UNINORADRIN

Indications

• Acute hypotension
• Septic shock
• Cardiogenic shock
• Neurogenic shock

Dosage

Children: For paediatric patients, dosing is typically initiated at 0.05 to 0.1 micrograms per kg per

Adults: The usual starting dose for adults is 0.05 to 0.5 micrograms per kg per minute, which may be titrated based on blood pressure response, typically aiming for a systolic blood pressure of 90 mmHg or greater.

Mechanism of action

Norepinephrine acts primarily as a peripheral vasoconstrictor by binding to alpha-adrenergic receptors, leading to increased vascular resistance and blood pressure. It also stimulates beta-adrenergic receptors, acting as an inotropic agent to enhance cardiac contractility and dilate coronary arteries. Its action is characterized by a strong agonistic effect on alpha-1 receptors, with lesser activity on beta-2 receptors, positioning it as a potent agent for increasing blood pressure and improving hemodynamic stability.

Pharmacodynamics

Noradrenaline's pharmacodynamic profile includes significant vasoconstriction through its action on alpha-1 and alpha-2 adrenergic receptors, resulting in elevated blood pressure and increased systemic vascular resistance. It also enhances myocardial contractility through stimulation of beta-1 receptors, although its primary utility lies in its ability to raise blood pressure in states of shock and hypotension.

Pharmacokinetics

Noradrenaline is administered intravenously due to its rapid onset of action and short half-life. It is metabolized primarily by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), leading to the formation of inactive metabolites. The elimination half-life is short, typically around 1-2 minutes, necessitating continuous infusion for sustained effects.

Adverse effects

• Hypertension
• Bradycardia
• Peripheral vasoconstriction
• Cardiovascular adverse effects

Interactions

• Beta-blockers (selective) - increases risk of hypertension and bradycardia
• Entacapone - increases risk of cardiovascular adverse effects
• Ergometrine - increases risk of peripheral vasoconstriction
• Opicapone - increases risk of cardiovascular adverse effects
• Tolcapone - increases effects

Pregnancy

Use with caution. Benefits should outweigh risks.

Breast-feeding

Use with caution. Effects on the infant are unknown.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Injection solution

Mechanism of action

Norepinephrine functions as a peripheral vasoconstrictor by acting on alpha-adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it's activity at the beta-adrenergic receptors. The pharmacological actions of norepinephrine and epinephrine have been extensively compared in vivo and in vitro. Both drugs are direct agonists on effector cells, and their actions differ mainly in the ratio of their effectiveness in stimulating alpha and beta2-receptors. They are approximately equipotent in stimulating beta1-receptors. Norepinephrine is a potent alpha agonist and has relatively little action on beta-2 receptors; however, it is somewhat less potent than epinephrine on the alpha receptors of most organs. During cold exposures there is an immediate release of catecholamines (e.g., norepinephrine, dopamine), which activate the sympathetic nervous system to reduce heat loss via peripheral vasoconstriction and shift substrate utilization toward fatty acid metabolism for heat production.

Pharmacodynamics

Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.