update December 08, 2014
Aspirin, paracetamol, other NSAIDs, and codeine in periodic conservative analgesic use have not been reported to cause hypoglycemia eg a few gm a day solo or in combination in well adults- despite deliberate overdose of these being notorious for causing fatal bleeding or liver failure with hypoglycemia, or respiratory failure.
But increasingly tramadol is incriminated in dangerous hypoglycemia: Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain JAMA Intern Med.December Tramadol is an increasingly widely used weak opioid analgesic , associated with adverse events of hypoglycemia. Analysis in United Kingdom Clinical Practice of treatnent with tramadol or codeine for noncancer pain between 1998 and 2012 included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol associated with increased risk of hospitalization for hypoglycemia in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). Conclusions tramadol (in contrst to codeine), TRIPLED risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.
update 4 March 2013 BAN DICLOFENAC? four years on, another call comes for the virtual banning of diclofenac, from no less than the Canadian Medical Association Journal , based on a new metanalysis of NSAID risks by University Toronto’s McGettigan and Henry .
As this column has long pointed out, diclofenac is apparently still the only NSAID that can kill suddenly without warning. There are many far safer alternatives eg naproxen, ibrufen; and no compelling clinical evidence or reason to use it let alone cox2 inhibitors except false beliefs and heavy marketing.
So as this columnist concluded in 2009, it is blatant fraud, negligence and potential indefensible homicide to continue recommending let alone using diclofenac simply for profiteering.
21June 2009 It is 4 months since this column last addressed nonsteroidal anti-inflammatory drugs NSAIDs.
A new study (from USA, UK and Canada – Ray 2009) of NSAIDs claims that in those with ischemic heart disease, the popular NSAIDS -diclofenac, ibuprofen or rofecoxib(Vioxx) – increased serious heart disease/ death by about 50-67% compared to nonusers; whereas naproxen over some 111000 patient years of use gives no significant risk or benefit.
A new study from Denmark (Fosbol 2009) this year looked at a million healthy individuals with no hospital admissions or selected therapy. Compared to no NSAID use, ibruprofen and naproxen gave no added risk of death/ myocardial infarction; diclofenac gave 67% increased risks, and the two coxibs (rofecoxib Vioxx; celecoxib Celebrex) increased risk 100%.
So we are led to believe that naproxen or ibuprofen is the NSAID mild-to-moderate analgesic of choice. Naturally the American Colleges and academia – who represent the Disease Industry, not patients- recommend yet other potentially toxic drugs- like the magical proton pump inhibitors- to counteract the adverse NSAIDS..
But is this just a myopic view beloved of big pharma, to promote their snake oils.?
Another new study from Denmark (Gislason 2009) of 110 000 patients after admission for heart failure in the 12 years 1994-2005, showed that 57% died; 9000 (8%) were rehospitalized with acute heart attack and 40 000 (38%) were rehospitalized with heart failure. Thus heart failure in a well-nourished population has a poor prognosis. In 36 000 who had used NSAIDs compared to non-users, risk of death was doubled on diclofenac; increased~67% on (rofe-or cele)coxibs; and was significantly increased 22-31% by all other NSAIDs including naproxen and ibruprofen.
It is common cause after 20 years that injected diclofenac is the only NSAID that can unpredictably cause sudden death. So it’s administration risks culpable homicide when it is totally unwarranted. No cases of sudden death from any oral NSAID including aspirin appear on Medline, apart perhaps from the risk of hyperacute asthma (Asamoto 1999).
But what of gastrointestinal bleeding risks of NSAIDS? a 2007 study in Japan (Yajima) scoped all orthopaedic patients who took NSAIDs for more than 4 wks: oral diclofenac increased risk of erosive gastric lesions sixfold. A new review from Seattle (Schlansky 2009) refers to Helicobacter synergism in all NSAID use.
WHAT IS THE NEED FOR NSAIDS? The Wikipedia entry on NSAIDs sums it up: it has almost four times as much text on the numerous adverse effects of NSAIDs as on their uses- in fact the article does not discuss the advantages of NSAIDS as analgesics; in fact it states plainly that alone just “their gastrointestinal effects are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States”.
