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MGA News

February 1997

Side effects of some medicines used to treat MG

Dr Stanley Freedman

All medicines and drugs have some unwanted effects, or side effects, and those commonly used to treat MG are no exceptions to this rule. The frequency and the seriousness of these unwanted effects vary greatly from drug to drug and from patient to patient, and, in deciding whether to use a particular treatment, a doctor has to weigh up the potential benefits and balance these against the risk of unwanted effects. In most cases, the benefits far outweigh the risks, but it is as well to understand the nature of the unwanted effects and the problems they can pose. For simplicity, I am only going to consider three groups of medicines: Pyridostigmine and similar drugs, Azathioprine and Steroids.


Pyridostigmine (a.k.a. Mestinon) and Neostigmine

These act by slowing the normal breakdown of Acetylcholine and therefore building up its concentration at the muscle receptor, which is where it is needed to transmit messages from the nerves to the muscles, and where the defect in MG is located. Unfortunately, Acetylcholine has important actions at numerous other sites in the body apart from the muscle receptors, and Pyridostigmine causes a lot of unwanted effects, most of which are not very serious but which are, none the less, very inconvenient. Thus, it may cause over activity of the muscle in the wall of the bladder and the bowel, which in turn may cause frequently of passing urine, or even incontinence, and abdominal discomfort and diarrhoea. The muscle controlling the pupil of the eye is also affected, and there may be difficulty in focusing. There are Acetylcholine receptors in the heart and so Pyridostigmine may cause a very slow heart beat, which can, in turn, cause dizziness. The activity of many glands is increased by Acetylcholine, and patients may notice increased sweating and production of saliva. All these unwanted effects can be prevented by taking another drug, Atropine (or a related drug) at the same time. The only really serious potential unwanted affect of Pyridostigmine is that if the dose is too high, it can make the muscle weakness of MG worse rather than better It is therefore important, when using Pyridostigmine, to emulate the admirable principle which some of the older readers of this article will remember from the adverts for ""Erasmic"" shaving cream" i.e. not too little, not too much, but just right! It is also important to emphasise that all the unwanted effects of Pyridostigmine are short-lasting, and that it does not cause any permanent or long-term problems.


Azathioprine

This drug depresses the immune system including the cells which produce the antibodies which are responsible for MG. It is extremely useful because it allows us to take much smaller doses of steroids than we would otherwise have to. It has to be taken for a least six months, and often for a year or more, before it is fully effective. It has several unwanted effects.

(i) Hypersensitivity

Some people have a hypersensitivity or allergy, to Azathioprine and develop fever, chills, joint and muscle pains, vomiting and dizziness. Usually soon after the start of treatment. It is, of course, important to make sure that the symptoms are due to Azathioprine and not to coincidental flu, but when this unwanted reaction occurs, treatment must be stopped and cannot usually be restarted. It is, unfortunately, impossible to forecast who will react to Azathioprine in this way.

(ii) Effects on the blood

Azathioprine depresses the formation of new blood cells, just as it depresses antibody-forming cells. It is therefore necessary to monitor the situation closely by performing frequent blood counts at the start of treatment and three to four times a year once treatment is established. If the count drops significantly, it may be necessary to stop treatment temporarily.

(iii) Susceptibility to Infection

As Azathioprine depresses immunity, it increases susceptibility to infections. Special care must be taken to avoid contact with shingles and chicken pox which are much more severe in patients with lowered immunity.

(iv) Effects on the Liver

Liver function may be upset by Azathioprine. This can be monitored by blood tests. The effects are reversible on stopping treatment or reducing the dose.

(v) Increased incidence of tumours?

This is the most controversial, unwanted effect of Azathioprine. There are reports of an increased frequency of tumours mainly of the lymph glands in patients with rheumatoid arthritis taking Azathioprine. The sort of tumours that occurred in these patients were those that respond well to treatment once Azathioprine is stopped. However, a more recent report in 755 patients taking Azathioprine for bowel disease and who were followed for up to 29 years found no increase in the number of tumours of any sort. There are no comparable figures for MG Patients, but, on the basis of current knowledge, there is little cause for alarm.


STEROIDS

These drugs receive a bad press, and yet there is no doubt that there are life-saving in many diseases, including MG and their use has enormously improved the treatment of MG and related diseases. They act in the same way as Azathioprine, by depressing the body's immune system.

The first thing to make clear is that these are not the steroids taken by some athletes and about which so much is written. These are more correctly named anabolic steroids, whereas those used for MG are properly known as corticosteriods, although for the sake of complicity I shall refer to them simply as "sterods". They occur naturally in the body as part of its defence and messenger systems although the dosage used in medicine are usually much higher than those occurring naturally. The most commonly used drug in this group is prednisolone, but others may be used, including prednisone, hydrocortisone and dexamethasone. They have numerous unwanted effects of varying severity and importance. All of these are less severe if steroids are taken on alternate days, rather than daily.

