Posts Tagged ‘receptors’

nisoldipine A calcium channel blocking agent of the nifedipine type. Used in mild to moderate hypertension pertension and in the prophylaxis of chronic angina.
Dose: 10 ing once daily before breakfast with adequate fluid, slowly increased as required up to 40 mg daily. Tablets to be swallowed whole, not chewed or crushed. It may react with sonic other drugs in common use, and grapefruit juice should be avoided. (Syscor). See pages 114 & 148, and ‘Fables 4 & 21.
nitrazepam A benzodiazepine used as a mild hypnotic when some degree of daytime sedation is acceptable.
Dose: 5-10 mg at night, with reduced doses for elderly patients, and in renal and’ hepatic dysfunction. Care is necessary in respiratory depression. Some dependence on nitrazepam may occur, so extended treatment should be avoided. The combined use of alcohol increases the hypnotic action. (Mogadon; Remnos). Set: page 152 and Table 22.
Nitrocine A solution of glyceryl trinitrate, for i.v. infusion in myocardial ischaemia and refractory angina.
nitrofurantoin An antibacterial agent with a wide range of activity against the majority of urinary pathogens. It is of value in cystitis and pyelitis, and in renal infections that have become resistant to other drugs. It is also used prophylactically but extended use requires care.
Dose: 400 mg daily; 50-100 mg at night for prophylaxis. It is ineffective in an alkaline urine. Nausea, rash and peripheral neuropathy are side-effects, and acute and chronic pulmonary reactions have been reported. (Furadantin; Macrobid).
nitroglycerine See glyceryl trinitrate. nitroprusside See sodium nitroprusside.
nitrous oxide The oldest inhalation anaesthetic. Supplied in blue cylinders, it is widely used for induction and as part of a mixed anaesthetic system. It is also used as
a 50% oxygen mixture as an inhalation analgesic in obstetrics.
nizatidine A potent and selective H,-receptor antagonist chemically distinct from cimetidine or ranitidine.
Dose: in the treatment of benign duodenal and gastric ulcer, single doses of 300 mg daily, taken in the evening, or 150 mg twice a day, and continued for 4 weeks, or for s weeks in gastric ulcer including non-steroidal anti-inflammatory agent (NSAID) -induced ulceration. Occasionally given by i.v. infusion in doses of300mg daily. For prophylactic maintenance, doses of 150 mg daily may be given for up to a year. Reduced doses should be given in renal impairment. Side-effects include headache, niyalgia, cough, pruritus and abnormal dreams. (Axi& Zinga). See page 162 and “Fable 27.
non-steroidal anti-inflammatory drugs (NSAIDs) A group of drugs with analgesic anti-inflammatory properties widely used in arthritic, rheumatoid and related conditions. The response to a NSAID and the incidence and severity of side-effects such as gastric irritation and renal toxicity vary considerably, and the best NSAID for an individual patient is the one that gives optimum relief with minimal side-effects. The NSAIDs, of which aspirin is the oldest example, act by interrupting the biosynthesis of prostaglandins from arachidonic acid, in which process the enzyme cycleoxygenase (COX) plays a key role. It is now known that COX exists in two forms identified as COX-1 and COX-2. The anti-inflammatory action of the NSAIDs appears to be linked with the inhibition of COX-2, whereas the unwanted side-effects are associated with COX- I inhibition. Different NSAIDs have varying degrees of activity against the different forms of COX, which may explain the differences in the therapeutic response and the incidence of side-effects. Recently, a NSAID (meloxicain) has been introduced that has a more selective inhibitory action on COX-2, with which the incidence of side-effects appears to be lower than with the older drugs, and so may have therapeutic advantages. In general, the response to a NSAID may take 1-3 weeks to develop fully, but monitoring for gastrointestinal bleeding may be advisable if treatment is extended. A NSAID should not be given to a patient with a history of asthma or hypersensitivity, nor when peptic ulcer is suspected or present. In all cases, treatment should be commenced with the lowest recommended dose, and caution is necessary in the elderly, and when renal or hepatic function is impaired. See page 165 and Table 29.
