NSAIDS Number 5 on the List of Top 10 Most Dangerous Drugs

Susanna Sisson's picture
NSAIDS drug risks and side effects

Non-steroidal anti-inflammatory drugs (NSAIDS) - Motrin, Bextra, Naproxen, Celebrex aspirin, Voltaren, Lodine, Indocin, Orudis, Toradol, Relafen, Daypro, Clinoril, Aleve or Naprosyn and others, are the most widely used drugs in the world. Most people experiencing mild to moderate pain, inflammation, cold and flu symptoms, menstrual pain or fever take NSAIDS and do so without really thinking of any dangers since most are available over the counter (OTC). The perception [4] is that they are innocuous, but that would be very far from the truth.

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All NSAIDs work by blocking hormone-like substances called prostaglandins, which are involved in pain and inflammation as well as many other bodily functions, including protecting the stomach lining from its own digestive fluids. Traditional NSAIDs block prostaglandins by inhibiting two enzymes – so-called COX-1, which plays a role in stomach protection, and COX-2, which is responsible for pain and inflammation. The newer celecoxib blocks only the COX-2 enzyme; for that reason it is less likely to cause damage to the stomach.

The side effects of NSAIDS are just not fully appreciated by the average consumer. [4] One research team led by Michael Wolfe et al (1999) helps put the problem into perspective for one such problem – gastrointestinal toxicity. According to conservative figures “…the annual number of hospitalizations in the United States for serious gastrointestinal complications is estimated to be more than 103,000. At an estimated cost of $15,000 – $20,000 per hospitalization, the annual direst costs of such complications exceed $2 Billion.” [1][4][14]

The emphasis of cost fails to recognize the more important mortality rate for patients hospitalized for NSAID-induced upper gastrointestinal bleeding which Wolfe estimates as about 5 to 10 percent.
The report further reports, “It has been estimated conservatively that 16,500 NSAID-related deaths occur among patients with rheumatoid arthritis or osteoarthritis every year in the United States. This figure is similar to Acquired Immune Deficiency Syndrome (AIDS) and considerably greater than the number of deaths from multiple myeloma, asthma, cervical cancer or Hodgkin’s disease.” [1] Yet as shocking as that figure is, the reality is that it is a very conservative number and included only deaths associated with NSAID prescriptions for rheumatoid arthritis and osteoarthritis. It did not take into account deaths from OTC NSAID products, and cardiotoxic influences of NSAIDs on mortality were not fully recognized at that time.

Side Effects of Aspirin and NSAIDS:
• Vomiting
• Nausea
• Ulcers
• Bleeding
• Constipation
• Diarrhea
• Reduced appetite
• Headache
• Dizziness
• Rash
• Drowsiness
• Allergic reaction
• Swelling of arms and legs due to fluid retention
• Kidney failure
• Liver failure
• Blood clots (DVT)
• Pulmonary Embolus (PE)
• Heart attack
• Stroke
• Death

New Warnings:
One source claims that nonsteroidal anti-inflammatory drugs (NSAIDs) may almost double the risk for venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE) according to an article published online September 24, 2014 in Rheumatology.

A study just published in the journal Rheumatology concludes that popular pain relievers called NSAIDs can raise the risk of developing blood clots in veins (venous thromboembolism or VTE) by 80 percent. Such clots can lead to life-threatening pulmonary embolisms (PE) in lungs. If a blood clot lodges in the lungs the risk of death within 30 days is 8 to 10 percent. [7][8]

NSAIDs have a previous history of causing life-threatening complications. Until ten years ago, when Vioxx (rofecoxib) was pulled off the market because it increased the likelihood of heart attacks or strokes, doctors had no idea that such pain relievers could trigger severe cardiovascular reactions. Since then, however, other studies have confirmed that NSAIDs increase the risk of blood clots (JAMA, Oct. 4, 2006).

Diagnosing deep vein thrombosis (a blood clot in a vein) can be tricky. Unlike a heart attack, symptoms can be subtle and harder to assess. The Center for Disease Control (CDC) estimates that anywhere from 300,000 to 600,000 people develop DVTs each year. Other experts put the numbers higher, closer to one million cases annually. If the clot lodges in a leg, the person may sense tightness, tenderness, swelling, redness or a feeling of heat in one leg. It the clot breaks loose and lodges in the lungs, symptoms can include shortness of breath, cough or generalized chest pain. These are medical emergencies and require immediate treatment.

In July 2015, The U.S. Food and Drug Administration (FDA) announced it is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke.

