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Theophylline and Anti-IgE Drugs for Asthma Treatment

Tuesday, May 19th, 2009

Theophylline
Theophylline-type drugs are also known as xanthines or methylxanthines. These drugs are chemically similar to caffeine. They cannot be inhaled, so are taken as tablets or syrup. They start working about 30 minutes after being taken and their effects last for 6-8 hours. Slow-release preparations take 90 minutes to start working, but they last 12-24 hours, and are therefore useful for nocturnal asthma.
In Britain, doctors generally regard theophylline-type drugs as reliever drugs (see p. 152), but rather risky ones whose use is only justified for people with severe asthma. They are given, as an additional treatment, to asthmatics who are not responding well to the usual drug programme (see p. 160). Unfortunately, fairly high doses are needed for theophylline-type drugs to act as relievers, i.e. to reverse bronchospasm. There is a very narrow margin between such a dose and one that causes major (and sometimes dangerous) side effects.
Such side effects usually occur when the doctor is still trying to work out the correct dose – this varies from one person to another, so prescribing theophylline-type drugs is no easy matter. Once you are established on a safe dose (and provided your general health and your intake of alcohol, nicotine and medicinal drugs does not vary – see p. 158) you can usually continue taking theophylline without serious side effects.
In the United States, many doctors also give theophyllinetype drugs, at much lower doses, to people with mild asthma. At these low doses they do not act as relievers, but they have a slight anti-inflammatory effect and therefore act as preventers. The risk of toxicity is much less. Taking low doses of theophylline allows people with mild asthma to reduce their use of beta-2 relievers. However, inhaled steroids are usually more effective in this role, and are the preferred treatment outside the United States.
Side effects
Typical side effects include nausea, vomiting, stomach pains, diarrhoea (sometimes with blood), headache, anxiety, restlessness, insomnia, dizziness, and a pounding heart or irregular heartbeat.
Any side effect of these drugs should be taken seriously and reported to your doctor as soon as possible. If you cannot get an appointment quickly, it may be best to stop taking the drug before seeing the doctor, as long as you have other drugs to control your asthma. Call your doctor for advice.
It is remarkably easy to overdose when taking these drugs at higher doses (see p. 157). Such overdoses can be fatal. The symptoms include repeated vomiting, shaking, feeling unusually hot, needing to urinate frequently, severe thirst, maniacal behaviour, and irregular heartbeat (palpitations). Delirium and convulsions may occur shortly afterwards, so get hospital treatment urgently if you have any of these symptoms.
Unfortunately, a serious overdose can sometimes occur in people who have taken theophylline-type drugs without trouble for many years. There may be no advance warning that anything is wrong - no mild side effects preceding the serious ones. To protect yourself against this, you need regular blood tests from your doctor.
One fundamental problem with theophylline-type drugs is that many different factors - including diet, illnesses other than asthma, and taking other drugs - can alter the way your body deals with the drug. If your liver is breaking down the drug more slowly than usual, the amount in your blood will rapidly increase, and can reach toxic levels.
These are steps that can help prevent an overdose with theophylline-type drugs:
• If you start taking a new drug of any kind, or stop taking a drug (especially the contraceptive pill), or if you change your intake of nicotine or alcohol, ask your doctor - preferably in advance - if your dose of theophylline-type drug needs to be changed.
• A great many drugs interact with theophylline-type drugs, including the new anti - leukotriene drugs. You should always be cautious with any new drug, but take particular care with two antibiotics - ciprofloxacin (brand name Ciproxin) and erythromycin (various brand names) - and with cimetidine (various brand names), used for stomach ulcers and heartburn.
• If you have flu vaccinations, or develop certain illnesses, especially viral infections, heart disease or liver disease, watch for the typical side effects of theophylline-type drugs (see above) and consult your doctor immediately if any occur. These conditions all change the effects of theophylline-type drugs.
• Don’t eat meals that are very high in fats or oils. A lot of fatty food causes too much of the drug to be released at once from the slow-release preparations and increases the risk of side effects. Avoid sudden, major, changes to your diet.
• See your doctor regularly for check-ups. Simply getting older changes your reaction to these drugs: your dose may need to change over the years.
• If you are at all forgetful about tablets, keep a careful record of when you have taken your theophylline-type drugs. Be very careful never to take a second dose by mistake.
• Talk to your doctor if you are not taking a slow-release form of theophylline (see box below for brand names). There are usually fewer side effects from these than from the ordinary forms of the drug.
• Wear a Medic Alert bracelet (see box on p. 95) saying that you are taking theophylline-type drugs. If you have a severe asthma attack and are taken to hospital, it is important that medical staff know this, so that they do not give you more drugs of this type.
While pregnant or breast-feeding, it may be advisable to stop taking theophylline-type drugs: discuss this with your doctor. Although the drugs do not affect most unborn or newborn babies, there are occasional reports of toxicity. Less seriously, theophylline-type drugs go through into breast milk, and may make babies irritable and restless. This problem can be solved by always taking the drug just after a feed - this reduces the amount in the milk.
Theophylline-type drugs might produce behavioural problems and learning difficulties in young children although this is unproven. Research shows that there are no problems for children over six.
Anti-IgE drugs
For asthmatics with strong allergic reactions, who are not doing well on ordinary treatment, the new anti-IgE drugs, such as omalizumab may be very valuable (see p. 149). They are given as a depot injection under the skin.
Some common brand names
Common brand names of theophylline-type drugs include: slow-release preparations — Lasma, Nuelin SA, Phyllocontin Continus, Slo-Phyllin, Theo-Dur, Uniphyllin Continus
ordinary preparations - Aminophylline, Nuelin Ketotifen
Ketotifen (brand name Zaditen) is an antihistamine (see p. 138), although it has other effects in addition to those of ordinary antihistamines. Most significantly, it stabilises mast cells in a similar way to cromoglycate.
One advantage of ketotifen to many people is that it is taken by mouth, in capsule, tablet or syrup form. When it was first introduced, doctors hoped that it would be of particular help in asthma, but it has not lived up to expectations. However, some asthmatics do find it effective. It is worth trying because, it it works, it could permit you to reduce your dose of steroids.
Ketotifen requires up to six weeks to take effect, so continue taking your previous drugs (e.g. steroids) for at least six weeks, or you will risk losing control of your asthma.
Side effects
Minor side effects from ketotifen include nausea, headache, increased appetite and weight gain, drowsiness, dry mouth and slight dizziness. Do not drive until you are sure that ketotifen does not make you drowsy. Alcohol may pack a more powerful punch than usual, so drink very moderately at first. If drowsiness is a problem, take the drug in the late evening. The sleepy feeling may wear off after a few weeks of taking the drug.
There are no serious side effects from ketotifen, except if taken with drugs for diabetes.
Anti-leukotriene drugs
Leukotrienes are among the messenger chemicals that are produced by mast cells during an allergic reaction (see box on p. 12). They help to perpetuate the inflammatory process begun by histamine, and they amplify the reaction by attracting more immune cells into the area.
The anti - leukotriene drugs fall into two distinct groups:
