Metaver

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

• Emergency treatment of acute hypotension
• Severe orthostatic hypotension due to autonomic dysfunction

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Initially by intravenous injection: 0.5–5 mg, then by intravenous infusion: 15–100 mg, adjusted according to response. By mouth: Initially 2.5 mg 3 times a day, increased if necessary up to 10 mg 3 times a day, with titration based on blood pressure measurements.

Mechanism of action

Metaraminol acts through peripheral vasoconstriction by being a pure alpha-1 adrenergic receptor agonist, leading to an increase in systemic blood pressure. Its mechanism involves the inhibition of adenyl cyclase, reducing cAMP production, and indirectly releasing norepinephrine from storage sites. This results in vasoconstriction, increased peripheral vascular resistance, and a resultant increase in blood pressure, although reflex bradycardia may occur.

Pharmacodynamics

Metaraminol is noted for its potent sympathomimetic effects, increasing both systolic and diastolic blood pressure. It finds clinical application in preventing and treating acute hypotensive states associated with spinal anesthesia, hemorrhage, medication reactions, surgical complications, and shock due to brain trauma or tumors. It primarily works on alpha-1 adrenergic receptors and has minimal impact on beta-adrenergic receptors, thereby increasing cardiac output slightly while constricting peripheral blood vessels.

Pharmacokinetics

Metaraminol's direct action leads to a proportional vasopressor effect based on plasma drug levels. Following intravenous administration, its actions are likely terminated by dilution in body fluids and tissue uptake. The pharmacokinetic profile includes a relatively quick onset of action, but specifics on half-life or metabolic pathways are not extensively detailed.

Contra-indications

• Aortic aneurysm
• Coronary vascular thrombosis
• Cirrhosis
• Diabetes mellitus
• Extravasation at injection site
• Hypertensive response
• Hyperthyroidism
• Myocardial infarction
• Peripheral vascular thrombosis
• Prinzmetal’s variant angina
• Severe orthostatic hypotension when corrective factors have been ruled out
• Uncorrected hypovolaemia

Adverse effects

• Bradycardia
• Cerebrovascular occlusion
• Chills
• Flushing
• Gastrointestinal discomfort
• Headache
• Nausea
• Palpitations
• Paraesthesia
• Piloerection
• Hepatic function abnormality
• Confusion
• Diarrhoea
• Vomiting

Interactions

• Other sympathomimetics
• Narrow-angle glaucoma
• Phaeochromocytoma
• Proliferative diabetic retinopathy
• Serious obliterative vascular disease

Precautions

• Monitor blood pressure and rate of flow frequently
• Cautious dose titration recommended during pregnancy
• Use of effective contraception advised in women of childbearing potential
• Careful administration in elderly patients
• May cause necrosis following extravasation

Pregnancy

May reduce placental perfusion; use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises caution-no information available.

Storage

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

Formulations

• Metaraminol 2.5mg/5ml solution for injection ampoules
• Metaraminol 5mg/10ml solution for injection ampoules
• Metaraminol 10mg/1ml solution for injection vials
• Metaraminol 10mg/1ml solution for injection pre-filled syringes

Mechanism of action

Metaraminol acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic & diastolic). Its effect is thought to be associated with the inhibition of adenyl cyclase which leads to an inhibition of the production of cAMP. Another effect of Metaraminol is that it releases norepinephrine from its storage sites indirectly. BY DIRECT ACTION ON ALPHA ADRENERGIC RECEPTORS & INDIRECT ACTION THROUGH THE RELEASE OF NOREPINEPHRINE FROM STORAGE SITES...PRODUCES VASOCONSTRICTION, INCREASED PERIPHERAL VASCULAR RESISTANCE, & A RESULTANT INCREASED BLOOD PRESSURE. REFLEX BRADYCARDIA USUALLY OCCURS &...RENAL & CEREBRAL BLOOD FLOW DECREASES. /BITARTRATE/ CARDIAC INOTROPY INCREASES, BUT LESS SO THAN WITH NOREPINEPHRINE & CARDIAC OUTPUT REMAINS UNCHANGED OR MAY SLIGHLY DECREASE IF BRADYCARDIA OCCURS. SOME BETA ADRENERGIC MEDIATED VASODILATION OCCURS WITH METARAMINOL, BUT ALPHA EFFECTS PREDOMINATE. /BITARTRATE/ FOLLOWING IV ADMIN OF 1.5 MG/KG TO RABBITS, THERE WAS A POSITIVE CORRELATION BETWEEN PLASMA DRUG LEVEL & ITS VASOPRESSOR EFFECT. DRUG IS APPARENTLY DIRECT-ACTING SYMPATHOMIMETIC AMINE & ITS ACTION IS PROBABLY TERMINATED BY ITS DILUTION IN BODY FLUIDS & TISSUE UPTAKE.

Pharmacodynamics

Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Metaraminol is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Metaraminol acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels.