Posts Tagged ‘mast cell’

lithium succinate Lithium succinate appears to have sonic antifungal and anti-inflammatory properties, and is used as an 8% ointment for seborrhoeic dermatitis. (Ftalith).
lodoxamide A mast cell stabilizer similar to sodium cromoglycate. Used as eye drops (0.1%) in allergic conjunctivitis. (Alomide).
Dose: in acute diarrhoea, 4 mg initially, followed by 2 nig as required, up to a maximum of 16 ing daily. In chronic diarrhoea, 4-8 nig daily, but care is necessary in the elderly to avoid faecal impaction. Loperamide is not suitable for children under 4 years of age, nor in patients with liver disease, as it may cause undesirable sedation. (Iniodium).
loprazolam A benzodiazepine hypnotic used mainly in the short-term treatment of insomnia and nocturnal arousal. Dose: 1-2 nig at bedtime. Side-effects include drowsiness, dizziness, dry mouth and headache. See page 152 and Table 22.
loratadine An antihistamine with the general action of that group of drugs, but with reduced sedative side-effects.
Dose: 10 nig dailv. (Clarityn). See page I 10 and Table 2.
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lofepramine An antidepressant of the irnipramine group, with similar actions and uses, but reduced sedative and anticholinergic side-effects.
Dose: 140-210 nig daily. (Gamanil). See page 128 and Table 11.
lofexidine A narcotic antagonist. It has a selective blocking action on brain nor-adrenaline, and is used for the rapid relief of opioid withdrawal symptoms associated with central sympathetic activity.
Dose: 200 pg twice a day, slowly increased as required over 7-10 days, before withdrawal over 2-4 days. Care is necessary in cardiac insufficiency and bradycardia. (Britl.olex).
lomotil A preparation of diphenoxylate with atropine, for the rapid control of diarrhoea. Dose: 2 tablets 6-hourly.
lomustine A slow-acting cytotoxic agent used in Hodgkin’s disease and solid tumours.
Dose: 130 ing/ni’body surface at intervals of (> 8 weeks. Side-effects, include anorexia. nausea, liver damage and niyelodeprm ion. Dosage should not be repeated until white cell and platelet counts have returned to an acceptable level. Reduced doses are given
when lomustine forms part of a multi-drug dosage scheme. (CCNU). See page 122 and Table 8.
loperamide A synthetic inhibitor of peristalsis.
lorazepam A short-acting anxiolytic/ hypnotic similar to diazepam, but less likely to cause next-day drowsiness. Dose: 1-4 mgdaily. It is also given in similar oral closes or by slow i.v. injection in doses of 50 pglkg for preoperative sedation and anuiesia. Occasionally used i.v. in status epilepticus in doses of 4 nig, but apnoea and hypotension are side-effects that may require resuscitation. fAtivan). See page 152 and Table 22.
lormetazepam A short-acting benzodiazepine hypnotic. It is useful in the treatment of insomnia in the elderly, but is less suitable for insomnia associated with early awakening.
Dose: 500 fig I nig at night. See page 152 and ‘]’able 22.
losartanV An angiotensin 11 receptor antagonist used in the treatment of hypertension.
Dose: 50ing daily The use of potassium-sparing diuretics should be avoided with losartan. It has the advantage of not causing the persistent dry cough associated with ACE inhibitors. (Cozaar). See page 148 and Table 21.
low molecular weight heparins See heparin.
loxapine Antipsychotic agent with the actions and uses of chlorpromazine. Dose: in acute and chronic psychoses, 25-50 mg daily, slowly increased as required. Maintenance doses range from 20-100111g daily. Side-effects are those of other anti-psychotic agents. but loxapine may cause nausea, vomiting and weight changes. f .oxapac). See page 168 and Table 30.
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magnesium hydroxide A mild antacid laxative, usually given in aqueous suspension as Cream of Magnesia, although tablet forms are also available. Cream of Magnesia is a useful antidote in mineral acid poisoning.