• those that bind to the receptors for leukotrienes, called leu kotriene- receptor antagonists. Currently, there are two drugs in this group, montelukast (brand name Singulair) and zafirlukast (brand name Accolate). A third drug, pranlukast, is in the pipeline and currently going through its safety trials.
• those that block the production of the leukotrienes altogether, called 5-lipoxygenase inhibitors. There is only one drug in this group at present, zileuton (brand names Leutrol, Zyflo); it is not yet available in Britain.
As regards tackling inflammation, the anti - leukotriene drugs work in a completely different way from either steroids or cromoglycate. This makes them useful as an add-on treatment, supplementing the effects of existing anti-allergy drugs.
For asthmatics, anti-leukotriene drugs may be particularly good in combination with antihistamines – whereas antihistamines alone are singularly unsuccessful in asthma (see p. 138). Recent research suggests that taking antihistamines together with antileukotriene drugs is an effective way to control airway inflammation. However, there have been no large-scale trials of this treatment option yet, and it may be a while before it comes into general use.
In the airways of people with asthma, leukotrienes can directly trigger bronchospasm (contraction of the airway muscles) as well as fostering inflammation and increasing mucus production. This multiple action of leukotrienes makes anti-leukotriene drugs very valuable for asthmatics because they act as both relievers (reversing bronchospasm) and preventers (tackling inflammation). They are especially useful for exercise-induced asthma.
All the anti-leukotriene drugs are taken in tablet form. If you are trying an anti - leu kotriene drug for the first time, don’t expect any noticeable effects to occur for about three days. Once you are taking the drug regularly, each dose requires 2-4 hours to have its full effect, but goes on working for 12-24 hours in total.
Although anti - leu kotriene drugs have a reliever effect, they cannot give you immediate relief from bronchospasm. Asthmatics must therefore carry a short-acting beta-2 reliever (see pp. 152-3) as well, in case of an asthma attack.
For those who dislike inhalers, or tend to forget to use them, the fact that these drugs are taken once a day in tablet form makes them an attractive option. However, they are expensive, and at present doctors prescribe them mainly for young children who have difficulty inhaling their usual drugs.
Side effects
The side effects noted in safety trials of these drugs were all minor ones:
• zafirlukast – headache, nausea, diarrhoea, pain
• montelukast – headache, diarrhoea, abdominal pain, cough, and flu-like symptoms
• zileuton – upset stomach
As with all new drugs, you should report any unusual symptoms to your doctor, just in case these represent a rare or longterm side effect of the drug (see p. 137).
Very occasionally montelukast provokes allergic reactions, with symptoms such as itchiness, widespread nettle rash (urticaria) or swelling (angioedema).
Zafirlukast and zileuton can both cause liver damage, but this is rare. Your liver function should be closely monitored by the doctor, by means of regular blood tests, and the drug withdrawn at the first sign of trouble. Montelukast can also affect the liver, but this is extremely rare.
The most worrying development noticed to date is the appearance, in a very few people taking zafirlukast or montelukast, of a disorder called Churg-Strauss Syndrome. The symptoms may include a blotchy purplish rash (due to vasculitis – see lower box on p. 73), a flu-like illness, worsening asthma, and numbness or tingling in the limbs. The heart, lungs and nerves are all affected, because eosinophils (see p. 19) are present in large numbers and cause damaging inflammation.
A study of the cases reported so far suggests that this syndrome may not be due to the anti-leukotriene drugs themselves but to other causes – usually (though not always) a reduction in the dose of steroids. Other patients who are not taking antileukotriene drugs, but are reducing or stopping steroids, may also (again, very rarely) develop Churg-Strauss Syndrome. Doctors now suspect that all these patients were already suffering from an underlying eosinophilic disease, which first showed itself simply as asthma, and was quelled by the steroid treatment prescribed for the asthma. The disease was thoroughly masked as long as the patient was using steroids, but when steroids were withdrawn, the underlying disease flared up, producing a wide range of symptoms. In most cases, reintroducing steroids brings these symptoms under control again.
Putting it all together
What is the ideal combination of all these asthma drugs? That is something your doctor can only work out slowly, because it varies from one individual to another.
The conventional approach to asthma treatment is to start patients on a short-acting beta-2 reliever and then, if the symptoms are not controlled, to add other drugs. This approach is called ’stepping up’. The standard steps, or stages, are as follows:
1. Use a short-acting beta-2 reliever only.
2. Add cromoglycate or low-dose inhaled steroids.
3. Try a higher dose of inhaled steroid or a long-acting beta-2 reliever.
4. Try out each of the following in turn: theophylline, anticholinergic drugs, cromoglycate and higher doses of beta-2 relievers (either inhaled or as tablets/syrup).
5. If there is still no success in controlling symptoms, add regular steroid tablets.
Short courses of steroid tablets may be used at any stage, for the control of sudden, severe, attacks.
Over the last ten years, there has been a change of strategy, and very few people are now kept on Stage 1. Inhaled steroids are now given to most asthmatics, even those with relatively mild asthma. Research from Sweden, where widespread use of
inhaled steroids first became general policy, shows considerable benefits to this approach.
If you have gone beyond Stage 2, ’stepping up’ is usually followed by ’stepping down’. In other words, when the symptoms have been well controlled for 3-6 months, doses of some drugs are reduced, or certain drugs stopped altogether. If the asthma flares up again, the dose is increased or the drug reinstated. If there are no problems, and symptoms remain stable for a month or two, another reduction is tried.
An entirely different approach to asthma management is now being tried with some patients – starting off with moderate to high doses of inhaled steroids (equivalent to Stage 3) and then ’stepping down’. The idea is to get the inflammation under control promptly and fully at the outset. This often seems to be the best strategy.
A few asthmatics don’t get much benefit from steroids. If your dose of steroid needs to be raised repeatedly, or you still need to use your reliever daily in spite of taking steroids, you may have steroid-resistant asthma. There are other drugs that can help, including anti-leukotriene drugs and the more powerful anti-allergy drugs (see p. 149).
Alcohol, caffeine and asthma
Some asthmatics experience bronchodilation (opening up of the airways) when they drink alcohol, while others experience
bronchospasm (tightening of the airways). For those whose airways open up, there is probably no harm in sometimes having a drink to relieve your asthma symptoms, assuming these are fairly mild. Clearly, it would not be a good idea to make a daily habit of this.
If your airways tighten up with alcohol, you will probably be pleased to hear that it may not be the alcohol itself. Alcoholic drinks contain a great variety of other ingredients, either derived from the original ingredients or generated during the fermentation process. Called ‘congeners’, these vary from one type of alcoholic drink to another, and they are often the culprits in asthma. So you may well find that, while one kind of alcoholic drink has a bad effect, another is fine.
Caffeine has a far more uniform effect — for most asthmatics it opens up the airways. However, the amount needed to relieve an asthma attack will also produce unpleasant side effects, such as a pounding heart or shaky hands. There are also long-term problems with such high doses of caffeine, including insomnia, headaches, nervousness and ‘restless legs’. It is much better to use your reliever inhaler to control an attack: the drug in the inhaler has been chemically tailored to give the maximum therapeutic benefit with the minimum of side effects. Anyone who consumes tea or coffee excessively can make themselves seriously ill, either physically or mentally, and it is not always obvious that caffeine is the cause (see p. 235).