Dose: 20 100 mg daily. It is given in nocturnal enuresis in doses of 10-20 mg nightly, but the duration of treatment should not exceed 3 months. (Allcgron). See page 128 and Table 11.
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noradrenaline (norepinephrine) The pressor hormone released at sympathetic nerve endings when such nerves are stimulated. It is also present with adrenaline in the medulla of the adrenal gland. It raises blood pressure mainly by a general vasoconstriction, whereas adrenaline acts by constricting the peripheral vessels and increasing the cardiac output. Noradrenaline is given by slow i.v. infusion in the treatment of shock, peripheral failure, and low blood pressure states, but the response may fluctuate with small variations in dose. The value of vasoconstrictors in shock is now questioned, as in shock the peripheral resistance may well be high, and the blood supply to essential organs such as the kidneys may be reduced.
Dose: 2-20 pg/niin, based on need and response. Great care must be taken to avoid extra-venous injection. (Levophed).
norethisterone An orally active progestogen. Used in amenorrhoea, functional uterine bleeding and dysmenorrhoea. Dose: 5-20 mg daily. In breast cancer, large doses up to 60 mg daily have been used. To postpone menstruation, 15 mg daily for 3 days have been used. In small doses, and in association with an oestrogen, norethisterone and related drugs are widely used as oral contraceptives. See page 264.
norfloxacin A quinolone antibacterial with the actions, uses and side-effects of cinoxacin and other quinolones.
Dose: in acute urinary tract infections, 801) mg daily for 3-10 days: in chronic infections continued for up to 12 weeks. ( I Itinor).
norgestrel (levonorgestrel) An orally active progesterone-like drug and inhibitor of ovulation. Used as a constituent of mixed oral contraceptive products, and as a ‘progestogen -only’ oral contraceptive. See page 264.
nortriptyline A tricyclic antidepressant with actions, uses and side-effects similar to those of amitriptyline, but with a reduced sedative activity.
NSAIDs See non-steroidal anti-inflamma-
tory drugs, page 168 and Table 29.
nystatin A fungicidal antibiotic, used in the treatment of intestinal, vaginal and superficial candidiasis. Oral tablets contain 500 000 units, pessaries contain 100 000 units; cream and ointment 1%. Dose: (oral) 2 million units daily. It is also used as pastilles of 100000 units for mouth infections.
octreotide A synthetic compound that inhibits the release of the growth hormone. It is used in acromegaly, which is caused by an overproduction of the growth hormone by a pituitary tumour and it is given in doses of 100-200pg 8-hourly by s.c. injection. It is also used in the symptomatic treatment of the carcinoid syndrome, in which the release of vasoactive substances by a gastro- pancreatic tumour causes flushing and severe diarrhoea.
Dose: 30 pg by s.c. injection, increased as needed up to 600 pg daily. It has no action on the cause of the syndrome. It is used occasionally in terminal care to reduce intestinal secretions and vomiting. Dose: 300-600 pg by s.c. infusion. (Sandostatin).
oestradloIlThe oestrogenic hormone controlling ovulation and menstruation. It has been used to control menopausal symptoms in doses of 10-20pg daily, but skin patches are now preferred for hormone replacement therapy (HRT). It is used occasionally as s.c. implants for long-term treatment. Oestradiol is also present in some cream preparations for menopausal atrophic vaginitis.
oestriol A natural oestrogen used in intravaginal cream to relieve the atrophic vaginitis and kraurosis vulvae associated with the menopause. Also given in doses of 1-32 mg daily for the genito-urinary symptoms linked with infections in oestrogen deficiency states. (Ovestin).

