Isoprenaline

Usage

• Isoprenaline is prescribed for bradycardia (slow heart rate), heart block, and Adams-Stokes attacks. It may also be used in some cases of cardiac arrest, bronchospasm during anesthesia, and as an adjunct treatment for shock (hypovolemic, septic, cardiogenic) and low cardiac output states. Off-label uses include Brugada syndrome and provocation of syncope during tilt table testing.
• Pharmacological Classification: β-adrenergic agonist, sympathomimetic, inotropic agent, chronotropic agent.
• Mechanism of Action: Isoprenaline primarily stimulates β1- and β2-adrenergic receptors. This leads to increased heart rate (chronotropic effect), increased force of heart contractions (inotropic effect), and relaxation of smooth muscle in the bronchi and blood vessels (vasodilation).

Alternate Names

• Isoproterenol (International Nonproprietary Name)
• Brand Names: Isuprel, Monico

How It Works

• Pharmacodynamics: Isoprenaline increases heart rate, myocardial contractility, and cardiac output. It also relaxes bronchial smooth muscle, leading to bronchodilation. Peripheral vasodilation may decrease diastolic blood pressure while systolic blood pressure may remain steady or increase slightly.
• Pharmacokinetics: Isoprenaline is rapidly absorbed after parenteral administration or inhalation. It is metabolized primarily in the liver by catechol-O-methyltransferase (COMT) and to a lesser extent by monoamine oxidase (MAO). The major metabolite is 3-O-methylisoprenaline, which has weak beta-blocking activity. Metabolites are excreted renally. The half-life is short, ranging from minutes after intravenous administration to up to 2 hours after subcutaneous administration.
• Mode of Action: Isoprenaline binds to β1- and β2-adrenergic receptors, which are G protein-coupled receptors. This binding activates adenylate cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A (PKA), which then phosphorylates various intracellular proteins. In cardiac muscle, this results in increased calcium influx and enhanced contractility. In smooth muscle, PKA phosphorylates myosin light chain kinase (MLCK), inactivating it and leading to relaxation.
• Receptor Binding: β1 and β2 adrenergic receptor agonist.
• Elimination Pathways: Primarily renal excretion of metabolites. Hepatic metabolism via COMT and CYP450 enzymes.

Dosage

Standard Dosage

Adults:

• Bradycardia and Heart Block: IV infusion 2–10 mcg/min, titrated to effect. Bolus injections can also be used.
• Shock: IV infusion 0.5–5 mcg/min, titrated to effect. Higher doses (up to 30 mcg/min or more) might be necessary in advanced shock.
• Bronchospasm during Anesthesia: IV bolus 10–20 mcg, repeated as needed.

Children:

• Pediatric dosing is not well-established. An initial IV infusion rate of 0.1 mcg/kg/min is recommended, titrated to effect, with a usual range of 0.1-1 mcg/kg/min. Safety and efficacy in children have not been fully established.
• Neonates: 0.05–1 mcg/kg/minute, titrated to effect. Consult with a clinical toxicologist for dosing in beta-blocker overdose.

Special Cases:

• Elderly Patients: Dosage should be carefully titrated, starting at the lower end of the range, due to potential for increased sensitivity.
• Patients with Renal Impairment: Dose adjustment is generally not required.
• Patients with Hepatic Dysfunction: Caution is advised, and dosage adjustments may be necessary.
• Patients with Comorbid Conditions: Caution is advised in patients with diabetes, hyperthyroidism, coronary artery disease, hypertension, and ischemic heart disease.

Clinical Use Cases

• Intubation: May be used for bradycardia during intubation.
• Surgical Procedures: May be used for intraoperative bradycardia or hypotension.
• Mechanical Ventilation: May be used for bradycardia in mechanically ventilated patients.
• Intensive Care Unit (ICU) Use: For management of shock, low cardiac output states, and some arrhythmias in critically ill patients.
• Emergency Situations: May be used for bradycardia or heart block, and as a temporary measure in cardiac arrest until defibrillation or pacing is available.

Dosage Adjustments

• Monitor heart rate, blood pressure, ECG, urine output, and other relevant parameters for dose titration and adjustment.
• Adjust dose based on patient response and comorbid conditions.

Side Effects

Common Side Effects

• Tachycardia, palpitations, nervousness, headache, dizziness, tremors, nausea, vomiting, flushing, sweating.

Rare but Serious Side Effects

• Severe arrhythmias (ventricular tachycardia, ventricular fibrillation), angina, hypotension, hypertension, myocardial ischemia, pulmonary edema, Adams-Stokes attacks.

Long-Term Effects

• Data on long-term effects are limited. Prolonged use can potentially worsen underlying heart conditions.

Adverse Drug Reactions (ADR)

• Severe arrhythmias, myocardial ischemia, and significant changes in blood pressure should be addressed immediately.

Contraindications

• Tachyarrhythmias (except in specific situations like Torsades de Pointes), tachycardia or heart block caused by digitalis toxicity, ventricular arrhythmias requiring inotropic therapy, angina pectoris, recent myocardial infarction, hypersensitivity to isoprenaline.

