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Pain killers and NSAIDS

Category: Medicines

Type

Involuntary

Introduction and description

Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are drugs with analgesic – pain killing -  and antipyretic (fever-reducing) effects. 

The term "nonsteroidal" is used to distinguish these drugs from steroids, which, among a broad range of other effects, have a similar pain killing and anti-inflammatory action.

NSAIDs exclude all those drugs based on the opium poppy and classified as narcotics such as codeine or morphine.

"According to my pal Tony the heading means "irreplaceable" and above the label at the bottom, are the Doctor's words - 'Dolores, are you ready for me to molest you '- but I think he's joking don't you? - or maybe he's not.  Anyway the product is an aspirin with caffeine."

What they do in detail

 Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), however the mechanism of aspirin, is irreversible inhibition.

COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid – see Linoleic acid.  It is thus extremely key in our metabolic processes.

  • COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid.
  • COX-2 is an enzyme expressed in inflammation, and it is inhibition of COX-2 that produces the pain reducing effects of NSAIDs.

When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result.  This handy litle slide also shows the results of interfering with the prostaglandin cycle.  The effects are to the left, the functions to the right.  I think one pathological effect of imbalance has been missed and that is infertility, given that prostaglandins affect semen viability.

Paracetamol (acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.

 

Now here I quote:

Many aspects of the mechanism of action of NSAIDs remain unexplained, and for this reason further COX pathways are being investigated. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely and alternative explanation models are being explored.

So they don't know how they work in detail, nor have they investigated the complete chain of cause and effects that these drugs have. 

Given that aspirin is now being prescribed by doctors to all patients with heart problems, this is, to say the least, a little worrying.

Side effects

NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. Most adverse effects are related to generalized inhibition of the major targets of NSAIDs: cyclooxygenases I and II.

These enzymes are not only involved in pain and inflammation pathogenesis but are also required in the gastrointestinal (GI) tract for mucosal protection and gut motility, and in the kidneys for functional integrity.

Thus, the mechanisms of NSAID toxicity are well understood, but the consequences are largely uncontrolled in clinical practice.

GI ulcers, including bleeding ulcers, may occur in several percent of all chronic unprotected, high-dose NSAID users.

Renal side effects may precipitate renal failure, resulting in acute dialysis and chronic retention. This includes sodium retention, resulting in arterial hypertension, heart failure, and atherosclerotic events.

Cardiovascular risk may be tripled by chronic high-dose NSAID use.

Off-target side effects include allergic reactions, drug-induced liver injury, and central nervous system effects.

Management of pain and inflammation must consider those risks and find alternative drugs or approaches to limit the negative impact of NSAIDs on mortality and morbidity.

Alternative drugs, low-dose/short-term use, but especially non-pharmacologic approaches, such as physiotherapy, exercise, neurophysiologic measures, and local therapies, need to be further utilized. The appalling equation "less pain-more deaths/morbidity" ultimately necessitates treatment optimization in the individual patient.  PMID:  25163793

Common skin side effects of systemic NSAIDs

One little reported side-effect of all these drugs is death. 

The following list provides figures for the number of deaths attributed to each of the products on the list below.  The figures were derived from eHealthme, whose results are based on US FDA reports.  Thus the statistics relate to the USA only, but give a good indicator:

