Medical Management

What is the role of medicines in management of asthma?

Use of medicines for management of asthma requires continuous monitoring. When your symptoms worsen, your doctor may add new medicines or increase the dose of medicines you take regularly. Similarly when the symptoms improve, some medicines may either be withdrawn or their dose decreased.

There are two kinds of medicines for asthma management:

Bronchodilators: Also known as reliever medicines these help to relax the muscles of the airways and therefore open them. Bronchodilators give relief during asthmatic attacks. They can also avoid attacks or reduce their severity. Normally, bronchodilators are recommended as inhalers but are also available as liquids, tablets, capsules and injections. There are three main categories of bronchodilators: (a) beta2 agonists, (b) methylxanthines and (c) anticholinergics.
(a) Beta2 agonists: These medicines stimulate the sympathetic nervous system which is a part of autonomous nervous system that controls all involuntary actions of the blood vessels, organs, etc. The sympathetic nervous system prepares the body for action by increasing the heart rate and stimulating other parts of the body.
The beta blockade theory for asthma has been discussed earlier. According to this theory, people with asthma have abnormal beta2 receptors and therefore the nerve impulses from the brain do not reach them. Receptors are special nerve endings that respond to various stimuli. When the nerve impulses do not reach beta2 receptors, there is narrowing of the airways. Beta2 agonists act on receptors of the lungs. An ‘agonist’ provokes. Thus, beta2 agonists provoke or stimulate beta2 receptors in the muscles around the airways. When these receptors are stimulated, the muscles of the airways relax and respiratory passages dilate.

Given below are the advantages and disadvantages of beta2 agonists:

• They are safe, short-acting medicines and relax the airways.
• They are available in various forms and therefore help individualize treatments.
• Beta2 agonist injections are effective in emergencies as they act quickly. Their effect however lasts only for twenty minutes.
• Two to three puffs of inhaled beta2 agonists taken before an exercise or exposure to cold air can prevent symptoms for about four hours.
• Long-acting beta2 agonists prevent symptoms at night or early in the morning. Their effect lasts for about twelve hours.
• Excessive use of these medicines indicates over¬ reliance on bronchodilators, which can lead to poor asthma control.
• Beta2 agonists are effective for controlling symptoms only for a short time. They are not effective for severe symptoms of asthma.
• The side effects of beta2 agonists such as shakiness, increased heart rate or palpitations are minimal if they are used as inhalers. These side effects normally disappear over a period of time.
• Beta2 agonists taken as tablets can cause more severe side effects such as nervousness, palpitation, cramps in the muscles, drowsiness or tremors as compared to inhalers.
Beta2 agonists can be either short acting or long¬ acting. Commonly used short-acting beta2 agonists are terbutaline and salbutamol.

Terbutaline: This medicine is available either as tablets or inhalation aerosol. The tablets need to be stored at room temperature in an airtight and light resistant container. The inhalation aerosol needs to be stored at room temperature away from excessive heat.

Terbutaline is effective for controlling wheezing and easing difficulty in breathing. It acts directly on the muscles of the airways and relaxes them.
Side effects: Minor side effects of terbutaline include anxiety, bad taste in the mouth, dizziness, headache, hot flushes, irritability, sleeplessness, loss of appetite, nausea, restlessness, increased sweating, vomiting or weakness. All these side effects disappear as the body adjusts to the medicine.
You need to consult your doctor immediately if you have major side effects such as increased wheezing or difficulty in breathing, muscle cramps or palpitations.

Terbutaline can interact with several medicines and you therefore need to inform your doctor about any medicines that you may be taking. Beta-blockers reduce the effectiveness of terbutaline. Beta-blockers are used for heart diseases, high blood pressure, migraine, etc. Some anti-depressants, anti-allergy medicines and over-the-counter cough, cold and sinus medicines can increase the side effects of terbutaline. If you are diabetic, it may be necessary to adjust the dose of insulin or oral anti-diabetic medicines after terbutaline is started.

Terbutaline should be used with caution and only, under the doctor’s supervision in the following situations if:

• You have had any allergies to other medicines in the past, especially medicines such as amphetamines, ephedrine, epinephrine, pseudoephedrine, etc.
• You have diabetes, glaucoma (increased pressure in the eyes), high blood pressure, heart disease, epilepsy, enlarged prostrate gland or diseases of the thyroid gland.
• You have to undergo surgery or some dental procedures.
• You are either pregnant or breast-feeding.
Do not puncture, break or burn the terbutaline inhalation aerosol container. This is because the medicine is filled under pressure and may explode. Do not exceed the dose of terbutaline above that recommended by your doctor. In case you do not get relief, consult your doctor.

