Cascade with GI Prostaglandin and Use of Topical NSAIDs vs Oral NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for their antiinflammatory, analgesic, and antipyretic effects. 1 NSAIDs generally work by blocking the production of prostaglandins (PGs) through the inhibition of two cyclooxygenase enzymes. 1 However, their use has been associated with potentially serious dose-dependent gastrointestinal (GI) complications such as upper GI bleeding. 2 GI complications resulting from NSAID use are among the most common drug side effects in the United States, due to the widespread use of NSAIDs. 2 Topical products were developed to provide well tolerated, effective targeted therapies, based on the drug’s pharmacokinetics and penetration to the site of action. 3

Topical therapies are delivered to the site of action, avoiding the first-pass metabolism of oral drugs. 3 Most importantly, topical NSAIDs were developed to reduce the risk of gastrointestinal (GI), cardiovascular (CV), and renal adverse events associated with oral NSAIDs. 3 This route possibly reduces gastrointestinal adverse reactions by maximizing local delivery and minimizing systemic toxicity. 5

The use of oral NSAIDS increase the risk of gastrointestinal (GI) complications. GI complications are generally thought to be mediated primarily through inhibition of mucosal cyclooxygenase-1 (COX-1) and resultant suppression of prostaglandin production. 2 Oral NSAIDS could inhibit PG-mediated effects on the gastrointestinal tract. This effect includes the inhibition of mucin production, HCO3 secretion, and mucosal proliferation. 1 COX-1 inhibition by the use of NSAIDs causes gastric hypermotility. 1 Gastric lesion that formed eventually because of increased mucosal permeability and myeloperoxidase activity comes up with this enhanced gastric hypermotility. 1

[email protected] In one study it was determined that GI adverse events associated with oral ibuprofen use make topical formulation a promising alternative for both human and veterinary medicine. 4 In another study with diclofenac, plasma levels after topical administration have been reported to fall within a range of 0.2% to 8% of those achieved after oral administration. 3 Thus, complications such as GI bleeding and gastric ulcerations associated with oral administration of NSAIDs as well as CV and renal toxicity, are less common following use of topical NSAIDs. 3

In addition, in a retrospective analysis of a rheumatoid arthritis patient database published in 2000, OTC ibuprofen and naproxen users had a relative risk for serious GI complications of approximately 3.5 compared with NSAID nonusers, and it is estimated that 1%–2% of continuous NSAID users experience a clinically significant upper GI event per year. 2 These findings represent a significant clinical concern, as patients taking NSAIDs experience a relative risk of upper GI bleeding and perforations of up to 4.7 compared with nonusers. 2

Prescription and OTC non-steroidal anti-inflammatory drugs (NSAIDs) are ubiquitous treatments for pain and inflammation; however, oral administration of these drugs may produce gastrointestinal (GI) side effects. 4 Transdermal (TD) administration of NSAIDs circumvents these adverse events by avoiding the GI tract and, presumably, achieves regional drug levels of therapeutic effect and thereby, fewer off-target complications. 4 Reduction of adverse drug reactions associated with the use of topical preparations of NSAIDs is being well considered to obtain high patient compliance and drug therapy efficacy. 5

References

1. Gunaydin C & Bilge S.S. Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level. Eurasian J Med 2018;50: 116-21.

2. Goldstein J.L & Cryer. B. Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies. Drug, Healthcare and Patient Safety 2015;7: 31-41.

3. Hagen M & Baker M. Skin penetration and tissue permeation after topical administration of diclofenac. Current Med Research and opinion, 33:9, 1623-1634.

4. Baranowski D.C etc. Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation. Journal of Pain Research 2018:11 2809-2819.

5. Khan M.R.U etc. Single Blind, Comparative Study of Ketoprofen Cream Vs Diclofenac and Piroxicam Cream in Management of Rheumatoid Arthritis Patients. International Journal of Pharma Science 2014:Vol 4, No 5: 697-701.