What Are the Medical Uses of Ergometrine?

Ergometrine, also known as D-lysergic acid -aminopropanol, is a class of drugs used to cause uterine contractions to treat vaginal postpartum bleeding. It was originally made from ergot ergot, but can now also be made from lysergic acid. Ergometrine is regulated because it can be used to make lysergic diethylamine (LSD). Ergometrine was discovered in 1932. It is included in the World Health Organization's Standard List of Essential Medicines, which contains all the most important medicines in the basic health system. Ergometrine is famous for its high quality and low price. In 2014, the wholesale price of each injection was between $ 0.12 and $ 0.41, and the total price of each pill was $ 0.01. In the United States, each dose is approximately $ 1.75 ^[1] .

Ergometrine is commonly used with its maleate salt, which directly affects uterine smooth muscle. The effect is strong and long-lasting. Its strength is related to the physiological state of the uterus and the dosage. It is mainly used to treat postpartum hemorrhage, poor uterine restoration, and excessive menstruation. It can be used orally, intramuscularly or intravenously.

Drug type: Essential medicines
Drug name: Ergometrine

English name: Ergometrine
Chinese alias: Ergometrine maleate
English alias: Cornocentin; Ergonovinum

Introduction to ergometrine compounds

Ergot new basebook information

Chinese name: Ergometrine

Chinese nickname: ergometrine malate; 9,1o-dideoxy-N-[(S) -2-hydroxy-1-methylethyl] -6-methylergotline-8-formamide; ergot malate Neobase; ergotine maleate; ergometrine maleate; dischlier

English name: Ergometrine

English alias: ergotocine; secacornin; secometrin; Ergobasin; ERGONOVINE; Ergometrine; Ergitrate; Cormocentin

CAS number: 60-79-7

Molecular formula: C ₁₉ H ₂₃ N ₃ O ₂

Molecular structure formula:

Molecular weight: 325.40500

Exact mass: 325.17900

PSA: 68.36000

LogP: 1.86340

Ergometrine Safety Information

Dangerous Goods Transport Code: UN 1544

Danger category code: R23 / 24/25

Safety instructions: 36/37 / 39-45 ^[1]

Physicochemical properties of ergometrine

This product is colorless crystal, MP 162-163 (decomposed), MP 212 (decomposed, bicrystalline); refractive index: + 91 ° (water); pK6.8, easily soluble in lower alcohol and ethyl acetate , Slightly soluble in chloroform. Slightly soluble in water, the solution showed blue fluorescence. Its maleate salt is white or light yellow microcrystalline powder, odorless, slightly hygroscopic, darkened when placed or exposed to light, MP 167 (decomposed), refractive index: + 48 ~ + 57 ° soluble Water (1:40), soluble in ethanol (1: 100), almost insoluble in chloroform and ether; water or alcohol solution has blue fluorescence, 1% aqueous solution is dextro-rotatory, and the pH is 3-5. Ergometrine tartrate is white, shiny, rough needle-like crystals, soluble in water and ethanol, slightly soluble in ether and chloroform. Its hydrochloride MP 245-246 ° C, (decomposed); refractive index: + 63 ° (water). L-body MP 159-162 ° C (decomposed), refractive index: -89 ° (water).

Ergometrine pharmacopeia standards

[Identification] (1) The aqueous solution of this product shows blue fluorescence. (2) Take about 1mg of this product, add 1ml of water to dissolve, and add 2ml of p-dimethylaminobenzaldehyde test. After 5 minutes, it will be dark blue. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 32).

[Check] Take 0.10g of acidity, dissolve it by adding 10ml of water, and measure it according to law (Appendix VIH). The pH value should be 3.6 ~ 4.4. The clarity of the solution is 0.10 g of this product. After adding 10 ml of water to dissolve, the solution should be clear. Relevant substances are taken from this product, accurately weighed, dissolved in ethanol-concentrated ammonia solution (9: 1) and quantitatively diluted to make a solution containing 5mg per 1ml and a solution containing 0.2mg per 1ml, respectively, as test solution (1) and test solution (2); take another reference of ergometrine maleate, accurately weigh, dissolve and quantitatively dilute with the above solvent to make a solution containing 5mg per 1ml, as the reference solution. According to the thin layer chromatography (Appendix VB) test, pick up the two solutions and point them on the same silica gel G thin plate, and use trioxane-methanol-water (25: 8: 1) as the developing agent. Dry and place under UV light (365nm) for inspection. The position and color of the main spot of the test solution (1) should be the same as the main spot of the reference solution. For comparison, it must not be deeper, and it must not show impurities spots other than the reference solution; the test solution (2) must not show any impurity spots except the main spot. Take this product for weight loss and dry it in a phosphorus pentoxide dryer to Constant weight, weight loss shall not exceed 2.0% (Appendix L).

[Content determination] Take about 60mg of this product, accurately weigh, add 20ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titration solution (0.05mol / L) until the solution is blue-green, and The results of the titrations are corrected with a blank test. Per 1ml of perchloric acid titration solution (0.05mol / L) is equivalent to 22.07mg of C19H23N3O2 · C4H4O4

[Category] Uterine contractions.