Salbutamol’ The uses, side effects, interactions with other medicines and precautions for salbutamol are the same as those described for terbutaline.

Long-acting beta2 agonists used for management of asthma include salmeterol and eformoterol. They are normally recommended for people who have frequent episodes of asthma at night and who are on oral anti-inflammatory medicines such as corticosteroids or on corticosteroid inhalers. These medicines do not treat the inflammation in the airways and result in opening of the airways for up to twelve hours after you take them. This medicine takes longer to act. This is why you should always carry a short-acting beta2 agonist with you for use when you need relief from acute symptoms.

Long-acting beta2 agonists are recommended for children above four years of age who have disturbed sleep because of asthma and who need frequent doses of short-acting beta2 agonists throughout the day. It is not yet clear if long-term use of long-acting beta2 agonists actually worsens asthma.

Salmeterol’ This medicine is available as inhalation aerosol. It protects against a wide range of asthma stimulants such as exercise, allergens, histamine, etc. It acts about half hour after inhalation and maximum effect is observed after two hours. This effect may last up to ten hours. Regular use of salmeterol may make it less effective.

Side effects: Minor side effects of salmeterol include anxiety, dizziness, drowsiness, dryness or irritation of the mouth or throat, increased heartbeat rate, hot flush, loss of appetite, nausea, increased sweating or weakness. Most of these side effects disappear as your body gets used to the medicine.

Salmeterol also reacts with several other medicines. Beta-blockers can decrease its effectiveness while some medicines for cough, cold, sinus, allergy and other bronchodilators can worsen its side effects.

Eformoterol The usage, side effects and interaction with other medicines for eformoterol are the same as those described for salmeterol.
(b) Methylxanthines: Until a few years back, methylxanthines were the main medicines used for management of asthma. However, in recent years, the use of inhalers has proven to be more effective. Exactly how methylxanthines work in the lungs is not clear. It is believed that these medicines act on the mast cells in the lungs and inhibit them from discharging chemicals such as histamine. Methylxanthines relax airway muscles and therefore open the airways. They are also believed to act as anti-inflammatory during the later phases of asthmatic attacks.
Theophylline and aminophylline are two common methylxanthine medicines. They are available as tablets or capsules. It is important to remember that caffeine is considered to be a methylxanthine. You therefore need to have tea, coffee and chocolates with caution while on methylxanthines.

Side effects: Most side effects of methylxanthines subside once you stop taking the medicines. You need to consult your doctor immediately if you have nausea, vomiting, diarrhoea, seizures, headache or palpitations. These are the symptoms of methylxanthine toxicity. You should also consult your doctor if you have other side effects such as sleeplessness, increased frequency of passing urine, indigestion or long ¬term digestive disturbances.

Methylxanthines can react with several other medicines. Beta-blockers can reduce the effectiveness of methylxanthines. These medicines can increase the side effects of several medicines taken for sinus, cough and cold and medicines used as blood thinners. They can decrease the effectiveness of medicines used for controlling epilepsy. Sudden change in the diet, such as taking high-protein and low carbohydrate diet can affect the action of methylxanthines.
(c) Anticholinergics: Common anticholinergics used for asthma are atropine and ipratropium bromide. Atropine has more side effects and is therefore not used very often.
Anticholinergics are not normally used as the first line of treatment for asthma. They are normally used along with beta2 agonists. Anticholinergics stimulate specific lung receptors in the vagus nerve. This nerve branches into the muscles that are responsible for opening the airways and mucus glands that discharge thick secretions in the airways. They reduce inflammation and relax the muscles of the airways.

Newer anticholinergics such as ipratropium bromide have fewer side effects because less medicine is absorbed into the lungs. This is why some doctors prefer to use them for relief from acute bronchospasm as an alternative to beta2 agonists.

Side effects: Dry mouth and throat, and increased wheezing are common side effects of anticholinergics. Anticholinergics are not effective for asthma triggered by exercise or allergens. They take long to act. Their maximum effect is observed after thirty to sixty minutes.