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Lugol’s solution An aqueous solution of iodine 5% and potassium iodide 10%. Used in the preoperative treatment of t hyrotoxicosis.
Dose: 0.3-1 ml.
lymecycline A soluble complex of tetracycline and lysine. It has the action and uses and side-effects of tetracycline, but is absorbed more readily.
Dose: 800 mg daily. (Tetralysal).
typressin An analogue of vasopressin used to control the polyuria of pituitary diabetes insipidus.
Dose: 2.5-10 units several times a day by nasal spray. Side-effects include nausea and abdominal pain. I.ypressin has some vasoconstrictor properties, and desmopressin is sometimes prellcrred. (Syntopressin).
lysuride (lisuride) A bromocriptine-like drug for the treatment of parkinsonism. II acts by stimulating any surviving dopamine receptors in the brain.
Dose: 200 pg at night with food,
irk ceased at weekly intervals according to response up to a maximum of 5 mg daily. Side-effects include nausea, dizziness and initial hypotensive reactions which may affect driving ability. (Revanil). See
page 160 and Table 26.
magnesium sulphate Epsom salts. A powerful saline aperient, producing loose stools by preventing the reabsorption of water.
Dose: 5- 15 g before breakfast. Used externally for the treatment of boils and carbuncles as a paste with glycerin. A marked loss of plasma magnesium may occur after severe diarrhoea or drug-induced diuresis, and may require the i.v. infection of magnesium sulphate in doses based on the degree of hypoinagnesacmia. It has also been given i.v. in a dose of 8 mmol in the emergency treatment of severe;U’rhythinias associated with hypokalaemia.
magnesium trisilicate A white insoluble powder, with mild but prolonged antacid effects. It was formerly widely used in the symptomatic treatment of peptic ulcer;
now used chiefly for dyspepsia.
Dose: 0.3-2 g.
malathion An organophosphorus insecticide. Used as a lotion 0.5% for lice and scabies as alternative to lindane or carbaryl.
mannitol A sugar that is not metabolized, and is used mainly as an osmotic diuretic. Dose: (after a test dose of 200 mg/kg) 50-200 g by slow i.v. infusion over 24 hours. Mannitol has also been used by i.v. infusion as a short-term ocular hypotensive agent in the treatment of glaucoma. It is also useful in cerebral oedema, given by rapid i.v. injection in a dose of I g/kg as a 2044, solution.
macrolides A group of antibiotics that differ chemically from the penicillins, yet have a similar pattern of activity. They are active orally and are useful in the treatment of penicillin-sensitive patients. Erythromycin is the most widely used member of the group, with clarithromycin and azithromycin as more recent introductions.
magnesium carbonate A white, insoluble powder with antacid and laxative properties.
Dose: 0J-4 g daily.
maprotiline A sedative antidepressant with a general action similar to that of the tricyclic drugs represented by amitriptyline. Dose: 25-150 mg daily. If given at night as a single dose, the sedative action may reduce the need for other drugs. It has milder anticholinergic side-effects than some related compounds, although skin rash is more common. (I udionlil). See page 128 and Table 11.
mebendazole An anthelmintic effective against most intestinal worms.

Dose: 100 mg once for threadworm, and 100 mg twice daily for 2 days against other infestations. Generally well tolerated, but it should not be given to children under 2 years of age. (Verniox).
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in oedematous states. A potassium supplement may be required. Care is necessary in renal and hepatic deficiency.
(KiYcaron). See page 148 and Table 21.
mebeverine An antispasmodic agent which, unlike the anticholinergic drugs, appears to have a direct action on the intestinal smooth muscle. It is useful in the treatment of gastrointestinal spasm and in the irritable bowel syndrome. Dose: .100 mg daily, before food. As with other antispasmodics, mebeverine should not be used in paralytic ileus. (Colofac).
medroxyprogesterone A synthetic progestogen.
