Therapy       

I. Adrenergic Bronchodilator

This word mainly a united word of Bronchus (plural: bronchi) and Dilator. Firstly, bronchus is simply either of the two main divisions of wind pipes that leads to the pair of lungs. In asthma patients these wind pipes are inflamed  (disease) due to interaction between inherent tendency and adverse environment such as allergen, air pollution, smoking (both active and passive), or seasonal changes attributed to influenza. Primarily main abnormality in asthma is inflammation of the mucous membrane inside the bronchial tubes. The continuous inflammation (swelling) generally causes narrowing of windpipes affecting normal breathing, inhalation of oxygen or exhalation of carbon-dioxide through these windpipes of lungs. 

• Adrenergic bronchodilators: Salbutamol (Asthalin, Ventorlin) and terbutaline (Bricanyl) and salmeterol (serobid) are examples.
• Anticholinergic bronchodilators: These works against certain nerves (called cholinergic) which tighten the air passages: ipratropium (Ipravent, Ipratope) is the only example.
• Xanthine bronchodilators: These are medicines related to coffee and tea which also open up air passages: theophylline (deriphylline) and aminophylline are examples.

It is important for the patient to know, which bronchodilator he is taking because it is safe to take bronchodilators of different kinds together as they are beneficial to do so. Contrary, it can be harmful to mix together two bronchodilators of the same kind.
 

Explanation
4 mg Salbutamol tablet when taken orally passes to stomach. After absorption into blood Salbutamol drug is distributed uniformally to all organs including lungs. Thus only small fraction of Salbutamol tablet reaches to lungs and gives benefit. Major portion of tablet is distributed in other organs. Whereas inhalers produce quick relief and dose is just 1 puff of 100 mg as drug gets directly deposited in the lung. Thus the dose of inhaler is just 1/40th of the oral dose of Salbutamol. If inhaler is taken through a spacer 20% dose goes into lungs and 80% retained in a spacer. Thus dose of drug reaching to the body is 1/200th part of a 4mg Tablet. The best way to use a bronchodilator in asthma is to breathe it directly into the lungs. There it can act quickly and efficiently just where it is needed.
 

When Bronchodilator Inhaler is needed?

For daily usage
Theophylline is frequently prescribed medication for the treatment chronic asthma in both the adults and children. It is usually given in sustained release forms. It is often given with other inhaled or oral medication. It is better to choose a particular time of day at which medication should be given. If a dose is forgotten, one should never double on a dose to make up for the one missed.

During acute attack
Inhaled bronchodilator are accepted as the first choice for the treatment of a sudden attack of asthma. If, however, a patient fails to respond to inhaled or injected bronchodilators, theophylline is administrated into the vein. If a  patient is taking oral theophylline tablet he should avoid theophyllin injection during acute attack.

Preparations of Theophylline

• As liquid :A common form of theophylline prescribed for small children is the liquid preparation. This is usually rapidly absorbed giving the advantage of a quick onset of action. One of the major disadvantage of liquid preparations is the quick absorption that may give rise to toxic levels of the drug and might be fatal at certain times. 
• Tablets: Tablets are available in two types of formulation: one short acting anhydrous variety which gets immediately absorbed in stomach and gives rise to high blood levels of theophylline which may cause toxicity. The other types of formulation is the introduction of sustained-release formulations. The main reason to develop these sustained release preparations is to reduce the erratic absorption as with anhydrous preparation and thereby reducing the toxicity.
• Theophylline with injection: The recommended route of injection Theophylline is intravenously. This type of therapy is reserved for those patients having asthma attacks with no response to inhaled and oral medications. Patient on oral Theophylline should never be injected since it can be a life threatening.

Reduce the dose of theophylline with

• Erythromycin.
• Cimetidine.
• Ciprofloxacin.
• Congestive cardiac failure.
• Hepatic failure.
• Fever.
• Old age.

Increase the dose  of theophylline with

• Phenobarbitone.
• High protein food.

If above mentioned dose adjustment are not made, the use of theophylline can lead to toxicity or sub optimal effect.

Adverse Effects
Various systems of the body, other than the lungs, can be affected by Theophylline. The side-effects with theophylline range in severity from mild to life threatening hence every patient on theophylline must know its adverse effects. These are as follows:

Common side-effects with an excess dose

• Nausea, burning of the stomach, vomiting and occasionally diarrhea. Usually seen at the  initiation of therapy.
• Headache, irritability, and insomnia (inability to fall asleep).
• Bed wetting (enuresis) specially in young children.
• Increased heart rate and sometimes skip beats.

Serious side-effects with very high dose

• Convulsions.
• Death.

When it is used in combination with other medications such as Erythromycin, Cimetidine and Ciprofloxacin, the chances of side-effects get enhanced.

Bronchodilatation with antimuscarinic drugs is attributed to inhibitation of vagal activityon airways smooth muscle; muscarinic antagonists cometitively blocking the effect of acetylcholine on muscarinic receptors.

Side effects do not pose a major problem with Ipratropium bromide because it is given by inhalation and is poorly absorbed. A dry mouth can occur and an unpleasant taste is reported. The slow onset of action is a disadvantage for some patients. Increased sputum viscosity is not a problem. Paradoxical bronchoconstriction has been reported with Ipratropium bromide, particularly when given by nebuliser solutions, the preservative added to the solution was probably more important. Preservative free nebuliser solution is now available.

