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Nombre de messages : 640
Date d'inscription : 09/03/2007

MessageSujet: THE CINOIDS, THE PERFECT ANALGESIC?   Ven 15 Jan - 21:28

The heart of the matter

Friday, January 15, 2010


Chronic arthritis is a very common problem, that affects many and many more of us as we age. Osteoarthritis is almost synonymous with aging. Of course, some are affected earlier, while others have more severe forms of arthritis, including rheumatoid arthritis. When we suffer all these pains, we wish we had a perfect analgesic.
From centuries ago, we found aspirin, which help many and was good while it lasted. But alas, it had the habit of causing gastric upsets, gastritis and worse still, gastric bleeding. Some of these side effects were dose related. If only we had something stronger? But aspirin was cardiac friendly. It protects the heart against heart attacks. From aspirin, we moved on to the non-steroidal anti-inflammatory drugs ( commonly called NSAID ). Well these drugs were a significant improvement on aspirin. They were more potent. But they too suffered from gastro-toxicity and they may also be cardiac unfriendly, being associated with a higher then usual incidence of heart attacks. Mainly because of the gastrotoxicity of aspirin and the NSAIDs, researchers were looking for potent analgesics without gastrotoxicity and if possible, cardiac friendly.

After much research, they found that drugs which inhibited the COX2 receptors may do some of these. The COX2 came on the scene. They were good analgesics, with only minimal gastrotoxicity ( so were well tolerated ), but the first agent approved ( rofecoxib ) when used widely, was found to be associated with an increase incidence of heart attacks. we now know that COX2 inhibitors were good for analgesia, well tolerated, but may affect your heart, some more then others.

The search continues. Over the weekend, I came across this paper describing a new group of analgesics codenamed the " CINODS ". These are a group of agents derived from the NSAIDs which were nitic oxide releasing ( NO derivatives of NSAIDs ). They were suppose to have the analgesic effects of NSAID, without gastric-toxicity, and lowers blood pressure, thereby lowering cardiac side effects. The first paper was published in the American Journal of Cardiology by Dr White WB et al. The paper is entitled, "Effects of the cyclooxygenase inhibiting nitric oxide donator naproxcinod versus naproxen on systemic blood pressure in patients with osteoarthritis. Am J Cardiol. 2009;104:840-845".This is an interesting groud breaking paper on a new class of drugs which could help patients with chronic pains. Of course we have heard much about the Nobel prize winning molecule, nitric oxide. How it helps the body do almost all good things since it have anti-oxidant properties. Looks like in this context, the analgesic part is the NSAID and the gastro, and cardiacfriendly part is the NO derivative.
I look forward to reading more about the CINODS. I just thought that I should introduce this new group of drugs to you all. If it works out as it is touted in this article, then perhaps we are nearer the perfect analgesic. Only time can tell.
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Nombre de messages : 515
Date d'inscription : 15/05/2008

MessageSujet: Re: THE CINOIDS, THE PERFECT ANALGESIC?   Ven 15 Jan - 22:36

question intéressante posée par un professionnel de la santé ,de nationalité Malaysienne à priori...un début de réponse avec le "label" FDA

a t il accés à la conclusion de WHITE :Am J Cardiol. 2009?

les derniers paragraphes
"Meta-analyses of traditional NSAIDs from the early
1990s suggested that NSAIDs could increase mean arterial
pressure by an average of 5 to 6 mm Hg in patients with
hypertension.15,16 The impact of these relatively small differences
(i.e., #5 mm Hg) in systolic BP in patient populations
with hypertension and vascular diseases has been
demonstrated in epidemiologic and large prospective clinical
trials.17–19 Differences of 3 to 4 mm Hg in systolic BP
control in an older population of patients with hypertension
with vascular diseases randomly assigned to 2 antihypertensive
treatment groups (amlodipine vs valsartan) resulted in a
significant relative increase in cardiac events of #40% in the
less well controlled group (valsartan recipients) during the first
6 months of the trial.19 The present study demonstrated that
naproxcinod was less likely to destabilize the control of
systolic BP compared to naproxen (Figure 3) and behaved
in a similar fashion to placebo in the entire study group as
well as in patients treated with antihypertensive therapies
involving blockade of the RAS.
This has important implications,
because most patients with hypertension are treated
with #1 of these agents in modern-day clinical practice.20

In conclusion, we would infer that the hypertensive burden
induced by traditional NSAIDs in patients with osteoarthritis
and hypertension could be reduced by an NO-donating
agent such as naproxcinod "
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