What is Brethine (terbutaline)?

What is Brethine (Terbutaline)?

Brethine is the brand name for terbutaline sulfate, a selective beta-2 adrenergic receptor agonist bronchodilator used primarily to treat acute bronchospasm in asthma and other obstructive airway diseases. 1

Pharmacological Classification and Mechanism

• Terbutaline is a short-acting beta-2 agonist (SABA) that works by stimulating beta-2 adrenergic receptors in bronchial smooth muscle, leading to relaxation and bronchodilation 1
• The drug increases intracellular cyclic AMP levels, which relaxes bronchial smooth muscle and inhibits release of inflammatory mediators from mast cells 1
• While preferentially selective for beta-2 receptors, 10-50% of cardiac beta receptors are also beta-2 subtype, explaining cardiovascular side effects even with "selective" agents 1

Clinical Indications and Routes of Administration

Acute Severe Asthma

• Nebulized terbutaline 5-10 mg is first-line therapy for acute severe asthma (defined as inability to speak full sentences, pulse >110 bpm, respiratory rate >25/min, peak flow <50% predicted) 2, 3
• Nebulized doses should be delivered via oxygen-driven nebulizer and can be repeated every 4-6 hours or given continuously until stabilization 2, 3
• Subcutaneous terbutaline 0.25-0.5 mg is indicated when patients fail to respond to nebulized therapy after 15-30 minutes, cannot cooperate with inhaled therapy due to severe bronchospasm, or when nebulizers are unavailable 4, 3
• Subcutaneous doses can be repeated every 20 minutes up to 3 doses 4

Pregnancy-Related Uses

• Terbutaline is classified as TGA Category A and FDA Category C for use in pregnancy 4
• It is considered "probably safe" during pregnancy and breastfeeding for asthma management 4
• Terbutaline has been used as a tocolytic agent to delay premature labor, though this is an off-label use 4, 5

Pharmacokinetics and Onset of Action

• Subcutaneous administration produces peak plasma concentrations of approximately 9.6 ng/mL at 0.5 hours, with clinical effects beginning within 5 minutes and peak bronchodilation at 30-60 minutes 1, 6
• Duration of action is 1.5-4 hours for subcutaneous administration 1
• Terminal half-life ranges from 2-5.7 hours depending on the study 1
• Inhaled terbutaline offers the fastest onset, maximal response, and longest duration compared to subcutaneous or oral routes 6

Important Side Effects and Safety Considerations

Cardiovascular Effects

• Tachycardia is the most consistent side effect, with heart rate increases of up to 25% above baseline, particularly with subcutaneous doses exceeding 0.25 mg 7
• Both maternal and fetal tachycardia can occur during pregnancy 4
• Terbutaline can induce atrial fibrillation through multiple mechanisms including increased automaticity, shortened atrial refractory period, and sympathetic activation 4

Metabolic Effects

• Systemic administration may cause maternal hyperglycemia and neonatal hypoglycemia 4
• These effects are more pronounced with systemic (subcutaneous/oral) versus inhaled administration 4

Tocolytic Effects

• Beta-2 agonists may inhibit uterine contractions during labor, which can be problematic if delivery is imminent 4

Critical Clinical Algorithms

For Acute Severe Asthma

1. Initial therapy: Oxygen 40-60% + nebulized terbutaline 10 mg (or salbutamol 5 mg) + systemic corticosteroids (prednisolone 30-60 mg PO or hydrocortisone 200 mg IV) 2, 3
2. Reassess at 15-30 minutes: Check peak flow, respiratory rate, pulse, ability to speak 3
3. If severe features persist: Administer subcutaneous terbutaline 0.25-0.5 mg 4, 3
4. If life-threatening features present: Consider IV aminophylline 250 mg over 20 minutes or IV terbutaline 250 mcg over 10 minutes 3

Dosing by Route

• Nebulized: 5-10 mg every 4-6 hours or continuously 2, 3
• Subcutaneous: 0.25-0.5 mg, repeat every 20 minutes up to 3 doses 4
• Oral: 2.5 mg every 6-8 hours for maintenance therapy 4, 6
• Inhaled (metered-dose): 0.375 mg provides effective bronchodilation within 5 minutes 6

Common Pitfalls and Contraindications

• Do not use terbutaline as monotherapy for acute asthma; always combine with systemic corticosteroids and consider adding ipratropium bromide 500 mcg 2
• Avoid subcutaneous doses >0.25 mg unless absolutely necessary, as tachycardia increases significantly with higher doses 7
• Do not use mucolytics (including bromhexine) in acute asthma, as they may worsen airway obstruction; reserve mucolytics only for bronchiectasis with thick secretions 2
• Monitor cardiac status in elderly patients or those with pre-existing tachycardia, as continuous cardiac monitoring is essential 8
• Terbutaline shows no superiority over salbutamol in efficacy (OR 0.99,95% CI 0.74-1.34), so drug selection can be based on availability and cost 8

Regulatory and Athletic Considerations

• Unlike salbutamol, terbutaline requires a therapeutic use exemption (TUE) for competitive athletes, as supratherapeutic doses via inhalation or oral routes are performance-enhancing 9
• The World Anti-Doping Agency has not established dosing or urine threshold limits for terbutaline, creating potential for abuse 9