(i) Weight and Appearance

This is the affect which concerns patients the most and Doctors the least. Sterods alter the distribution of body fat, causing more fat on the face and trunk, with less on the legs and arms, giving a general picture which has been graphically described by one of my colleagues as that of a lemon on two matchsticks. Like most of the unwanted effects of steroids, this one varies in severity according to the dose and individual susceptibility. Most patients will notice little alteration in their appearance at maintenance doses of 10-15mg per day. There is also no doubt that many patients gain a lot of weight when taking steroids. This is due not so much to an affect on metabolism as to stimulation of the appetite and can be controlled by careful attention to diet. Another unfortunate affect is the occurrence of a skin rash like acne, which may require treatment to control it.

(ii) Effects on glucose handling

Steroids make the body less capable of dealing with glucose and other sugars. They therefore adversely affect diabetic patients, who may require an increase in the dose of their injection or tablets, and they may also induce mild diabetes in patients who didn't previously have it. Again, strict dietary control may be necessary to counter effect this.

(iii) Thinning of bones

This is probably the most serious long-term unwanted affect of steroids. It is part of a generalised effect on body tissues that also involves muscle and skin (see below). It results in thinning and consequently in weakening of bones and particularly of the bones in the spine and the pelvis. This may result in fractures which can occur after a mild injury or even spontaneously. The affect is worse in those who are already at risk of thinning of their bones, i.e. older people and women past the age of childbearing. It is most likely to occur at doses of 10mg per day or more, and at maintenance levels of 7.5 mg or less one is pretty safe from this complication. It is now well established that exercise particularly weight-bearing exercise such as walking and aerobics helps to avid or reverse the bone thinning associated with ageing. and it is probable that it will also protect against the effects of steroids. It is also important to have am adequate diet with plenty of calcium, protein and Vitamin D. There are now also available drugs (such as etidronate) which are being used successfully to treat bone thinning.

(iv) Effects on other body tissues

Steroids tend to break down body tissues, and particularly to deplete them of protein. This results in the bone thinning already discussed, and also in wasting of the muscles and thinning of the skin. Muscle wasting results in weakness. It can be counteracted by exercises, although they have to be quite severe and really stress the muscles, which may be impossible in MG. Thinning of the skin leads to it being easily cut or broken, and also to increased susceptibility to the affects of sunlight.

(v) Salt and Water Retention

Steroids form part of the body's natural system of conserving salt and water. Steroid treatment sometimes therefore leads to abnormal retention of salt and water in the body, with some puffiness or swelling around the ankles which is not a serious problem.

(vi) Psychological Effects

To those of us who take steroids, and also our families and friends, the mental effects are striking, especially on alternate day treatment when we can appreciate the contrast between steroid and non-steroid days. Elation, feeling like superman, talkativeness - these and similar feelings will be readily recognised by may of you. Families and friends of MG Patients on steroids will often recognise uncharacteristic irritability on steroid days. Occasionally, more profound and worrying psychological symptoms may occur, and serious depression can result - but usually only if this tendency was present before the start of treatment.

(vii) Insomnia

This is a common accompaniment of steroid therapy, and can be sufficient of a nuisance to require treatment with mild sedatives or tranquillisers taken at night.

(viii) Susceptibility to Infection

The same considerations apply to steroids as were described above for Azathioprine - only more so!

(ix) Effects on the stomach

Steroids irritate the lining of the stomach and gullet and often cause quite severe indigestion. Tablets should never be taken on an empty stomach. Less frequently they cause stomach or duodenal ulcers. Fortunately, modern treatment of these problems is safe and effective, and does not adversely affect MG.

(x) Effects on the body's reaction to stress

Normally, when we are in a situation of physical or psychological stress, the body reacts by increasing its output of steroids. This automatic regulation is lost when we take steroid treatment, and so it is vital, in order to cover unforeseen emergencies, to carry a card or wear a bracelet stating that the bearer is on steroid treatment and giving the current dose and the phone number of a reliable hospital or general practice contact.

(xi) Cataract

There is an increased chance of developing cataracts in the lenses of the eyes when taking sterods and unfortunately there seems to be no way of avoiding this.

This is a pretty frightening list and there are other, rarer, complications of steroid therapy which I have not described. However, I should like to re-emphasise three points I have made already.

* In doses equivalent to 10 mg per day, or less, you are very unlikely to run into serious trouble (and remember the importance of drugs like Azathioprine which enable one to reduce the steroid dose).

* Alternate day dosing reduces the incidence and severity of unwanted effects.

* For most of us, the benefits of steroid treatment far outweigh its risks.

MGA NEWS February 1997
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