What Is Ephedrine?

Ephedrine, prevention of bronchial asthma attacks and relief of mild asthma attacks, is not effective for acute severe asthma attacks. Used for hypotension and chronic hypotension caused by subarachnoid anesthesia or epidural anesthesia. Treat nasal congestion and swelling caused by various reasons.

Introduction to ephedrine compounds

Ephedra Basebook Information

Chinese name: ephedrine

Chinese alias: 1-N, 2-dimethyl--hydroxyphenethylamine; 2-methylamino-1-phenyl-1-propanol; 1R, 2S-ephedrine; 1-methylaminobenzyl alcohol; (1R, 2S) -2-methylamino-phenylpropane-1-ol

English name: (-)-ephedrine

English aliases: L-ephedrine; Ephedral; Fedrin; Nasol; Benzenemethanol, a-[(1S) -1- (methylamino) ethyl]-, (aR)-

CAS number: 299-42-3

Molecular formula: C ₁₀ H ₁₅ NO

Molecular weight: 165.23200

Exact mass: 165.11500

PSA: 32.26000

LogP: 1.71880

Ephedrine physicochemical properties

Melting point: 37-39 ° C (lit.)

Properties: Commonly used as its hydrochloride, it is white needle-like crystal or crystalline powder, odorless and bitter. Soluble in water, soluble in ethanol, insoluble in chloroform or ether.

Ephedrine Safety Information

Customs Code: 2939490090

Danger category code: R22

Safety instructions: S22; S25 ^[1]

Ephedrine production method

1. Ephedrine can be extracted from ephedra. The stems and branches of Ephedra spp. Were cut to a length of 2 to 4 cm, 7 times the amount of water was added, and hot-pressed at 0 15 MPa for 5 times. A total of 16 hours were required to obtain an aqueous solution containing ephedra total alkali. After the decoction was alkalized to pH 12 with sodium hydroxide, it was extracted with twice the amount of toluene at 60-70 ° C. A 2% oxalic acid solution was added to the toluene extract, so that the pH of the toluene layer was 7, and the total ephedrine base in the toluene extract was transferred to the oxalic acid solution. The toluene layer was separated to obtain a dilute solution of ephedrine total base. The dilute solution of oxalic acid containing alkaloids was concentrated under reduced pressure at 70 ° C and cooled to 30 ° C. Ephedrine oxalate had little solubility in water, crystals were precipitated, and centrifuged to obtain crude ephedrine oxalate. The mother liquor contains pseudoephedrine oxalate. Add 8-10 times water and 1.5% activated carbon to the crude ephedrine oxalate, boil, filter, and add the calcium chloride solution to the filtrate under stirring until no more precipitation or turbidity occurs, and a ephedrine hydrochloride solution can be obtained. Then, add sodium sulfide solution to a pH of 7.5-8, and leave the impurities such as calcium oxalate and iron sulfide to stand. After filtration, take the supernatant and add hydrochloric acid to adjust the pH to 6-6.5, suction filter, concentrate the solution under reduced pressure, and cool. To 30 , crystallize, centrifuge, and dry to obtain the finished product. The above mother liquor containing pseudoephedrine oxalate can be alkalized with sodium hydroxide to isolate pseudoephedrine, and then acylated, transposed, hydrolyzed, and neutralized to obtain ephedrine oxalate crystals, and then processed according to the method described above to obtain ephedrine hydrochloride. Salt ^[1] .

Ephedrine uses

Ephedrine is an adrenaline-like drug. It can excite the sympathetic nerve, and its effect is longer than that of epinephrine; it can relax the bronchial smooth muscle and constrict blood vessels; it has a significant central excitatory effect. Clinically, it is mainly used to treat habitual bronchial asthma and prevent asthma attacks. It is not as effective as epinephrine for severe bronchial asthma, but it is better than epinephrine when it is used for nasal mucosal congestion and nasal congestion ^[1] .

Ephedrine Pharmacopoeia Standard

[Identification] (1) Take about 10mg of this product, add 1ml of water to dissolve, add 2 drops of copper sulfate test solution and 20% sodium hydroxide solution 1ml, that is blue-violet; add 1ml of ether, shake, place, ether layer Violet red appears, and the water layer turns blue. (2) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 387). (3) Identification of chlorides in aqueous solution of this product (Appendix III).