ofloxacin A fluorinated quinolone with the actions, uses and side-effects of other quinolones such as ciprofloxacin and norfloxacin. It is used mainly in urinary and lower respiratory tract infections. Dose: wii nig daily as a single morning dose. Dose in severe infections 200-400 mg daily by i.v. injection. An occasional side-effect is tendon damage with pain and inflammation, which requires immediate withdrawal of the drug. Exposure to strong sunlight should be avoided. (Tarivid). Also used as eye drops (0.3%) for superficial eye infections. (Exocin).
olanzapineV An antipsychotic agent for the treatment of schizophrenia. It has a more selective action on certain 5-H’I'- receptors, and is less likely to cause extra-pyramidal side-effects.
Dose: 10 mg as a single daily dose, slowly increased as required. Maintenance dose 5-20 mg daily. Side-effects include
sedation and weight gain. (Zyprexa). See page 168 and Table 30.
olsalazine A compound formed from mesalazine, and used in the treatment of ulcerative colitis. It is more slowly
absorbed, and reaches the colon largely unchanged, where it is broken down by intestinal bacteria to release the active metabolite mesalazine.
Dose: 1-3 g daily in acute mild ulcerative colitis; I g daily for maintenance, often for long periods. The common side-effect is a watery diarrhoea. Salicylate sensitivity is a contraindication. Patients are now advised to report any bruising, bleeding or
malaise. I( a blood dyscrasia is suspected, a blood count should be made -,in(] the drug withdrawn. (Dipentuni). See page 172 and Table 32.
ondansetron A potent antiemetic, of value in the nausea and vomiting associated with cancer chemotherapy. Such vomiting appears to be induced by the release of serotonin, which acts on receptors in the gut as well as stimulating the chernoreceptor trigger zone in the brain. Ondansetron is a specific (5—HT,) serotonin blocking agent, and is given before the commencement of cytotoxic treatment or radiotherapy.
Dose: 24 mg daily; in severe vomiting an initial dose of 8 ing is given by slow i.v. injection, followed by I ing/hrly for 24 hours by continuous i.v. infusion, followed by oral therapy. Side-effects are an initial sense of warmth, headache an(] constipation. (Zofran). See page 158.
topium The dried juice from the capsules of the opium poppy. See morphine.
orciprenaline A synipathomimetic agent with the bronchodilator properties of isoprenaline. It is used for the relief of obstructive airway conditions, although more selective drugs of the salbutarnol type are often preferred.
Dose: up to 80 ang daily; by aerosol inhalation up to 12 puffs (9mg) daily. Side-effects include tremor and tachycardia. (Ahiperil). See page 118 and Table 6.
orphenadrine A spasmolytic drug, used in the treatment of parkinsonism, and for the relief of voluntary muscle spasm. Dose: 150-400 nig daily. It may also be given by i.m. injection in doses of 60 mg. In parkinsonism it tends to control the rigidity more than the tremor. Side-effects are anticholinergic and include dryness of the mouth, dizziness and visual disturbances. Weight gain has occurred with high doses. (Disipal; Norflex). See
page 160 and Table 26.
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omeprazole An inhibitor of the enzyme I I*K’A'I’Pase.’rhat enzyme controls the final stage of gastric acid production, and its inhibition by omeprazole is of value in peptic ulcer resistant to H, receptor antagonists, and in reflux oesophagitis, where such agents are not always effective. Dose: in benign gastric and duodenal ulcer, 20-40 ing as it single daily dose for 4-8 weeks. Larger doses may be required in the Zollinger—Ellison syndrome. Side-effects such as nausea, gasiro-intestinal disturbances and headaches are usually mild. (Losec). See page 162 and Table 27.
oxazepam A benzodiazepine with the actions, uses and side-effects of diazepam. It is useful in acute anxiety and panic states.
Dose: 45-120 mg daily. See page 117 and Table 5.
oxerutins A mixture of rutosides (flavonoid derivatives) which is claimed to reduce capillary fragility and permeability. It has been used in venous disorders of the lower limbs.
Dose: 750-1000 nig daily. (Paroven).

