NSAIDs

Introduction

Non-steroid anti-inflammatory drugs, or in short NSAIDs, are commonly used for their

Anti-inflammatory,
Analgesic (pain killer) and
Antipyretic (anti-fever) effects.

They can be classified into

Non-selective (traditional), e.g. diclofenac, ibuprofen, mefenamic acid and naproxen.
COX-2 selective, e.g. celecoxib and etoricoxib.

NOTE: Different from NSAIDs, paracetamol does not have anti-inflammatory actions.

Efficacy

According to British National Formulary,

Though differences in anti-inflammatory activity between NSAIDs are small, but there is considerable variation in individual response and tolerance to these drugs. About 60% of patients will respond to any of the NSAIDs; of the others, those who do not respond to one may well respond to another.
Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory may not be achieved (or may not be clinically accessible) for up to 3 weeks.

NOTE: The concomitant use of two or more NSAIDs was associated with an excess risk of adverse effects such as hepatic injury, acute renal failure and gastrointestinal bleeding.

Gastrointestinal Toxicity

To minimize the risk of gastrointestinal adverse effects, patients are often being counselled to take NSAIDs with or after food.

Sometimes, gastroprotection with proton pump inhibitors is considered.
However, there is a study to show that quicker onset of action of pain relief could be expected if we take the NSAIDs with empty stomach.

The odds ratio of peptic ulcer with different NSAIDs is not the same.

To illustrate, in a 1994 study, of the non-selective NSAIDs, it showed that ibuprofen and diclofenac considered lowest risk, and ketoprofen and azapropazone considered highest with the risk of peptic ulcer bleeding.
The risk also increases with higher doses of NSAIDs.

It is generally accepted that the inhibition of cyclo-oxygenase-1 (COX-1) plays a role in the adverse gastrointestinal effects of the NSAIDs.

The selective inhibition of the other isoform, COX-2, by NSAIDs such as celecoxib and etoricoxib, may cause less gastrotoxicity than the non-selective inhibition of the traditional NSAIDs.
A 2003 study shows that the incidence of endoscopically detected ulcers was significantly lower with etoricoxib 120 mg than with ibuprofen 2400 mg.

Patients should seek medical attention if they are having black stools or dark coffee-coloured vomit.

Cardiovascular Events

COX-2 inhibitors cause fewer GI side effects than non-selective NSAIDs, but are associated with an increased risk of cardiovascular events (e.g. myocardial infarction and stroke).

Renal Impairment

All NSAIDs including COX-2 inhibitors can cause renal impairment.

The term "triple whammy" refers to the concurrent use of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin-II receptor blocker (ARB), with a diuretic and a non-steroidal anti-inflammatory drug (NSAID). All these are known to have the potential to decrease renal function.

The concurrent use of a triple therapy combination was associated with an increased rate of acute kidney injury by 31%, with the highest risk observed in the first 30 days of use.
Hence, ideally, oral NSAIDs should be avoided when managing long-term pain condition in patients taking ACE inhibitors/ARBs and diuretics.

Few practical suggestions should include

Paracetamol as an alternative or weak opioids for strong pain.
Topical analgesia such as diclofenac or ketoprofen gel
Try to use NSAIDs at the lowest dose for shortest duration (if the use is much needed)

NSAID Allergy

If one develops allergic reaction to a NSAID, patients are often warned to avoid taking other NSAIDs.

But, there are many patients who are allergic to one particular NSAIDs but okay with another.

In general, since bronchospasm and urticaria are most commonly caused by COX-1 inhibition, rather than an immunologic mechanism, most immediate reactions are assumed to be caused by this mechanism.

Desensitization may be considered for both IgE-mediated reactions and for nonimmunologic anaphylactic reactions related to NSAIDs.
Alternatively, a COX-2 selective agent may be considered, since it is unlikely to trigger COX-1-related bronchospasm and differs chemically from the triggering agent.

Acute Necrotising Encephalopathy of Childhood

Use of rectal NSAID should be avoided for fever management in children.

Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mefenamic acid, is associated with significant increase in the mortality rate of influenza encephalopathy.

Potential Harms of NSAID Use During Pregnancy

In general, NSAIDs should be avoided in pregnancy and must be avoided after 30 weeks' gestation because of the risk of

Miscarriage in early pregnancy; however, evidence of this effect is conflicting.
Oligohydramnios via effects on foetal renal function when an NSAID is used after 20 weeks' gestation.
Premature closure of the ductus arteriosus, and delayed labour and birth, when an NSAID is used after 30 weeks' gestation.
Peripartum haemorrhage, especially with complicated deliveries, due to effects on maternal platelet function.

However, there continues to be a role for NSAID use during pregnancy in some circumstances (e.g. ankylosing spondylitis, rheumatoid arthritis).

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