indication

For the treatment of bronchospasm, chronic bronchitis, asthma, and emphysema.

pharmacology

Orciprenaline (also known as metaproterenol), a synthetic amine, is structurally and pharmacologically similar to isoproterenol. Orciprenaline is used exclusively as a bronchodilator. The pharmacologic effects of beta adrenergic agonist drugs, such as orciprenaline, are at least in part attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

mechanism of action

Orciprenaline is a moderately selective beta(2)-adrenergic agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle, with minimal or no effect on alpha-adrenergic receptors. Intracellularly, the actions of orciprenaline are mediated by cAMP, the production of which is augmented by beta stimulation. The drug is believed to work by activating adenylate cyclase, the enzyme responsible for producing the cellular mediator cAMP.

toxicity

Symptoms of overdose include angina, hypertension or hypotension, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise and insomnia. LD₅₀=42 mg/kg (orally in rat).

biotransformation

Hepatic and gastric. The major metabolite, orciprenaline-3-0-sulfate, is produced in the gastrointestinal tract. Orciprenaline is not metabolized by catechol-0-methyltransferase nor have glucuronide conjugates been isolated to date.

absorption

3% (oral bioavailability of 40%)

half life

6 hours

drug interactions

Acebutolol: Antagonism

Alseroxylon: Increased arterial pressure

Amitriptyline: The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.

Amoxapine: The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of orciprenaline.

Atenolol: Antagonism

Betaxolol: Beta-Blockers (Beta1 Selective) like betaxolol may diminish the bronchodilatory effect of Beta2-Agonists like orciprenaline. Therapy should be monitored.

Bevantolol: Antagonism

Bisoprolol: Antagonism

Carteolol: Antagonism

Carvedilol: Antagonism

Clomipramine: The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of orciprenaline.

Deserpidine: Increased arterial pressure

Desipramine: The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of orciprenaline.

Doxepin: The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of orciprenaline.

Esmolol: Antagonism

Imipramine: The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of orciprenaline.

Isocarboxazid: Increased arterial pressure

Labetalol: Antagonism

Linezolid: Possible increase of arterial pressure

Methyldopa: Increased arterial pressure

Metoprolol: Antagonism

Midodrine: Increased arterial pressure

Moclobemide: Moclobemide increases the sympathomimetic effect of orciprenaline.

Nadolol: Antagonism

Nortriptyline: The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of orciprenaline.

Oxprenolol: Antagonism

Pargyline: Increased arterial pressure

Penbutolol: Antagonism

Phenelzine: Increased arterial pressure

Pindolol: Antagonism

Practolol: Antagonism

Propranolol: Antagonism

Protriptyline: The tricyclic antidepressant, protriptyline, increases the sympathomimetic effect of orciprenaline.

Rasagiline: Increased arterial pressure

Reserpine: Increased arterial pressure

Sotalol: Antagonism

Timolol: Antagonism

Tranylcypromine: Increased arterial pressure

Trimipramine: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of orciprenaline.