Dose: in endometriosis 30 mg daily for 90 days; in dysfunctional uterine bleeding and secondary amenorrhoea: 2.3-10 mg daily for 5-10 days, starling on l6th-2 Ist day of cycle and repeated for 2-3 cycles. Large doses of 400 mg-1.5 g daily are given in breast, endometrial, prostate and other hormone-dependent cancers, or 250mg– I g weekly by deep i.m. inJection. (Farlutal; proves). Depot-proves is a long-acting product used by i.m. injection is a contraceptive. but only after fit][ counselling.
megestrol An orally active progestogen. It is used in oestrogen-dependent breast cancer, and acts by suppressing the uptake of oestrogens by the cancer cells.
Dose: 160 mg daily. Nausea and fluid retention with weight gain are occasional side-effects. (Megace). See page 122.
meloxicarn A recently introduced non-steroidal anti-inflammatory drug (NSAID) indicated in the short-term treatment of acute osteo-arthritis and the longer-term treatment of rheumatoid conditions. Dose: 7.5-15 mg once daily with food; half doses for the elderly. Suppositories of 15 mg are also available. The side-effects are basically those of the NSAI Ds in general. Meloxicam has a more selective action on cyclo-oxygenase, the enzyme involved in the biosynthesis of prostaglandins, and is less likely to cause gastrointestinal disturbance, but it has no cytoprotective action, and is not suitable for patients with peptic ulcer. (Niobic). See page 165 and Table 29.
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mefenamic acid A non-steroidal anti-inflammatory analgesic agent used to relieve moderate pain in arthritic and rheumatoid conditions, and other states requiring mild analgesic therapy such as dysmenorrhoea. Dose: 1.5 g daily after food. Side-effects are drowsiness an(] haemolytic anaemia. Diarrhoea is an indication that the drug should be withdrawn. (Ponstan). See page 165 and Table 29.
rnefloquine A drug for the prophylaxis and treatment ofchloroquine-resistant malaria. Dose: lot- short -term prophylaxis 250 mg weekly, starting 1 week before exposure and for 4 weeks after return. Doses for treatment require specialist advice. Side-effects include gastrointestinal disturbances, dizziness and weakness. It is contraindicated in patients with a history of neu ro- psych iatric disturbance, and is not suitable for use in severe renal or hepatic impairment. (Lirium). See halofantrine.
mefruside A diuretic useful in the treatment of hypertension and oedema. Dose: 25-50 mg daily in the morning, according to need and response; 25-100 mg
melphalan An alkylating agent of the mustine type. Used mainly in myelomas, lymphomas and some solid tumours. Dose: 150-300 gg/kg daily for 4-6 days, repeated after 1-2 months. In myeloma it is also given by regional perfusion. The injection solution is highly irritant and contact should be avoided. Side-effects include myelo-depression, nausea, rash and pruritus. (Alkeran). See page 122 and ‘rabic 8.
menadiol A water-soluble form of vitamin K. Dose: 10 ing daily. (Synkavit) Phytorneii,dionc i.% now preferred.
menotrophin Human menopausal gonadotrophin containing follicle-stimulating hormone and luteinizing hormone. It is used in the treatment of anovulatory sterility. The dose depends on individual hormone assays and response. The use of the drug has resulted in multiple births. It is also given to males to stimulate spermatogenesis. (Humegon; Normegon).
menthol Colourless crystals obtained from oil of peppermint. Used as spray or drops for nasopharyngeal inflammation.

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).

Various anti-allergy drugs
An allergic reaction is a lengthy, complex process, and the various anti-allergy drugs all work on different stages of that process. That is why it often makes sense to use several different drugs for the same allergic condition: they each tackle the problem in their own way.
Steroids (see p. 140) intervene at a very late stage, quelling the inflammation that follows on from an allergic reaction. Using a steroid is rather like calling the fire brigade to put out a fire, whereas using an antihistamine (see p. 138) is like having fire-proof doors, to prevent the fire spreading at an early stage. Cromoglycate-type drugs (see below) intervene at an even earlier stage. They are like basic fire prevention - teaching children not to play with matches, or fitting smoke detectors.