Acupuncture
Acupuncture shot to fame in the West in 1972, when James Reston, a correspondent for the New York Times, fell ill with appendicitis while covering President Nixon’s historic

trip to China. Following the removal of his appendix, he received acupuncture treatment for pain, and was highly impressed with its effects.
His Chinese doctor invited Reston to witness the use of acupuncture in anaesthesia, and he reported the remarkable fact that patients undergoing surgery could be free from pain

with just a few tiny needles inserted into carefully chosen points on the body. They remained alert and talkative throughout the operation.
Traditional Chinese medicine has enjoyed a good reputation in the West ever since, but what few people realise is that acupuncture anaesthesia is a very new invention. Surgery

was not traditionally practised in China and it was only in the 1950s, after Chairman Mao had urged Chinese doctors to unify Western and Chinese medicine, that the anaesthetic

potential of acupuncture was discovered.
The remarkable effects of acupuncture anaesthesia made a huge impression on doctors in the West – a high-profile success that has had both good and bad results. On the positive

side, conventional medicine has been prepared to take acupuncture seriously, and to undertake some research into its effects. On the negative side, most
of that research has concerned pain control – the effects of acupuncture on the endorphins. These are natural painkilling compounds produced by the body (their effects are

mimicked by opiate drugs such as morphine and heroin).
Western researchers have paid little attention to how acupuncture affects most other aspects of health, including the immune system and allergic diseases. One exception to this

is asthma, where certain nerves do play a large part in producing the symptoms (see box on p. 235).
Treating the person
Diagnosis and treatment are far more orientated towards the individual patient-, in traditional Chinese medicine, and diagnostic labels such as ‘allergy’ or `hayfever’ are less

important than the particular character of a person’s Qi (see box on p. 215), as detected by the acupuncturist. A traditional Chinese acupuncturist pays great attention to the

quality of the different pulses and takes them at the start of every appointment, and at intervals during treatment, to check how the Qi flow has changed. Each treatment session

is unique and tailored to the individual’s condition at that particular moment.
This makes it very difficult to carry out conventional scientific research into traditional acupuncture.
In an effort to make acupuncture accessible to research, a more Westernised and formulaic approach has been developed, using orthodox medical diagnosis and needling a set of

acupuncture points that are prescribed for that medical condition. Experts in traditional acupuncture feel that this approach – first name the disease, then apply a standard

remedy – will often fail, and is missing the whole point of acupuncture.
That is not the only problem with Westernised acupuncture, as Dr David Eisenberg of Harvard University, a leading expert on acupuncture, points out. He describes a typical

acupuncture session in China: ‘Each time the acupuncturist inserts a needle, he or she asks the patient, “Do you have it or not?” referring to the patient’s “obtaining the Qi”

(de Qi). The question asks whether the patient has felt a sensation of fullness, distension, pins and needles, or the like, from the insertion of the needle in the spot being

used… Most Chinese have experienced acupuncture and they understand the phenomenon of de Qi… By contrast, most Western patients seeking acupuncture therapy know nothing of

the phenomenon of de Qi. Not knowing what sensations they should anticipate, they cannot tell the acupuncturist whether a needle is in the right place. When both therapist and

patient know little about de Qi, as frequently occurs in Western acupuncture clinics, the result is bound to be disappointing.’ Fortunately it is possible to find acupuncturists

who have been properly trained, and the sensation of ‘obtaining the Qi’ is perfectly detectable, even to a sceptical Westerner, so look for someone who pays attention to this.
There can be emotional and psychological reactions to acupuncture, so make sure that you also feel relaxed with your acupuncturist and that there is a certain empathy between

you.
Does acupuncture work for allergies?
According to Chinese theories, acupuncture can have some benefits in any illness – if you are ill, your flow of Qi must be disturbed, and it will help to put that right. Indeed,

most people do feel a sense of well-being after an acupuncture session.
To look at this from a Western scientific perspective, acupuncture can stimulate your body to increase its production of endorphins (see p. 214). This gives you a mild high,

similar to that you’d get from running for a couple of hours. Feeling relaxed and confident helps most people to cope better, and gives them a new perspective on life’s

problems. Since the mind plays some part in almost all illness (if only to aggravate the effects of an underlying physical problem), inducing a more positive state of mind can

be of benefit.
As regards more specific effects, several studies show that acupuncture can have a small, short-term effect in opening up the airways of asthmatics. This is not surprising

because acupuncture affects the autonomic nervous system, the ‘auto-pilot’ section of the nervous system (see box on p. 235) which can tighten or relax the muscles around the

airways. A short-term effect is just that – it doesn’t treat the real problem. What matters more in asthma is the long-term impact of any treatment on the underlying

inflammation of the airways (see p. 36). Although some studies of acupuncture treatment have found a reduction in inflammation, other studies have not. However, only one study

to date used an individualised approach to acupuncture, as opposed to a same-for-everyone formula. It is interesting that this study did find good long-term effects on airway

inflammation.
The larger picture
Acupuncture is just one element of Chinese medicine, which has several other techniques available. In China (and in some Chinese clinics in the West) these techniques are used

together, as different ways of tackling the same problem. No traditional Chinese doctor would dream of trying to treat every patient with acupuncture alone and, in the case of a

patient with allergies, herbal remedies would usually be a central part of the treatment.
A recent and very careful scientific study from Germany took this combined approach with hayfever, and showed some benefit. The patients were treated with both acupuncture and

herbal treatment, using a standardised regime but with additional acupuncture points and herbs chosen to suit the individual. Those treated reported a substantial improvement in

