Isoprenaline

Isoprenaline (isoproterenol) is a potent non-selective beta-adrenergic receptor agonist with widespread applications in cardiovascular and pulmonary medicine. As a synthetic catecholamine, isoprenaline exerts its physiological effects through stimulation of beta-1 adrenergic receptors in the myocardium, enhancing chronotropic and inotropic activity, and beta-2 receptors in the bronchial smooth muscle, facilitating bronchodilation. Due to its profound hemodynamic influence, isoprenaline is principally utilised in the management of severe bradycardia, atrioventricular (AV) block, and specific pulmonary conditions. Despite its historical prominence, contemporary therapeutic strategies have largely favoured more receptor-selective pharmacologic agents due to the non-selective nature of isoprenaline's adrenergic stimulation and associated risk of adverse effects.

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Clinical Indications

The clinical indications for isoprenaline have evolved with the advent of newer, more selective beta-agonists and cardiac stimulants. However, it remains a critical therapeutic agent in specific scenarios:

• Refractory bradycardia and AV block – Utilised as a temporising measure in symptomatic bradyarrhythmias and high-degree AV block when transvenous pacing is not immediately available.
• Pulmonary applications – Historically employed as a bronchodilator in obstructive airway diseases, although largely supplanted by selective beta-2 agonists such as salbutamol and formoterol.
• Cardiac stress testing – Isoprenaline can be used to induce controlled tachycardia to assess myocardial perfusion and arrhythmogenic potential in clinical electrophysiology.
• Adjunctive therapy in shock states – Occasionally employed in distributive and cardiogenic shock where enhanced cardiac output is required, though its use is limited due to tachyarrhythmic potential.

Pharmacokinetics and Administration

Isoprenaline exhibits rapid pharmacokinetic properties, necessitating continuous infusion for sustained therapeutic efficacy.

• Absorption – Poor oral bioavailability due to extensive first-pass metabolism; intravenous (IV) administration is preferred.
• Metabolism – Rapidly metabolised by catechol-O-methyltransferase (COMT) in the liver; minimal monoamine oxidase (MAO) involvement.
• Excretion – Metabolites excreted primarily via renal pathways.
• Half-life – Approximately 2–5 minutes; necessitating continuous IV infusion for prolonged effects.

Dosing Guidelines

• IV infusion: 0.01–0.1 mcg/kg/min, titrated to hemodynamic response.
• Inhalation: Previously utilised for asthma at 80–160 mcg per dose, but now obsolete.
• Intramuscular (IM) and Subcutaneous (SC) routes: Limited use; occasionally considered in emergency scenarios where IV access is delayed.

Dose Adjustments in Special Populations

Renal Dysfunction

Isoprenaline is primarily metabolised hepatically, with renal clearance of metabolites. In patients with renal impairment, dose adjustments are typically unnecessary; however, vigilance is required in end-stage renal disease (ESRD) due to electrolyte disturbances that may potentiate arrhythmogenic effects.

Hepatic Dysfunction

Since hepatic metabolism is the primary route of elimination, significant liver impairment may prolong drug effects. Dose reduction and close monitoring of hepatic function are recommended in severe hepatic insufficiency.

Geriatric Considerations

Elderly individuals demonstrate increased sensitivity to beta-adrenergic agonists due to age-related receptor downregulation. The propensity for tachyarrhythmias, myocardial ischemia, and hypertension necessitates conservative dosing and stringent cardiovascular monitoring.

Paediatric Considerations

In neonates and paediatric populations, careful titration is imperative due to immature hepatic metabolism and heightened cardiovascular reactivity. The risk of profound tachycardia necessitates lower initial dosing with gradual titration.

Adverse Effects and Risk Considerations

The non-selective beta-adrenergic activity of isoprenaline predisposes patients to a spectrum of adverse effects:

Common Adverse Effects

• Sinus tachycardia and palpitations
• Tremors and muscle cramps
• Nausea and vomiting
• Dizziness and headache

Serious Adverse Effects

• Ventricular arrhythmias – Due to excessive beta-1 stimulation, particularly in predisposed individuals.
• Hypotension – Secondary to vasodilatory beta-2 effects, particularly with high doses.
• Myocardial ischemia – Particularly in patients with underlying coronary artery disease (CAD).
• Hyperglycaemia – Resulting from beta-2 receptor-mediated glycogenolysis and gluconeogenesis.

Drug Interactions

Isoprenaline demonstrates clinically significant interactions with various pharmacologic agents:

• Beta-blockers (e.g., metoprolol, propranolol) – Competitive antagonism leading to diminished efficacy.
• MAO inhibitors (e.g., phenelzine, tranylcypromine) – Risk of exaggerated adrenergic responses.
• Loop diuretics and thiazides – Potential for hypokalaemia-induced arrhythmias.
• Digoxin – Augmented risk of arrhythmogenesis, necessitating serum level monitoring.
• Volatile anaesthetics (e.g., halothane, isoflurane) – Potentiation of dysrhythmias, necessitating caution during surgery.

Comparative Analysis with Other Beta-Adrenergic Agonists

Drug	Beta-1 Activity	Beta-2 Activity	Half-life	Clinical Application
Isoprenaline	High	High	2–5 min	Bradycardia, AV block
Dobutamine	Selective	Minimal	2 min	Cardiogenic shock, CHF
Salbutamol	Minimal	High	4–6 hrs	Asthma, COPD
Epinephrine	High	High	2 min	Anaphylaxis, cardiac arrest

Precautionary Measures

• Electrocardiographic (ECG) Monitoring – Mandatory during IV administration to detect arrhythmic complications.
• Blood Pressure Surveillance – Continuous monitoring is crucial in hypotensive patients receiving isoprenaline infusion.
• Cautious Use in Myocardial Ischemia – Risk of exacerbating myocardial oxygen demand mandates extreme caution.

Toxicity, Overdose, and Management

Clinical Manifestations of Overdose

• Severe tachyarrhythmias (ventricular tachycardia, fibrillation)
• Profound hypotension or hypertensive crisis
• Myocardial ischemia and infarction
• Metabolic disturbances (lactic acidosis, hyperglycaemia)

Management Strategies

• Immediate cessation of infusion
• Beta-blocker administration (e.g., esmolol, metoprolol) for counteracting excessive beta-adrenergic stimulation
• IV fluids and vasopressors (e.g., phenylephrine) to restore hemodynamic stability
• Electrolyte correction (potassium, magnesium) to mitigate arrhythmogenic risk

Recent Advances and 2025 Clinical Guidelines

• ESC 2025 guidelines advocate isoprenaline’s use only in critical care settings with rigorous monitoring.
• NICE 2025 guidelines endorse its application as a bridging therapy for AV block prior to pacemaker implantation.
• Ongoing clinical trials are investigating novel beta-adrenergic modulators with greater receptor selectivity to mitigate adverse effects.

Facts to Remember

• Isoprenaline is a non-selective beta-agonist, affecting both cardiac and respiratory systems.
• It has a very short half-life, requiring continuous infusion for sustained effects.
• Beta-blockers can completely reverse its action, making concurrent use inadvisable unless for diagnostic purposes.
• Not commonly used for asthma due to the availability of selective beta-2 agonists like salbutamol.
• Can induce severe tachyarrhythmias, necessitating ECG monitoring.

References

1. British National Formulary (BNF) 2025 Edition.
2. European Society of Cardiology Guidelines 2025.
3. National Institute for Health and Care Excellence (NICE) 2025 Recommendations.
4. Clinical Pharmacology and Therapeutics Journal, 2025.
5. Harrison’s Principles of Internal Medicine, 21st Edition.