Category Archives: Prednisone side effects

Rheumatoid arthritis drugs… which ones are friendly to the heart and which ones aren’t!

Rheumatoid arthritis (RA) is a chronic, autoimmune systemic disease which affects approximately two million Americans. While the symptoms that bring the patient to the doctor are the joint swelling and pain, the area of most concern may not be the joints.  It is well established that cardiovascular risk is markedly increased in RA and in fact it is this complication that shortens lifespan by between ten to fifteen years.

A number of clinical studies have retrospectively examined the relationship between certain medications and the risk of cardiovascular events.  The report card has provided some real surprises.heart-attack_0

For example, methotrexate, the workhorse disease modifying anti-rheumatic drug (DMARD) of choice reduces cardiovascular mortality by almost 70 per cent. The mechanism is felt to be due to a reduction of atherosclerotic plaque formation as well as increased clearance of foam cells (Solomon DH, et al. Circulation 2003; 11: 1303-1307).

The other major player in the treatment of RA is the TNF inhibitor group.  These are used in more than 50 per cent of RA patients in the US. These drugs apparently reduce the risk of cardiovascular events by almost 50 per cent (Gonzalaz A, et al. Ann Rheum Dis. 2008; 67: 64-69). Why this occurs is still not clearly understood.

Steroids have been used to treat RA since the early 1950’s.  Steroids have been shown to worsen cardiovascular risk because of their effects on both blood pressure as well as blood glucose.  Steroid use in RA has been associated with increased carotid plaque formation as well as increased arterial stiffness.  So what dose is a safe dose?  The answer is still unknown.

Non-steroidal anti-inflammatory drugs (NSAIDS) raise blood pressure.  Randomized clinical trials have shown that cardiovascular risk is associated with COX-2 inhibitors but also with non-selective COX drugs also.  The upshot? All NSAIDS regardless of class, are associated with increased cardiovascular risk.

Hydroxychloroquine, a drug often used to treat mild RA, is associated with a decrease in diabetes and may also improve lipid status.  Actemra increases lipid profile but the long term effects are still unknown.  Leflunomide (Arava) increases blood pressure.  The eventual effects are still a subject of conjecture.

So what about aspirin?  This medication is used for cardiovascular prophylaxis.  In higher doses it also has anti-inflammatory effects although these are limited by the potential gastrointestinal side effects known to be caused by high dose aspirin. It is well known that other NSAIDS should not be used in patients taking aspirin for cardiovascular prophylaxis since they blunt that effect.

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What’s a safe dose of prednisone? Is there such a thing?

A spirited debate was published in the Rheumatologist, a magazine I get. The topic was the use of prednisone in rheumatoid arthritis.  Recent guidelines produced by the American College of Rheumatology regarding treatment of rheumatoid arthritis omitted the use of prednisone.

prednisone-5Dr. John Kirwan, a professor at the University of Bristol, who wrote several papers showing that prednisone had disease-modifying effects and held back the destructive processes of rheumatoid arthritis (RA) made his pitch. He advocated the use of prednisone in combination therapy for this condition.

Dr. Theodore Pincus, a professor at NYU, advocated the use of low dose prednisone (less than or equal to 5 mgs a day). He provided evidence that it was safe and effective at that dose.

Dr. Anthony S. Russell, a professor at the University of Alberta issued the counterpoint. He provided historical data showing that prednisone had long term toxicity without significant benefit (in his opinion.)

With all due respect to Dr. Russell, much of the data he cited was old data when higher doses of prednisone were used.  He also contended that primary care doctors would be tempted to use prednisone if they saw rheumatologists using it.

My opinion is this.  I use low dose prednisone a lot in my practice.  By low dose, I mean 5 mgs or less. I think it is effective as an add- on therapy.  It is also a great “bridge” if the patient is transitioning therapies. I have seen very little long term toxicity associated with this low dose approach.  And I think the benefits derived from improved activities of daily living far outweigh the negatives. I do think that doses higher than 5 mgs should be avoided if possible. I also don’t think the primary care issue is that big a deal although I admit… I have seen some indiscriminate use in my community.

 

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Prednisone Side Effects

Prednisone – sometimes it’s mispelled as “prednizone”-is a generic, inexpensive, and commonly used medicine in arthritis treatment.

The diseases for which corticosteroids are most often used are rheumatoid arthritis, lupus, psoriatic arthritis, ankylosing spondylitis, Reiter’s disease, polymyalgia rheumatica and temporal arteritis, polymyositis and dermatomyositis, gout and pseudogout, sarcoidosis, and the arthritis accompanying inflammatory bowel disease.

It is catabolic (meaning it breaks down tissue) and anti-inflammatory.

When taken chronically it can suppress the ability of the adrenal glands to make its own steroid, particularly if the average daily dose of prednisone is greater than 7.5 mgs.

Other factors that constrain the ability of the adrenals to perform are if therapy continues for more than a few weeks or months, if doses are given late in the day or in divided doses throughout the day, or if long-acting corticosteroid preparations are used.

Patients who require high doses of prednisone (more than 20 mgs a day) for extended periods of time always develop side-effects.

Taking steroids on an alternate day (every other day) schedule reduces the chance of adrenal insufficiency but does not eliminate it.

Other side-effects include:

“Moon face”

Elevated blood sugar and diabetes

Elevated cholesterol and triglycerides

Fluid retention

Obesity

Acne

Increased blood pressure

Electrolyte abnormalities such as low potassium serum levels

Hardening of the arteries

Hirsutism (abnormal hair distribution)

Easy bruising

Thinning of the skin

Cataracts and glaucoma

Purple striae (stretch marks)

Poor wound healing

Muscle wasting

Susceptibility to infection and masking of infection leading to sepsis and death

Psychosis

Avascular necrosis (dead bone)

Sweating

Inflammation of the pancreas

Stomach ulcers (particularly if used with non-steroidal anti-inflammatory drugs

Obviously, patients must be counseled as to the relative risks and benefits, and the lowest possible steroid dose should be used.

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