how they felt generally –but not in the specific symptoms of hayfever.
The flow of energy
Acupuncture is rooted in ancient Chinese ideas of the human body. which are radically different from those of Western medicine:
•    Vital energy. called Oi or Chi (and always pronounced ‘thee’). is what distinguishes living bodies from dead ones. It should flow easily and harmoniously thrOLIC11011i

the body nourishing and protecting the organs. When the flow of Qi is blocked, or becomes unbalanced. then illness develops. - Channels called meridians are the conduits for Qi

in the body. They mostly run vertically (i.e. from head to toe) and the points where acupuncture needles are inserted all lie on these meridians.
•    The flow of Qi can be measured by carefully taking pulses — not just one pulse as in Western medicine, but several different kinds of pulse.
•    By detecting disturbances in the flow of Qi, and correcting them, existing illness can be cured, and incipient illness prevented, before there are any obvious symptoms.
The nature of the meridians and the acupuncture points remains a mystery to Western doctors. Some parts of the meridians run roughly along the lines of certain nerves or blood

vessels, but they do not follow them exactly. The acupuncture points have no anatomical reality — there is nothing to see either on the surface or under the skin. However, many

are located near major nerve endings or over deep pressure receptors.

Drugs for Asthma
The drug treatment of asthma is far more complex than for any other allergic disease. Drugs prescribed for asthma fall into two basic categories: those that open up the airways by relaxing the airway muscles, called relievers, and those that treat the inflammation in the lining of the airways, called preventers. The former offer a ‘quick fix’ - like taking an aspirin when you have a headache. Just as the actual cause of the headache is not treated by an aspirin, so the actual cause of the asthma attack is not addressed by relievers. Preventers, on the other hand, tackle the basic problem - the inflammation that triggers the contraction of the airway muscles (see p. 36).
In the past ten years, there has been a quiet revolution in asthma treatment, with far more people being given preventer inhalers, usually low-dose steroids. The aim is to get the airways in better condition, with the inflammation thoroughly damped down, so that the airway muscles don’t go into spasm. The ultimate objective is to make people far less reliant on reliever inhalers, because the potential hazards of over-using them are now realised.
The details of modern asthma management, and the different approaches used, are described on p. 160, following the discussion of the main types of drug used for asthma treatment.
Beta-2 relievers (beta-agonists)
Our airways open up when we produce adrenaline. This is the body’s natural response to feeling angry or frightened. The adrenaline widens the airways so that we can run faster or fight more vigorously.
Adrenaline (epinephrine), given as a drug, was among the earliest treatments for asthma. However, it also stimulates the heart to beat faster and raises
the blood pressure. While it is useful for emergency treatment (see p. 155) the side effects make it too hazardous for routine use.
The beta-2 relievers work by mimicking adrenaline – they bind to the same receptors in the airways, the beta-2 receptors. Binding to these receptors stimulates the airway muscles to relax, so that the airways open up.
In other respects, the beta-2 relievers are not like adrenaline. Clever chemical manipulation has made them sufficiently different from adrenaline to have little effect on the heart and other organs, when taken at normal doses.
Beta-2 relievers are best taken by inhalation. Although tablets and syrup are available these are far more likely to bring on side effects, because the dose needed is so much bigger.
Inhaled beta-2 relievers target the drug directly on the airways, so the dose can be smaller. They also have the great advantage of taking effect soon after being inhaled, and giving full relief from airway narrowing within 10-15 minutes.
There are two different kinds of beta-2 relievers:
•    the traditional short-acting beta-2 relievers whose effects last for 3-6 hours (usually about four). The modern consensus is that these should be used only when needed, not taken routinely.
•    the newer long-acting beta-2 relievers, which last up to 12 hours. These drugs are prescribed for more severe forms of asthma (see p. 154), and are generally used routinely, twice a day.
A key question for asthma sufferers is: How often can short-acting beta-2 relievers be used? Ideas about this have changed considerably over the last 20 years, and no doctor would now want to have patients using a Ventolin inhaler five, six or more times a day - something that was quite common in the past. This level of need for beta-2 relievers indicates that the asthma is poorly controlled and requires treatment with a preventer, to quell the inflammation in the airways.