Steroids in Allergy Treatment

Tuesday, May 19th, 2009

Few drugs create quite so much alarm as corticosteroids. To some extent, this alarm is justified — if

over-used, they have dangerous side effects. But rejecting them entirely is a great mistake, because

they are safe at the right dose, and immensely useful for a variety of allergic symptoms. With the

information given here, you can use steroids as safely and effectively as possible.
Although their proper name is corticosteroids, these drugs are commonly — and rather inaccurately —

called steroids. This name adds to their doubtful reputation by confusing them with the notorious

anabolic steroids (see box on p. 142). However, the term ’steroids’ is used for corticosteroids in this

book, simply because that is the name most people recognise.
Steroids do not deal with the allergic reaction itself, unlike antihistamines (see p. 138) or

cromoglycate (see p. 148). Instead, they tackle the consequences of the allergic reaction,

inflammation.
What exactly is inflammation? The visible features of this phenomenon – for example, if it occurs in

the skin, around a scratch or cut – are redness and slight swelling. There is also soreness, and some

warmth. All these effects are produced by an influx of immune cells, intent on protecting the broken

skin from infection. These immune cells generate messenger chemicals (see box on p. 10) which boost the

inflammation, as well as attracting yet more immune cells to the area. When inflammation affects

delicate membranes, as when you suffer a sore throat for example, there can be a great deal more

swelling and discomfort.
The inflammation that follows allergic reactions is very similar to that provoked by infection,

although the balance of immune cells and messenger chemicals is slightly different. Eosinophils (see p.

19) play a particularly important role in sustaining the inflammation produced by allergies.
This influx of eosinophils and other immune cells, which lights the fires of inflammation, occurs some

hours after the allergic response itself. It is known as the Late Phase Reaction (see p. 13). Steroids

work well for allergies because they curtail the Late Phase Reaction and have a calming effect on

various immune cells, especially the eosinophils.
Steroid phobia
So many patients have a profound objection to taking steroids that doctors call it, half-jokingly,

’steroid phobia’. One of the hazards of giving information about potential side effects – as in this

book – is that it may encourage ’steroid phobia’. That would be a tragedy, because steroids really are

useful drugs that can do you a lot of good and very little harm, if used correctly. The risks are very

small when the steroids are used at low to medium doses, and targeted directly onto the inflammation.

