Several Potential Dangers Associated with NSAIDS

This last week, the NUNM grand rounds speaker, Catherine Clinton, ND, addressed the potential dangers in utilizing aspirin and NSAIDs as anti-inflammatory agents, especially in children. Aspirins and NSAIDS are ubiquitously used in primary care practice as reversible (Ibuprofen,naproxen) or irreversible (aspirin) COX-1 or Cox-2 inhibitors. COX enzymes are instrumental in regulating thromboxanes, prostaglandins, and platelet aggregation. Though, it is well documented and considered that there is a danger in using aspirin with children, due to the development of Reye’s syndrome, but other NSAIDs, such as naproxen, ibuprofen, and acetaminophen are commonly considered safe, and used relatively without question in children and adults.

NSAIDs and COX-1 and COX-2 Enzymes

Dr. Clinton points out that NSAIDs retain some of the same side effects as aspirin, and some others, and are not the safe, benign agents, as commonly marketed. NSAIDs can also induce asthma, as well as documented correlations with meningitis, and angioedema.^1,2 More commonly, it is documented that 2.5 million patients experience a nephrotic event from NSAID use annually.³ The proposed mechanism of action of renal complications in these cases has to do with COX-2 enzymes contributing to the regulation of intravascular volume, renin release, as well as sodium balance; inhibition may be causing edema and elevations in blood pressure. Likewise, COX-1 enzymes are important in the physiological protection of gastric mucosa – prostaglandins help protect the stomach lining from its acidic environment, maintains blood flow in the mucosa. Inhibition of the COX-1 enzymes is implicated in a marked increase in gastric and intestinal damage in NSAID users versus non-users.⁴ This can result in increased intestinal permeability, and inflammatory complications in the GI tract, including symptoms such as anemia, malabsorption, protein loss, ileal dysfunction, diarrhea, and mucosal ulceration.⁵ A recent study referred to by Dr. Clinton also touched on microbiome changes which occur due to NSAID use, which could also be a factor in small intestine damage.

Cardiovascular, Fertility, and Miscarriage Risks

Cardiovascular risks are listed on prescription NSAID labels include an elevated risk of heart attack and stroke even as early as the first week of NSAID use. The risks increase at higher doses. Perhaps the most interesting point discussed was that there is quite a significant decrease in fertility amongst women NSAID users. One study showed that only 6.3 percent of women on diclofenac ovulated compared with 100 percent of controls – 25%(naproxen), 27.3% (etoricoxib).⁶ There is also a question of miscarriage risk.⁷

Acetaminophen and ADHD

Acetaminophen has also been shown to be associated with ADHD symptoms when used during pregnancy.⁸ It has also been shown to deplete glutathione levels.⁹

Stay Tuned for More…

Dr. Clinton will be following up on this short news brief soon in a full-length article in NDNR, addressing these risk factors in depth, as well as others. Stay tuned.

Sources:

1. Rodríguez SC1, Olguín AM, Miralles CP, Viladrich PF. Characteristics of meningitis caused by Ibuprofen: report of 2 cases with recurrent episodes and review of the literature. Medicine (Baltimore). 2006 Jul;85(4):214-20.
2. Sánchez-Borges M1, Capriles-Hulett A, Caballero-Fonseca F. NSAID-induced urticaria and angioedema: a reappraisal of its clinical management. Am J Clin Dermatol. 2002;3(9):599-607.
3. Cheng HF1, Harris RC. Renal effects of non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Curr Pharm Des. 2005;11(14):1795-804.
4. Graham DY. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005 Jan;3(1):55-9.
5. G Sigthorsson, J Tibble, J Hayllar. Intestinal permeability and inflammation in patients on NSAIDs. Gut 1998;43:506–511
6. Salman, Sami. Non-steroidal anti-inflammatory drugs inhibit ovulation after just 10 days. EUROPEAN LEAGUE AGAINST RHEUMATISM. June 2015
7. Sharon Daniel, Gideon Koren, Eitan Lunenfeld, Natalya Bilenko, Ronit Ratzon, Amalia Levy. Fetal exposure to nonsteroidal anti-inflammatory drugs and spontaneous abortions. CMAJ, February 2014 DOI: 10.1503/cmaj.130605
8. PLoS One. 2014 Sep 24;9(9):e108210. Associations between acetaminophen use during pregnancy and ADHD symptoms measured at ages 7 and 11 years. Thompson JM, Waldie KE, Wall CR.
9. Dimova S, Hoet PH, Dinsdale D, Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol. 2005 Aug;37(8):1727-37.

Node Smith, associate editor for NDNR, is a fifth year naturopathic medical student at NUNM, where he has been instrumental in maintaining a firm connection to the philosophy and heritage of naturopathic medicine amongst the next generation of docs. He helped found the first multi-generational experiential retreat, which brings elders, alumni, and students together for a weekend campout where naturopathic medicine and medical philosophy are experienced in nature. Three years ago he helped found the non-profit, Association for Naturopathic ReVitalization (ANR), for which he serves as the board chairman. ANR has a mission to inspire health practitioners to embody the naturopathic principles through experiential education. Node also has a firm belief that the next era of naturopathic medicine will see a resurgence of in-patient facilities which use fasting, earthing, hydrotherapy and homeopathy to bring people back from chronic diseases of modern living; he is involved in numerous conversations and projects to bring about this vision.