Detailed policy on beta-2 relievers still varies from one part of the world to another. British guidelines state that anyone who needs to use a short-acting beta-2 reliever more than once a day, or who suffers from nocturnal asthma, should be given a preventer as well. The international guideline is more stringent: if a short-acting beta-2 reliever is needed more than three times a week, a preventer should also be prescribed.
How safe are these drugs in the long term? The cause of the big re-think on beta-2 relievers was an epidemic of asthma-related deaths in New Zealand between 1976 and 1988. The death rate from severe asthma attacks was 2-4 times its previous level for a while, and over a thousand New Zealanders died in the epidemic.
There has been a huge controversy over what exactly caused these deaths. Most researchers now agree that the main cause was a new brand of inhaler that delivered a double dose of the drug fenoterol, a short-acting beta-2 reliever with a very powerful effect on the airways and quite high levels of side effects involving the heart. The same brand of inhaler may have been linked to increased death rates in Canada and Germany.
Research suggests that the problem was greatest in New Zealand because sales of the new inhaler were highest there, and because many patients got their inhalers through repeat prescriptions. As a result, people whose asthma was deteriorating badly were not seen by a doctor and were using large amounts of beta-2 reliever, rather than taking preventer drugs. This is now believed to be a major cause of asthma deaths. There are three separate factors involved:
•    The beta-2 reliever covers up the effects of the severe inflammation of the airways. People feel reasonably well, because the reliever is opening up their airways, and don’t realise just how bad their asthma really is. The untreated inflammation in the airways can eventually lead to a very serious, and potentially fatal, asthma attack.
•    The short-acting beta-2 reliever, used regularly, makes the airways more sensitive to exercise, and to allergens such as dust mite or pollen. This means that an asthmatic who is already allergic to these allergens reacts to them at much lower levels in the air.
•    The airways become less and less responsive to the beta-2 reliever itself, so that when a serious attack occurs, requiring hospital treatment, huge doses of beta-2 reliever are needed to open up the airways. These massive doses carry a risk of serious side effects involving the heart.
The details of the New Zealand epidemic still evoke controversy. Was fenoterol itself, which is stronger than other beta-2 relievers, the cause of the deaths? Or was it just that the inhaler delivered a double dose - would any short-acting beta-2 reliever be dangerous at twice the normal dose? Or was it over-use of all beta-2 relievers and lack of preventer drugs?
Some common brand names
Common brand names include:
short-acting beta-2 relievers in inhalers - Aerolin, Airomir, Bricanyl, Ventolin short-acting beta-2 relievers in tablets - Bambec, Bricanyl, Volmax short-acting beta-2 relievers in syrup - Monovent, Ventolin
long-acting beta-2 relievers in inhalers - Bambec, Foradil, Oxis, Serevent
Until this is resolved, safety-conscious asthmatics may want to assume that any of these possibilities could be correct. An ultra-cautious approach would include:
•    Avoiding fenoterol (it is no longer available in Britain, except in the Duovent inhaler, combined with an anti -choli nerg ic drug)
•    Not using double-dose inhalers of any beta-2 reliever (i.e. inhalers that deliver 200mcg/ micrograms per puff)
•    Not routinely taking two puffs of a single-dose inhaler (check with your doctor if you have been told to take two puffs)
•    Using any short-acting beta-2 reliever only I as needed’ – which should be once a day or less according to British guidelines. Note that, with this level of use, there is absolutely no risk from these drugs: it is only regular over-use that is damaging and dangerous.
•    Using a peak-flow meter and ensuring that you are assessed regularly by your doctor
•    Always taking your preventer medication as prescribed.
Since about 1990, the death rate from asthma has been falling, particularly in countries with a policy of reducing use of beta-2 relievers, and increasing inhaled steroids. The death rate in New Zealand is now the lowest it has been for 50 years, and at the same level as in other Western countries.
Unnecessary alarm
While investigating the causes of the New Zealand epidemic, medical researchers discovered that patients inhaling a short-acting beta-2 reliever four times a day had more irritable airways after just two weeks. Their airways were also less responsive to the drug, even after this brief period of use.
Some researchers began to ask if the asthma epidemic itself – the increasing number of cases of asthma – could actually be due to these drugs. Maybe children with mild wheezing, which might have cleared up if left untreated (and which would have gone untreated in the past) were becoming full-blown asthmatics because they were now using beta-2 inhalers?
Many doctors became very concerned about these questions, and a leading medical journal