Even with high doses, the serious side effects can generally be avoided. Please don’t use the

information here to scare yourself – instead, use it to protect yourself while getting the most from

steroid treatment.
A few effects on other body processes remain, even with the new steroids:
•    Raised blood pressure – this can occur even with short-term use of steroids.
•    Children may stop growing, or grow more slowly. Usually they make up for this later.
•    Quite commonly, there is increased hunger (though you don’t actually need more food, and will

put on weight if you eat more than usual). Insomnia and an agitated, edgy feeling during the day may

occur. These are minor side effects, and no cause for concern.
•    Side effects in the eye can occur: there is an increased risk of glaucoma and, with prolonged

use, cataracts.
•    Long-term use can also result in loss of minerals from the bones, leading to thinning and

fragility (osteoporosis).
•    Psychological changes may occur. Some people experi- ece euphoria or greatly increased energy

levels – with the opposite effects occurring when the course of steroids ends. At worst, steroids can

trigger paranoia or severe depression and suicidal feelings. (These effects are more likely to occur in

those with a history of mental illness. If you are concerned about this aspect, discuss the possible

risks with your doctor before taking steroid tablets.)
•    Epileptics may suffer more frequent or more severe seizures.
•    Very rarely, stomach ulcers develop, or other side effects in the digestive system.
•    The skin may become thin, and the small blood vessels beneath it more fragile, leading to easy

bruising and stretch marks (striae). This is also a potential problem with steroid creams (see p. 146).

Elderly patients are much more susceptible to this side effect.
•    Some diabetics need more insulin. in addition, anyone with the potential to develop diabetes is

more likely to do so, but only if taking steroid tablets long term. The diabetes usually goes when the

steroids are stopped.
•    A few men suffer impotence, but only with long-term use of tablets. This can be treated, so see

your doctor. Women may have irregular periods.
•    Damage to the hip bones may rarely occur, usually with excessive doses of steroid tablets. This

is called avascular necrosis and may require hip replacement.
In addition to these effects on other body processes, there are also some side effects that arise from

the steroids’ suppression of the inflammation. These can occur even with short courses. Again, however,

these problems can almost always be prevented, or treated, or reversed if detected at an early stage.
•    Skin wounds may be slow to heal, and are more likely to become infected because of reduced

immunity. This is not a serious problem – just keep all cuts as clean as possible.
•    Infections by viruses and fungi (e.g. Candida – see box on p. 83), may occur more readily.
•    Some infections may be masked initially because fever is suppressed by the steroids.
•    Chickenpox and measles can be far more serious – even fatal – if steroid tablets are being

taken, or have been taken for more than three weeks within the last three months. This is something to

be very careful about (see item 15 on p. 143).
•    Prolonged use can increase the risk of chest infections.
•    Vaccination with live vaccines can cause problems.
•    Older people who once suffered from tuberculosis (TB) may find it comes back.
•    Steroids can lead to pregnancy if using an IUD, because IUDs work by inducing mild inflammation

in the womb.
The most insidious effect of steroids – and remember again that this is only a hazard of prolonged

high-dose treatment – is adrenal suppression. When steroid tablets are taken for more than three weeks,

the adrenal glands’ own ability to produce cortisol (see p. 141) starts to be slightly suppressed. The

longer the course of steroids, the greater the effect. Stopping the steroids abruptly leaves the body

without enough cortisol to protect itself, which, in the very worst cases, can lead to collapse. Less

obviously, there may be greater vulnerability to the effects of accidents, serious illnesses, surgery

or childbirth – demanding events that would normally stimulate a rise in cortisol production to help

the body cope with the stress.
If you take a short course of steroid tablets during this period, there is more risk of side effects

than normal. Adrenal suppression can last for 6-12 months after steroid treatment ends. It may be two

years before the body can cope with surgery unaided and you will need low doses of steroids to get you

through stress of this kind.
Will I look like a weight-lifter?
Absolutely not. The steroids taken by unscrupulous athletes to pump up their muscles artificially are

anabolic steroids. They are entirely different from the corticosteroids used to treat allergies.
Mimicking nature
All corticosteroids are chemically very similar to a substance known as cortisol that is produced

naturally by the body. Cortisol – which is a hormone made in the adrenal glands, located near the

kidneys – has a great number of different effects, apart from damping down inflammation. It regulates

the action of the kidneys, moves proteins out of the muscles and bones, and alters the pattern of fat

distribution.
Like other hormones and chemical messengers that the body produces, cortisol achieves its effects by

binding to receptors on target cells (e.g. immune cells, muscle cells and the cells that make up the

kidneys). These receptors vary a little, which gives researchers scope for making a synthetic version

of the hormone, cunningly modified so that it binds well to one kind of receptor (the one on the immune

cells, for example) but not so well to another (the one on the kidneys).
Hydrocortisone, the original steroid drug, is identical to cortisol, but the newer steroids have been

modified chemically to have the maximum effect on inflammation and minimal effects on other body

processes. While hydrocortisone can only be used for allergies at very low doses (as in

non-prescription hydrocortisone cream), the modified steroids can be used at higher doses.
The side effects of steroid drugs are of two basic kinds:
•    those due to suppression of inflammation (the desired effect of the drugs) because this

partially reduces immunity to disease
•    those due to the effects of steroids on other body processes – undesirable effects which have,

as far as possible, been designed out of the modern drugs.
These different side effects are discussed in more detail on p. 142. First, it is important to look at

