Action And Clinical Pharmacology: Methoxamine is an alpha-receptor stimulant which produces a prompt and prolonged rise in blood pressure following parenteral administration.
It acts by exclusively stimulating alpha-adrenergic receptors and hence causes vasoconstriction. Raised arterial pressure stimulates reflex vagal inhibitory effects on the heart, and it is by this effect that methoxamine curtails supraventricular tachycardia.
The major pharmacological effect of methoxamine is a potent, prolonged pressor action following parenteral administration. Methoxamine differs from most other sympathomimetic amines both in animals and in humans by having a predominantly peripheral action and lacking inotropic and chronotropic effects. Methoxamine has less arrhythmogenic potential than other sympathomimetic amines and rarely causes ventricular tachycardia, fibrillation, or increased sinoatrial rate. On occasion, a decrease in cardiac rate develops as the blood pressure increases. This bradycardia is apparently caused by a carotid sinus reflex mediated over the vagus nerve. It is abolished by atropine.
Evidence for direct action on blood vessels is provided by the observation of intense constriction along the course of a vein into which methoxamine has been injected. Methoxamine also increases central venous pressure and has the distinct advantage of being free of central stimulating action. Pressor action without central stimulation may be especially desirable in patients undergoing surgery under spinal anesthesia.
Methoxamine does not increase the irritability of the cyclopropane-sensitized heart. It is a safe pressor agent for use during cyclopropane anesthesia. It has already been noted that methoxamine tends to slow the ventricular rate; large doses may produce bradycardia, but do not cause ventricular tachycardia, fibrillation, or an increased sino-atrial rate.
Tachyphylaxis has not been a clinical problem.
Following i.v. administration of methoxamine in dogs and humans, the peak pressor effect occurs within 0.5 to 2 minutes. In a group of surgical patients, the duration of the pressor effect following a single i.v. dose of 2 to 4 mg of methoxamine was 10 to 15 minutes. No clinical pharmacology studies are available concerning the onset and duration of action after administration of recommended i.m. doses (10 to 15 mg). With administration of 10 to 40 mg methoxamine i.m. to patients, however, the peak effect occurs within 15 to 20 minutes, and the duration of action is approximately 1 1/2 hours.
It has been shown by cardiac catheterization that methoxamine does not increase cardiac output or stroke volume, although it does increase right auricular and ventricular pressure by increasing venous pressure. It has been shown repeatedly that it does not affect cardiac irritability and that it tends to slow rather than to increase heart rate. Also, it has a marked power to raise total peripheral resistance. Studies have indicated that increased force of cardiac contractions can occur without direct stimulation of the heart, probably due to the general improvement in circulation resulting from the increase in arterial pressure. These actions contribute to the restoration of circulatory function, without unduly increasing the work of the cardiac musculature.
Indications And Clinical Uses: Intended for supporting, restoring or maintaining blood pressure during anesthesia (including cyclopropane anesthesia). It is especially useful to counteract the fall in blood pressure that commonly follows the administration of a spinal anesthetic. This pressor agent is particularly indicated just before surgery on patients who are poor risks and who have low blood pressure and where emergency operations are involved. It may also be helpful in treating postoperative collapse. The drug is not to be regarded as a substitute for blood, plasma, or other measures indicated in the treatment of shock.
Methoxamine is indicated in the treatment of shock due to traumatic, surgical or medical conditions, including acute myocardial infarction, in which it is desired to increase peripheral resistance without producing myocardial stimulation.
The i.v. administration of methoxamine promptly terminates episodes of paroxysmal supraventricular tachycardia. Normal rhythm of the heart is restored, usually in less than 1 minute. No adverse effect on the heart has been observed. The reversion from paroxysmal to normal rhythm following methoxamine administration is mediated through the baroreceptors in the carotid sinus and aortic arch. The stimulation of the vagus nerves in turn acts on the pacemaker of the heart to slow it down. Current practice, however, favors use of antiarrhythmic drugs such as verapamil, beta-blockers or adenosine for termination of paroxysmal supraventricular tachycardia.
Contra-Indications: In patients with severe hypertension, or in patients who are hypersensitive to methoxamine. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: The use of methoxamine in patients receiving MAO inhibitors, tricyclic antidepressants or oxytocic agents such as vasopressin or certain ergot alkaloids may result in potentiation of the pressor effect (see Precautions, Drug Interactions).
Contains potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Pregnancy: Methoxamine has been shown to decrease uterine blood flow, decrease fetal heart rate and adversely affect the fetal acid-base status in pregnant ewes and monkeys at doses comparable to those used in humans. There are no adequate and well-controlled studies in pregnant women. There has been one report of a fetal death; the mother received methoxamine concomitantly with several other drugs. A direct causal relationship to methoxamine was not established. Methoxamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Precautions: General: Methoxamine, like other vasopressor agents, should be used with caution in patients with hyperthyroidism, bradycardia, partial heart block, myocardial disease, or severe arteriosclerosis. Caution should be exercised to avoid overdosage, preventing undesirable high blood pressure and/or bradycardia. Note: bradycardia may be abolished with atropine (see Overdose: Symptoms and Treatment). Also caution should be taken when methoxamine is used closely following the parenteral injection of ergot alkaloids to avoid an excessive rise in blood pressure.
Children: Safety and effectiveness in children have not been established.
Pregnancy: see Warnings, Pregnancy.