All designer drugs are dangerous in overdose. Without overdose, paracetamol has no risk – and the Wikipedia entry thereon is balanced and highly favourable even for infants. We know well that paracetamol- a fatal liver toxin in overdose- should not be marketed without a built-in simple liver (and antineuritic) protective of eg (carbo-or N-acetyl-)cysteine, alphalipoic acid and vitamin BCo. But the Disease – Big Pharma Industry is not interested in prevention- Only Disease Pays. And Regulators, lobbyists and legislators protect their source of work and income- the Drug Industry.
Fish oil (EPA+DHA) is probably the most beneficial NSAID supplement we have (- perhaps ahead of other front-runners like vitamins C, D, magnesium and CoQ10-) halving all sudden deaths, and reducing by at least a third all major chronic degenerative diseases from CVD to diabetes, arthritis, learning, depression, behaviour disorders. Industry wont pay for head-on comparative trials. But the trial evidence suggests that fish oil and oral EDTA have better risk-benefit than aspirin and other antiplatelet agents, NSAIDs and warfarin.
We know that for moderate trauma and small – medium (even knee) joint pain/ contusions, self-massage with any natural NSAID like arnica or wintergreen is all that is needed, combined if necessary orally with up to 3 to 4gm paracetamol /day +- if needed a little codeine. Prior 2002 found no significant difference in pain relief between paracetamol and naproxen in tension headache.
For more serious pain, short of strong opioids, there is in fact no overall trial evidence that weak opioids or NSAIDs are better than eg hypnotherapy, or acupuncture, or judicious paracetamol; to which latter if necessary a little codeine can be added as step-up analgesia. The latter agents have none of the deadly risk of NSAIDs. Amadio 1984 showed that of Peripherally Acting Analgesics: ” paracetamol at up to 4 g per day compares favorably in analgesic potency to aspirin and other NSAIDs, and should be considered the treatment of choice for mild-to-moderate pain”. Skovlund 1991 showed no significant difference between naproxen and paracetamol in postpartum uterine spasms.
Six RCTs – five in mostly European peoples and one in Hong Kong- found paracetamol equal to diclofenac (Voltaren) – March 1994 in arthritis; Brevik 1999 and Kubitzek 2003 in dental surgery; Hoogewijs 2000 and Woo 2006 after trauma; and Munishankar 2008 after Caesarian section. In a Cochrane analysis 2003, Towheed showed that in the one placebo-controlled RCT in osteoarthritis, paracetamol was clearly superior to placebo with a similar safety profile. And the general principle of therapy applies, that if required, combination of analgesics from different groups is better than single drug therapy. But given the many potentially fatal risks of the NSAIDs – compared to paracetamol, opioids and if indicated aspirin – there is no compelling reason to add NSAIDs for pain.
We know that it is negligent to initially sentence people with spontaneous mild-moderate head/neck/backache or tendonitis at the shoulder, elbow, knee etc to bedrest, NSAIDS, opioids or referral for xrays, scans or surgery. 95% will settle rapidly with reassurance, posture instruction and simple topicals and paracetamol analgesia. Otherwise most pain will disappear with firm reassurance with brief simple laying on of hands eg massage and traction with gentle rotational manipulation and instruction in auto-reinforcement – pressure point eg earlobe pressure, or acupuncture, or hypnosis. And most of the remainder resolve quickly with simple targeted injection with a little local anaesthetic plus depot steroid.
And we know that with judicious use, topical corticosteroid injection – never mind judicious brief systemic steroid (corticosteroid, calciferol, testosterone) has little or no risk and far greater target and multisystemic benefit than NSAIDs; and for chronic conditions, like fish oil at least address the underlying pathogenic mechanisms/causes- whereas NSAIDs and paracetamol ignore these.
Is drug-speeded resolution of inflammation essential and beneficial except for the drug vendor? A careful RCT by Bradley ea from Indiana University in 1992 observed that “joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee osteoarthritis”.
So why are synthetic NSAIDs and especially the Coxibs still used? Why do academics and Regulators still allow, promote them for routine use, other than to profit Big Pharma, and cause perhaps a quarter million deaths a year globally?