[Check] The clarity of the solution is 1.0g of this product. After dissolving in 20ml of water, the solution should be clear. Take pH 1.0g of this product, add 20ml of water to dissolve, add 1 drop of methyl red indicator solution, if it is yellow, add 0.10ml of sulfuric acid titration solution (0.01mol / L), the strain will turn red; if it is light red, add hydroxide The sodium titration solution (0.02mol / L) was 0.10ml, and the strain became yellow. Sulfate was taken from l.Og of this product and checked according to law (Appendix III B). It must not be more concentrated (0.010%) than the control solution made from 1.0 ml of standard potassium sulfate solution. Take about 50mg of this substance, put it in a 50ml volumetric flask, add the mobile phase to dissolve and dilute to the mark, shake well, and use it as the test solution; take a precise amount of 1ml, place it in a 100ml volumetric flask, dissolve and dilute to Scale and shake well as control solution. Tested according to high performance liquid chromatography (Appendix VD), using octadecylsilicon bonded silica gel as filler; phosphate buffer solution (take potassium dihydrogen phosphate 6.8g, triethylamine 5ml, phosphoric acid 4ml, add water to 1000ml, adjust the pH to 3.0 ± 0.1) with dilute phosphoric acid or triethylamine-acetonitrile (90:10) as the mobile phase; the detection wavelength is 210nm. The number of theoretical plates is not less than 3000 calculated from the ephedrine hydrochloride peak. Take 10 l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range; and then accurately measure 10 l each of the test solution and the control solution and inject them into the liquid chromatography. Instrument, record the chromatogram to the main component peak retention time twice. If there are impurity peaks in the chromatogram of the test solution, the sum of the area of each impurity peak must not be greater than 0.5 times (0.5%) the main peak area of the control solution. Loss on drying: Take this product and dry to constant weight at 105 ° C. Lose weight should not exceed 0.5% (Appendix L). The ignition residue shall not exceed 0.1% (Appendix N). Take l.Og of this product, add 23ml of water to dissolve it, add 2ml of acetate buffer (pH3.5), and check according to law (Appendix H first method), the content of heavy metals must not exceed 20 parts per million.

[Content determination] Take about 0.15g of this product, accurately weigh, add 10ml of glacial acetic acid, heat and dissolve, add 4ml of mercury acetate test solution and 1 drop of crystal violet indicator solution, and use chlorochloric acid titration solution (0.1mol / L ) Titrate until the solution appears emerald green, and correct the result of the titration with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 20.17mg of C ₁₀ H ₁₅ NOHC1 ^[2] .

[Category] 2 adrenergic receptor agonist.

[Storage] Keep sealed.

Ephedrine Drug Description

Ephedrine Pharmacology

It can directly stimulate the adrenergic receptors, or it can indirectly activate the adrenergic receptors by promoting the release of norepinephrine from the adrenergic nerve endings. It has an agonistic effect on and receptors: cardiovascular system: make the skin and mucous And splanchnic blood vessels contract, blood flow decreases; coronary and cerebral blood vessels dilate, and blood flow increases. Blood pressure increased and pulse pressure increased after medication. Increased cardiac contractility and increased cardiac output. As the blood pressure rises reflexively excites the vagus nerve, the heart rate remains unchanged or slightly slower. Bronchi: relaxes the bronchial smooth muscle; its -effect can still make the bronchial mucosa blood vessels constrict, reduce congestion and edema, and help to improve small airway obstruction. However, long-term application may cause excessive contraction of mucosal blood vessels, increase capillary pressure, and increase congestion and edema. In addition, the alpha effect can aggravate bronchial smooth muscle spasm. Central nervous system: Excite the cerebral cortex and the subcortical center, and produce mental excitement, insomnia, restlessness, and tremor. It is easily absorbed from the intestine after oral administration and can enter the cerebrospinal fluid through the blood-brain barrier. Vd is 3 ~ 4L / kg. After absorption, only a small amount of deamination is oxidized, and 79% is excreted in the original form through the urine. The effect is weaker and longer lasting than adrenaline, and t1 / 2 is 3 ~ 4 hours.

