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NSAIDS (Cox enzyme inhibitors) Anti-inflammatory drugs - WARNING!

Non steroidal Anti-inflammatory drugs (NSAIDS) are taken to relieve pain and inflammation - the better known NSAIDS are Aspirin (Beyer®), Ibuprofen (Motrin®, Advil®), naproxen (Aleve®) and Celebrex. Most NSAIDS accomplish this much appreciated feat by blocking both of the COX-1 and COX-2 enzymes, which would otherwise produce the PROinflammatory Series 2 prostaglandins (PG-2) . Another name for NSAIDS is COX inhibitors or coxibs for short. Celebrex® blocks only the COX-2 enzyme.

LOW DOSE aspirin is largely used as a prevention for CVD and heart attacks - but there is some evidence that concurrent use with other NSAIDS, which generally do not have this CVD prevention benefit, may inhibit aspirin's antiplatelet effect.

Use of Cox-1 inhibitor NSAIDs (e.g. Aleve and ibuprofens:Advil, Motrin) significantly increases risk of death

Unfortunately, when NSAIDs block the COX-1 enzyme the body loses some important functions provided by this enzyme - including:

✔  Maintaining the integrity of mucosal cells lining the stomach and intestines

✔  Promoting blood clotting

✔  Helping maintain kidney function.

The loss of such protective functions easily explains the unwanted side-effects of using COX-1 inhibiting NSAIDs -  in fact, extended use of COX-1 inhibiting NSAIDS can cause GI discomfort and stomach ulcers leading to internal bleeding. A 2000 analysis including data of 250,000 patients from 15 randomized clinical trials, found that, on average, one of 1220 patients who take NSAIDs for at least two months will die as a result of gastroduodenal complications. This presents a pretty significant risk of dying! --- In perspective, it is 1000 times more perilous than taking a single flight.

Number Needed To Kill Individual Drug Risk with NSAIDs Tramèr MR, Moore RA, Reynolds DJM, McQuay HJ (2000) Quantitative estimation of rare adverse events which follow a biological progression
– a new model applied to chronicNSAID use. Pain 85:169–182

And to hammer home this alarming risk  - comparing data published from pre-1997 to that from 1997-2008, mortality in patients suffering from an upper gastrointestinal bleed or perforation has fallen from 1 in 9 to 1 in 13 overall, but has actually increased from about 1 in 7 to 1 in 5 in those exposed to NSAIDs.

S.Straube et al, Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. 2009 Jun 5;BMC Gastroenterol. 9:41.

 

Selective COX-2 inhibitor NSAIDs

Newer NSAID drugs

In light of problems caused by inhibiting COX-1, newer NSAIDS selectively block only the Cox-2 enzyme.

-   Celebrex

-    Obscenely expensive Vioxx® was an attempt at suppressing COX-2, whilst preserving COX-1 - it failed - causing tens of thousands of deaths due to heart attack or stroke.

NOTE: unlike aspirin, COX-2 inhibitors are not effective for preventing strokes or heart-attacks in individuals at high risk for such.

Salicylates - promising anti-inflammatory drugs

Do not affect the Cox enzymes at all, but instead inhibit the master factor in inflammation called NF-kB - which is activated in response to stress, cytokines [E.g. TNF, IL-1b], free radicals, UV radiation, ionizing radiation, oxidized LDL, bacterial / viral infections, cocaiine);

Generic form called salsalate is better tolerated than sodium salicylate

Salicylates not only reduce inflammation, they also lower blood glucose - in 2013, researchers published results of stage 2 of a clinical trial called TINSAL-T2D (Targeting Inflammation using Salsalate in Type 2 Diabetes), which involved 286 participants who could not adequately control their blood sugar levels with edication.  48 weeks of treatment lowered HbA1C by 37% more than placebo group.

The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial.

Alternative, NATURAL, SELECTIVE COX-2 Inhibitors

-   Many phytonutrients contain selective COX-2 inhibitors - including, amongst many others:

✔  Polyphenols (thought to be anthocyanins) in cherries

✔  Curcumin in curries and yellow mustard (not brown or Dijon)

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