NOREPIBIL INJECTION (Each ampoule contains Noradrenaline (Norepinephrine) Bitartrate 4mg/ml)

Indications

• Used as a stabilizing agent in pharmaceuticals
• Used in food products as a preservative or acidity regulator

Dosage

Children: Refer to specific product information for dosing recommendations in children, as pediatric dosing guidelines will depend on the formulation and indication.

Adults: Refer to specific product information for detailed dosing recommendations, as the dosage of bitartrate can vary based on its use in different formulations.

Mechanism of action

Bitartrate acts primarily as a buffering agent, helping to maintain pH balance in formulations. It may enhance the solubility of specific active ingredients, thereby facilitating their absorption and efficacy. The precise mechanisms may vary depending on the specific bitartrate compound and its application.

Pharmacodynamics

The pharmacodynamics of bitartrate compounds are largely dependent on their specific use. Generally, bitartrate can influence the pharmacokinetics of co-administered drugs by altering their solubility and stability. This can lead to increased absorption and improved therapeutic outcomes. The effects on the central nervous system or other systems are not well characterized, as bitartrate is primarily used for its physicochemical properties rather than direct pharmacological effects.

Pharmacokinetics

The pharmacokinetics of bitartrate compounds largely depend on the specific formulation and the active ingredients involved. Generally, bitartrate salts are expected to dissociate in the gastrointestinal tract, contributing to the systemic availability of the active drug. The absorption, distribution, metabolism, and excretion profiles will vary based on the formulation and route of administration.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Bitartrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Bitartrate is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

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

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.