Magnesium sulfate

Pharmacological properties

with parenteral administration it has a hypotensive, arteriolodilating, antiarrhythmic, sedative, anticonvulsant, diuretic, antispasmodic, tocolytic effect. compensates for the deficiency of magnesium in the body, is a physiological calcium antagonist. regulates metabolic processes, neuron-chemical transmission and muscle excitability, prevents the flow of calcium ions through the presynaptic membrane, reduces the amount of acetylcholine in the peripheral and central nervous system, exhibits a sedative, hypnotic or narcotic effect depending on the dose, and has an antispasmodic effect. reduces the excitability of the respiratory center; when administered in high doses, it can cause respiratory depression.

The antihypertensive and antiarrhythmic effect of magnesium is due to a decrease in the excitability of cardiomyocytes, restoration of ion equilibrium, stabilization of cell membranes, disruption of the sodium flow, calcium flow that slowly enters, and unilateral potassium flow, expansion of the coronary arteries, a decrease in the total peripheral vascular resistance, platelet aggregation, and also spasms and sedative effects.

Sedative and anticonvulsant effects of magnesium are associated with a decrease in the release of acetylcholine from neuromuscular synapses, inhibition of neuromuscular transmission, and a direct inhibitory effect on the central nervous system.

The tocolytic effect develops as a result of the inhibition of the ability to reduce myometrium (decreased absorption, binding and distribution of calcium in smooth muscle cells), vasodilation and increased blood flow in the uterus. Magnesium has an antispasmodic effect during urinary retention, is an antidote for poisoning with salts of heavy metals.

Systemic effects develop almost instantly after i / v and 1 hour after i / m administration, their duration is 30 minutes and 3-4 hours, respectively.

Pharmacokinetics It penetrates the BBB and the placenta, is excreted in breast milk, the concentration of which is 2 times higher than that in blood plasma. It is excreted by the kidneys, the rate of renal excretion is proportional to the concentration in the blood plasma and the level of glomerular filtration. The plasma concentration at which an anticonvulsant effect develops is 2–3.5 mmol / L.

Indications

Hypertensive crisis; ventricular arrhythmias (tachycardia type pirouette); convulsive syndrome; eclampsia; hypomagnesemia; increased need for magnesium;

in the complex therapy of preterm birth; angina pectoris; in case of poisoning with salts of heavy metals, tetraethyl lead, soluble barium salts (antidote).

Application

Assign IM, IV slowly or as an IV infusion. the frequency of administration and dose are individual depending on the indications and therapeutic effect. with infusion, the drug should be diluted with 0.9% sodium chloride or 5% glucose. with iv injection, the rate of administration should usually not exceed 150 mg / min (0.6 ml / min), with the exception of the treatment of arrhythmias and eclampsia of pregnant women.

Hypomagnesemia. In case of moderate hypomagnesemia (0.5–0.7 mmol / l), 4 ml (1 g of magnesium sulfate) are to be administered to adults every 6 hours.

In severe hypomagnesemia (0.5 mmol / l) with i.v. administration, the total dose should be increased to 1 ml / kg body weight (250 mg / kg) and administered in parts for 4 hours. As an iv infusion in severe hypomagnesemia 20 ml of the drug (5 g of magnesium sulfate) add to 1 liter of 0.9% solution of sodium chloride or 5% glucose and enter for at least 3 hours

The maximum daily dose for iv administration is 72 ml (18 g). If necessary, repeat the infusion for several days.

AH. In case of AH of stage I – II, administer 5–10–20 ml daily i / m. The course of treatment is 15–20 injections, while along with a decrease in blood pressure, a decrease in the severity of angina can be observed.

Hypertensive crisis.Inject 10–20 ml IM or IV slowly.

Arrhythmias. To stop arrhythmias, inject 4–8 ml iv (1–2 g of magnesium sulfate) for 5–10 min, repeat the injection if necessary (total administration of up to 4 g of magnesium sulfate).

It is possible to administer first at a loading dose of 8 ml for at least 5 minutes, followed by infusion of 20 ml of the drug diluted with 0.9% sodium chloride or 5% glucose, for at least 6 hours, or first 8 ml for at least 30 min followed by infusion for at least 12 hours

Ischemic stroke. 10–20 ml iv for 5–7 days.