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Facts about NSAIDS:
• An estimated 60 million Americans regularly use NSAIDs, resulting in clinically significant upper GI complications in up to 2% of users (1.2 million cases).
• The American public seemed delighted. According to one survey, 23 million Americans use a nonprescription NSAID like ibuprofen or naproxen (Aleve) every day. [7]
• More than 80% of patients developing GI complications have no prior symptoms or warning signals.
• GI hemorrhages due to NSAID use result in up to 120,000 hospital admissions annually.
• Estimates are that more than 16,500 persons die from NSAID-related GI adverse events each year in the U.S. alone. [1]
• Risk of bleeding may be related to reactive oxidative stress (ROS). [12]
• NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
• The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
• The risk appears greater at higher doses.
• It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
• In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
• Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
• There is an increased risk of heart failure with NSAID use.
• In patients with or without Alzheimer’s disease who were on warfarin taking NSAIDs increased their risk of bleeding. [11]
• Concomitant use of diuretics and NSAIDs, a 2-fold increased risk of hospitalization for CHF [Congestive Heart Failure] was found compared with periods of diuretic used only.

Drug Interactions:
People taking medication for health problems such as blood pressure, seizures, arthritis (Methotrexate) psychiatric disorders (Lithium), warfarin, or other NSAIDS or aspirin should consult with their doctor about interactions. NSAIDS can make some drugs more potent such as lithium and make other drugs less effective such as some drugs prescribed for high blood pressure. [13][20]

Pediatric concerns:
Commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to acute kidney injury (AKI) in pediatric patients, particularly those suffering from dehydration, suggest the results of a study published Pediatric Nephrology in October 2015. [19] Parents need to be acutely aware and cautious of given their child NSAIDS if they are exhibiting signs of dehydration or have been suffering from severe diarrhea.

Children and teenagers should not be give aspirin due to the risk of Reyes Syndrome, a serious and potentially fatal disease of the liver. [22]

Potential Benefits or Not
Long-term use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs may reduce the risk of colon cancer, according to a new study.

Researchers included more than 10,000 patients with colorectal cancer and more than 100,000 control participants. They analyzed data on their aspirin and nonaspirin NSAID use, health conditions and history of colonoscopy. Taking 75 to 150 milligrams of aspirin daily for five years or longer was associated with a 27 percent reduced risk for colon cancer. Five or more years of non-aspirin NSAID use was associated with a 30 to 45 percent lower risk. The authors say the potential use of these medications for the prevention of colorectal cancer is limited by gastrointestinal and cardiovascular risks. They say potential harms will need to be balanced against preventive benefits. [16]

While some studies have shown that regular use of aspirin or non-aspirin NSAIDS can reduce the risk of colorectal cancer in high risk patitents by about 30 percent, new research published in March 2015 claims there is an important exception: in people with certain genetic variants these drugs can actually increase the risk of colon cancer. [17] Certainly any possible benefit would have to be weighed against other negative side effects.

What should you do if you experience pain?
Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic says, "We're not telling the public if they have pain that they should suffer, but do take as small a dose of a medicine as is appropriate, and take it for only as long as you need it.” [21]

Natural Alternatives:
For those who would like to consider non-drug and nutritional ways to relieve aches and pains, there are a number of alternatives to NSAIDs. They include the spice turmeric, the Indian herb boswellia, juices (tart cherry, pomegranate, or vinegar with apple and grape) as well as home remedies like Certo and grape juice or gin-soaked raisins, arnica montana cream or oral form and brown seaweed which has potent anti-inflammatory properties.

Resources:
1. http://updates.pain-topics.org/2010/03/nsaid-dangers-may-limit-pain-relief.html
2. http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm
3. https://www.nlm.nih.gov/medlineplus/videos/news/NSAID_082515.html
4. http://www.ncbi.nlm.nih.gov/pubmed/16265706
5. http://aramis.stanford.edu/downloads/GI..NSAID.pdf
6. http://rheumatology.oxfordjournals.org/content/early/2014/09/22/rheumatology.keu408.abstract
7. http://www.peoplespharmacy.com/2014/09/29/new-research-confirms-that-nsaids-can-be-deadly/
8. http://www.ncbi.nlm.nih.gov/pubmed/25252703
9. http://www.ncbi.nlm.nih.gov/pubmed/21592304
10. http://www.medscape.com/viewarticle/832286
11. http://www.ncbi.nlm.nih.gov/pubmed/26476844
12. http://www.ncbi.nlm.nih.gov/pubmed/26457127
13. http://link.springer.com/article/10.2165/00003495-198530010-00004
14. http://www.nejm.org/doi/full/10.1056/NEJM199906173402407
15. http://www.ncbi.nlm.nih.gov/pubmed/24463282
16. http://jnci.oxfordjournals.org/content/94/4/252.full
17. http://www.reuters.com/article/2015/03/17/us-health-cancer-aspirin-idUSKBN0MD1SZ20150317
18. http://www.medscape.com/viewarticle/778763
19. http://www.ncbi.nlm.nih.gov/pubmed/25895445
20. http://www.nhs.uk/Conditions/Anti-inflammatories-non-steroidal/Pages/Interactions-othermedicines.aspx
21. http://www.npr.org/sections/health-shots/2015/07/10/421788461/fda-boosts-its-heart-attack-warning-on-nsaids-sows-confusion
22. http://www.rxlist.com/nsaids_nonsteroidal_antiinflammatory_drugs-page2/drugs-condition.htm

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