Storage Shade, sealed, and stored in a cold place.

Ergometrine drug description

Ergometrine pharmacology

It is highly selective for uterine smooth muscle and directly acts on uterine smooth muscle. The effect is strong and long-lasting. The effect is related to the physiological state of the uterus and the dose of medication. Pregnant uterus is more sensitive than non-pregnant uterus, mature uterus is more sensitive than immature uterus, and it is most sensitive to uterus before labor or after labor. It differs from oxytocin mainly in that it has a strong contraction effect not only on the uterine floor but also on the uterine neck. A slightly larger dose will produce tonic contraction, so it is not suitable for oxytocin and induction of labor; but because of uterine muscle rigidity Sexual contraction mechanically compresses blood vessels in the muscle fibers while preventing bleeding. Absorption is fast and complete after oral or intramuscular injection. About 6 to 15 minutes after oral administration and about 2 to 3 minutes after intramuscular injection, the contractions begin to take effect, and the effect lasts for 3 hours; the effect is immediate after intravenous injection, the effect is about 45 minutes, and the rhythmic contraction can last for 3 hours. Metabolized in the liver, excreted by the kidneys with urine.

Ergometrine indications

For the treatment of postpartum uterine bleeding, postpartum uterine insufficiency (accelerated uterine recovery), menstruation and so on.

Ergometrine Usage and Dosage

1. Intravenous or intramuscular injection: 0.1 to 0.2 mg once. Intravenous injection can be diluted with 20% 25% glucose injection. 0.5 mg once a day, 1 mg a day.

2. Uterine wall injection: 0.2mg is injected directly into the myometrium during cesarean delivery; 0.2mg can be injected into the cervix for postoperative or postpartum abortion, and the left and right sides of the cervix can be injected.

3. Oral: 0.2 ~ 0.5 mg once, 1 or 2 times a day.

Ergometrine adverse reactions

(1) Adverse reactions are rare due to short medication time. Some patients may experience nausea, vomiting, cold sweats, and pale complexions after administration. When administered intravenously, headache, dizziness, tinnitus, abdominal pain, nausea, vomiting, chest pain, palpitations, dyspnea, and slow heart rate may occur, so intravenous injection should not be used routinely. Severe hypertension may also occur suddenly, and symptoms can be improved or even disappeared after using chlorpromazine. Although the following adverse reactions are rare, you should pay attention to: such as chest pain caused by coronary artery spasm, severe headache caused by sudden rise in blood pressure, itching of the skin, pain in limbs or back pain, pale hands and feet, cold legs, weakness, shortness of breath (possibly Is an allergic reaction). (2) If used improperly, ergot poisoning may occur, manifested as persistent diarrhea, pale and cold skin on hands, feet, and lower limbs, weak heartbeat, persistent vomiting, and convulsions.

Ergometrine contraindications

Disable this product before delivery of the fetus and placenta, otherwise the placenta can be embedded in the uterine cavity. If this product is used before delivery of the fetus, ankylosing uterine contraction may occur, resulting in hypoxia or intracranial hemorrhage. Patients with pregnancy-induced hypertension, coronary heart disease, and those allergic to this product are prohibited.

Ergometrine precautions

(1) Cross-allergic reactions are shown between ergot preparations. Patients cannot tolerate other ergot preparations, nor can they tolerate this product. (2) It can be excreted through milk, which may cause ergot-like toxicity in infants; it may also inhibit lactation, and it is not suitable for breastfeeding women. (3) Patients with hypertension, atherosclerosis, vasospasm, occlusive peripheral vascular disease, coronary heart disease, hypocalcemia, pregnancy-induced hypertension syndrome, sepsis, liver or renal insufficiency should be used with caution. (4) Insufficiency of uterine recovery is often accompanied by intrauterine infection. The use of ergot preparation alone may cause the infection to spread. Generally, anti-infective drugs should be used in combination. (5) A large number of smokers are prone to vasoconstriction or pain after application.

Ergometrine drug interactions

(1) This product has synergistic effects with oxytocin and other ergot preparations, so it should not be used in combination. (2) This product should not be used in combination with booster drugs, otherwise it will increase blood pressure and cause severe headache. (3) This product can reduce the uterine contraction effect when used equally with anesthetic ether, thiopental, halothane and morphine. (4) This product should not be used together with vasoconstrictor drugs (including epinephrine in local anesthetic solution). (5) Do not smoke too much during taking this product, so as not to cause vasoconstriction or spasm.

Ergometrine poisoning

Ergometrine is commonly used with its maleate salt, which directly affects uterine smooth muscle. It is mainly used to treat postpartum hemorrhage, poor uterine restoration, and excessive menstruation. Intravenous, intramuscular or oral doses are usually 0.2-0.5mg / time, extreme dose 0.5mg / time, 1mg / d. Intravenous injection should not be used for routine use, and a single dose should not exceed 0.5mg.

Clinical manifestation

1. Due to short medication time, adverse reactions are rare. Some patients may experience nausea, vomiting, cold sweats, and pale complexions after administration.