Anti - leukotnene drugs (see p. 149) work at roughly the same stage of the process as anti-histamines but tackle an entirely different aspect of the allergic reaction.
Cromoglycate-type drugs
These drugs are also referred to as mast-cell stabilisers or mast-cell Mockers.
There are three drugs in this group, sodium cromoglycate (also spelled cromoglicate), nedocromil sodium, and lodoxamide. All operate at an early stage of the allergic reaction, stopping it before it actually starts. They stabilise the outer membrane of the mast cells (see box on p. 12), which prevents the allergic response from occurring.
Some common brand names
Common brand names of cromoglycate-type drugs include:
inhalers - Cromogen Easi-Breathe, Intal, Tilade
eye drops - Hay-Crom, Opticrom, Rapitil, Vividrin, Viz-on nose sprays - Rynacrom, Vividrin
capsules - Nalcrom
This is a far more satisfactory way of dealing with an allergic reaction than trying to tackle it after the reaction has occurred. But from a purely practical point of view, it has a drawback. I order to work at all, these drugs must reach the mast cells in advance of the allergen. They are of very little use if taken after the allergic reaction has begun.
For those who are taking cromoglycate-type drugs on a regular schedule, several times a day, it is very important to be conscientious about taking them on time. This maintains the protective effect of the drug, without any gaps.
If you are using these drugs on an ‘as-needed’ basis, you should take them 30 minutes before an allergen is encountered. or 30 minutes before a bout of exercise, if they are being prescribed for exercise-induced asthma. (Note that children sometimes respond differently, getting protection from these drugs immediately.)
The effect of these drugs takes time to build up. You should take them regularly for at least four weeks before deciding whether they are helping you or not.
One point in favour of cromoglycate-type drugs is that they are extremely safe, with few or no side effects in most people. Sadly, they do not work for everyone. A fairly high percentage of children respond well to them, but the response rate is much lower for adults. Nevertheless, adult allergy sufferers, especially those who need steroids to control their symptoms, should always be given the opportunity to try out these drugs. When cromoglycate-type drugs do work, they are very effective and almost always trouble-free, so they are a good alternative to steroids.
Both sodium cromoglycate and nedocromil sodium are available in inhaler form for asthma (see p. 157). Sodium cromoglycate is also available as nose drops for hayfever and other nasal allergies.
All three drugs are available as eye drops. Recent evidence suggests that sodium cromoglycate drops are less effective than the other two, particularly for the treatment of severe allergic conjunctivitis (inflammation of the eye).
Sodium cromoglycate is available in capsule form for food allergy. Note that these capsules are of very limited value in food allergy, and are certainly not a substitute for food avoidance. They do reduce sensitivity a little and can sometimes be helpful for those with multiple food allergies (see p. 67).
Side effects
There are no serious side effects at all for nedocromil sodium. cromoglycate can, very rarely, cause joint pain and swelling. An allergic reaction to the drug itself is even more uncommon. Stop taking the drug and see your doctor promptly if either of these occurs.
The only other side effects that have occasionally been reported are headache, nausea and vomiting. None of these indicates any damaging effect by the drugs – they are all minor side effects.
Eye drops containing these drugs may cause stinging and burning when inserted, but this is a minor side effect and usually wears off. Flushing and dizziness have sometimes been reported with lodoxamide eye drops.
Nose drops may also cause local irritation. This could be due to the drug itself, in which case it is a minor side effect. Alternatively, the irritation may be due to the preservative used or some other non-drug ingredient (see box on p. 33).
Occasionally cromoglycate nose drops cause bronchospasm – contraction of the airway muscles – but this tends to wear off quite quickly. Bronchospasm can also occur when cromoglycate-type drugs are inhaled (see p. 157).
Anti - leu kotriene drugs
These drugs, which have a set of very specific effects (see p. 159), were originally designed to treat asthma. Their potential for treating other allergic diseases is currently being explored:
•    Several studies show that they work well for perennial allergic rhinitis brought on by allergens such as house-dust mite. They also have some effect on hayfever, but standard treatment (such as antihistamines plus a steroid spray for the nose) is more effective.
