NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
In the 1st information bulletin we noted that rheumatoid arthritis (RA) is an inflammatory disorder. It is therefore logical to use medications that can control inflammation. Non steroidal anti-inflammatory drugs (NSAIDs) and steroids are the two anti-inflammatory agents used for this purpose.
What are NSAIDs ?
These are commonly known as pain-killers (a wrong term). This includes drugs like aspirin, ibuprofen, indomethacin, diclofenac, piroxicam, naproxen, celecoxib and rofecoxib.
How do NSAIDs act ?
The process of inflammation is mediated by many chemical substances, the most important being prostaglandins. Prostaglandins are normally secreted in many tissues (e.g. stomach, kidney) and are essential for their normal functioning. Prostaglandins that are liberated secondary to tissue injury produce inflammation (pain, swelling, tenderness and warmth).
NSAIDs suppress the formation of prostaglandins, thus reducing the inflammation and control the symptoms of inflammation i.e. joint swelling, pain and stiffness. There is improvement in mobility and function. Patients are distinctly comfortable.
Do NSAIDs prevent disease progression and joint damage ?
No. NSAIDs are pure relievers of symptoms, and therefore total reliance on NSAIDs to treat RA is not correct. Disease modifying drugs (to be covered in subsequent communication) must be used simultaneously.
What are the side-effects of NSAIDs ?
NSAIDs can cause significant side-effects. As already pointed out, prostaglandins have important physiological function. Their suppression by NSAIDs leads to these side-effects. The most common side-effects involve the gastrointestinal tract (especially stomach), kidney and platelets. In stomach this causes dyspepsia (acidity a term very loosely used by patients and lay people), ulceration, bleeding and perforation. While dyspepsia is common, other side-effects are not common. In addition there can be chest discomfort – burning sensation due to inflammation, and ulceration of oesophagus and inflammation of small and large intestines.
Side effects on the kidney which could sometimes be serious, are seen mostly in patients who have associated liver, heart, kidney diseases and low proteins in the blood. Most of the kidney side effects are generally reversible on discontinuation of the NSAID. It is not clear if long-term use results in irreversible, clinically significant renal failure. Some patients of bronchial (a small proportion) asthma have aspirin sensitivity. NSAIDs should not be used in this group of asthmatics.
The fear about side-effects of NSAIDs, though true to a certain extent, is exaggerated. This unfortunately results in lack of compliance, and inadequate dosage. While the danger of side-effects is not diminished, the relief is inadequate. The absolute blanket rule of not to use NSAIDs with a past history of such complications is not warranted. When necessary, NSAIDs can be used with due care and under observation.
How can the side-effects of NSAIDs be diminished ?
| There are some simple measures : |
| 1. |
Not to take NSAIDs on empty stomach |
| 2. |
To use minimum effective dose (but not suboptimal dose). |
| 3. |
Reduce NSAID consumption as the disease gets controlled. Once fully controlled, NSAIDs can be stopped and used as required or on SOS basis. |
| 4. |
Not to use NSAID in combination. Not only is the efficacy not enhanced, but the toxicity might in fact be increased. |
| 5. |
Avoid NSAIDs in high risk patients (see below).
Concomitant use of antacids and other drugs that decrease stomach acid secretion is not indicated and not necessary (indications discussed later). |
| Who are at high-risk of side-effects ? |
| (Stomach complications) |
| 1. |
Elderly (persons over 60 years of age). |
| 2. |
Females. |
| 3. |
Past history of stomach ulcer, bleeding, or perforation. |
| 4. |
Smoking, alcohol consumption. |
| 5. |
Simultaneous use of corticosteroids (but in practice this combination often is necessary and can be used under observation). High risk patients can be given medication to reduce gastric acidity. Misoprostal is a synthetic prostaglandin. It antagonises the harmful effects of NSAIDs on the stomach permitting NSAID therapy. The drug is not easily available in India and is expensive. |
Are there no safe NSAIDs ?
The risk of side-effects does vary between different NSAIDs. Thus indomethacin has more side-effects than brufen or diclofenac. Recently COX-2 inhibitors have been introduced. These newer NSAIDs suppress prostaglandins that lead to inflammation (i.e. injury induced), but do not suppress the prostaglandin necessary for physiological functions. Thus while inflammation is controlled, the normal physiological function is not disturbed. These are thus good alternatives for patients with stomach intolerance to usual NSAIDs. These can also be useful in high risk patients out-lined above. Their potency and efficacy is similar to old NSAIDs.
(Safety of NSAIDs in pregnancy, breast feeding, etc will be discussed in a subsequent bulletin).
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