the crucial difference between taking steroids in tablet form and applying them directly to the

affected area. Much unnecessary anxiety can be avoided by understanding this difference.
Targeting steroids
The risks of steroids fall dramatically if, instead of taking them in tablet form, you put them exactly

where they are needed: that means drops for the nose or eyes, inhalers to get the drug into the

airways, or creams and ointments to target the skin.
The medical term for this is topical application, and it is infinitely preferable to taking steroid

tablets. When a drug is swallowed, it does its job by being absorbed through the stomach lining into

the bloodstream, and then being carried around the body in the blood. This is called systemic treatment

because it reaches the whole body-system via the blood.
The areas that need the drug – the itchy skin or inflamed airways – get their dose, but so does every

other part of the body. In order to get a useful amount to the afflicted parts, a fairly large total

dose has to be taken which inevitably affects the rest of the body, making the drug far more hazardous.
When a drug is targeted precisely, in sprays, drops, creams or inhalers, the dose used can be very much

smaller. Some of the drug does get into the bloodstream, by penetrating the skin or the membranes of

the nose or airways, and entering the tiny blood vessels that lie just below. But the amount reaching

the bloodstream is usually minuscule compared with the amount in the blood when you take steroid

tablets. Systemic side effects –those due to the drug going round in the blood (see below) – are

usually avoided, although there may be some local side effects, where the drug is applied.
Only with very powerful doses – as in the steroid inhalers used for severe asthma, or high-potency

creams for eczema – do topical steroids reach the bloodstream in sufficient amounts to cause systemic

side effects. You have to be on these treatments for a long time, or be overdoing the dose (a possible

hazard with creams for eczema), to run the risk of systemic side effects.
Steroid tablets
Short courses of steroid tablets – which means three weeks or less – are pretty safe. They are usually

sufficient to get the inflammation under control, and can be taken three or four times a year without

creating any problems.
Even if you have no choice but to take steroid tablets on a long-term basis, remember that the serious

side effects can usually be avoided, or reversed if caught early (see p. 143).
Side effects
Apart from changes that may (rarely) occur in the stomach lining, the side effects of steroid tablets

are all systemic side effects.
In the early days of steroid use, a set of side effects that resemble a disease known as Cushing’s

Syndrome were frequently seen. The side effects included deposits of fat on the shoulders and abdomen,

and around the face, producing a ,moon face’, water retention resulting in puffiness, weakening of the

bones, easy bruising, acne and muscle wasting. All these changes are due to the unwanted effects of

steroids on other body processes, not to any effect on inflammation.
With the new and improved steroids (see left), plus a much more watchful approach by doctors, these

severe side effects have become very rare, but they can still occur in those on high-dose steroid

tablets. As long as they are noticed in good time (see p. 143) the problem can be reversed.
Using steroid tablets safely
Those taking steroid tablets for more than three weeks, or taking a lot of short courses, can protect

themselves from serious side effects in the following ways:
1. Weigh yourself every day. Should your weight suddenly start to rise, despite eating normally,

consult your doctor: this may be a sign of water retention.
2. If you develop hip pain, swollen ankles, muscle weakness or acne tell your doctor.
3. Get your blood pressure checked regularly by the doctor.
4. Get your eyes checked regularly by an optician, who can detect any problems before there is

irreversible damage.
5. In the case of children, make sure the child’s growth is being monitored carefully by the doctor.
6. Stay as active as possible, with plenty of vigorous exercise, to protect against osteoporosis. Avoid

getting too thin, as this is also a risk factor for osteoporosis. Reduce your salt intake and don’t

drink too much alcohol. Ask your doctor to order a bone-density measurement periodically. Following the

menopause, women on steroid tablets should consider taking hormone replacement therapy (HRT) as this

protects against osteoporosis.
7. Persistent unexplained back pain must be reported to your doctor: this can be a sign of

osteoporosis. If you fracture your wrist in a fall (a Colles’ fracture) make sure your doctor knows

about this, and prescribes urgent drug treatment for osteoporosis.
8. See your doctor if you are over-tired, thirsty, or need to pass urine much more frequently – these

can sometimes be signs of diabetes.
9. Take your tablets after food to protect the stomach. See your doctor if you have persistent

indigestion: coated forms of the tablets may help.
10. If you ever produce black, tarry stools, call your doctor immediately. This is generally a sign of

bleeding from the digestive tract.
11. With your doctor’s permission, take all your daily steroids as a single dose in the morning. The

long gap between one dose and the next stimulates the body to maintain its own steroid-making abilities

and so reduces the risk of adrenal suppression. It can also protect against growth problems in

children. Even greater protection comes from taking steroids on alternate days – one day on, one day

off – although not everyone can keep their symptoms under control with this regime. Obviously, you must

consult your doctor before you try. Your dose may need adjusting.
12. Adrenal suppression puts you at risk during any medical procedure. Tell your doctor, dentist, and

anyone treating you in an emergency – even if you stopped taking steroids up to two years earlier. You

should also carry a Steroid Card at all times, in case you are unconscious. These cards are available

from your doctor.
13. Ask the doctor what you should do if you develop any kind of infection or suffer an accident. It is

often necessary to increase the dose of steroid tablets.
14. Tell your doctor if you have ever had tuberculosis, as this can recur.
15. If you or your child have not had measles or chickenpox, avoid contact with anyone suffering from

these diseases – or from shingles (herpes zoster) which is caused by the chickenpox virus. See your

doctor promptly if there is any contact with someone infected. Emergency treatment to combat the virus