•    They are especially useful for both rhinitis and asthma in patients suffering from triad (see box on p. 28). Research shows that they also reduce asthmatic reactions to very small test doses of aspirin, but they don’t give protection against anaphylaxis brought on by normal doses.
•    They have also been used successfully in cases of chronic urticaria and for some patients with delayed pressure urticaria. It seems plausible that they would also be helpful for chronic urticarla linked to aspirin sensitivity.
•    Preliminary trials suggest that these drugs might be useful in atopic eczema. Some studies show a very good response that allows a reduction in steroid creams.
•    Montelukast works very well for eosinophilic gastroenteritis and eosinophilic oesophagitis (see p. 72), according to some new studies.
For side effects of these drugs see pp. 159-60.
Anti-IgE drugs
Since the antibody IgE (see box on p. 12) is such a crucial player in allergic reactions, developing drugs that disable this antibody should help allergy sufferers. The first such drug is omalizumab (brand name Xolair) which was licensed for use in the United States in 2003. It is expected to become available in Britain some time in the next few years.
Omalizumab binds to IgE antibodies and stops them from interacting with mast cells, so blocking any allergic reaction. The drug is given as a ‘depot injection’, just under the skin, every 2-4 weeks. It is gradually released from the injection site and moves around the body in the blood, mopping up IgE molecules.
At present, omalizumab is used for severe hayfever and for people with asthma who are not responding well to the usual treatments. It is only worth using if there is clear evidence that allergies play a part in the asthma. Patients who use omalizumab are often able to reduce their dose of inhaled steroids – and they suffer fewer serious asthma attacks and have better lung function. Some patients can even stop using steroids completely.
Other anti-IgE drugs are in the pipeline. Pilot studies show that one works very well for peanut allergy: after just four injections, sensitivity to the allergen falls sharply, reducing the risk of anaphylaxis from traces of peanut eaten accidentally.
More powerful anti-allergy drugs
Occasionally people with severe allergies, who are on constant high doses of steroid tablets, or who fail to respond to steroids, need treatment with powerful anti-inflammatory drugs, such as methotrexate or cyclosporin. These suppress the immune system, and extremely careful monitoring for side effects is needed.
Adrenaline (epinephrine)
Anyone who has suffered anaphylactic shock (see p. 58) should be carrying a special syringe, called an auto-injector, loaded with adrenaline. The injector is very simple to operate and is designed for emergencies. Most allergy sufferers, even children, can give themselves the injection – or a parent or other adult can give it.
Some asthmatics, and those with food allergy who suffer swelling of the throat, may be given adrenaline in inhaler form as well (see pp. 155-6). This can be useful as an additional treatment but it’s definitely not a substitute for an injector.
See pp. 98-9 for instructions on using adrenaline in a crisis.
Wherever you go, take your injector with you. Always keep it close at hand: you need to be able to use it within minutes of the allergic reaction starting. You may be unable to speak (and therefore unable to ask someone else to fetch it) quite soon after the attack begins. The injector must never be refrigerated. It can also be damaged by sunlight and excess heat.
If you live in the countryside or in an area with a poor ambulance sevice, or if you are going camping or hiking somewhere remote, ask your doctor for a second injector, or one that can deliver multiple injections. Also ask about the maximum number of injections that can be given, and never exceed this total. Some doctors believe everyone should have two injectors, just in case the first dose doesn’t do the trick and help is slow in coming.
It is vital that you are shown exactly how to use the auto-injector. Canadian researchers discovered that only one in four
Some common brand names
Common brand names of adrenaline preparations include: auto-injectors – Anapen, EpiPen
inhalers – AsthmaHaler Mist, Bronkaid, Epiphrine
health professionals got the technique correct when demonstrating how to use an auto-injector In this study, pharmacists were much the best as regards accurate instructions. Dummy injectors are useful for training purposes and most pharmacies have them.
