Hidden confusion: the options for treating asthma
BMJ 2002; 324 doi: https://doi.org/10.1136/sbmj.0204104 (Published 01 April 2002) Cite this as: BMJ 2002;324:0204104
- Daniel Aston, fourth year medical student1
For a respiratory consultant who sees patients with asthma every day it is probably second nature to prescribe a “Ventolin metered dose inhaler with a Volumatic spacer.” They will know that the patient will soon be happily inhaling salbutamol because the two devices fit together properly and the correct drug has been prescribed.
For medical students attached to a respiratory firm for less than two months, it is difficult not to envisage prescribing a “Serevent metered dose inhaler with a Nebuhaler spacer” in the hope that the patient will somehow be able to get a good dose of fluticasone from them.
Confused? Not surprising, as asthma treatment is a confusing business to all but the very experienced. This article will try to clear up some of the confusion and explain some of the other points about treating asthma.
Criteria for prescribing an asthma drug by its trade name
The pharmacokinetics of a drug differ from one brand to another
The therapeutic range is close to the toxic range
The toxic effects of the drug are potentially serious
The drugs
Generic or brand name?
The British Thoracic Society's guidelines have been developed to provide a structured approach to treating asthma.12 However, with the vast array of drugs--and devices for administering them--the reality of treating asthma may seem more complicated and confusing than a glance at the guidelines first suggests. Each drug has a generic name and a trade name, and there is more than one drug for most indications.
The first step of the guidelines recommends that the patient is started on a short acting β2 agonist. The physician then has a choice between salbutamol and terbutaline (generic names)--that is, tradenames Ventolin and Bricanyl.
In step two of the guidelines, there's a similar problem with the names of inhaled steroid. There are three main ones--beclometasone (formerly known as beclomethasone), budesonide, and fluticasone--each one with corresponding trade name (Becotide, Pulmicort, and Flixotide respectively).
The same problem continues throughout the treatment framework laid out by the guidelines, and there is little hard evidence to show that one treatment is superior or has better bioavailability than another. No trials, for example, have looked at salbutamol compared with terbutaline.
It is best to prescribe drugs by using their generic name rather than their trade name (although patients tend to know them by their trade name, so doctors should be familiar with both). There is one circumstance, however, when it is a better idea to use the trade name when prescribing treatment for asthma, and this is when a drug fulfils the three criteria shown in the box.
One drug that should, therefore, be prescribed by its trade name is theophylline, and this is especially true for modified release preparations of this drug. Potential toxic effects of theophylline include convulsions and cardiac arrhythmias. Examples of modified release theophylline include Nuelin SA and Theo-Dur.
In later steps of the guidelines, other drugs that may be used include the long acting β2 agonists (salmeterol and formoterol--Serevent and Oxis respectively) and the antimuscarinics (ipratropium and oxitropium--Atrovent and Oxivent respectively).
Combination therapies
Combination preparations are available of either steroid and long acting β2 agonist, or antimuscarinic and short acting β2 agonist. The former is a combination of fluticasone and salmeterol (Seretide) or budesonide and formoterol (Symbicort), and the latter is a combination of ipratropium and salbutamol (Combivent). Each combination therapy comes in different types depending on the relative amounts of each drug in the combination.
Most authorities advise against prescribing these therapies--but there is no problem with prescribing more than one drug provided that they are not in a ready made preparation. The British National Formulary says that these combination therapies are “less suitable for prescribing,” and they are not mentioned in the British Thoracic Society's guidelines.
One interesting question, however, is whether the compliance rate of patients using inhaled steroids would increase if the steroid was regularly prescribed in a combined preparation with a β2 agonist. It potentially adds some immediate effect to a drug that, as far as the patient is concerned, has no noticeable immediate effect.
This raises the question of whether patients would overuse inhalers containing steroid. For now, the best advice is probably to educate patients about the importance of both types of drug in separate inhalers.
Devices and routes of administration
The names of drugs for treating asthma are confusing enough, but when this is combined with the fact that there is a vast array of devices for delivering these drugs, the situation becomes almost bewildering.
Inhalers
Probably the best way of dividing up the different devices is into metered dose inhalers (often known as MDIs) and dry powder inhalers (DPIs).
Metered dose inhalers
MDIs are the most commonly prescribed devices for delivering asthma drugs. They provide an effective dose of the drug close to where it is required and therefore give a rapid response.
The fact that the drug is inhaled means that the dose can be much lower than if the drug was given orally, and so the MDI “gets around” the problem of systemic side effects. This is especially true for the inhaled steroids, which have many side effects if given orally for a long time but few if given with an MDI.
