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HEXOPRENALlNE, EFFECTIVE WITH FEWER SIDE-EFFECTS

Hexoprenaline. N .N..(2 -(3 .4-dihydroxyphenyl).. 2 -bydroxyethyl] hexamethylenediamine, sulphate is a selective ' ~l-adrenoreceptor which is act ive in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in tile treatment of bronchospasm associated with obstructive airways diseases. including , bronchitis and emphysema. Both in animals and humans, hexoprenaline is markedly longer in action than other catechol-containing ~1", such as and rim iterol. It protects asthmatic patients against bronchoconstriction induced by histamine, acetylcholine and allergens and is effective by inhalation and by the oral and intravenous routes. and similar to in onset and duration of action. Significant effects on tbe cardiovascular system are seen after oral or inhaled doses, only at levels several fold greater than those required for significant broncbodilatation, though a pronounced increase in heart rate occurs a few minutes after intravenous administration, and a moderate increase may occur after repeated oral dosage. Hexoprenaline bas been given to asthmatic patients with of all grades of severity, and to others with cardiac disease, by all three routes of administration without causing adverse cardiovascular effects. like other sympathomimetic amines, it has a lipolytic and . glycogenolytic effect. but this does not apparently interfere significantly with glucose utilisation in diabetic patient.. inhaling the drug or receiving it intravenously. In general, hexoprenaline does not affect blood-gas values or acid-base status, though one trial reported a significant hypoxemia following inhalation of 400llg hexoprenaline. Its inhibition of uterine activity, which reflects activity at ~l - adrenoreceptors, in the aJl,;ence of significant cardiovascular effects, may have therapeutic application in the suppression of labour contractions, at least by the intravenous route.

How does it rate in comparative trials? Single- and multiple-dose studies or oral hex oprenaline in asthmatic patients have shown the drug to have superior bronchodilatc properties to placebo and trimetoquinol, but to be not significantly different from . Direct comparison suggests that hexoprenaline by metered aerosol is more selective than orciprenaline or salbutamol, producing less cardiac stimulation for a greater or similar degree of bronchodilatation. Inhaled solutions of hexoprenaline at concentrations of 0.025 % and I % are at least as effective as orciprenaline or isoprenaline 2 %, with fewer side-effects and a greater degree ofbronchodilatation. Intravenous hexoprenaline 5~g was as effective as orciprenaline at 100 times tbis dose, and produced significantly fewer side­ effects and a lesser degree of . AOd in long-term studies In long-term studies, patients have usuaUy been treated ini tially, and particularly in severe or hospilalised cases. by intravenous hexoprenaline. Oral hexoprenaline has then been substituted for maintenance therapy, supplemented in many patients by inhaled drug from metered aerosols. The average long-term improvement in pulmonary function has been about 20 to 2596. In a I"year study, oral hexoprenaline was significantly beller than in terms of fewer side-effects, though fenoteroi produced a greater degree of improvement in pulmonary function: bexoprenaline was particularly suitable in a sub-group of patients with cardiac disease. who experienced tachycardia, anginal pain and palpitations with fenoterol but not with hexoprenaline. Hexoprenaline alone is not recommended in status asthmaticus, by any route of administration, though it may be given intravenously together with and corticosteroids for severe acute attacks of asthma. Subsequent maintenance therapy can then be carried out with oral.and/or inhaled drug.

A tow incidence of side-effects is its main advantage There have been few reports of significant side-elfects following the acute administration of hexoprenaline by inhalation. An initial transient mild ·tachycardia may occasionally occur, which is usually not subjectively apparent to the patienl. After intravenous injection. and sometimes aner inhalation , a transient reddening of the skin may be observed in particularly sensitive vascular areas. Palpitations and skeletal muscle tremor have been observed with high or €umulative doses of oral or inhaled hexoprenaline over a short period of time, and occur in a dose-dependent manner following intravenous adminir.tration. Overdosage may produce fine tremor, general unrest, dizziness, and perspiration but gastrointestinal effects are rare.

Are there any contraindications? There are no specific conlraindications to hexoprenaline, though the same precautions as to its use apply as they do to other sympathomimetic substances. It should be used with caution in patients with thyrotOXicosis, hypertension, cardiac disease, diabetes mellitus, and renal or hepatic dysfunction, and in those who are hypersensitive to sympathomimetic drugs.

Pinder. R.M . et al.: Drugs t4: 1-28 Uul 1977)(50 ~re~rasJ

INPHARMA 30th July. 1977 pl3