Convulsive syndrome. Adults prescribe 5-10-20 ml / m. Children should be given IM in the amount of 0.08–0.16 ml / kg body weight (20–40 mg / kg).

Toxicosis of pregnant women. 10–20 ml 1-2 times a day intramuscularly (can be combined with the simultaneous administration of antipsychotics).

In case of preeclampsia or eclampsia, i / m or iv. First, inject 10 ml once into each buttock or iv 16 ml (4 g of magnesium sulfate) for 3-4 minutes. Then continue to administer 16–20 ml (4–5 g) i / m every 4 hours or 4–8 ml / h (1–2 g / h) iv / drop with constant monitoring of tendon reflexes and respiratory function. Therapy should be continued until the attack stops. The maximum daily dose is 40 g of magnesium sulfate, with impaired renal function - 20 g / 48 h.

Anesthesia for childbirth. 5-10-20 ml / m, if necessary, combine magnesium sulfate with analgesics.

Urinary retention. In case of urinary retention and lead colic, administer 5–10 ml of drug IM or 5–10 ml iv diluted 5 times with 25% solution of magnesium sulfate (also prescribed as an enema).

Like an antidote. In case of intoxication with mercury, arsenic, and tetraethyl lead, 5–10 ml of 25% solution of magnesium sulfate diluted 2.5–5 times diluted with iv should be administered. In case of poisoning with soluble barium salts, inject 4-8 ml iv or wash the stomach with 1% magnesium sulfate solution.

Newborns. In case of intracranial hypertension and severe asphyxia in newborns, administer intramuscularly, starting with a dose of 0.2 ml / kg / day, increasing it on the 3-4th day to 0.8 ml / kg / day for 3-8 days in complex therapy. To eliminate magnesium deficiency in newborns, prescribe 0.5-0.8 ml / kg of body weight 1 time per day for 5-8 days.

Contraindications

Increased individual sensitivity to the components of the drug; arterial hypotension, severe bradycardia (heart rate 55 beats / min), av blockade, conditions caused by calcium deficiency and depression of the respiratory center, cachexia, impaired renal function, severe hepatic or renal failure, myasthenia gravis, malignant neoplasms.

Side effects

From the respiratory system, chest and mediastinal organs: shortness of breath, respiratory depression.

From the digestive tract: nausea, vomiting.

From the kidneys and urinary system: polyuria.

From the side of metabolism, metabolism: hypocalcemia, hypophosphatemia, hyperosmolar dehydration.

From the nervous system: headache, dizziness, general weakness, drowsiness, confusion, loss of consciousness, decreased tendon reflexes, diplopia, speech disorders, tremors and numbness of the limbs.

From the psyche: mood depression, anxiety.

From the cardiovascular system: arterial hypotension, bradycardia, palpitations, conduction disturbance, hot flashes, prolonged P – Q interval and expansion of the QRS complex on an ECG, arrhythmia, coma, cardiac arrest.

From the immune system: hypersensitivity reactions, including anaphylactic shock, angioedema.

On the part of the skin and subcutaneous tissue: hyperemia, itching, rash, urticaria.

From the musculoskeletal system and connective tissue: muscle weakness.

From the reproductive system and function of the mammary glands: atony of the uterus.

General disorders and reactions at the injection site: hyperthermic syndrome, chills, increased sweating, hyperemia, edema, pain.

special instructions

Before starting therapy, you should determine the level of magnesium in the blood. in adults, the normal level of magnesium in the blood plasma is 0.75–1.26 mmol / l.

When using the drug, it should be borne in mind that increased excretion of magnesium in the urine occurs with an increase in extracellular fluid, enlargement of the renal vessels, hypercalcemia, increased excretion of sodium in the urine, with the appointment of osmotic diuretics (urea, mannitol, glucose), loop diuretics (furosemide, ethacrylic acid , thiazides), with cardiac glycosides, calcitonin, thyroidin, with prolonged administration of deoxycorticosterone acetate (more than 3-4 days). A slowdown in the excretion of magnesium is observed with the introduction of parathyroid hormone. With renal failure, magnesium excretion slows down, and with repeated injections, its accumulation may occur. Therefore, in elderly patients and in patients with severe renal impairment, the dose of the drug should not exceed 20 g of magnesium sulfate (81 mmol Mg²⁺) within 48 hours, patients with oliguria or severe renal impairment should not be administered iv sulfate iv rapidly. Urinary tract infections accelerate the precipitation of ammonia-magnesium phosphates, while magnesiotherapy is temporarily not recommended. With a violation of the excretion of magnesium after parenteral administration of magnesium sulfate, hypermagnesemia is possible.

