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
·
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.
Side effects25
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,
maternal-thyrotoxicosis.
Other Uses:
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.
Salbutamol
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
· Exercise
· Animal hair, fur or feathers
· Animal danders
· House-dust mites
· Pollen
· Indoor fungi
· Air Pollution & Irritants (fumes from gas, oil, kerosene, perfumes)
· Rhinitis-Sinusitis
· Gastroesophageal reflux
· Aspirin Sensitivity
· Sulphite Sensitivity
· Beta-Blockers
· 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.