3. NSAIDs

NSAIDs are generally considered non-specific analgesic medications and these are commonly prescribed for inflammation-derived acute pain. This class of drugs acts mainly through the inhibition COX (cyclooxygenase) synthesis, this then leads to a decreased in the synthesis of prostaglandin [35]. Being widely diffused, NSAIDs are often used in combination with further on-going treatments, leading to final effects dependent on drug-drug interactions [1]. However, prescribers should take into account the intrinsic risk of NSAIDs' ADRs (Table 2).


Table 2. The intrinsic risk of ADRs associated with NSAIDs [7, 40].

Complications involving the gastrointestinal tract as a consequence of NSAID use are common, especially in combination with the presence of risk factors [36]. NSAIDs exert their effects through the inhibition of COX and the pharmacological inhibition of COX (both 1 and 2 isoenzymes) works to provide relief from the symptoms of inflammation and pain.

This NSAID-induced decrease in prostaglandin synthesis is responsible for side effects such as dyspepsia, abdominal pain, nausea, vomiting, heartburn, haemorrhage (NSAIDs could also lead to prolongation of bleeding time and a significantly increased risk of haemorrhage by altering vascular homeostasis), ulceration, perforation or obstruction [37].Therefore, COX-2 specific inhibitors, for example celecoxib, have a lower risk of causing gastrointestinal related ADRs [38].

NSAIDs are also a cause of renal complications. Acute renal failure is a possible consequence of NSAID use. While this is an intrinsic risk of NSAID medications, it is more likely to occur in geriatric patients and in patients using enzyme inhibitors (ACEIs) or angiotensin receptor II blockers [39]. NSAIDs are the class of medicines that are most commonly associated with hypersensitivity reactions. Because of this, it is generally not recommended to use NSAIDs even after having an unrelated hypersensitivity reaction or having positive allergy tests. NSAID-triggered hypersensitivity reactions can result in respiratory complications or in dermatological problems [40, 41].

Long-term NSAID use is often associated with cardiovascular complications such as strokes and myocardial infarctions, especially with COX-2 inhibitor therapy. This is an important factor to consider in patients with pre-existing cardiovascular diseases, where the use of NSAIDs could potentially worsen their condition, especially in combination with other drug treatments [42, 43]. Liver toxicity is also commonly associated with NSAID use, in particular nimesulide, making this medication particularly unsuitable for long-term applications in patients affected by chronic conditions [44].

Health care providers should also ensure that NSAIDs are prescribed properly and monitored closely considering the aforementioned ADRs; this can be done by precision treatment of patients.

Physicians should first consider prescribing the lowest effective dose of NSAIDs to those who have not found alleviation of pain after taking paracetamol. Patients who require NSAIDs have to be treated according to their gastrointestinal risk profile, because the use of NSAID is associated with increased ADRs of the entire GI tract, thus increasing mortality. Therefore, a gastro-protective pharmacologic agent such as misoprostol should be prescribed along with the NSAID even though it may not completely eradicate the risk of ADRs such as bleeding, the incidence of ulcer disease will be reduced [45].

Furthermore, physicians should be precise when evaluating patients for NSAID therapy especially in patients with existing cardiovascular conditions as the use of these medications could increase the risk of cardiovascular events occurring. Namely, celecoxib carries the highest risk of coronary artery events at high doses and thus one should consider an alternative like naproxen in place of its use [45].