published an article with the provocative title: ‘Worldwide worsening wheezing – is the cure the cause?’ That was in 1992. Since then, much more research has been done, and it is clear that this particular fear about beta-2 relievers was unfounded.
Unfortunately, there are a few books and other publications around that are spreading unnecessary alarm about these drugs by reporting the debate as it was in 1992. They have taken up that question ‘Is the cure the cause?’, assumed that the answer is ‘yes’, and ignored all the subsequent research, which shows the opposite.
Beta-2 relievers in severe asthma
A few patients with severe asthma remain breathless and wheezy, even though they are inhaling moderate doses of a steroid preventer every day. Increasing the dose of inhaled steroids does not make a huge difference to their symptoms, and it substantially raises the risk of steroid side effects.
Taking a long-acting beta-2 reliever often works wonders for such patients. These relatively new drugs relax the airway muscles, and go on working for 12 hours or more.
There has obviously been concern about long-acting beta-2 relievers having the same sort of insidious side effects as their short-acting colleagues (see p. 153), and so increasing the likelihood of deaths from asthma. However, studies of people taking these drugs suggest that the risks are minimal. Certainly, long-acting drugs taken twice a day are very much safer than short-acting drugs taken four times a day.
Other studies show that the chemical differences of the long-acting drugs, as well as prolonging their effects, also give them a more complex set of actions in the body. For example, they improve the effect of steroids in calming inflammation, and may even have some small anti-inflammatory effect of their own.
Doctors believe that, for patients with troublesome asthma, the benefits of long-acting beta-2 relievers greatly outweigh the risks. But they should only be used in combination with inhaled steroids. Various other options, such as allergen avoidance and the new anti - leukotriene drugs (see p. 159), should probably be investigated as well.
If you are taking long-acting beta-2 relievers, do use them regularly, once every 12 hours – the good effect gradually builds up with consistent use.
Generally speaking, you should not take additional doses in between. These are not intended for use if you have a sudden asthma attack – your doctor will prescribe a short-acting beta-2 reliever for this. This limitation on the use of long-acting beta-2 relievers is certainly appropriate for salmeterol (which was the first of the long-acting beta-2 relievers to be developed) because it is very slow to take effect on the airways. However, one of the newer long-acting beta-2 relievers, called formoterol, begins to work just as quickly as a short-acting beta-2 reliever. Formoterol could, in theory, be used on an ‘as-needed’ basis to combat asthma attacks. You may want to discuss this possibility with your doctor.
Finally, don’t stop taking your preventer drug (e.g. inhaled steroid or cromoglycate), even if you feel a lot better. Long-acting beta-2 relievers are not a substitute for preventers.
Some patients with very severe asthma need to take regular doses of short-acting beta-2 relievers as well as long-acting beta-2 relievers. You should obviously follow the advice of your asthma specialist closely if you are on this kind of drug regime, and not change anything without approval. However, it might be worth discussing other options, such as anti -leukotriene drugs. In addition, do all you can to combat your asthma in other ways – by reducing allergen exposure, avoiding asthma triggers (see p. 39), and employing various other self-help measures (see p. 41).
Immediate side effects of beta-2 relievers
Minor immediate side effects of these drugs include:
•    headache
•    nervousness, trembling, restlessness, anxiety; children may become more excitable, and some are badly behaved or even aggressive.
•    flushing
•    dry mouth
•    muscle cramps.
These side effects – all of which are due to the resemblance of beta-2 relievers to adrenaline – usually wear off relatively quickly. Some long-acting beta-2 relievers may cause nausea and vomiting.
A pounding heart is usually a relatively minor side effect, but it can be more serious, and should be reported to your doctor.
A few asthmatics find that their airways tighten up when these drugs are inhaled, rather than opening. This is called paradoxical bronchoconstriction. If this happens, stop using the inhaler and see your doctor as soon as you can.
Even more rarely, asthmatics can develop allergic reactions to the drugs, or suffer hallucinations or seizures. Obviously you should stop using the inhaler immediately if you experience side effects of this kind, and should see your doctor.
There can be an interaction between beta-2 relievers and other drugs or medical conditions. Should you need a diuretic, tell the doctor or pharmacist that you are also taking a beta-2 reliever, and ask which diuretics are safe. If you have high blood pressure, a heart problem, or a thyroid condition, make sure the doctor remembers this when prescribing beta-2 relievers.
Adrenaline inhalers