The problem with MDIs is that they are difficult to use: a lot of coordination is needed between pressing the button and inhaling correctly. One recent study has suggested that incorrect technique among MDI users may be as high as 38%.3 This illustrates how important it is in the management of asthma to educate and frequently review patients.
However, even with this support, some patients (especially young people) will need drugs via an alternative route. One solution that may make technique less of a problem is to use a breath actuated inhaler. This works in the same way as a normal MDI, but there is no button to press on the device. The patient inhales, and the device sprays the correct dose of drug automatically through the nozzle during the breath.
Dry powder inhalers
The dry powder inhalers have the same advantages as the MDIs but without the problem of the coordination needed to use them. Unfortunately, the actual amount of drug delivered to the patient using these devices varies substantially depending on age, sex, disease, and breathing cycle.4
Spacer devices
To reduce further the coordination needed to use an MDI, spacer devices may be used. These are plastic chambers into which the drug is administered through the MDI at one end, and the patient breathes in through a valve at the other. The patient should be told to breathe through the spacer as soon as possible after the drug has been actuated from the MDI, and only one actuation at a time is recommended. This is because the half life of the drug in the spacer is usually estimated at only 10 seconds. The amount of drug delivered by spacers varies substantially between devices and drugs.
The advantage of using a spacer is that a greater proportion of the drug reaches the lungs and a smaller proportion remains in the oropharynx, compared with the proportions delivered through an MDI alone. For this reason, children using inhaled steroids (especially at high doses) are strongly advised to use a spacer.
There are two main spacers--the Volumatic and the Nebuhaler--but unfortunately the MDIs made by each company will not fit the other company's spacer device. There are several solutions to this problem. The first is to prescribe a particular MDI and a spacer and allow the friendly local pharmacist to sort out the correct spacer to go with whichever MDI you have prescribed. Alternatively, a table listing the compatibilities between spacers and inhalers is available in the British National Formulary.5 There is also the AeroChamber spacer, which will fit MDIs made by any company. However, at least one study found this device to be less effective than the Volumatic or Nebuhaler in terms of the amount of the drug delivered to the lungs compared with the MDI alone.6
Nebulisers
Nebulisers are used to give high doses of inhaled drugs--particularly the β2 agonists and ipratropium. They work by converting a solution of the drug into a vapour that can then be inhaled, and they are often used to treat acute exacerbations or chronic severe asthma. Again, they vary in terms of the amount of drug delivered, and this depends on the type of nebuliser and the drug. They are also not available on the NHS in England and Wales and cannot be easily transported from place to place.
Oral and intravenous
Other routes of administration also exist. Some drugs are given orally--a common example being the β2 agonists in young children and also oral prednisolone over short time periods. The leukotriene antagonists (montelukast and zafirlukast--Singulair and Accolate respectively) can also be given as chewable tablets.
Sometimes drugs are given intravenously--but usually only in the treatment of acute severe asthma. If intravenous aminophylline is to be used in a patient who is resistant to β2 agonists it is extremely important to ensure that the patient is not already taking aminophylline or theophylline orally. The risk of giving a patient too high a dose of these drugs in such circumstances is great as the difference between a therapeutic and a toxic dose of the drug is small. As mentioned earlier, convulsions and cardiac arrhythmias may occur as a result.
CFC-free inhalers
In 1987 the Montreal Protocol committed all signatory nations--the United Kingdom included--to outlaw the production of chlorofluorocarbons (CFCs). There is therefore a move away from metered dose inhalers that use CFCs as their propellant, and these will probably not be available within a few years. Instead, new metered dose inhalers that use hydrofluoroalkanes7 are starting to be used, and these do not damage the ozone layer. These new inhalers will look different and even “taste” different from the CFC models -- but evidence suggests that bioavailability of salbutamol via these new inhalers is equivalent to that of the CFC models. This is not the case for inhaled steroids. In poorly controlled asthma, 100 μg of CFC-containing beclometasone can be substituted with 100 μg of CFC-free beclometasone, budesonide, or fluticasone. In well controlled asthma, however, 200-250 μg of CFC-containing beclometasone must be substituted with 100 μg of CFC-free eclomethasone or budesonide or with 100 μg of fluticasone.
Currently, only one CFC-free steroid inhaler is available (Qvar),but more will follow shortly. Just to muddy the waters further, it is likely that dose ratios may differ between the old, CFC-containing metered dose inhalers and the new, CFC-free versions.8
Notes
Originally published as: Student BMJ 2002;10:104