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 Fournier, Suissa, eaJAMA 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?



  1. Why use paracetamol/acetaminophen? It’s liver toxic to an equal degree that NSAIDS are cardiotoxic. Curcumin and omega 3 oils are very effective natural remedies.

  2. thanks Fred,
    agreed with reservations. This review of 21 June focused on the even higher risks of NSAIDs. See the subsequent columns (search paracetamol) pointing out options to paracetamolsuch as you suggest. Where do 40 years of evidence support that chronic paracetamol in prudent dose- especially with some simple protectants- is liver-or -kidney toxic long term?

  3. Pingback: INDEX « Healthspanlife – the Official Life! Blog

  4. Pingback: THE FRAUD OF BIG PHARMA MODERN CHRONIC DRUGS « Healthspanlife – the Official Life! Blog

  5. the difference between paracetamol and traditional NSAIDs is that it has no anti-inflammatory properties. Paracetamol is very good in children to reduce fever and mild pain. In chronic inflammation e.g. rheumatoid arthritis or a surgical post-OP trauma associated with inflammation patients will need this anti-inflammatory effects of traditional NSAIDs. Among traditional NSAIDs there are a lot of differences (that is the reason why we have so many different ones!) from different elimination time, different COX1/COX2 inhibition ratios and slightly different mechanisms of action leading to different efficacy and side effect profiles. You will have to take at least 1 g (=1000 mg) paracetamol to achieve comparable analgesia of 75 mg diclofenac – so it is obvious that there are differences in potency. Paracetamol is the right choice for people at high risk (gastrointestinal bleeding) with a liver in good shape.
    Patients with severe or chronic pain often take a more potent drug to get relief – that is true for the Danish study where the use of more and less potent drugs was compared – one should not compare seriously ill patients taking diclofenac with younger people taking less potent drugs to treat headache or dysmenorrhea (differences in prescription behaviour). If there are side-effects in a patient a good physician will think about a reduction in dose because high doses of drugs will cause more adverse events, but that is something that was found by Paracelsus, and he was a clever guy. My message is: 1 think about what you really need 2 assessment of risks 3choice of the drug and if there are side-effects 4 try to reduce the dose and 5 switch to another drug. This will take time!

  6. thanks Gerd,
    as http://en.wikipedia.org/wiki/Paracetamol discusses, paracetamol does indeed have some nonsteroidal antiinflammatory properties. But unlike the traditional NSAIDs, it has never been reported in recommended dose to assoicate with increased heart failure or gastrointestinal bleeding or hypertension , given always the absence of obvious liver & kidney impairment.
    So the question remains: why prescribe NSAIDs when paracetamol in recommended dose, with or without lowdose codeine if indicated, avoids the life-threatening and unpredictable hazards of NSAIDs including COX inhibitors.
    The cardinal ule of medicine has always been: avoid potential harm, whether by commission or omission. so dont prescribe potentially lethal drugs- eg NSAIDs- unless severe pain justifies it, or milder analgesia has been tried. In infants it seems prudent to alternate paracetamol and mefanemic acid for common (eg viral, teething) pain and fever to keep individual drug exposure lower, with judicious tepid sponging if temperature still exceeds the ~39C threshold for concern about febrile convulsions, and with supplementary vitamins and some cysteine salt to protect both the lungs (as mucolytic) , liver and kidneys.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s