Adverse Reactions
After taking one of these drugs, if your patient suffers an adverse
event, you should consider completing an online 'yellow card'
(Fig 1).
The most common and significant side-effects are:
Other side-effects might occur, so you should always check a suitable reference source, such as the British National Formulary (BNF), before use of these drugs. In addition, each drug may be associated with certain specific side-effects, that are not applicable to other drugs, e.g. topical ketoprofen can be associated with photosensitivity, so patients should be advised to avoid sunlight whilst using it.
Yellow card
All adverse events should be reported for new drugs, which have a black triangle by them in the BNF, or for serious events [5].
For example, it is known that NSAIDs cause gastric ulcers, but if the ulcer is serious enough for the patient to require hospitalization, then that event should be reported.
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Gastric Gastric side-effects range in severity from mild nausea and discomfort, to bleeding gastric ulcers. The mucus layer prevents gastric acid attacking the stomach wall. Although PGE2 inhibits the secretion of gastric acid, it also encourages the formation of mucus in the stomach. Because NSAIDs reduce the production of PGE2, the normally effective barrier to gastric acid is reduced, which can result in the common side-effects of nausea and discomfort, with the potential for the development of gastric ulceration. A recent meta-analysis has shown that both the traditional NSAIDs and the COX-2 inhibitors increase the risk of gastric side-effects, though COX-2 inhibitors have a lesser effect [6]. A review paper estimated that the risk, for low-risk patients per 10 000 patient years for symptomatic ulcers, ranges from 30, for COX-2 inhibitors, to >100, for naproxen, [7]. This compares to a baseline of <10 for the general population who are not taking NSAIDs. The elderly are at greater risk [7]. The British National Formulary (BNF) gives examples of the drugs that carry the highest risk [8]:
The general advice is to always use the smallest dose possible for the shortest length of time. If a patient is at risk of gastric side-effects, then appropriate gastric protection should also be prescribed. However, NSAIDs and COX-2 inhibitors should be avoided in patients with a history of gastrointestinal disease. |
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Renal PGI2 and PGE2 are both associated with regulating renal blood flow [9]. In susceptible individuals, inhibiting the production of these two prostaglandins can result in renal impairment. However, this is reversible if the drugs are stopped. They can also be associated with fluid and electrolyte retention, which can worsen other conditions such as hypertension and heart failure. |
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Asthma Approximately 20% of adults with asthma have sensitivity to aspirin [10]. There is cross-reactivity with other NSAIDs and so these drugs should be avoided in sensitive patients. Careful history taking is needed because, sometimes, patients may not associate over-the-counter remedies that they have taken, such as ibuprofen, with their worsening asthma. |
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Platelet effects Aspirin has an irreversible effect on platelets. It reduces platelet aggregation and clot formation. Its effect lasts for approximately 7-10 days after stopping the drug, which is the remaining lifespan of the affected platelets, hence the need to stop it about a week before surgery. The risks of stopping or continuing aspirin preoperatively should be considered on an individual patient basis. There may also be a need to stop other NSAIDs a day or two preoperatively. You should check your local guidance. This effect is used in certain groups of patients to prevent occurrence of complications such as myocardial infarction, strokes and transient ischaemic attacks (TIA). It has become more apparent recently that NSAIDs antagonize the effect of aspirin, whereas COX-2 inhibitors appear not to. |
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Cardiovascular In 2004, it became apparent that the COX-2 inhibitors were associated with an increased risk of cardiovascular events, including death. Subsequent to this, researchers reviewed the safety data on all NSAIDs and found that most of these drugs carry a risk of cardiovascular side-effects, in particular thrombotic effects, such as myocardial infarction and stroke. A report by the MHRA in 2010 describes the cardiovascular risk associated with these drugs, not only in patients who are at high risk, but also all other patients [11]. This report shows that diclofenac carried a similar risk to the COX-2 inhibitors, as did high-dose ibuprofen. On the other hand low-dose ibuprofen and naproxen did not seem to carry the same risk. The current MHRA recommendations are that naproxen would be the drug of choice for patients at risk of cardiovascular events [12]. NSAIDs are also associated with an increase in blood pressure, and should therefore be used with caution in hypertensive patients. |