When the adrenaline auto-injectors expire, they can be very useful for practising with, or for showing a new baby-sitter or teacher – practise on an orange or grapefruit.
If you are taking beta-blockers (e.g. for a heart condition or anxiety), adrenaline may not have much effect.
Heavy daily use of beta-2 relievers for asthma (see p. 152) will also make adrenaline less effective when you need it.
Side effects
The important side effects of adrenaline involve the heart. Anyone with a heart condition should be given special advice in advance by their doctor about using adrenaline. The same goes for people with diabetes, hyperthyroidism or high blood pressure, and anyone taking tricyclic anti-depressants. There are quite a few minor side effects from adrenaline, such as anxiety, trembling, nausea. sweating, dizziness and cold extremities. These soon wear off.
Drugs that can make you worse
Aspirin and its relatives have a very bad effect on some people with rhinitis and/or asthma (see box on p. 151). Unfortunately, recent research shows that paracetamol is not safe either. It makes asthma more likely to develop in those who do not yet have the disease, and increases the severity of asthma symptoms for those who do. Unlike aspirin, paracetamol affects everyone, because it lowers the levels of a natural antioxidant, called glutathione, which the body makes to protect the lungs from oxidants. The greatest effects are seen in people who take paracetamol regularly (once a week or more), but even an occasional dose makes some difference.
All the other drugs that can make you worse are prescription drugs, and your doctor should be alert to the dangers. But doctors are overworked and sometimes forget, so it is sensible to know about the risks for yourself. If you have any doubt about the drugs you are taking, ask a pharmacist.
Beta-blockers are a major hazard for people with allergies. They can make the airways contract, and can bring on a serious asthma attack. They also make anaphylaxis more likely in someone who already has allergic reactions (see p. 59) and they increase the risk of a severe reaction to
immunotherapy (see p. 166) or skin-prick tests (see p. 91). Beta-blockers are prescribed for high blood pressure, angina and other heart problems, migraine and thyroid disease. There are alternative drugs in all cases. Sometimes asthma develops in people who have been taking beta-blockers for years. The beta-blockers are not responsible for this, but once asthma has begun, they will make symptoms worse. Eye drops for the treatment of glaucoma may also contain beta-blockers and can have a bad effect on asthmatics.
ACE inhibitors, used for heart conditions, may cause a cough and airway narrowing. They may also increase the risk of a severe reaction to immunotherapy.
Female hormones affect asthmatics, so taking the contraceptive pill or hormone replacement therapy (HRT) may make asthma worse. Progesterone-only contraceptive pills tend to cause fewer problems.
The drug isoniazid (INH), prescribed for tuberculosis, makes the body far more susceptible to histamine in foods (see p. 200).
An allergic reaction to a specific drug (e.g. penicillin) can also occur in some people, resulting in urticaria, or even anaphylactic shock.
Aspirin sensitivity
Aspirin sensitivity is not an allergic reaction, because neither IgE nor mast cells are involved. What causes this problem is a metabolic abnormality — a malfunction in one aspect of the body’s chemistry. The details of this are very complicated: you may want to skip the next three paragraphs and
simply read about how to cope with the problem.
The exact nature of aspirin sensitivity is still far from clear, but it seems to involve a relatively poor production of prostaglandins, combined with a plentiful production of leukotrienes. Both these substances are messenger chemicals which, broadly speaking, promote inflammation. But the details of their pro-inflammatory activities differ. It seems that, ideally, the body should have a harmonious balance between the two, and an imbalance produces problems.
Both prostaglandins and leukotrienes are manufactured from certain fats that are found in the diet. These fats, the raw materials, are worked on initially by two different enzymes — one that leads to the production of prostaglandins and another that leads to the production of leukotrienes.
If one of these enzymes is defective, it may mean that the other is oversupplied with raw materials, resulting in a serious imbalance between prostaglandins and leukotrienes. In those with aspirin sensitivity, or at risk of developing aspirin sensitivity, the enzyme that produces prostaglandins seems to be defective.
