NSAIDs Pharmacology
Introduction
NSAIDs are non-steroidal anti-inflammatory drugs – important medicines widely used in the treatment of pain, antithrombosis and inflammation. Here, we review the fundamental details about NSAIDs pharmacology you need to know.
There are three primary indications of NSAIDs:
- Anti-inflammatory effect
- Analgesia – predominantly mild-to-moderate pain
- Antithrombosis – seen with low-dose aspirin, for example
There are many different types and classes of NSAID. Below, we list some of the most common classes and examples for your review.
| Class | Drug |
|---|---|
| Salicylates | Aspirin Diflunisal |
| Propionic acid derivatives | Ibuprofen Naproxen Flurbiprofen Ketoprofen |
| Acetic acid derivatives | Indomethacin Ketorolac Diclofenac Sulindac |
| Enolic acid derivatives | Piroxicam Meloxicam |
| Anthranilic acid derivatives | Mefenamic acid |
| COX-2 inhibitors | Celecoxib |
With these indications and classification in mind, let’s turn our attention to how NSAIDs work – their mechanism of action.
How do NSAIDs Work
At the most fundamental level, NSAIDs work by inhibiting the cyclooxygenase, or COX, enzyme. The COX enzyme is used to produce pro-inflammatory mediators – known as prostaglandins and thromboxanes – from arachidonic acid.
There are three isoforms of the COX enzyme, but only the first two are clinically significant:
- COX-1– a constitutive form of the enzyme that stimulates prostaglandin synthesis to preserve the functional integrity of the stomach lining; to ensure that renal perfusion is maintained; and to inhibit thrombus formation at the vascular endothelium.
- COX-2– an inducible form of the enzyme that is expressed as a product of inflammatory stimuli. In other words, stimulation of COX-2 leads to both pain and inflammation.
Therefore, the clinical effects of NSAIDs are mediated via COX-2 inhibition, whereas COX-1 inhibition is linked to their adverse effect profile (see below).
NSAIDs act via reversible inhibition of these enzymes, except aspirin, which acts as a ireversible inhibitor of these enzymes.
NSAIDs reduce fever via a different means – namely, by reducing hypothalamic prostaglandin synthesis that otherwise leads to elevated prostaglandin E2 levels.
Side Effects
Given NSAIDs pharmacology, it is perhaps unsurprising that they are associated with a wide range of potential adverse effects.
These include:
- Cardiovascular – NSAIDs are, depending on the NSAID in question, linked to an increased risk of myocardial infarction, stroke and other thromboembolic effects. For example – ibuprofen has the lowest risk, whereas celecoxib is associated with a much higher risk. Aspirin is an exception. Low dose aspirin has antiplatelet effects.
- Gastrointestinal– bleeding, ulceration, dyspepsia, nausea and diarrhea. Food can decrease the risk of these effects. NSAIDs directly irritate the gastrointestinal tract. Again, it depends on the NSAID. Drugs such as ibuprofen and diclofenac have a lower risk of GI effects compared to piroxicam, ketoprofen and indomethacin.
- Renal – NSAIDs damage the kidney and can contribute to chronic kidney disease (CKD). Ordinarily, prostaglandins dilate renal afferent arterioles, maintaining normal GFR. NSAIDs, then, lead to unopposed constriction of this arteriole – decreasing GFR. This can lead to sodium and fluid retention, whilst also increasing blood pressure – worsening established heart failure.
Other adverse effects of NSAIDs include hypersensitivity reactions and photosensitivity.
Clinical Pharmacology
When we talk about NSAIDs pharmacology, there are various clinical factors to consider – some of which we’ve touched upon. These include:
- NSAIDs are not recommended during pregnancy; the risk being highest in the third trimester where NSAIDs can cause premature closure of the fetal ductus arteriosus. NSAIDs also carry a higher risk of miscarriage.
- Taking an NSAID alongside an ACE inhibitor and diuretic constitutes what is referred to as the “triple whammy effect”, whereby the risk of renal failure increases substantially.
- Aspirin is taken at low doses to impart its antiplatelet effect.
- NSAIDs increase the seizure risk associated with fluoroquinolone drugs.
- Due to their gastrointestinal adverse effect profile, NSAIDs should be used cautiously in patients with established inflammatory bowel disease.
- NSAIDs should be avoided in patients with severe renal impairment, heart failure, liver failure, or in whom NSAIDs may precipitate a hypersensitivity reaction.
- Corticosteroids increase the risk of NSAID-associated ulcers; that SSRIs and venlafaxine increase the risk of NSAID-linked bleeding; and that the bleeding risk of warfarin is enhanced when taken with NSAIDs.
- NSAIDs reduce the therapeutic effects of antihypertensive drugs.
- NSAIDs inhibit the elimination of drugs that depend on renal elimination, such as lithium and methotrexate.
- NSAIDs should be taken with food to reduce GI adverse effects.
The pharmacology of NSAIDs is important; informing the clinical details you need to know to answer NAPLEX questions in your upcoming pharmacy exam. Here, we’ve put together the fundamental details you must know.
To test your knowledge of the clinical practice of NSAIDs, become a registered member of NAPLEX Study Guide today. There, you receive instant access to all the learning tools you need to pass your next pharmacy test.
