ESMOCARD 100 mg/10 ml

Indications

• Short-term treatment of supraventricular arrhythmias (including atrial fibrillation and atrial flutter)
• Control of tachycardia and hypertension in the perioperative period

Dosage

Children: Neonate: 0.5–2 mg/kg once daily, may be given in 2 divided doses. Child (1 month–11 years): 0.5–2 mg/kg once daily, may be given in 2 divided doses. Child (12–17 years):

Adults: Administer 500 micrograms/kg as a loading dose over 1 minute, followed by a continuous infusion of 50 micrograms/kg/minute, with adjustments made according to clinical response.

Mechanism of action

Esmolol works by selectively blocking beta-1 adrenergic receptors in the heart. This blockade leads to a decrease in heart rate and myocardial contractility, thereby reducing cardiac output and oxygen demand. The drug's rapid metabolism by esterases in red blood cells contributes to its short duration of action, allowing for precise control of heart rate in acute situations.

Pharmacodynamics

The pharmacodynamic effects of esmolol include a reduction in heart rate, myocardial contractility, and overall cardiac workload. Its rapid onset and offset of action allow for quick adjustments in heart rate, making it useful for managing conditions such as atrial fibrillation and atrial flutter, particularly in perioperative settings.

Pharmacokinetics

Esmolol is administered intravenously and has a rapid onset of action, typically within 1-2 minutes. It is extensively metabolized by esterases in the plasma, leading to a very short half-life of approximately 9 minutes. Its elimination is primarily through hydrolysis, and it is not significantly excreted unchanged in the urine. The volume of distribution is around 3-4 L/kg, and protein binding is approximately 95%. Due to its rapid metabolism, careful titration and monitoring are required during administration.

Contra-indications

• Severe bradycardia
• Severe hypotension
• Cardiogenic shock
• Decompensated heart failure
• Known hypersensitivity to esmolol or any of its components

Adverse effects

• Drowsiness
• Hypoglycaemia
• Bronchospasm
• Hypotension
• Heart block
• Nausea
• Vomiting
• Fatigue
• Skin reactions
• Pulmonary edema

Interactions

• Caution with other beta-blockers
• May interact with antihypertensive medications
• Caution with drugs that affect heart rate and blood pressure (e.g., digoxin, calcium channel blockers)
• May enhance the effects of other medications that cause bradycardia

Precautions

• Use with caution in patients with a history of asthma or chronic obstructive pulmonary disease
• Monitor heart rate and blood pressure closely during therapy
• Caution in patients with hepatic impairment
• Consider dose adjustments in renal impairment

Pregnancy

Avoid use during pregnancy unless clearly necessary, as safety in pregnancy has not been established.

Breast-feeding

Manufacturers advise avoidance; presence in breast milk is unknown.

Storage

Store at room temperature, protect from light. Do not freeze.

Formulations

• Esmolol hydrochloride 10 mg per 1 ml solution for injection vials
• Esmolol hydrochloride 100 mg/10 ml solution for injection
• Esmolol hydrochloride 2.5 g/250 ml solution for infusion

Indications

• Supraventricular tachycardia
• Atrial fibrillation or flutter
• Perioperative hypertension
• Tachycardia during acute myocardial infarction

Dosage

Children: Refer to the BNF for Children for specific dosing information in paediatric patients.

Adults: The initial intravenous dose is typically 500 mcg/kg over 1 minute, followed by a continuous infusion of 50 mcg/kg/min, adjusted based on clinical response.

Mechanism of action

Esmolol works by blocking the agonistic effects of sympathetic neurotransmitters on beta-1 adrenergic receptors in the heart, leading to decreased heart rate and myocardial contractility. This selective blockade reduces adrenergic stimulation of cardiac pacemaker potentials, contributing to its antiarrhythmic properties. At lower doses, esmolol predominantly affects beta-1 receptors, while at higher doses it may also block beta-2 receptors.

Pharmacodynamics

Esmolol exhibits a rapid onset of action, typically within minutes, and a short half-life of approximately 9 minutes due to its rapid hydrolysis by esterases in the blood. This pharmacodynamic profile allows for precise control of heart rate and blood pressure during acute interventions.

Pharmacokinetics

Esmolol is administered intravenously and has a rapid distribution phase. The drug is extensively metabolized in the bloodstream by esterases, leading to its short duration of action. The elimination half-life is approximately 9 minutes, and its pharmacokinetics are not significantly altered by renal function due to its rapid metabolism. The volume of distribution is around 4 L/kg.

Interactions

• propafenone+esmolol: Moderate (increases risk of cardiovascular adverse effects)

Pregnancy

Esmolol is classified as category C. Risk cannot be ruled out and should only be used if the benefits outweigh the risks.

Breast-feeding

Esmolol is not recommended during breastfeeding as it is excreted in breast milk and may affect the infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Esmolol hydrochloride injection

Dosage

Children: Refer to the specific drug's prescribing information for paediatric dosing guidelines.

Adults: Refer to the specific drug's prescribing information for adult dosing guidelines.

Mechanism of action

The mechanism of action of hydrochloride salts varies depending on the specific drug. Generally, the drug's active ingredient interacts with specific receptors or enzymes in the body, leading to its therapeutic effects. For instance, an antihistamine hydrochloride would block H1 receptors, reducing allergic symptoms, while an antidepressant hydrochloride may inhibit the reuptake of neurotransmitters such as serotonin or norepinephrine.

Pharmacodynamics

Pharmacodynamics is dependent on the active pharmaceutical ingredient within the hydrochloride formulation. For example, in the case of an antidepressant, the drug would increase the concentration of neurotransmitters in the synaptic cleft, contributing to mood elevation and anxiety reduction. The onset and duration of action will vary with the specific drug, influencing the therapeutic regimen prescribed.

Pharmacokinetics

Pharmacokinetics of hydrochloride salts are influenced by the specific drug’s absorption, distribution, metabolism, and excretion. Generally, these drugs are well absorbed from the gastrointestinal tract. They may undergo first-pass metabolism in the liver, impacting their bioavailability. The half-life, volume of distribution, and elimination routes can vary significantly depending on the drug's characteristics.

Contra-indications

• Hypersensitivity to hydrochloride or any excipients
• Severe renal impairment
• Acute narrow-angle glaucoma

Adverse effects

• Dry mouth
• Dizziness
• Headache
• Constipation
• Nausea
• Fatigue
• Urinary retention

Interactions

• Anticholinergic drugs may enhance the anticholinergic effects
• CNS depressants may increase sedation
• Increased risk of toxicity with other medications that are renally excreted

Precautions

• Use with caution in patients with prostate hypertrophy
• Monitor in patients with a history of seizures
• Consider potential for overlap with other medications affecting CNS

Pregnancy

Hydrochloride should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydrochloride is excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solutions
• Injectable solutions

Mechanism of action

Similar to other beta-blockers, esmolol blocks the agonistic effect of the sympathetic neurotransmitters by competing for receptor binding sites. Because it predominantly blocks the beta-1 receptors in cardiac tissue, it is said to be cardioselective. In general, so-called cardioselective beta-blockers are relatively cardioselective; at lower doses they block beta-1 receptors only but begin to block beta-2 receptors as the dose increases. At therapeutic dosages, esmolol does not have intrinsic sympathomimetic activity (ISA) or membrane-stabilizing (quinidine-like) activity. Antiarrhythmic activity is due to blockade of adrenergic stimulation of cardiac pacemaker potentials. In the Vaughan Williams classification of antiarrhythmics, beta-blockers are considered to be class II agents.