B. Salmeterol

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B. Salmeterol

Introduction

Recently, a new class of long acting ▀2-agonist, Salmeterol xinafoate (Serevent«) has been introduced. Its role in asthma is still debated although it is extremely useful in teh control of night time symptoms. Recent research has shown that addition of Salmeterol to when asthma begins to get of of control may better at controlling symptoms than increasing the dose of inhaled steroids as suggested by the British Thoracic Society guidelines (which are now being revised and may include this step).

Pharmacology

Salmeterol is similar in structure to salbutamol except that it has the addition of a long non-polar side chain. Salmeterol is a highly selective ▀2-adrenoreceptor agonist, being at least as equipotent as isoprenaline as a bronchodilator. It is 15 times more potent than salbutamol at the ▀2-receptor, but at the cardiac ▀1-receptor, it is 4 times less potent than salbutamol and 10,000 times less potent than isoprenaline. Salmeterol has been shown to protect against bronchoconstriction caused by histamine, methacholine and exercise, and in suppressing late phase bronchoconstriction suggesting that it has some degree of anti-inflammatory activity in addition to its bronchodilator role. It has been shown to suppress the release of inflammatory mediators in the lung and the migration of inflammatory cells. It is postulated that the prolonged duration of action of salmeterol is due to the long side chain that may attach itself onto an exo-receptor site near to or within the ▀2-receptor. This may allow the active phenylethanolamine head of salmeterol to oscillate in and out of the ▀2-receptor site repeatedly stimulating it. The action of salmeterol can be competitively reversed by ▀2-antagonists, but when the antagonist is removed, the muscle relaxant activity returns without further dosing with salmeterol, suggesting that it may be permanently anchored near the ▀2-receptor site.

Pharmacokinetics

Salmeterol can be administered as an aerosol or inhaled as a powder. Its onset of action is slightly slower than that of other inhaled ▀2-agonists and therefore, should not be used as an as required (reliever) drug. Its duration of action is up to 12 hours so that twice daily dosing is sufficient to control the symptoms of mild asthma. Salmeterol is rapidly absorbed from the lung and is rapidly eliminated with a plasma half life of between 2-8 hours. Salmeterol is extensively metabolised.

Therapeutic Use

Because of the slower onset of action of salmeterol compared with other ▀2-agonists, it is recommended to be used as a prophylactic agent rather than in the relief of acute symptoms. Because of its long duration of action, salmeterol can control the symptoms of asthma for up to 12 hours after dosing, with little evidence of tachyphylaxis to its effects. However, there is concern that this prolonged bronchodilatation may mask underlying inflammation in the lung the consequence of which in the long term is unknown. For this reason, the use of salmeterol is at present only recommended in those patients whose asthma symptoms are poorly controlled on moderate or high doses of inhaled steroids. However, the addition of salmeterol is complementary to, rather than instead of inhaled steroids. Whether salmeterol has an effect on the underlying disease process remains to be determined, and until then, its sole use in the management of asthma cannot be recommended.

Side effects and Overdosage

The side effect profile is similar to that of other ▀2-agonists with tremor and palpitations being the most prominent, and there is a risk of hypokalaemia in overdosage. The incidence of side effects is dose related, and patients develop seem to develop tachyphylaxis to the unwanted side effects with time with no reduction in bronchodilator properties.

Further Reading

Clark TJH, Yernault JC (eds). Proceedings of the first "Serevent International Symposium". European Respiratory Journal. 1991;1(Review 4).

Ullman A, Svedmyr N. Salmeterol, a new long acting inhaled 2-adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax. 1988;43:674-8..


A. Salmeterol

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