must be started promptly.
16. When being vaccinated, remind the doctor or nurse that you are taking steroid tablets.
17. Never stop taking steroid tablets abruptly if you have been taking them for more than three weeks,

as some degree of adrenal suppression may already have begun. Your body needs time to recover its

natural level of activity, so reduce the dosage gradually. Get precise instructions from your doctor

about how to do this.
18. If you are asthmatic, at the end of any course of steroid tablets lasting more than three weeks, be

extra careful about exposure to allergens and asthma triggers. You may be more vulnerable to severe

asthma attacks for as much as a year after long-term steroid tablets are stopped, or the dosage

reduced.
Watch out for adrenal suppression
If you develop any of the following symptoms after stopping steroids,
or while reducing the dose, call your doctor as soon as possible:
•    muscle weakness; muscle and joint pain
•    feeling ‘under the weather’
•    mental changes
•    scaly or flaking skin
•    breathlessness
•    lack of appetite; or nausea and vomiting
•    fever and weight loss
•    painful itchy lumps on the skin.
Note that, very rarely, withdrawal of steroid tablets, or lowering the dose, can unmask a disease

called Churg-Strauss Syndrome (see p. 160).
Steroid nose drops and sprays
Most steroid nose drops and nasal sprays contain very low doses of the drug, and produce no significant

side effects when used for short periods of time. The safety of these preparations is such that several

are available without prescription.
Steroid drops and sprays for the nose are a very effective way of treating hayfever and perennial

allergic rhinitis. They can be used after the symptoms have begun, or in advance of encountering the

allergen.
Steroid nose drops are also useful in reducing the size of nasal polyps (see p. 30) but only if the

drops are inserted correctly. Kneel down and, bending your neck forward as much as possible, put the

crown of your head on the floor. Now put the drops in and stay in this position for several minutes

while the drops reach their target. Once the polyps have shrunk, the drops can be replaced by a steroid

spray which will keep them under control.
Always stick to the stated dose, as with any drugs – don’t use the drops or spray more often than you

should. If you have a cold or other infection in the nose, stop using steroid drops and sprays until it

is better. Following surgical operations on the nose, ask your doctor’s advice before using steroid

drops or sprays.
Side effects
Minor short-term side effects may include dryness and irritation in the nose and throat, and

disturbances of smell and taste. Nosebleeds might occur and should be reported to your doctor. When

inserting the drops, try to keep them away from the central partition of the nose (the septum), as this

is
the part most vulnerable to bleeding. If you are a long-term user of steroid nose drops, your doctor

should check the membranes in your nose regularly, to be sure that they are not becoming thinned. Eye

checks may also be advisable with long-term use, as glaucoma can occur.
Allergic reactions to the steroid are possible, and they can cause bronchospasm (contraction of the

airway muscles) though this is unusual. You should obviously stop using the drops and see your doctor

if this occurs.
With very high doses of steroids in the nose, or prolonged treatment, some systemic side effects might

occur. The main cause for concern is children’s growth (see box on p. 145) – their height should be

checked regularly.
Steroid eye drops
Steroid eye drops are sometimes given for severe inflammation of the eye during the hayfever season.

However, the eye is vulnerable to infections if treated with steroid drops, and such treatment requires

close medical supervision.
Side effects
Be extremely careful about infections – don’t rub your eyes with your fingers, for example, or dry

around your eyes with a towel unless it is absolutely clean. Follow your doctor’s instructions very

carefully, and go back immediately if your eyes become more uncomfortable, if redness increases, or if

you have any other cause for concern.
Steroid eye drops are rarely used for more than a few weeks. With prolonged use, there is a risk of two

serious side effects, glaucoma and cataract.
Using two lots of steroid
Allergy sufferers who need steroid nose drops or a nasal spray, as well as a steroid inhaler, often

worry that they are getting too much steroid overall.
In fact there is no cause for concern, unless you are taking very high doses of inhaled steroid, in

which case talk the matter over with your doctor. The amount in most nose drops and sprays is quite

small and the same is true of steroid eye drops. In all cases, relatively little gets into the

bloodstream.
If you have allergies in the nose, this may well be making your asthma worse, and using steroid nose

drops can be very helpful for the asthma symptoms (see p. 39).
Inhaled steroids and children’s growth
If an asthmatic child inhales relatively high doses of steroids for many years, his or her growth can

be stunted. However, only a small number of children need these high doses, and with low to moderate

doses most children’s growth is unaffected. They may experience a short-term slow-down in growth, but

their eventual height should be normal.
Unfortunately, there are a few children whose growth is stunted even by relatively low doses of inhaled

steroids - and it is impossible to predict which children will respond in this way. However, if it is

noticed in good time, and if the steroids can be withdrawn safely, the child’s growth rate will almost

certainly recover.
Your GP or paediatrician should be monitoring your child’s growth. You can also measure this yourself,

and go back to the doctor if you are concerned. Keep the risks in perspective - uncontrolled severe

asthma also stunts children’s growth, as well as endangering the child in far more serious ways, so

don’t stop using the steroid inhaler.
Steroid inhalers
Inhaled steroids are a key part of the modern treatment of asthma (see p. 157). As with other topical

treatments, inhaled steroids are a great deal safer than steroid tablets. However, some of the drug

does get into the bloodstream, and with high-dose inhaled steroids taken for several years, the levels

can be high enough to cause systemic side effects such as osteoporosis (see p. 142).
The dose is the crucial factor here. The packaging or information leaflet that comes with your inhaler

will tell you how much of the drug is delivered with each inhalation. To interpret the information

about side effects correctly, you need to know your total daily consumption of inhaled steroid, and

whether this corresponds to a low, medium or high dose:
•    For budesonide or beclomethasone, two of the more common steroids, less than 400mcg

(micrograms) per day counts as a low dose for adults and children over the age of five. A moderate dose

is 500-800mcg per day, and more than 800mcg a day is a high dose.
•    For fluticasone (Flixotide), halve these figures (i.e. more than 400mcg a day is a high dose).
•    In the case of children under five, all these figures should be halved (e.g. a high dose of

beclomethasone is more than 400mcg a day).
•    For other steroids, check with your pharmacist.
Anyone taking a low or moderate dose has very little to worry about as regards systemic side effects.

