Chemistry - A synthetic sympathomimetic amine, terbutaline sulfate occurs as a slightly bitter-tasting, white to gray-white, crystalline powder that may have a faint odor of acetic acid. One gram is soluble in 1.5 ml of water or 250 ml of alcohol. The commercially available injection has its pH adjusted to 3-5 with hydrochloric acid.
Storage/Stability/Compatibility - Terbutaline tablets should be stored in tight containers at room temperature (15-30°C). Tablets have an expiration date of 3 years beyond the date of manufacture. Terbutaline injection should be stored at room temperature (15-30°C), and protected from light. The injection has an expiration date of 2 years after the date of manufacture. Terbutaline injection is stable over a pH range of 1-7. Discolored solutions should not be used. It is compatible with D5W and aminophylline.
Pharmacology - Terbutaline stimulates beta-adrenergic receptors found principally in bronchial, vascular, and uterine smooth muscles (beta2) and bronchial and vascular smooth muscle relaxation occurs with resultant reduced airway resistance. At usual doses it has little effect on cardiac (beta1) receptors and usually does not cause direct cardiostimulatory effects. Occasionally, a tachycardia develops which may be a result of either direct beta stimulation or a reflex response secondary to peripheral vasodilation. Terbutaline has virtually no alpha-adrenergic activity.
Uses/Indications - Terbutaline is used as a bronchodilating agent in the adjunctive treatment of cardiopulmonary diseases (including tracheobronchitis, collapsing trachea, pulmonary edema, and allergic bronchitis) in small animals.
It has been used occasionally in horses for its bronchodilating effects, but adverse effects have limited its use in this species. A related compound, clenbuterol, has been used to a much greater extent for treating bronchoconstriction in the horse, but it is not available commercially in the United States.
Oral and intravenous terbutaline has been used successfully (in humans) in the inhibition of premature labor symptoms.
Pharmacokinetics - The pharmacokinetics of this agent have apparently not been thoroughly studied in domestic animals. In humans, only about 33-50% of an oral dose is absorbed; peak bronchial effects occur within 2-3 hours and activity persists for up to 8 hours. Terbutaline is well absorbed following SQ administration with an onset of action occurring within 15 minutes, peak effects at 30-60 minutes, and a duration of activity for up to 4 hours.
Terbutaline is distributed into milk, but at levels of approximately 1% of the oral dose given to the mother. Terbutaline is principally excreted unchanged in the urine (60%), but is also metabolized in the liver to an inactive sulfate conjugate.
Contraindications/Precautions - Terbutaline is contraindicated in patients hypersensitive to it. One veterinary school formulary (Schultz 1986) states that terbutaline is contraindicated in dogs and cats with heart disease, especially with CHF or cardiomyopathy. It should be used with caution in patients with diabetes, hyperthyroidism, hypertension, seizure disorders, or cardiac disease (especially with concurrent arrhythmias).
Adverse Effects/Warnings - Most adverse effects are dose-related and are those that would be expected with sympathomimetic agents, including increased heart rate, tremors, CNS excitement (nervousness) and dizziness. These effects are generally transient and mild and do not require discontinuation of therapy. After parenteral injection in horses, sweating and CNS excitation have been reported.
Transient hypokalemia has been reported in humans receiving beta-adrenergic agents. If an animal is susceptible to developing hypokalemia, it is suggested that additional serum potassium monitoring be done early in therapy.
Overdosage - Symptoms of significant overdose after systemic administration may include arrhythmias (bradycardia, tachycardia, heart block, extrasystoles), hypertension, fever, vomiting, mydriasis, and CNS stimulation. If a recent oral ingestion, it should be handled like other overdoses (empty gut, give activated charcoal and a cathartic) if the animal does not have significant cardiac or CNS effects. If cardiac arrhythmias require treatment, a beta blocking agent (e.g., propranolol) can be used, but may precipitate bronchoconstriction.
Drug Interactions - Use of terbutaline with other sympathomimetic amines may increase the risk of developing adverse cardiovascular effects. Beta-adrenergic blocking agents (e.g., propranolol) may antagonize the actions of terbutaline. Tricyclic antidepressants or monoamine oxidase inhibitors may potentiate the vascular effects of terbutaline. Use with inhalation anesthetics (e.g., halothane, isoflurane, methoxyflurane), may predispose the patient to ventricular arrhythmias, particularly in patients with preexisting cardiac disease—use cautiously. Use with digitalis glycosides may increase the risk of cardiac arrhythmias.
a) 0.0033 mg/kg IV (Robinson 1987)
b) 0.025 mg/kg once daily PO; 0.0033 mg/kg IV (Schultz 1986)
c) 0.13 mg/kg PO q8h (McConnell and Hughey 1987)
d) 30 mg PO tid (in a 450 kg horse); usually used in combination with aminphylline and prednisone. (Duran 1992)
Monitoring Parameters -
1) Clinical symptom improvement; auscultation
2) Cardiac rate, rhythm (if indicated)
3) Serum potassium, early in therapy if animal susceptible to hypokalemia
Client Information - Contact veterinarian if animal’s condition deteriorates or becomes acutely ill.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Terbutaline Sulfate Oral Tablets 2.5 mg, 5 mg; Brethine® (Geigy); Bricanyl® (Hoechst Marion Roussel); (Rx)
Terbutaline Injection 1 mg/ml in 2 ml amps with 1 ml fill; Brethine® (Geigy), Bricanyl®S (Hoechst Marion Roussel); (Rx)
Also available in a metered-dose inhaler.
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