Through the minefield – NSAIDs for the confused
Reproduced from Issue 120 of Arthritis Today
Professor Howard Bird Howard Bird, Professor of Pharmacological Rheumatology at the University of Leeds, guides readers through the complicated world of non-steroidal anti-inflammatory drugs.
Many patients with arthritis rely on non-steroidal anti-inflammatory drugs (NSAIDs). In relieving the inflammation of arthritis they are likely to relieve both pain and stiffness, but this is not without cost as they cause more side effects than plain analgesics alone.
Because of this they should only be prescribed when other options have been considered. For osteoarthritis, which is predominantly non-inflammatory, and other non-inflammatory conditions such as fibromyalgia, analgesics and rest may suffice.
Recent arc-funded work at the City Hospital, Nottingham, has shown that educational advice given to patients by rheumatology nurse practitioners – including advice on weight reduction, aerobic exercise, massage and relaxation techniques – substantially reduced the need for tablets. And not only is education important but rest also has a role. However, gentle, paced exercise is regarded as essential, and a physiotherapist will encourage the patient to concentrate on building up muscle strength around the affected joint to protect it.
Painkillers may still be needed.
Paracetamol is available over the counter in small amounts but if it fails to relieve pain in two or three days, your doctor should be willing to prescribe a generic preparation such as Co-Proxamol. This is particularly popular because it gives a slight psychological "lift". Co-Codamol or Co-Dydramol are similar drugs which also contain paracetamol but the added mix of a small amount of a second more potent painkiller (codeine or dihydrocodeine respectively) seems to be more effective.
But if these simple measures fail to help, you family doctor may well resort to an NSAID. Apart from ibuprofen (Neurofen) which is available over the counter in a relatively low dose, all must be prescribed by your doctor.
They will certainly be required if you have rheumatoid arthritis, although here, the prescription of a disease modifying anti-rheumatic drug (DMARD) to reduce the overall disease activity remains a better policy and allows you to reduce your consumption of NSAIDs.
Some 46 NSAIDs are available to your doctor, although many of these are re-formulations of earlier drugs. They all act by blocking a basic enzyme that not only causes inflammation in the joints but which is also protective at certain sites of the body, particularly the stomach and kidneys. Using NSAIDS is always a calculated gamble, balancing the likely benefit for the arthritis against the side effects they may cause. So you should always take care, and with the help of your doctor to ensure you take the lowest dose possible, building up gradually, rather than starting with a very high dose and later trying to reduce this.
NSAIDs are relatives of asprin
NSAIDs do not necessarily have to be taken by mouth. They are available in topical form that can be pasted onto the skin over painful joints, and are absorbed through the skin, although this is not as rapidly as through the stomach. The drug then passes around the whole body, so side effects have still been reported from this route.
All NSAIDs are distant relatives of aspirin, first used in 1763. Indomethacin and phenylbutazone (now withdrawn except for hospital use in ankylosing spondylitis) were introduced in the 1960s, both parenting related drugs, in which pharmaceutical companies attempted to breed out the more serious side effects. The parent compound indomethacin is still used today, but it is not first choice.
A major breakthrough followed some ten years later when Boots introduced the first of the proprionic acids (Ibuprofen), and drugs related to this have continued to be produced.
The above family groupings often forgotten by GPs do have some relevance to side effects. Indomethacin is more likely to cause fluid retention with swelling in the leg, mental confusion or dizziness. Phenylbutazone was particularly potent;it damages the bone marrow. Proprionic acids are more likely to cause skin rash. All cause gastro intestinal side effects (propionic acid less than the others).
NSAIDS can also be classified according to their half-life – the length of time it takes the drug to be destroyed in the liver. The range of half-lives for NSAIDs varies from half an hour up to 72 hours. The practical point here is that a drug with a half life of three to four hours needs to be taken up to four times a day to remain effective.
Drugs with a half-life of around eight hours can be taken twice a day, and those with a half-life of up to 18 hours are suitable for daily dosing. If pain is persistent throughout the day and night, once daily might be preferable but if pain only occurs for a few hours each day (eg, provoked by a morning shopping trip) rational treatment is to take a single dose of NSAID with short half life just before this event, thus significantly reducing total consumption.
The third classification of NSAIDS which may be helpful in prescribing is by pharmacological properties. The basic mechanism of action of all compounds is to block an enzyme called cyclo-oxygenase (COX) which make prostaglandins harmful at the joints but protective of the stomach and kidneys.
Recent research has confirmed that this single enzyme is actually closely related to two iso-enzymes, COX-1 which makes prostaglandins responsible for protecting the stomach and kidneys, and COX-2 which makes prostaglandins which exclusively damage the joints. So selective COX-2 inhibitors (drugs which exclusively inhibit this second enzyme) reduce inflammation at the joint without as many side effects.
This discovery has led not only to the development of drugs that exclusively block COX-2 but has also produced a scramble among pharmaceutical companies to urgently re-examine their earlier drugs to ascertain whether they may have more COX-2 blocking activity than had originally been thought.
Etodolac, which has been available for years, has modest COX-2 selectivity. Then Meloxicam was manufactured as a drug that was also fairly effective in blocking COX-2. Chemical modification has led to the highly specific blockers like celecoxib, rofecoxib and etoricoxib.
This whole field has recently been reviewed by the National Institute for Clinical Excellence (NICE) on the basis of careful analysis. They felt that the greater cost of selective COX-2 inhibitors was justified when balancing this against the cost of treating the side effects caused by the less selective drugs.
At present, their formal advice is that selective COX-2 inhibitors should be considered and probably used in those over 65 years of age because gastric side effects including ulceration and perforation are greater in this group.
Mainly because of its action on platelets in the blood, aspirin in a dose much lower than used in arthritis, protects from heart attack and stroke. At this low dose it rarely causes side effects. The majority of NSAIDs do not have this protective action, and many may reduce the cardio benefit of aspirin in the doses used to control arthritis. Current evidence (which may yet change) suggests that if an NSAID and aspirin need to be given together, the highly selective COX-2 inhibitors are the best.
New groups of NSAIDs may yet appear. Perhaps this article has confused further! But if you are anxious about your current NSAID you may wish to show this article to your doctor and discuss it with him or her.