Only those inhaling high-dose steroids for many years need feel concerned.
If you may be at risk of systemic side effects, follow the protective measures described for steroid

tablets on p. 143. Apart from growth suppression in children (see box above) the most likely effects

are osteoporosis, adrenal suppression, and a recurrence of tuberculosis.
You can minimise the risk of systemic side effects from
steroid inhalers by swallowing as little as possible of the steroid. Always rinse out your mouth,

gargle, and spit out the water after using your inhaler. Using your steroid inhaler morning and

evening, just before brushing your teeth, will make it much easier to remember to do this.
Bear in mind that inhaling steroids regularly will help you avoid the need for steroid tablets.

Asthmatics who are worried about side effects sometimes skip doses of their inhaled steroids, then find

their asthma is much worse and that they need a course of steroid tablets. Frequent courses of tablets

increase the risk of serious side effects.
Minor local side effects of inhaled steroids include hoarseness and short-lived coughing due to direct

irritation of the throat. These are no cause for concern.
If you are regularly inhaling steroids from a nebuliser, make sure the mask fits really well (see p.

163).
Because steroids reduce the immune defences a little, one common side effect of inhaling them is a

throat infection by Candida (see upper box on p. 83). Oesophageal infections with Candida can also

happen but these are rare; the symptoms are heartburn and indigestion. Gargling with warm water after

each inhalation will help prevent Candida infections. There are also anti-fungal lozenges, if you are

still having trouble.
Keep inhaled steroids away from your lips if you suffer from cold sores (herpes infections around the

mouth). These can be made worse with steroids.
Fortunately, other infections are no more common when using inhaled steroids. This includes chest

infections.
Recent research has found other side effects in children using high doses of inhaled steroids. Cough

and thirst are common, while hoarseness and loss of voice affect quite a few. Behavioural problems also

occur, including hyperactivity, mood swings, excitability, sleep disturbances, depression, and even

hallucinations.
Steroid creams and ointments
Steroid creams and ointments are used for both atopic eczema and contact dermatitis. By delivering the

drug to the place where it is needed, they reduce the dose required to an absolute minimum and, if used

correctly, are very safe. Dr Ernst Epstein, a dermatologist at the University of California, observes

‘All too often I encounter children who are miserable with uncontrolled atopic dermatitis because of

their parents’ unjustified fears of steroid side effects. It is cruel to the child and the family to

forgo topical medication.’
It is very important to use a steroid cream of the right strength. For example, applying a 1%

hydrocortisone cream (available without prescription) to severe atopic eczema will be of no value.

Similarly, only applying a prescribed cream occasionally, or only once a day when the doctor said three

times a day, will mean that the rash never really succumbs to the treatment.
Keeping old tubes of steroid cream in the bathroom cabinet, and using these rather than the newly

prescribed cream, is another frequent mistake. If the earlier prescription was for a weaker steroid

cream, that is not quite up to the job, you won’t get the symptoms under control.
Inadequate treatment means that the rash goes on longer, so you probably apply more steroid in the long

run – which exposes you to a greater risk of local side effects. It is far better to use a moderately

strong steroid cream for a short period of time and get the inflammation fully under control.
Remember that steroid creams are absorbed far more effectively immediately after a bath or shower, so

this is a good time to apply them (see p. 48).
Don’t stop using steroid creams too soon. The skin looks healthy and happy long before it is completely

healed underneath. You must continue until the ‘hidden healing’ has occurred. As a rough guide, the

point when the skin looks good is just the halfway point: so the steroid creams should be continued for

the same length of time again. If it took three weeks to get to the point where the skin looks fine,

then you should go on applying the steroid creams for another three weeks after that.
Generally speaking, it is a good idea to phase out steroid creams slowly, especially after using them

for a long period of time. Stopping abruptly may cause the rash to flare up again –this is called a

rebound effect.
Once you have atopic eczema under good control, you will still need some steroid cream at home for

dealing with relapses. As soon as you notice any rough, itchy skin, apply the cream twice daily for

three days, then once daily for another three days. This should be enough to curb the outbreak of

eczema before it really gets going.
Side effects
To assess the risk of side effects from your steroid cream or oirtment, you need to know how strong it

is. Four grades are recognised: mild (corresponding to non-prescription hydrocortisone cream),

moderately potent, potent and very potent. Ask your doctor or pharmacist which grade corresponds to

your cream, so that you can make sense of the information given below.
Unfortunately, if steroid creams are not used correctly, there are some quite serious local side

effects. Any steroid cream that is strong enough to work is also strong enough to produce side effects

if over-used, so this is a delicate balancing act. The main local side effects are thinning of the skin

and striae (stretch marks). Teenagers and pregnant women are particularly susceptible to stretch marks

if using steroid creams.
It is important to take care because these side effects can be irreversible. The stretch marks, for