Ephedrine pharmacokinetics

Oral is quickly absorbed and can enter the cerebrospinal fluid through the blood-brain barrier. It takes effect for 15-60 minutes after oral administration, and lasts for 3-5 hours. T1 / 2 is about 3 hours when the urine pH is 5 and about 6 hours when the urine pH is 6.3. After absorption, only a small amount is deaminated and oxidized, and most of it is excreted from the urine in its original form ^[3] .

Ephedrine indications

Prevention of bronchial asthma attacks and relief of mild asthma attacks are not effective for acute severe asthma attacks. Used for hypotension and chronic hypotension caused by subarachnoid anesthesia or epidural anesthesia. Treat nasal congestion and swelling caused by various reasons.

Ephedrine dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Ephedrine adverse reactions

Long-term use can cause adverse reactions such as tremor, anxiety, insomnia, headache, palpitations, fever, and sweating. When taking at night, often take sedative hypnotics such as phenobarbital to prevent insomnia.

Ephedrine contraindications

Hyperthyroidism, hypertension, arteriosclerosis, angina pectoris, etc. are contraindicated.

Ephedrine precautions

Cross-allergic reactions Allergic to other sympathomimetic amines, such as epinephrine, isoprenaline, etc., are also allergic to this product.

If you have headaches, anxiety, tachycardia, dizziness, sweating and other symptoms, you should stop taking medicine or adjust the dose.

Repeated medication in a short period of time, the effect can be gradually weakened (rapid tolerance phenomenon), can be restored after a few hours of stopping the drug. If not more than 3 times a day, the phenomenon of tolerance is not obvious.

Medication for pregnant and lactating women

Use of this product to maintain blood pressure during cesarean section anesthesia can speed up fetal heartbeat. It should not be used when maternal blood pressure exceeds 17.3 / 10.7kPa (130 / 80mmHg).

This product can be secreted into milk, banned during lactation ^[3]

Medication for children

Children, 0.5 to 1 mg / kg each time, 3 times a day.

Medication for elderly patients

This product can cause increased blood pressure, dysuria, and mental excitement, and the elderly should be used with caution ^[3] .

Ephedrine drug interactions

Ephedrine is used in combination with barbiturates, diphenhydramine, and theophylline, through the central inhibition, anti-allergy, anti-choline, release of bronchospasm and reduction of glandular secretion through the latter.

Avoid combining with monoamine oxidase inhibitors such as Youjiangning to avoid high blood pressure from bow I.

Combined with adrenal corticosteroids, this product can increase their metabolic clearance, and the dose of corticosteroids must be adjusted.

Urine alkalizing agents, such as antacids, calcium or magnesium carbonates, citrates, sodium bicarbonate, etc., affect the excretion of this product in the urine, increase the half-life of this product, and prolong the action time, especially If urine remains alkaline for several days or longer, most patients will cause ephedrine poisoning, and the dosage of this product should be adjusted.

(3) When combined with alpha-blockers such as phentolamine, prazosin, tolazoline, and phenothiazines, it can counteract the pressure effect of this product.

Equivalent to general anesthetics such as chloroform, halothane, and isoflurane, can make the myocardium more sensitive to sympathomimetic amines, and there is a risk of ventricular arrhythmia. When used together, the dosage of this product should be reduced.

When used with tricyclic antidepressants such as maprotiline, it reduces the pressure effect of this product

Combined with digitalis, it can cause arrhythmia.

Used together with ergometrine, ergotamine or oxytocin, it can exacerbate vasoconstriction and cause severe hypertension or peripheral tissue ischemia.

Rhenium is used in combination with doxapram, both of which can increase the pressure effect ^[3] .

Ephedrine preparation

Tablets: 15mg each; 25mg; 30mg. Injection: 30mg (1ml); 50mg (1ml) each. Nasal drops: 0.5% (pediatric); 1% (adult); 2% (for examination, surgery or hemostasis).