2. Acute poisoning

(1) Gastrointestinal symptoms, burning pain in the stomach, vomiting, thirst, difficulty swallowing, diarrhea, etc.

(2) Edema on the face and extremities, chilled skin, itching, skin necrosis, intestinal tract and uterine contraction.

(3) Muscle tonic contraction, headache, tinnitus, hearing impairment, pupil narrowing, blurred vision, aphasia, inability to walk, hemiplegia, insanity, convulsions, coma, etc.

(4) Increased or decreased blood pressure, tachycardia or bradycardia, angina pectoris, myocardial infarction.

treatment

Key points in the treatment of ergometrine poisoning:

1. Oral poisoning can first drink 100ml of 20% medicinal charcoal suspension, then induce vomiting and catharsis with magnesium sulfate, and then protect the digestive tract mucosa with milk.

2. Proper fluid replacement to promote excretion of poisons and maintain water and electrolyte balance.

3. To improve and eliminate the symptoms of the cardiovascular system, papaverine, tolazoline, etc. can be given.

4. Use appropriate amount of low molecular dextran and heparin to prevent blood clotting.

5. If there is a tendency to necrosis, 0.5% to 1% lidocaine can be used for paraspinal closure.

6. Symptomatic treatment ^[2] .

Ergometrine

Injection: 0.2mg (1ml); 0.5mg (1ml) each.

^[3-6]

Ergometrine injection

Drug Name

Common name: Ergometrine maleate injection

English name: Ergometrine Maleate Injection

Phonetic script: Mlisun Mijio Xinjin Zhusheye

The main ingredients of this product are: ergometrine maleate. Its chemical name is: 6-methyl-N-[(S) -1-methyl-2-hydroxyethyl] -9,10-didehydroergoline-8-b-formamide maleate salt.

Molecular weight:

[Character]

This product is a colorless or almost colorless clear liquid with slight blue fluorescence.

[Pharmacology and Toxicology]

This product is a uterine contraction drug.

Can directly affect the uterine smooth muscle, the effect is strong and long-lasting. Large doses can make the uterine muscles to contract tightly, can make the blood vessels in the uterine muscles of the placenta to be compressed to stop bleeding, and increase the sensitivity of the uterus to uterine contraction drugs in late pregnancy.

Pharmacokinetics

Completely absorbed after oral or intramuscular injection. Oral administration is about 6 to 15 minutes, intramuscular injection is 2 to 3 minutes, the contractions begin to take effect, the effect lasts 3 hours, and the intravenous injection immediately takes effect. The effect is promised for 45 minutes, and the rhythmic contraction can last for 3 hours. This product is metabolized in the liver and excreted by the kidneys with urine.

[Indications]

1. It is mainly used for the prevention and treatment of postpartum or post-abortion uterine bleeding due to weak uterine contraction or poor contraction.

2. For postpartum uterine insufficiency and accelerate uterine recovery.

Dosage

Intramuscular or intravenous injection of 0.2 mg, if necessary, can be repeated once every 2 to 4 hours, up to 5 times. For intravenous injections, inject slowly after dilution, at least 1 minute.

Adverse reactions

1. Due to the shorter administration time of postpartum or postpartum uterine bleeding, some adverse reactions to the drug are less common than other ergot alkaloids. However, when administered intravenously, headache, dizziness, tinnitus, abdominal pain, nausea, vomiting, chest pain, palpitations, dyspnea, and slow heart rate may occur; severe hypertension may also occur suddenly, which can be improved after using chlorpromazine It even disappeared.

2. If not used properly, ergot poisoning may occur, manifested as persistent diarrhea, pale coldness in the skin of hands, feet and lower limbs, weak heartbeat, persistent vomiting, and convulsions.

[Taboo]

Use of this product before delivery of the fetus may cause uterine tonic contraction, resulting in hypoxia or intracranial hemorrhage; use of the placenta before delivery can place the placenta in the uterine cavity.

Precautions

1. The following conditions should be used with caution: coronary heart disease, which can cause myocardial infarction during vasospasm; liver damage; severe hypertension, including pregnancy-induced hypertension syndrome; hypocalcemia; may increase occlusive peripheral vascular disease; Impaired renal function; sepsis.

2. Cross-allergic reactions, patients can not tolerate other ergot preparations, as well as this product.

[Pregnant and lactating women]

This product can be excreted through milk and may inhibit lactation. Ergot-like toxicity can occur in infants. Although not much harm has been found clinically, the advantages and disadvantages of lactating women should be weighed.

medicine interactions

Avoid co-use with other ergot alkaloids; Do not use with vasoconstrictor drugs (including those contained in local anesthetic solution); Use with booster drugs, there is a risk of severe hypertension or even cerebrovascular rupture; prohibited Excessive smoking can cause vasoconstriction or contracture.

[Drug overdose]

The amount should not be large and the time is too long, ergot-like poisoning and ergot gangrene can occur when the amount is excessive.

specification

(1) 1ml: 0.2mg (2) 1ml: 0.5mg

Storage

Shaded, sealed, and stored in a cold place ^[7] .