example, may fade in time but never entirely disappear. Sustained over-use of steroid creams can

produce permanent thinning of the skin. Thinning of the ski on the face may produce redness, with small

blood vessels shoving through. The fingertips may develop painful cracks.
Note that these side effects can come on very gradually.. Some may be mistaken for symptoms of the

disease itself.
Other local side effects may include an outbreak of spots that look rather like acne. Increased

hairiness or change in skin colour are also possible. Fortunately these effects are reversible.
To avoid side effects, follow the instructions for using steroid creams carefully, and don’t apply too

much or too often. If you have not been given clear instructions by your doctor on the quantity to use,

go back and ask for more information. Ideally, you should actually be shown the correct amount of the

cream to use each time. Remember to wash your fingers after applying steroid creams
If potent or very potent steroid creams are slapped on W& abandon, enough is absorbed into the

bloodstream to produce systemic side effects, comparable to those that can occur with steroid tablets

(see p. 142).
With very potent steroid creams, used for a long period of time, there is some risk of slight systemic

side effects even though the instructions for use are carefully followed. Young children more

susceptible. Bear in mind that covering the skin with cages after applying the cream increases the

amount absorbed into the bloodstream. The degree of adrenal suppression caused by using the cream (see

p. 142) is probably going to remain unnoticed in everyday life, but a major illness, accident,

childbirth or a surgical operation might reveal the problem – so tell medical what you have been using.
Different areas of the body respond differently to steroids creams. The skin of the face, and within

skin folds.
sensitive and generally requires a lower-strength cream, while the palms of the hands and the soles of

the feet require a higher strength. The genitals and the area around the anus are particularly

sensitive, and can become permanently damaged (and then a source of intense discomfort) by strong

steroid creams: some dermatologists recommend using nothing stronger than 1 % hydrocortisone.
Make sure you see your doctor regularly when using steroid creams continuously, especially if:
•    you are using very potent steroid cream
•    you are applying potent or moderately potent steroid cream over more than 20% of your body for

more than a month
•    you are applying potent steroid cream to a baby or young child.
The vehicle – the cream or ointment base in which the steroid is carried – is important because

sensitivity reactions can occur to certain of its ingredients (see p. 45). Eczema sufferers can even

become sensitised to the steroid itself, and this problem is difficult to diagnose because patch tests

with steroids often give false negatives (see box on p. 91). If you are not getting better, ask the

doctor if this could be the explanation. (If a rash gets worse and starts to spread when you begin

using steroid creams, go back and see the doctor very promptly – you may have an infection called

tinea, or ringworm, which flourishes all the more when steroid creams are applied.)
Tacrolimus and pimecrolimus
These are new treatments for atopic eczema. They are not steroids, but are covered here because they

are an alternative to steroid creams and ointments, and if you are comparing the two treatments it may

help to have the information on them side-by-side.
Tacrolimus ointment (brand name Protopic) is for the treatment of moderate to severe atopic eczema, and

pimecrolimus ointment (brand name Elidel) is for milder atopic eczema, especially in children.
These drugs are immunomodulatory rather than immune-suppressive – they adjust the balance of immune

reactions in the
skin. Unlike with steroid creams, there is no risk of thinning the skin, so they can be used on

delicate areas like the face and eyelids.
These treatments are generally used for patients who are not getting better with moisturisers and

steroid creams. Because they cost so much more (about ten times as much as topical steroid treatment),

and since much of the fear of steroid creams is unfounded, doctors are reluctant to prescribe

tacrolimus ointment ,on demand’. With time, the cost of these treatments may fall.
One important advantage of tacrolimus and pimecrolimus ointments is that they may have good effects

that persist after you have stopped using them. And the benefits are cumulative: in one trial where

babies with atopic eczema were treated with pimecrolimus ointment on an as-needed basis, most had fewer

and fewer flare-ups as the months went by. This was not true of babies being treated with steroid

cream.
As with topical steroids, the effect of tacrolimus and pimecrolimus on infections such as

Staphylococcus aureus is surprisingly beneficial: the enormous improvement in the surface structure of

the skin keeps bacteria out. But heavily infected skin should be thoroughly treated with antibiotics

before you start. While using the ointment, watch out for any signs of infection, especially herpes

(see p. 44), and see your doctor immediately.
Minimise your exposure to UV light – in sunlight and sunlamps – because of the tendency of UV to

provoke skin cancers. With the dampening effect that tacrolimus has on the immune system, the risk of

skin cancers may be a little higher.
Don’t apply anything else to the skin (not even moisturisers) within two hours of putting on the

tacrolimus ointment – they dilute the treatment too much. And don’t apply tacrolimus ointment

underneath bandages or other dressings.
Side effects
A few patients find that, while using tacrolimus ointment, skin in areas not being treated actually

gets worse. Talk to your doctor if this happens. Other possible side effects include stinging and

burning when applied, or redness. These are nothing to worry about, and usually lessen with time.
Some common brand names
Common brand names of steroids include:
nose drops – Betnesol, Vista-Methasone
nasal sprays – Beclometasone, Beconase, Flixonase, Nasacort, Nasonex, Rhinocort Aqua, Syntaris eye

drops – Betnesol, Cloburate, Maxidex, Predsol, Vista-Methasone
inhalers – Aerobec, Becloforte, Beclometasone, Becotide, Flixotide, Pulmicort
tablets – Betnesol, Cortisyl, Dexamethasone, Medrone, Prednesol, Prednisolone,
creams – Adcortyl, Betnovate, Dermovate, Fucibet, Synalar