Drug Interactions

• Adrenaline: Avoid concomitant use due to additive cardiac stimulant effects.
• Digitalis: Use with caution due to increased risk of arrhythmias.
• Halogenated Anesthetics (e.g., halothane): Use with caution due to increased risk of myocardial sensitization.
• Chlorpromazine, Monoamine Oxidase Inhibitors (MAOIs): Avoid concomitant use as these can potentiate the effects of isoprenaline.
• Methylxanthines (e.g., aminophylline, theophylline), Corticosteroids: Use with caution due to additive cardiotoxic potential.
• Beta-blockers: May reduce the effects of isoprenaline.
• COMT Inhibitors (e.g., entacapone): May increase isoprenaline levels and toxicity.
• Many other drugs can interact with isoprenaline. Consult a drug interaction database for a comprehensive list.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA). Animal reproduction studies have not been conducted. Use only if clearly needed, weighing the potential benefits against the risks to the fetus. Isoprenaline may inhibit uterine contractions and delay labor. No clinical evidence of teratogenic effects has been observed.
• Breastfeeding: Excretion in breast milk is unknown. Caution should be exercised when administering to a nursing mother.

Drug Profile Summary

• Mechanism of Action: β1- and β2-adrenergic receptor agonist, increasing heart rate and contractility, and relaxing smooth muscle.
• Side Effects: Tachycardia, palpitations, nervousness, headache, dizziness, tremors, nausea, vomiting. Serious side effects: arrhythmias, angina, hypotension.
• Contraindications: Tachyarrhythmias, digitalis-induced heart block, angina, recent myocardial infarction.
• Drug Interactions: Numerous drug interactions, including adrenaline, digitalis, halogenated anesthetics, MAOIs, methylxanthines, corticosteroids, beta-blockers, COMT inhibitors.
• Pregnancy & Breastfeeding: Pregnancy Category C; use with caution. Excretion in breast milk unknown.
• Dosage: Varies depending on indication; titrate to effect.
• Monitoring Parameters: Heart rate, ECG, blood pressure, urine output, central venous pressure (if applicable), and other relevant parameters.

Popular Combinations

Information on popular drug combinations for isoprenaline is limited in the provided sources.

Precautions

• General Precautions: Monitor closely for adverse effects, particularly cardiovascular. Correct hypovolemia before administration. Use with caution in patients with cardiovascular disease, diabetes, hyperthyroidism, and ischemic heart disease. Monitor potassium levels, especially when used with theophylline.
• Specific Populations: Refer to dosage adjustments for elderly, renal, and hepatic impairment.
• Pregnant Women: Use only if clearly needed, weighing benefits against potential risks to the fetus.
• Breastfeeding Mothers: Use with caution.
• Children & Elderly: Titrate dosages carefully.
• Lifestyle Considerations: No specific lifestyle considerations mentioned in the provided texts.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Isoprenaline?

A: The dosage varies depending on the indication and patient’s condition. It’s crucial to start with the lowest recommended dose and titrate upwards based on patient response and monitoring parameters. Refer to the Dosage section above for more details.

Q2: How should Isoprenaline be administered?

A: Isoprenaline can be administered intravenously (IV) as a bolus injection or continuous infusion, subcutaneously (SC), intramuscularly (IM), or intracardially. IV infusion is preferred for most indications. For IV administration, dilute with a compatible solution (e.g., 5% glucose, 0.9% sodium chloride).

Q3: What are the most common side effects of Isoprenaline?

A: Common side effects include tachycardia, palpitations, nervousness, headache, dizziness, tremors, nausea, vomiting, flushing, and sweating.

Q4: What are the contraindications for Isoprenaline?

A: Contraindications include tachyarrhythmias (except in specific circumstances), digitalis-induced tachycardia or heart block, ventricular arrhythmias requiring inotropic therapy, angina pectoris, recent myocardial infarction, and hypersensitivity to isoprenaline.

Q5: Does Isoprenaline interact with other medications?

A: Yes, Isoprenaline has numerous drug interactions. It’s important to consult a drug interaction database and exercise caution when co-administering with other medications. Some important interactions include those with adrenaline, digitalis, halothane, MAOIs, methylxanthines, corticosteroids, beta-blockers, and COMT inhibitors.

Q6: Can Isoprenaline be used during pregnancy or breastfeeding?

A: Isoprenaline is a Pregnancy Category C drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Its excretion in breast milk is unknown, so caution should be used during breastfeeding.

Q7: What monitoring parameters should be considered when using Isoprenaline?

A: Heart rate, ECG, blood pressure, urine output, and central venous pressure (when applicable) should be monitored closely. Additional monitoring may be necessary based on the patient’s condition.

Q8: What should be done in case of Isoprenaline overdose?

A: Discontinue Isoprenaline immediately. Supportive care and symptomatic treatment should be provided, focusing on managing arrhythmias and other cardiovascular effects. Beta-blockers may be considered as an antidote, but caution is needed due to the potential for bronchospasm.

Q9: Are there any age-specific considerations for Isoprenaline dosing?

A: While there are no specific dosage adjustments for elderly patients based solely on age, careful titration starting at the lower end of the dose range is crucial due to increased sensitivity. Pediatric dosing is not well-established and should be individualized based on weight and monitored closely.

Q10: What are the signs of isoprenaline toxicity?

A: Signs of isoprenaline toxicity may include severe tachycardia, palpitations, angina, significant hypertension or hypotension, serious arrhythmias, myocardial ischemia, pulmonary edema, and symptoms related to central nervous system stimulation like headache, nervousness and tremors.