New Developments
The identification of different types of muscarinic receptors in the airways raises the possibility of developing drugs that can inhibit vagal activity on airway smooth mucles more selectively. A drug that was a competitive antagonist at the M1 and M3 receptor, or an M2 agonist would be expected to be more effective than the current drugs.

Nebuliser Therapy for Asthma
The breathing difficulty in asthma arise because of narrowing of the air passages of the lungs. It seems sensible therefore to treat asthma by breathing medicines directly into the narrowed air passages. Many of these medicines will open up ("dilate") the air passages (or "bronchi") and so are known as bronchodilators.

What is a nebuliser?
A nebuliser is a device which makes a mist out of a liquid by blowing air or oxygen through it. There are several designs of nebuliser but all have four essential parts:

• The nebuliser unit itself - a small container into which the liquid medicine is put and through which air or oxygen can be blown, to make the mist.
• A source of compressed gas. This is likely to be the oxygen supply in hospital or health centres but for home use will be a small electrical air pump. A pump rather like the foot pump which is used to inflate car tyres is marketed as an alternative.
• A mouthpiece or mask which can be attached to the outlet from the nebuliser so that the mist can be breathed in.
• The medicine which is to be nebulised made up in a suitable solution to be put into the nebuliser unit.

An alternative design is the ultra-sonic nebuliser. This creates a mist by sending vibrations through the liquid medicine.

Which drug may be used in nebuliser?
Nebuliser are used chiefly for bronchodilators, medicines which give quick relief from asthmatic wheezing through they can also be used for certain protective medicines. Some of these medicines come in a single dose ampule or plastic capsule ready to use. With others you have to measure out a set amount of medicine from a bottle, either using a syringe or a dropper. This then needs to be mixed with a dilute salt solution. This solution must be what is called normal saline. You must not use the tap, distilled or sterile water.

When is nebuliser treatment needed?
For the emergency treatment of acute asthma,

• Acute severe attack of asthma respond so well to nebulised bronchodilators that injections of these medicines are rarely needed now. Nebulisers have become part of the routine treatment for patients admitted to hospital with acute asthma. Quite a number of doctors now have nebulisers in their health centres and may take them out to patient's homes. In a few areas ambulance personnel can use nebulisers. Finally some patients have their own nebuliser to treat acute attack under the guidance of their doctors.

For giving protective therapy to small children,

• Below the age of about four to five years children find it difficult to use any of the ordinary inhalers. Yet the regular use of the protective medicine sodium cromoglycate can make a great difference to their lives. So it is given in a nebuliser. The dose is the same as that in the Fintal spincaps which can therefore replace the nebuliser as soon as they are old enough to use it. Beclomethasone (Becotide) has also recently become available a nebuliser solution suitable for young children.

Rules of using a nebuliser
Learn all  about your nebuliser from your doctor, nurse or physiotherapist. You must know how to set up the nebuliser and air pump, how to keep it clean and understand in simple terms how it works.

Be sure you know,

• What medicine you are to use.
• How much you need.
• When to take it.

If you have been advised to use  a nebuliser for acute attacks, learn what warning signals you should look for that indicate nebuliser use. It may be,

• A failure of your usual reading.
• A drop in you flow reading.
• A rise in your pulse rate.

Work out with your doctor what you should do after using the nebuliser for an acute attack. It may be,

• That you should contact your doctor.
• That you should repeat the nebuliser a certain number of times.
• That you should start steroids tablets.

If you have been advised to use your nebuliser regularly, make sure you keep to the scheme advised. The regular use of nebulisers does not mean that you can stop protective medicines such as steroid aerosols or sodium cromoglycate . On the contrary the aim should be to use protective medicines continually so that the use of nebulised bronchodilators can be kept to a minimum.

It is important to be aware of possible side-effects of nebulised medicines,

• With most bronchodilators this may be trembling of the hands or excessive thumping of the heart. Less often there may be giddiness or headaches.
• With sodium cromoglycate (Fintal) there are no side-effects.

Are there any dangers in using nebulised medicines ?
With the protective medicines Budesonide the answer is : very rarely. With the nebulised bronchodilators the answer is that there can be dangers. The dose you are using is often more than twenty times the amount you would take in ordinary inhaler. So the chance of side-effects must be greater. Trembling of the hands is annoying but not serious. A rapid or irregular heart beat can be serious. Fortunately young children and most adults seem to be able to take these sort of doses without any problems. However in the elderly, the heart may already be affected in some way so that care has to be taken. This is why it is advisable for patients using a nebuliser, especially the elderly, to be regularly supervised by a doctor experienced in handling asthmatic patients.

Some final do's and don't

• Don't just go out and buy a nebuliser because you have heard it is a "good thing". Seek medical advice. It may be good for you or it may not be. Your doctor will tell you if he thinks it will help.  
• Do keep a regular check on asthma. You can do this with a peak flow meter at home, and indeed some doctors will not allow asthmatics to have a nebuliser unless they keep a record of their peak flow.  
• Don't miss follow up visits to your doctor.  
• Do arrange to have your air pump unit serviced regularly- once every three to six months is about right, and keep the nebuliser unit clean, replacing it if it is tarnished or damaged.