Adrenaline inhalers are for use in emergencies. Technically, they are not available in Britain, but they can be imported under special licence, and your doctor may be persuaded to obtain one for you if he or she thinks it might be useful. They are given to people who have asthma and have sometimes had attacks of anaphylaxis (see p. 58), for example in reaction to food, latex or an insect sting. The inhaler provides prompt emergency treatment for the kind of severe asthma attack that you may experience during anaphylaxis.
You should probably be carrying an adrenaline auto-injector as well, as you may need to use both (see p. 98). Those who usually have fairly mild reactions to their allergen can use the inhaler first, to treat symptoms in the mouth, throat and airways. If other symptoms develop, such as faintness or widespread nettle rash,
Asthma alert
If you ever find that your short-acting beta-2 reliever has no effect within ten minutes, or is needed more than once every four hours, this indicates a serious asthma attack and you need urgent medical help (see p. 100).
During a severe asthma attack, while getting to hospital or waiting for a doctor to arrive, up to 30 puffs of a short-acting beta-2 reliever should be taken as an emergency treatment, to get the airways open. There is a risk of death if you don’t use the reliever fully in this situation. (This emergency dose is safe for almost everyone, but there may be risks if you have a heart condition – get detailed advice from your doctor in advance.)
then the adrenaline injector can be used. Those with a history of more severe reactions should start with the adrenaline injector and then use the inhaler if there are still symptoms in the mouth or airways.
Don’t exceed the maximum number of puffs stated on the canister, as the propellant can cause problems. If you have a heart condition, your doctor will advise you about using this kind of treatment safely - adrenaline can affect the heart.
Ephedrine
Ephedrine and orciprenaline (brand name Alupent) belong to the previous generation of reliever drugs. They are chemically very similar to adrenaline and therefore cause a lot of side effects, especially involving the heart.
These drugs are no longer recommended, and will soon be phased out completely. Some older asthmatics may still be using them, just because they have been on them for years and no one has reviewed their treatment.
If you are taking such drugs, ask your doctor about switching to a newer form of reliever - it will be more effective in treating your asthma, as well as having fewer side effects.
Anti -cho linerg ics
These drugs, also known as anti-muscarinics, are relievers. However, they work in a completely different way from the beta-2 relievers. They block the action of the parasympathetic nervous system, a set of nerves that are the biological equivalent of auto-pilot - working without the intervention of conscious thought. The parasympathetic nervous system has many effects on the body, including keeping the airway muscles nicely toned (see box on p. 235). By blocking the parasympathetic, anticholinergics help the airway muscles to relax.
Anti-cholinergics are taken by inhaler, and require 30-90 minutes to achieve their full effects. They should continue working for 3-6 hours.
Some common brand names
Common brand names of anti-cholinergics include: inhalers – Atrovent, Oxivent
nasal spray - Rinatec
For most asthmatics, especially those with a strong allergic component to their asthma, anti-cholinergics are generally less effective than beta-2 relievers. But they are useful to children under one year, who may not respond to beta-2 relievers. They also have a role where asthma is combined with chronic bronchitis -here the anti -choli nerg ics can sometimes be more effective than beta-2 relievers - and they are particularly useful for asthma with a lot of mucus, because blocking the parasympathetic tends to reduce mucus production. For severe asthmatics, anticholinergics may be combined with beta-2 relievers.
Anti -choli nerg ics should be taken only when needed, not regularly several times a day. If used regularly, they can make the airways more sensitive, just as short-acting beta-2 relievers can (see p. 153).
Side effects
Minor side effects of anti-cholinergics may include a dry mouth, blurred vision, constipation, and irritation of the mouth and throat. A few people suffer nausea or difficulty in passing urine.
Serious side effects are rare. Any increase in the stickiness of the sputum coughed up may be a cause for concern, especially in children. If there is an increase in wheezing or coughing, stop taking the drug and see your doctor.
If you already have glaucoma or prostate problems you should be monitored carefully by your doctor, as these conditions can get worse with anti -choli nerg ic drugs.
When anti -choli nerg ics are used in a nebuliser, it is vital that the mask fits well (see p. 163).
Anti-cholinergics for the nose
Another use for anti-cholinergics is in nasal sprays, for the treatment of vasomotor rhinitis, a non-allergic condition that is frequently mistaken for allergic rhinitis (see p. 29). In this disorder, the constant flow of mucus is caused by a malfunction of the parasympathetic nervous system, which is why anti-cholinergics work well.