Anti-inflammatory medicines: About a decade ago, a panel of international experts identified asthma as an ongoing problem where there is inflammation of the airways. They, therefore, recommended anti-inflammatory medicines for prevention of symptoms of asthma, such as wheezing and breathlessness.

Anti-inflammatory medicines act deep inside the airways where inflammation begins. They block production of chemicals inside the mast cells. As mentioned earlier, mast cells release chemical substances as a reaction to allergens. When anti-inflammatory medicines act on the mast cells, they reduce or reverse swelling in the airways. They also reduce sensitivity of the airways to various allergens. Lesser reaction to allergens prevents inflammation and helps keep airways open. It is important to remember that the effect of some anti-inflammatory medicines begins several days or weeks after you start taking them. This is why you should not give them up within a few days if there is no obvious improvement in symptoms.

There are three main types of anti-inflammatory medicines: (a) steroids, (b) non-steroids and (c) anti-allergic medicines.

Steroids can be either taken as pills or inhaled. Oral steroids lead to several serious side effects and this is why many people with asthma feel that all types of steroids are ‘bad’. This is not true. Inhaled steroids have lesser side-effects.

Oral steroids: are often used as a last alternative in case of severe uncontrolled asthma or acute attacks. Oral steroids are synthetic forms of natural steroids produced by the adrenal glands. Adrenal glands are small organs that are located just above the kidneys.
They produce several hormones that affect many important functions in the body:
Common oral steroids used for management of asthma include betamethasone, dexamethasone, cortisone, hydrocortisone, prednisone and methylprednisolone. All oral steroids have severe side effects if used for a long period. This is why oral steroids are used very carefully in the management of asthma.
The dose of oral steroids depends on the severity of asthma. Your doctor will recommend tests such as peak flow and spirometry to assess the dose of steroids required. Normally, steroid dose is tapered off over a period of one to three weeks. It is desirable that you take steroids early in the morning so that they match the body’s natural schedule for steroid production. However, in case of severe asthma, you may have to take it at night too.

Advantages of oral steroids include the following: They are powerful anti-inflammatory medicines. . They offer fast and dramatic relief from symptoms of asthma in life-threatening situations.

• Although some steroids are effective only after a few hours, their protective effect lasts longer.
• They can be used for a short duration to control symptoms of asthma before starting long-term medicines that have fewer side effects
Oral steroids have several disadvantages. When you start taking oral steroids, the adrenal glands stop producing natural steroids. Once you stop taking steroids, natural production of steroids resumes only after some time. In the intervening period, you may suffer withdrawal symptoms such as weakness, fatigue, body ache or fever. It is important that you don’t stop steroids suddenly as it can be very dangerous, especially if you have been taking them for a long time.

Listed below are the common side effects of oral steroids:

• Increased fluid retention in the body
• Osteoporosis, a condition in which there is loss of bone tissue and as a result, the bones become brittle and liable to fracture
• Increased appetite and therefore weight gain
• High blood pressure
• High blood sugar levels
• Weakness in the muscles
• Increased risk of ulcers in the stomach
• Cataract, a condition in which there is opacity of the lens of the eyes and causes blurred vision
• Changes in the skin such as pimples, rashes, thin skin that is easily bruised, etc. retarded growth in children. Excessive hair growth in various parts of the body.

Inhaled steroids are very useful for management of asthma because they are inhaled straight into the airways. Thus, they act locally and very little medicine is absorbed into the blood stream. Inhaled steroids reduce swelling in the airways and improve upon opening of the airways by the bronchodilators. Your doctor is likely to prescribe inhaled beta2 agonist with an inhaled steroid. Beta2 agonist is inhaled first so that the airways open. When you inhale steroids next, they are able to penetrate deeper into the airways.

Inhaled steroids have several advantages:

• Their side effects are significantly lower than those of oral steroids.
• They are in the form of nebulizers and dry powder. They are therefore more effective.
• Inhaled steroids significantly reduce inflammation in the airways if they are used continuously for about one month
• They improve breathing and reduce sensitivity of the airways to allergens.
Although inhaled steroids have fewer side effects as compared to oral steroids; they can cause unpleasant symptoms similar to those caused by oral steroids if used for a long time in very high doses. The most common side effect of inhaled steroids is candidiasis, an infection caused by a yeast present in the mouth and back of the throat. Candidiasis is more common if you have diabetes or if you take antibiotics along with inhaled steroids. Common symptoms of candidiasis include white patches at the back of the throat, unpleasant and sticky sensation in the mouth or throat, sore throat and difficulty in swallowing.