Labor and Delivery: If vasopressor drugs are used to correct hypotension or are added to the local anesthetic solution during labor and delivery, some oxytocic drugs (vasopressin, ergotamine, ergonovine, methylergonovine) may cause severe persistent hypertension (see Drug Interactions). Note: In pregnant animals, methoxamine has been shown to decrease uterine blood flow, possibly resulting in fetal asphyxia. Uterine hypertonus and fetal bradycardia may also be produced (see Adverse Effects and Warnings, Pregnancy).
Lactation: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when methoxamine is administered to a nursing woman.
Drug Interactions: The pressor effect of methoxamine may be markedly potentiated when methoxamine is used in conjunction with MAO inhibitors, tricyclic antidepressants, vasopressin or ergot alkaloids such as ergotamine, ergonovine or methylergonovine, sympathomimetic agents such as decongestants, some appetite suppressants and amphetamine-like psychostimulants. Therefore, when initiating pressor therapy in patients receiving these drugs, the initial dose should be small and given with caution (see Warnings).
Cardiovascular: Methoxamine should not be administered unless facilities are available to measure systemic blood pressure frequently. The effect of increased arterial pressure on a patient with pre-existing vascular disease or impairment of myocardial function should be considered before administering methoxamine Injection.
Use methoxamine Injection with care in patients with poor left ventricular function as the increase in peripheral resistance, which is brought about by methoxamine, may cause or exacerbate cardiac failure.
The use of methoxamine injection is not a substitute for replacement of lost intravascular fluids and care should be taken to ensure adequate provision of i.v. fluid, plasma or blood before or during recourse to methoxamine injection.
Laboratory Tests: Methoxamine may increase plasma cortisol and ACTH levels. Caution should be used when interpreting plasma cortisol and ACTH levels in a patient concurrently receiving methoxamine.
Carcinogenesis, Mutagenesis, Impairment of Fertility: No long-term animal studies have been performed to evaluate the potential of methoxamine in these areas.
Adverse Reactions: The following adverse reactions have been observed, but there are insufficient data to support an estimate of their frequency: Cardiovascular: excessive blood pressure elevations particularly with high dosage, ventricular ectopic beats, reflex bradycardia.
Gastrointestinal: nausea, vomiting (often projectile).
CNS: headache (often severe), anxiety.
Integumentary: sweating, pilomotor response; feeling of cold and other skin sensations resulting from piloerection.
Genitourinary: uterine hypertonus, fetal bradycardia (see Precautions, Labor and Delivery), urinary urgency.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage of methoxamine may be manifested as an undesirable elevation in blood pressure and/or bradycardia. Should a clinically significant elevation of blood pressure occur that requires treatment, it may be immediately reversed with an alpha-adrenergic blocking agent (e.g., phentolamine). Bradycardia may be abolished by atropine.
Dosage And Administration: Blood volume depletion should always be corrected before any vasopressor is administered.
Methoxamine is administered either i.m. or i.v. In emergencies or where a serious vasomotor collapse has occurred, i.v. injection is desirable. The i.m. route alone is recommended where there is no emergency.
When administered i.v., large veins are preferred to prevent extravasation of methoxamine injection. Extravasation may cause necrosis and sloughing of surrounding tissue. The infusion site should be monitored closely for free flow. The usual i.v. dose of methoxamine, for emergencies, is 3 to 5 mg, injected slowly. I.V. injection may be supplemented by i.m. injections to provide a more prolonged effect. The usual i.m. dose is 10 to 15 mg given shortly before or at the time of administering spinal anesthesia to prevent a fall in blood pressure. The tendency for the blood pressure to fall is greater with higher levels of spinal anesthesia, hence, the dosage may be adjusted accordingly; 10 mg may be adequate at lower spinal levels while 15 to 20 mg may be required at high levels of spinal anesthesia. Repeated doses may be given if necessary, but time should be allowed for the previous dose to act (about 15 minutes, see Pharmacology).
For purposes of correcting a fall in blood pressure, an i.m. injection of 10 to 15 mg may be given depending on the degree of fall. In cases where the systolic pressure falls to 60 mm Hg or less, or whenever an emergency exists, an i.v. injection of 3 to 5 mg is indicated. This i.v. dose may be accompanied by 10 to 15 mg i.m. to provide a more prolonged effect.
For preoperative and postoperative use in cases of only moderate hypotension, 5 to 10 mg i.m. may be adequate.
For the treatment of hypotension associated with acute myocardial infarction or prolonged shock due to other causes, methoxamine may be administered in dilute solution by slow i.v. infusion. A solution of dextrose 5% in 250 mL of distilled water containing methoxamine 35 to 40 mg is administered at the rate required to provide an optimal response.
For termination of episodes of supraventricular tachycardia not responsive to other modes of therapy, the usual dose of methoxamine is 10 mg i.v., administered by slow push (i.e., 3 to 5 minutes).
Availability And Storage: Each mL of sterile aqueous solution contains: methoxamine HCl 20 mg. Nonmedicinal ingredients: citric acid anhydrous and sodium citrate (added as buffers), carbon dioxide, potassium metabisulfite (added as an antioxidant), sodium chloride and water for injection. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Store at controlled room temperature between 15 and 30°C, and protect from light. Ampuls of 1 mL, boxes of 10.
VASOXYL® Glaxo Wellcome Methoxamine HCl Vasopressor