Isoprenaline

Isoprenaline

Trade names	Isuprel
Clinical data
Drug class	Synthetic catecholamine
Contraindications	Tachyarrhythmia, tachycardia
Routes of administration	IV, IM, subcutaneous, inhalation
Dosage	Treatment of AV block or cardiac arrest: IV - 0.02-0.06 mg, then 0.01-0.2 mg depending on ventricular rate IM - 0.2 mg, then 0.02-1 mg depending on ventricular rate Subcutaneous - 0.2 mg, then 0.15-0.2 mg depending on ventricular rate Treatment of hypovolemic and septic shock, low cardiac output, CHF: IV - 0.5-5 mcg/min continuous infusion, titrate to goal HR, CVP, SBP, or urine output Treatment of cardiogenic shock: IV - 0.5-20 mcg/min continuous infusion Treatment of bronchospasm: IV - 0.01-0.02 mg PRN Treatment of symptomatic bradycardia: IV - 20-60 mcg initial bolus, then 10-20 mcg as needed until goal HR and rhythm response met Treatment of ventricular tachyarrhythmia in patients with short QT or Brugada syndrome: IV - 2-10 mcg/min continuous infusion
Dosage
Pharmacodynamics
Mechanism of action	Beta agonism
Adverse effects	Tachycardia, hypertension, hypotension, ventricular arrhythmia, Adam-stokes syndrome, angina, skin necrosis
Pharmacokinetics
Onset of action	Immediate
Duration of action	10-15 minutes
Metabolism	Liver metabolism by COMT
Physical and chemical data
Formula	C11H17NO3
Molar mass	211.258 g/mol
Article quality
Editor rating	Comprehensive
User likes	0

Isoprenaline (also known as isoproterenol) is a direct-acting synthetic catecholamine. It has agonist activity at both beta-1 and beta-2 adrenergic receptors. Its approved uses are in the treatment of AV block and cardiac arrest secondary to heart block, when pacemaker therapy is not available or ineffective. However, it is also used clinically in the treatment of symptomatic bradycardia, bronchospasm, shock, arrhythmia secondary to conduction abnormalities, and to induce arrhythmia or syncope.

Uses

• AV block not requiring pacing
• Cardiac arrest from heart block when pacemaker therapy is unavailable
• Bradycardia, especially in cardiac transplant patients
• Acute bronchospasm
• Cardiogenic shock
• Hypovolemic and septic shock,  congestive heart failure
• For electrophysiological procedures: to provoke ventricular arrhythmias
• For tilt table testing: to provoke syncope
• Treatment of beta-blocker overdose
• Short QT syndrome
• Torsades de pointes
• Electrical storm in patients with Brugada syndrome

Contraindications

Absolute contraindications

• Tachyarrhythmias, including atrial fibrillation, atrial flutter, ventricular fibrillation
• Digitalis toxicity-induced AV block
• Tachycardia
• Pheochromocytoma

Precautions

• Diabetes mellitus, as it induces glycogenolysis and insulin resistance
• Hyperthyroidism, as it can induce thyroid storm
• Children with refractory asthma, as its use in this population can result in clinical deterioration, myocardial necrosis, congestive heart failure, and death
• Recent myocardial infarction, ischemic heart disease
• Hypovolemia causing hypotension
• Hypertension
• Sulfite hypersensitivity

Pharmacology

Pharmacodynamics

Mechanism of action

Isoprenaline is a potent nonselective beta agonist. Upon binding beta-1 adrenergic receptors, it increases intracellular calcium in cardiac myocytes, with positive inotropic, lusitropic, chronotropic, and dromotropic effects. Beta-1 activation also activates the RAAS system in the kidney. Upon binding beta-2 adrenergic receptors, it increases intracellular cAMP and PKA, inactivating myosin light chain kinase. Thus, agonism of these beta-2 receptors results in the relaxation of smooth muscle, peripheral vasodilation, bronchial dilation, and uterine smooth muscle relaxation.  Isoprenaline also induces hepatic glycogenolysis and release of glucagon from the pancreas via beta-2 adrenergic activity.

Adverse effects

• Headache
• Dizziness
• Nausea
• Flushing
• Fatigue
• Diaphoresis
• Mild tremor
• Weakness
• Blurred Vision
• Tachycardia
• Hypertension
• Hypotension
• Ventricular arrhythmia or PVCs
• Adams-Stokes syndrome
• Dyspnea
• Hypokalemia
• Hyperglycemia
• Angina
• Skin necrosis

Pharmacokinetics

• Poor substrate for MAO and not taken up by neurons to the same extent as epinephrine and norepinephrine, leading to a longer duration of action
• Metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) to the 3-O-methyl isoproterenol metabolite, which is subsequently conjugated with sulfate
• Excretion occurs via the urine
• Onset of action: immediate
• Duration of action 10-15 minutes
• Plasma half-life: 2.5-5 minutes

Chemistry and formulation

Isoprenaline hydrochloride is 3,4-Dihydroxy-alpha-(isopropylamino) methyl benzyl alcohol hydrochloride, a synthetic sympathomimetic amine that is structurally related to epinephrine but acts almost exclusively on beta adrenergic receptors.