The risk of candidiasis can be greatly reduced if you inhale steroids using a spacer. This is because spacer allows the medicine to enter the lungs directly rather than through the mouth and throat. Spacers and their use are discussed later in the book. You can prevent candidiasis by rinsing your mouth after each inhalation treatment. Gargle with warm water to remove residual medicine in your throat for enhanced protection.

Inhaled steroids normally recommended for management of asthma include the following:

Beclomethasone: This steroid is used frequently. The dose depends upon the severity of asthma and the type of inhalation delivery system. It is normally recommended in the doses of fifty, one hundred or two hundred and fifty micrograms per inhalation if taken with metered dose inhalers. The dose with autohaler varies from four hundred to two thousand micrograms per day for adults and two to four hundred micrograms per day for children.

Budesonide: This is an effective and widely used inhaled steroid. It is normally used once a day by adults who are able to control their symptoms with up to four hundred micrograms of inhaled steroid per day. Budesonide can also be given to infants and young children through nebulizers.

The dose of budesonide varies from fifty to two hundred micrograms per inhalation if given through metered dose inhalers. If given through turbuhalers, it varies from four hundred to twenty-four hundred micrograms per day for adults and two to eight hundred micrograms per day for children.

Fluticasone: This medicine is twice as effective as beclomethasone and budesonide. This medicine is normally recommended for children above four years of age and adults if they have either one or more of the following four conditions:

• There is a high risk of developing osteoporosis, a condition in which there is loss of bone mass.
• There are significant side effects of steroids.
• Asthma control is poor, as indicated by continued or worsening symptoms or excessive use ofbeta2 agonists.
• Lung functions are less than expected.
Fluticasone can be inhaled through a metered dose inhaler and is recommended in the dose of fifty, one hundred and twenty-five or two hundred and fifty micrograms per inhalation. The dose for adults or children above sixteen years varies from one hundred to one thousand micrograms twice a day. Children below four years are normally given fifty to hundred micrograms of fluticasone twice a day.

Non-steroidal anti-inflammatory medicines used for asthma are also called mast cell stabilizers. They are long term medicines that reduce early and delayed symptom of asthmatic attack. These medicines prevent the release of chemical substances from the mast cells in response to inflammation and allergic reactions. Mast cell stabilizers are available as metered dose inhalers, powder inhalers and in nebuliser form. Several research studies are underway for development of newer varieties of anti-inflammatory medicines.

Mast cell stabilizers have several advantages. They have fewer side effects as compared to most other asthma medicines. Regular use of mast cell stabilizers prevents swelling of the inner lining of the airways, especially in response to cold air, allergens and some irritant gases. They can replace steroids and theophylline, especially if you have mild and persistent asthma. Mast cell stabilizers are very useful in treatment of asthma in children. This is because allergy is one of the main causes of asthma in children. These medicines can also prevent exercise induced asthma if taken half hour before starting any exercise.

Disadvantages of mast cell stabilizers are as follows:

• They do not relieve symptoms once asthmatic attack starts. They can only control asthma caused by some particular factors.

• They need to be taken four times a day and therefore there is a risk of missing doses.
• They act slowly. Some medicines in this group begin to show results only after three to six weeks.
• They leave an unpleasant taste in the mouth.
• They can cause minor side effects such as throat irritation, skin rashes, dry cough or nausea.
Common mast cell stabilizers used for management of asthma include:

Sodium chromoglycate: This medicine prevents both, immediate and late asthma response to triggers or inducers. It inhibits release of chemical substances from the mast cells in response to an allergen. It is often recommended as an initial preventive therapy for children with frequent attacks of asthma. It can also effectively control mild asthma in adults.
Sodium chromoglycate is normally taken with a metered dose inhaler although dry powder forms are also available in some countries. Its benefits can be observed after about one to two weeks. Sometimes the benefits may be observed even after four weeks.

The preferred dose of sodium chromoglycate is one milligram per inhalation, with two to three inhalations about twice or thrice a day. The actual dose will however depend upon the severity of asthma.