  • Paracetemol - On Aug, 24, 2014: of the 69,428 people reported to have side effects when taking Acetaminophen , 1,772 people (2.55%) have Death
  • Aspirin - On Aug, 19, 2014: 160,999 people reported to have side effects when taking Aspirin. Among them, 3,623 people (2.25%) have Death
  • Diclofenac sodium -  On Aug, 13, 2014: 14,184 people reported to have side effects when taking Diclofenac sodium. Among them, 169 people (1.19%) have Death
  •  Ibuprofen - On Aug, 16, 2014: 57,899 people reported to have side effects when taking Ibuprofen. Among them, 881 people (1.52%) have Death
  •  Tylenol - On Aug, 23, 2014: 53,021 people reported to have side effects when taking Tylenol. Among them, 1,001 people (1.89%) have Death
  •  Ziconotide, also known as Prialt - On Aug, 11, 2014: 692 people reported to have side effects when taking Prialt. Among them, 12 people (1.73%) have Death
  • Rofecoxib  has now been withdrawn over safety concerns. It was approved by the Food and Drug Administration (FDA) on May 20, 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx.  "Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time".  On Aug, 3, 2014: 107,334 people reported to have side effects when taking Vioxx. Among them, 4,659 people (4.34%) have Death
  •  Naproxen - On Aug, 14, 2014: 20,449 people reported to have side effects when taking Naproxen. Among them, 298 people (1.46%) have Death
  •  Midol - On Aug, 24, 2014: 780 people reported to have side effects when taking Midol. Among them, 2 people (0.26%) have Death.
  • Indomethacin - On Aug, 16, 2014: 6,005 people reported to have side effects when taking Indomethacin. Among them, 100 people (1.67%) have Death
  •  Lortab - On Aug, 10, 2014: 15,744 people reported to have side effects when taking Lortab. Among them, 451 people (2.86%) have Death.
  •  Etodolac - On Aug, 26, 2014: 4,408 people reported to have side effects when taking Etodolac. Among them, 62 people (1.41%) have Death.
  •  Excedrin - On Aug, 20, 2014: 7,219 people reported to have side effects when taking Excedrin. Among them, 41 people (0.57%) have Death.

Source:  Wikipedia, derived from patient reports

Paracetemol

One major drug within this class is Paracetemol and this has quite a history of hallucinatory effects.  Paracetamol toxicity is caused by excessive use or overdose of the analgesic drug paracetamol (called acetaminophen in North America). Mainly causing liver injury, paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States and the United Kingdom it is the most common cause of acute liver failure. 

The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 4g. Higher doses lead to increasing risk of toxicity. In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity. Toxicity can also occur when multiple smaller doses within 24 hours exceeds these levels. 

In rare individuals, paracetamol toxicity can result from normal use. This may be due to individual ("idiosyncratic") differences in the expression and activity of certain enzymes in one of the metabolic pathways that handle paracetamol.

In England and Wales an estimated 41,200 cases of paracetamol poisoning occurred in 1989 to 1990, with a mortality of 0.40%. It is estimated that 150 to 200 deaths and 15 to 20 liver transplants occur as a result of poisoning each year in England and Wales.

Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, 2,600 hospitalizations, and 458 deaths due to acute liver failure per year. A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the USA found that paracetamol was the cause of 41% of all cases in adults, and 25% of cases in children.

How it works

Pain killers and NSAIDs provide no healing capability, they temporarily mask pain and, as we have seen, used regularly can result in damage to our system.  When damaged, a whole cascade of side effects then results in the hallucinations, near death or out of body experiences recorded.  Thus the principle causes of these hallucinations is likely to be

  • Extreme pain - the gastric pain or liver damage caused .  

References and further reading

  • Liver damage with non-narcotic analgesics - Prescott LF
  • Eur J Clin Pharmacol. 2014 Aug 28. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. - Wehling M.  Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg,  Germany

Observations

The following observations group the hallucinations and actually cover several thousand hallucinations that have been caused by these drugs.  All the figures shown come from the eHealthme web site derived from SEDA and FDA figures.  If you click the name, it will take you to the ehealthme webite where a comprehensive list of all side effects - not just hallucinations can be viewed

Observation identifiers

Observation name

No of observations

000546

Paracetemol

503

000547

Aspirin

889

000548

Diclofenac

103

000549

Ibuprofen

685

000550

Tylenol

279

000551

Ziconotide

38

000552

Rofecoxib

161

000553

Naproxen

145

000554

Midol

120

000555

Indomethacin

22

000556

Lortab

463

000557

Etodolac

31

000558

Excedrin

8

000559

Near death from pain killers

1

000560

Near death from pain killers

1

002258

Vicodin experience

1

 

TOTAL

3450

Related observations