulcer disease 60-fold. If treatment with an NSAID cannot be avoided, proton pump inhibitors may be necessary. Although misoprostol has been shown to reduce the risk of gastrointestinal complications in this setting, it causes diarrhoea, abdominal pain, and loose stools in 10% to 15% of patients at therapeutic doses, and so has limited clinical usefulness.
Cardiovascular toxicity
The selective COX-2 inhibitor rofecoxib was withdrawn worldwide in September 2004 because of an increase in myocardial infarction and stroke during its use. There is evidence that cardiovascular risk is a more general property of NSAIDs other than aspirin. It is therefore recommended to use the lowest possible dose of any NSAID for the shortest possible duration. Fish oil can be used as an NSAID-sparing drug, and has the added benefit of reducing cardiovascular risk
Other cardiovascular risks should be closely monitored and managed actively in patients taking NSAIDs. See Cardiovascular disease risk reduction in the Cardiovascular guidelines for further information.
Low-dose aspirin may reduce the increased cardiovascular risk associated with NSAIDs, but will increase gastrointestinal adverse effects. However, patients requiring low-dose aspirin for cardiovascular protection should continue to take it regardless of their need for NSAIDs.
Some NSAIDs, such as ibuprofen, can interfere with the effect of low-dose aspirin on platelets, and separation in time of dose is suggested. Diclofenac does not have this effect.
Renal toxicity
All NSAIDs can cause renal impairment. Maintenance of renal function is dependent on prostaglandins generated by COX-2; therefore, renal toxicity is not less with COX-2–selective inhibitors. Adverse effects on renal function are particularly problematic when NSAIDs are used perioperatively in older and sicker patients, and in patients with pre-existing renal impairment. Other risk factors include congestive heart failure, cirrhosis, a salt-reduced diet and co-administration of diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, cyclosporin or aspirin. Patients at risk should be closely monitored if treatment with NSAIDs is unavoidable.
Other toxicity
NSAIDs can also cause oedema, hypertension and congestive heart failure. Some drugs have specific problems; for example, indomethacin can cause headache, confusion and drowsiness.
| System | Adverse effects |
| cardiovascular | rise in blood pressure, fluid retention, myocardial infarction |
| neurological | headaches, confusion, hallucinations, depersonalisation reactions, depression, tremor, aseptic meningitis, tinnitus, vertigo, neuropathy, toxic amblyopia, transient transparent corneal deposits |
| gastrointestinal | nausea, vomiting, dyspepsia, diarrhoea, constipation, gastric mucosal irritation, superficial erosions, peptic ulceration, oesophagitis and strictures, faecal blood loss, major gastrointestinal haemorrhage, penetrating ulcers, small bowel erosions |
| haematological | anaemia, bone marrow depression, decreased platelet aggregation |
| hepatic | hepatotoxicity, fulminant hepatic failure |
| renal | glomerulopathy, interstitial nephritis, changes in renal blood flow leading to a fall in glomerular filtration rate, alterations in tubular function, reduction in diuretic-induced natriuresis, inhibition of renin release, oedema |
| other | precipitation of asthma in patients with nasal polyps, skin rashes |
Comments
Post a Comment