Nedochromil sodium: This non-steroidal medicine is different in its chemical composition from sodium chromoglycate and steroids. Just like sodium chromoglycate, it also prevents early and late asthmatic reactions to allergens or exercise.

Nedochromil sodium is normally recommended for mild to moderate persistent asthma in adults and children above two years of age who have very frequent asthmatic attacks. The normal dose of this medicine is about two milligrams per inhalation if taken through a metered dose inhaler.

Anti-allergic medicines: Several studies are underway to determine the use of anti-allergic medicines for effective control of allergies. These medicines are believed to reduce the activity of mast cells or inhibit release of chemical substances from these cells.

Anti-allergic medicines may be useful in controlling mild to moderate asthma. They may also reduce the need for other medicines. Benefits are normally seen after about two months of regular treatment.

The main disadvantage of anti-allergic medicines is that they act only if the cause of asthma is exposure to allergens. Also, they are unable to reduce the need for inhaled medicines. Anti-allergic medicines can cause drowsiness during the first few weeks of treatment.

Other medicines

A new group of medicines called anti-Ieukotriene medicines have been introduced for treatment of asthma during the last few years. Leukotrienes are chemical messengers that are produced by inflamed cells in order to communicate with each other. There are two types of leukotriene medicines. One which prevents the production of leukotrienes and another which prevents the chemicals of inflamed cells from reaching specific receptors.

Anti-Ieukotriene medicines protect against narrowing of the airways if they are taken before exercise or exposure to allergens or cold. They also decrease both, early and late asthmatic reactions. Since these medicines are very new, many doctors do not prefer to use them as a routine treatment for asthma.

Antihistamines: This is a group of medicines that block the effect of a chemical compound called histamine. Histamine is released from the mast cells in response to an allergic reaction. Antihistamines are used for allergic reactions such as itching, redness or swelling in the skin, eyes and nose. Many people believe that since asthma and allergy often go together, these medicines can be used to reduce swelling of the inner lining of the airways. This is however not always true. In fact some antihistamines may make asthma worse. These medicines cause drying of the inner lining of the airways and therefore increase the risk of mucus plugs blocking the smaller airways. Dry lining may also cause narrowing of the airways. This is why it is desirable that you avoid self-medication with antihistamines if you have minor illnesses such as skin rash, common cold, etc.

Antihistamines are normally not recommended or are used with caution if you (a) have allergy to any medicine, (b) are pregnant, (c) are breast-feeding or (d) are taking any other medicines. Antihistamines are also avoided if you have major health problems such as high blood pressure, diabetes or glaucoma.

Decongestants: These medicines are normally taken to reduce congestion in the nose when you have a common cold. They result in narrowing of the blood vessels in the inner lining of the nose. As a result, there is reduced swelling, inflammation and mucus production in the nasal passages.

Decongestants are used in various forms such as tablets, syrups, nasal drops or sprays. They are often used indiscriminately for common health problems such as colds or allergies. Commonly used decongestants include pseudoephedrine, phenylephrine and phenylpropanolamine. All these medicines can cause minor side effects such as nervousness and headache. These side effects worsen if decongestants are taken with asthma medicines. It is important to remember that if you use these medicines for a long period of time, congestion of the nose may reappear or worsen after you stop them.

Expectorants and mucolytics: Expectorants help to make the mucus in the upper airways loose and thin. As a result, coughing becomes easier and the mucus is easily removed from the airways. Mucolytics are medicines that either destroy or dissolve excessive mucus in the airways.

There are several types of expectorants and mucolytics. Each of these medicines can produce a wide range of reactions. Some of these may actually irritate airways that are inflamed because of asthma, while some others increase secretion of mucus in the lungs. It is therefore desirable that you avoid self-medication with expectorants and mucolytics especially while on treatment for asthma.

Antibiotics: Antibiotics are medicines that cure bacterial infections. Most asthma causing infections are viral and antibiotics do not cure viral infections, hence, they playa limited role in routine treatment of asthma. Antibiotics are recommended only if laboratory tests and clinical evidence indicate that there is a specific bacterial infection.

Antacids: In case you are not able to control symptoms of heartburn or gastric reflux through measures discussed earlier, your doctor may recommend antacids. These are medicines that control the excess secretion of acids in the stomach.

Commonly used antacids include cisapride, omeprazole and ranitidine.