Even in the absence of aspirin, this imbalance in the production of prostaglandins and leukotrienes causes problems. It leads to symptoms such as chronic urticaria (see p. 51) or rhinitis, nasal polyps and asthma (a cluster of symptoms that is commonly called triad — see box on p. 28).
Taking aspirin can make the imbalance between prostaglandins and leukotrienes even worse in a person with this underlying abnormality. Aspirin exerts its painkilling effects by disabling the main prostaglandin-making enzyme — the enzyme that is already defective.
When someone with aspirin sensitivity takes aspirin, they may suffer worsening asthma, a severe asthma attack or — the worst-case scenario —collapse. This is a potentially fatal reaction, similar to anaphylaxis, requiring emergency medical treatment (see p. 101).
The greatest puzzle about aspirin sensitivity is why it often takes so long to develop in someone who already has the symptoms of triad —indicating the basic metabolic abnormality. It may be as much as 20 years from when someone has their first triad symptoms to when they begin reacting badly to aspirin.
If you have triad symptoms already, but no aspirin sensitivity yet, what should you do? Unfortunately, there are no safe tests for aspirin sensitivity at present — taking a small dose of aspirin and seeing what happens is very hazardous. It is probably best to assume that you are going to become sensitive to aspirin at some stage, and avoid all aspirin and aspirin-like drugs. Caution is the best plan here because aspirin sensitivity can come on very suddenly, and be life-threatening the very first time it occurs. Note
that some triad sufferers have polyps and rhinitis but no asthma until they actually develop aspirin sensitivity — a dose of aspirin suddenly brings on their first asthma attack plus other symptoms of aspirin sensitivity.
Avoiding aspirin itself is not difficult, but aspirin-like drugs pose more of a problem. Every year there are a number of deaths from these drugs. Some cases occur because a busy doctor momentarily forgets that a patient should not take these drugs. The drugs that need to be avoided are all known as non-steroidal anti-inflammatory drugs (NSAIDs), COX-1 inhibitors or COX-2 inhibitors. However you will not see any of these names on the packet. These drugs are very widely used for pain relief (e.g. in headache and backache remedies such as Nurofen), for the treatment of arthritis, and for several other inflammatory diseases.
There are dozens of non-steroidal anti-inflammatory drugs available, and many are sold under several different brand names. The list grows every year, as new drugs or new brands are launched. The only way to avoid these drugs is to be very cautious:
•    When buying any cold- or flu-remedies, painkillers, medicines for sprains or sports injuries (including those you apply directly to the skin), headache tablets or migraine tablets, always buy them at a chemist’s shop rather than a supermarket, and check with the pharmacist that they do not contain aspirin or aspirin-like drugs.
•    Be cautious also about remedies for an upset stomach. A few (e.g. Alka-Seltzer) contain aspirin.
•    Don’t take any drugs unless you are 100% sure of what they contain. Remember that the ingredients of a familiar brand name can sometimes change — read the label every time.
•    When a doctor prescribes any new drug, always mention that you are sensitive to aspirin, or that you have triad symptoms. Alternatively, check with the pharmacist when the prescription is filled.
•    Aspirin-free painkillers almost always contain paracetamol, a drug which can cause a severe reaction (similar to the collapse induced by aspirin itself) in about 5% of those with aspirin sensitivity. If you are taking paracetamol for the first time, start with half a tablet. Be sure that, for the next 2-3 hours, you have a way of getting to hospital quickly should you start to feel ill. (Note that paracetamol has another entirely separate effect, increasing the severity of asthma, and it is best not to take it too often — see box on p. 150.)
Avoiding all aspirin-like drugs will prevent you having anaphylaxis or severe attacks of asthma. Unfortunately, triad symptoms will not go away however careful you are about avoiding aspirin.
It is well worth trying the new anti-leukotriene drugs (see p. 149), especially if you have aspirin-induced asthma. They seem to help with triad symptoms by curtailing the activities of leukotrienes and so redressing the balance between leukotrienes and prostaglandins.