Use with caution in case of myasthenia gravis and respiratory diseases. With prolonged use of the drug, monitoring of the cardiovascular system, tendon reflexes, kidney function and respiratory rate is recommended.

In / in the introduction of magnesium sulfate is carried out slowly: with too high a speed of administration, hypermagnesemia is possible (symptoms - nausea, paresthesia, sedation, hypoventilation up to apnea, decrease in deep tendon reflexes). Concomitant Parenteral Administration of Vitamin B₆ and insulin increase the effectiveness of magnesiotherapy.

If necessary, the simultaneous introduction of magnesium sulfate and calcium preparations, they should be injected into different veins, while it should be borne in mind that the level of magnesium depends on the level of calcium in the body.

Use during pregnancy and lactation. During pregnancy, magnesium sulfate is used with caution, taking into account the concentration of magnesium in the blood, in cases where the expected therapeutic effect exceeds the potential risk to the fetus. When pain relief during childbirth, the possibility of suppressing the contractility of the muscles of the uterus should be considered, which requires the use of rhodostimulating agents.

If necessary, the use of the drug should stop breast-feeding.

Children. The drug can be used in pediatric practice.

The ability to influence the speed of reactions when driving vehicles or working with other mechanisms. Patients should be warned about the need to be careful when working with potentially dangerous mechanisms or driving vehicles, since the drug has a sedative effect.

Interactions

Calcium ions have an antagonistic effect with respect to magnesium ions, which leads to their simultaneous use to reduce the pharmacological effects of magnesium sulfate. enhances the effect of drugs that inhibit the central nervous system (drugs, analgesics). with the simultaneous use of muscle relaxants and nifedipine, neuromuscular blockade is enhanced. simultaneous use with calcium channel blockers, such as nifedipine, can lead to an imbalance in calcium balance and muscle function.

Barbiturates, narcotic analgesics and antihypertensive drugs increase the likelihood of depression of the respiratory center.

Cardiac glycosides increase the risk of conduction disturbance and AV block.

The effect of antithrombotic agents, vitamin K antagonists, isoniazid, non-selective inhibitors of neuronal reuptake of monoamines is reduced.

Mexiletine excretion may be slowed. A dose review may be required.

Propafenone - the effect of both drugs is enhanced and the risk of a toxic effect increases.

It violates the absorption of tetracycline antibiotics, intestinal obstruction is possible, weakens the effect of streptomycin and tobramycin.

Incompatibility. It is pharmaceutically incompatible (a precipitate forms) with calcium preparations, ethanol (in high concentrations), alkali metal carbonates, bicarbonates and phosphates, salts of arsenic acid, barium, strontium, clindamycin phosphate, sodium hydrocortisone succinate, polymyxin B sulfate, procaine hydrochloride, salicylamides and t . At Mg concentrations²⁺ 10 mmol / ml in mixtures for complete parenteral nutrition distribution of fat emulsions is possible.

Overdose

Symptoms: signs of hypermagnesemia in order of increasing plasma concentration of magnesium:

• decrease in deep tendon reflexes (2–3.5 mmol / l);
• prolongation of the P – Q interval and expansion of the QRS complex on the ECG (2.5–5 mmol / l);
• loss of deep tendon reflexes (4–5 mmol / l);
• inhibition of the respiratory center (5-6.5 mmol / l);
• violation of conduction of the heart (7.5 mmol / l);
• cardiac arrest (12.5 mmol / l).

In addition, hyperhidrosis, anxiety, lethargy, polyuria, uterine atony are possible.

Treatment: A specific antidote is calcium preparations (calcium chloride or gluconate), which should be administered iv slowly. With moderate hypermagnesemia, the appointment of furosemide is possible. Respiratory depression is eliminated by the introduction of iv 10–10 ml of 10% calcium chloride solution, oxygen inhalation, and artificial lung ventilation. In severe cases, peritoneal dialysis or hemodialysis is indicated. The appointment of symptomatic corrective functions of the cardiovascular and central nervous system.

Storage conditions

At a temperature not exceeding 25 ° C. do not freeze.