In its capacity as a short acting beta 2 agonist salbutamol can be delivered to its site of action in a variety of ways:
Metered Does Inhalers: These are the commonest method of delivery of salbutamol as they are small and convenient to carry and deliver a meter does of the drug directly to the lungs.
Nebulisers: Another common form of delivering the drug this also delivers the drug straight to the lungs however over a longer period of time. The inhaled forms of salbutamol have a faster onset of action, fewer side effects, and are more effective than the syrup or tablet forms.
Solution (Injections +
syrups): Salbutamol can be injected (intravenous, subcutaneous or
intramuscular) to treat very severe asthma or the solution can be inhaled. Each
millilitre of Ventolin inhalation solution contains 5 mg of salbutamol (as 6 mg
of salbutamol sulphate) in an aqueous solution containing benzalkonium
chloride. Sulphuric acid is used to adjust the pH to between 3 and 5. Ventolin
inhalation solution contains no sulphating agents. Ventolin inhalation solution
is a clear, colourless to light yellow solution.
Ventolin syrup contains 2 mg of salbutamol as 2.4 mg of salbutamol sulphate in each 5 ml.
Tablets + extended release tablets: Each Ventolin tablet contains 2 or 4 mg of salbutamol as 2.4 or 4.8 mg, respectively, of salbutamol sulphate. Each Proventil Repetab extended-release tablet contains a total of 4 mg (2 mg in the coating for immediate release and 2 mg in the core for release after several hours) of salbutamol as 4.8 mg of salbutamol sulphate. The inactive ingredients for salbutamol extended-release tablets include: butylparaben, calcium phosphate, calcium sulphate, lactose, magnesium stearate, oleic acid and titanium dioxide.
The slower acting extended release tablets have a duration of action of at least 12 hours after a single dose. It can be used with anti-inflammatory drugs for long term control of symptoms, especially night coughs and to prevent exercise induced asthma.
Salbutamol can be delivered in several different forms:
· Salbutamol sulphate: molecular weight of 576.7, empirical formula (C13H21NO3)2·H2SO4, a white crystalline powder, soluble in water and slightly soluble in ethanol.
· Salbutamol hydrochloride
Salbutamol is still commonly delivered as a racemic mixture (+,-) salbutamol, even though S-Salbutamol is know to have a detrimental effect on asthma suffers (in fact the exact opposite effect of the R Isomer, see Bioactivity). Although the racemic mixture does have, overall, a beneficial effect the R isomer alone is much more effective is asthma treatment.
The side effects of salbutamol generally result from the drugs action on muscles such as cramps or tremors. Other side effects come from the drugs action on beta 1 adrenoceptors in cardiac muscle (500 time less binding than beta 2) generally causing vasodillation with resulting effect on blood pressure and the heart.
More common side effects include: Aggression, agitation, cough, diarrhoea, dizziness, excitement, general bodily discomfort, headache, heartburn, increased appetite, increased blood pressure, indigestion, irritability, laboured breathing, light-headedness, muscle cramps, nausea, nervousness, nightmares, nosebleed, over activity, palpitations, rapid heartbeat, rash, ringing in the ears, shakiness, sleeplessness, stomach ache, stuffy nose, throat irritation, tooth discoloration, tremors, vomiting, wheezing, worsening bronchospasm.
Less common side effects include: Chest pain or discomfort, difficulty urinating, drowsiness, dry mouth and throat, flushing, high blood pressure, muscle spasm, restlessness, sweating, unusual taste, vertigo, weakness.
Rare side effects following
the use of inhaled salbutamol include: Hoarseness, skin rash or hives,
hypokalemia, myocardial insufficiency, heart failure, angina-pectoris,
hypertension, severe cardiovascular disease, diabetes-mellitus,
Salbutamols only other documented use is in obstetrics in uncomplicated premature labor.
Salbutamol is a drug used in the treatment of asthma, a chronic lung disease caused by inflammation of the lower airways. Asthma causes the airways to become sensitive, swollen and inflamed, even when there are no visible symptoms and thus causes hyper-responsiveness of tissues lining the bronchi to certain triggers. The most serious symptom is the constriction of the smooth muscle lining the bronchi of the lungs. This symptom was so important that asthma was previously characterised as a periodic bronchospasm. This reduces airflow and thus makes breathing hard or, in fatal cases, impossible. Affecting some 15 million Americans1 and more than 3 million in the UK6, asthma continues to increase in both incidence and severity despite vast improvements in both therapeutic options and understanding of the disease over the years.
These increases have yet to be adequately explained, but the number and frequency of hospitalisations due to asthma, along with the attendant expenditures, continue to escalate. More people of all ages are being treated for asthma now than ever, and the number of children receiving treatment continues to escalate.
Crystals Under a Polarized Light Microscope:
Reproduced with the permission of Michael W. Davidson
The cost of asthma to the community is truly staggering. An estimated $6 billion4 is spent on treating asthma in the USA alone. Other expenses such as and estimated $1 billion5 for the loss in productivity by working parents caring for children who miss school due to asthma mean that asthma treatment is a very important area.
With asthma affecting 1 in 7 school children in the UK6 (1 in 25 adults) asthma has an affect on a huge number of families in the United Kingdom.
An idea of the huge scale of asthma world-wide can be seen from a more comprehensive list of asthma statistics (and their sources), to numerous to be usefully include in this section: ASTHMA STATISTICS
The causes of asthma are not
fully understood however, like its related allergic conditions eczema and
hay fever, asthma often runs in the family and may be inherited. It is thought
there are probably several other, environmental, factors that contribute to
someone developing asthma, such as housing and diet. It is hypothesised that
intense exposure to allergens and triggers (notably airborne chemical irritants
or particles) can precipitate asthma. It is also known that smoking during
pregnancy increases the chance of a child developing asthma. Contrary to one
common misconception there is no evidence that traffic pollution causes asthma,
although poor air quality can be a trigger
Although the cause of asthma is not fully understood the mode of action of most triggers is better understood. A trigger is any object or action which causes an asthma attack. Common triggers include:
· Tobacco smoke
· Animal hair, fur or feathers
· Animal danders
· House-dust mites
· Indoor fungi
· Air Pollution & Irritants (fumes from gas, oil, kerosene, perfumes)
· Gastroesophageal reflux
· Aspirin Sensitivity
· Sulphite Sensitivity
· Infections (such as colds or ëflu)
· Food additives
· Weather changes
Salbutamol can be taken either orally or more commonly using an inhaler device. The inhaler ensures that very small amounts of medication are delivered directly into the lungs.
There are two main types of asthma medication:
· Quick Relief medications:
· Long-term control or preventive medications
Inhaled Salbutamol is the most commonly used quick-relief medication. First market by Galaxo in 1969 and now by Allen & Hanburys it is in the top 150 prescribed drugs.
One of the most interesting factors in the chemistry and biochemistry of salbutamol is the opposite biological effect observed for the R and S isomer of the drug. The R isomer effects dilation of the smooth muscle whereas the S isomer, via a different pathway, causes constriction of this same muscle.