LEVOPHERINE

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

• Septic shock
• Cardiogenic shock
• Severe hypotension
• Acute heart failure

Dosage

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

Adults: The usual starting dose is 0.05 to 0.1 micrograms/kg/min, which may be titrated to achieve the desired blood pressure response.

Mechanism of action

Norepinephrine functions as a peripheral vasoconstrictor by acting on alpha-adrenergic receptors. It stimulates the heart as an inotropic agent and dilates coronary arteries through its activity on beta-adrenergic receptors. The drug is a potent alpha agonist with relatively little action on beta-2 receptors, making it effective in raising systemic vascular resistance and blood pressure.

Pharmacodynamics

Norepinephrine acts on alpha-1 and alpha-2 adrenergic receptors, leading to vasoconstriction and an increase in systemic vascular resistance. Its primary effect is to elevate blood pressure by increasing peripheral vascular resistance, making it critical in the treatment of hypotensive states.

Pharmacokinetics

Norepinephrine is rapidly metabolized in the body, primarily by catechol-O-methyltransferase and monoamine oxidase. Its half-life is short, necessitating continuous intravenous infusion for sustained effects. The distribution volume is low, and it is primarily excreted in urine as metabolites.

Contra-indications

• hypersensitivity to norepinephrine
• uncontrolled hypertension
• hypovolemia
• mesenteric or peripheral vascular thrombosis

Adverse effects

• arrhythmias
• hypertension
• bradycardia
• extravasation leading to tissue necrosis
• anxiety
• headache
• nausea
• palpitations

Interactions

• MAO inhibitors may enhance the pressor effects of norepinephrine
• tricyclic antidepressants may increase the risk of hypertension
• general anesthetics may increase the risk of cardiovascular effects
• adrenergic blockers may antagonize the effects of norepinephrine

Precautions

• monitor blood pressure continuously during administration
• ensure adequate hydration before use
• use with caution in patients with cardiovascular disease
• avoid extravasation; if occurs, treat promptly

Pregnancy

Norepinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as category C.

Breast-feeding

It is unknown whether norepinephrine is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

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

Formulations

• solution for injection

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.