Autohaler

Uses

Autohaler is a catecholamine non-selective beta-adrenergic agonist typically used to treat bradycardia and heart block.

Autohaler is indicated to treat mild or transient episodes of heart block not requiring electric shock or pacemakers, serious episodes of heart block and Adams-Stokes attacks not caused by ventricular tachycardia or fibrillation, and bronchospasm during anesthesia. Autohaler is also indicated for cases of cardiac arrest until preferable treatments like electric shock and pacemakers are available. Autohaler is also indicated as an adjunct therapy to fluid and electrolyte replacement therapy in hypovolemic shock, septic shock, hypoperfusion, congestive heart failure, and cardiogenic shock.

Autohaler is also used to associated treatment for these conditions: Adams-Stokes attacks, Bradycardia, Bronchospasm, Cardiac Arrest (CA), Cardiac electrical storm, Congestive Heart Failure (CHF), Hypoperfusion, Septic Shock, Serious Heart Block, Shock, Cardiogenic, Shock, Hypovolemic, Short QT syndrome, Syncope, Torsades de Pointes, Transient Heart Block, Arrhythmia of ventricular origin, Beta blocker overdose, Mild Heart Block

How Autohaler works

Autohaler is a non-selective beta adrenergic receptor agonist. Agonism of beta-1 and beta-2 adrenergic receptors causes the alpha subunit of G-protein coupled receptors to exchange GMP for GTP, activating them, and allowing the alpha subunit to dissociate from the beta and gamma subunits. Dissociation of the alpha subunit activates adenylate cyclase, converting ATP to cyclic AMP. Cyclic AMP activates protein kinase A (PKA), which phosphorylates cardiac L-type calcium channels such as Ca_v1.2. These channels depolarize cells by inward active transport of calcium ions.

Agonism of beta-1 adrenergic receptors lead to increased strength of contractility, conduction of nerve impulses, speed of relaxation, and rate in the heart.

Agonism of beta-2 adrenergic receptors leads to glycogenolysis in the liver, glucagon release from the pancreas, and activation of the renin-angiotensin-aldosterone system.

In the alveoli, agonism of beta-2 adrenergic receptors, activates similar pathways to the heart, however the end result is regulation of sodium channels, the cystic fibrosis transmembrane conductance regulator (CFTR), and sodium potassium ATPase. PKA phosphorylates scaffolding proteins and sodium channels, increasing the number of sodium channels on the apical side of alveolar cells and increasing active transport of sodium ions into cells. Agonism of beta-2 adrenergic receptors can also increase chloride ion transport across CFTR. Together, these actions lead to passive transport of water out of the alveoli, and the clearance of alveolar fluid.

Toxicity

Patients experiencing an overdose may present with tachycardia, arrhythmias, palpitations, angina, hypotension, or hypertension. Overdose should be treated by reducing or stopping administration of isoprenaline and monitoring blood pressure, pulse, respiration, and ECG.

In rats, the LD₅₀ is 2221 mg/kg orally, 128 mg/kg intraperitoneally, and 600 mg/kg subcutaneously. In mice, the LD₅₀ is 1260 orally and 450 mg/kg intraperitoneally.

Food Interaction

Volume of Distribution

In pediatric patients, the volume of distribution was 216 ± 57 mL/kg.

Elimination Route

Data regarding absorption kinetics of isoprenaline are not readily available.

Half Life

The half life of intravenous isoprenaline is 2.5-5 minutes. Oral isoprenaline has a half life of 40 minutes.

Clearance

In pediatric patients, the clearance of isoprenaline was 42.5 ± 5.0 mL/kg/min.

Elimination Route

Autohaler is 12.2-27.0% recovered in the feces and 59.1-106.8% recovered in the urine after 48 hours. The majority of the recovered dose in the urine is conjugated isoprenaline, with 6.5-16.2% free isoprenaline, and 2.6-11.4% 3-O-methylisoprenaline and conjugates.

Innovators Monograph

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