Chinese name dexamethasone
dexamethasone
Has antiinflammatory, detoxicating, antiallergic, and antirheumatic effects.
Other names include dexamethasone, cortisone and medroxyprogesterone acetate.
Chemical formula C22H29FO5
catalogue
Physical and chemical properties of 1
2 pharmacological action
3 history
4 determination method
5 Compatibility contraindications
Six signs
7 doses
8 Adverse reactions
9 related data
Preparation method of 10
Physical and chemical properties of 1
edit
Chemical name: (1 1β, 16α)-9- fluoro-1,17,21-trihydroxy-/kloc-0.
Manufacturing patent: U.S. patent 3,007,923 (1961,Laboratory. France. Chimio, the others. )，GerPat 1， 1 13，690 ( 196 1)。 Co.), British patent 869,511(to Upjohn).
Si Nuo. : 50-02-2
Molecular formula: C22H29FO5
Molecular weight: 392.5
Solubility: ethanol: 1 mg/ml.
Stability: stability. Flammable. Inconsistent with strong oxidant, strong alkali, anhydride and acyl chloride. May be sensitive to light.
2 pharmacological action
edit
Dexamethasone, also known as flumethasone, flumethylprednisolone and demisone, is a glucocorticoid. Its derivatives include hydrocortisone and prednisone. Its pharmacological effects are mainly anti-inflammatory, anti-toxic, anti-allergic and anti-rheumatism, and it is widely used in clinic. It is easily absorbed from the digestive tract, and its plasma T 1/2 is 190 minutes, and its tissue T 1/2 is 3 days. After intramuscular injection of dexamethasone sodium phosphate or dexamethasone acetate, the plasma concentration reached its peak at 1 hour and 8 hours respectively. The plasma protein binding rate of this product is lower than other corticosteroids. The anti-inflammatory activity of 0.75 mg of this product is equivalent to 5 mg of prednisolone. Adrenal corticosteroids have stronger anti-inflammatory, anti-allergic and anti-toxic effects than prednisone, and have less water and sodium retention and potassium excretion. Intramuscular injection or intravenous drip can inhibit pituitary-adrenal gland.
1. Anti-inflammatory effect: This product can reduce and prevent the reaction of tissues to inflammation, thus reducing the manifestations of inflammation. Hormones inhibit the aggregation and phagocytosis of inflammatory cells (including macrophages and leukocytes), the release of lysosomal enzymes and the synthesis and release of inflammatory chemical mediators.
2. Immunosuppression: including preventing or inhibiting cell-mediated immune response and delayed allergic response, reducing the number of T lymphocytes, monocytes and eosinophils, reducing the binding ability of immunoglobulin to cell surface receptors, and inhibiting the synthesis and release of interleukin, thus reducing the transformation of T lymphocytes to lymphocytes and alleviating the expansion of primary immune response. Can reduce the immune complex through the basement membrane, and can reduce the concentration of complement components and immunoglobulin.
The product is easily absorbed from digestive tract. The plasma T 1/2 was 190 minutes, and the tissue T 1/2 was 3 days. After intramuscular injection of dexamethasone sodium phosphate or dexamethasone acetate, the plasma concentration reached the peak at 65438 0 hours and 8 hours respectively. The plasma protein binding rate of this product is lower than other corticosteroids, and the anti-inflammatory activity of 0.75mg of this product is equivalent to 5mg of prednisolone.
3 history
edit
Dexamethasone was synthesized by Arth and Oliveto in 1958, Merck &; The company produces dexamethasone sodium phosphate. Up to now, the number of dexamethasone derivatives on the market has exceeded 12.
Dexamethasone (Figure 3)
Dexamethasone (Figure 3)
Dexamethasone (Figure 4)
Dexamethasone (Figure 4)
The chemical structure of dexamethasone is that fluorine atom is introduced into the 9α position of prednisolone B ring and methyl group is introduced into the 16α position of D ring; 9α fluoride and 16α methyl significantly enhanced its anti-inflammatory activity, while 16α methyl significantly reduced the side effects of dexamethasone in water and sodium retention. The clinical bioequivalent dose ratio of dexamethasone to prednisolone is 0.75:5, and the biological half-life is 36-54 hours, which belongs to long-acting glucocorticoid.
Dexamethasone, like other glucocorticoids, has pharmacological effects such as anti-inflammatory, anti-endotoxin, immunosuppression, anti-shock and stress response, so it is widely used in various departments to treat many diseases, such as autoimmune diseases, allergies, inflammation, asthma, dermatology and ophthalmology. Dexamethasone sodium phosphate injection is an indispensable first-aid medicine to save dying patients. In recent ten years, clinicians have used dexamethasone sodium phosphate to treat and prevent drug allergy caused by various Chinese and western medicines and to treat fever caused by viral cold, so that the clinical dosage of dexamethasone has increased year by year. So far, China has become the largest dexamethasone market in the world.
4 determination method
edit
Method name: Dexamethasone-Dexamethasone-HPLC.
Scope of application: Determination of dexamethasone in dexamethasone bulk drug by HPLC.
This method is suitable for dexamethasone bulk drug.
Methods: The sample was dissolved in methanol, diluted with mobile phase and separated by HPLC. The peak area of dexamethasone was detected by ultraviolet absorption detector at 240nm wavelength, and its content was calculated.
Reagent: 1. acetonitrile
2. Methanol
Instruments and equipment: 1. tool
1. 1 HPLC
1.2 column
With octadecylsilane bonded silica gel as filler, the theoretical plate number should be not less than 3000 calculated by dexamethasone peak.
1.3 ultraviolet absorption detector
2. Chromatographic conditions
2. 1 mobile phase: acetonitrile water =4 6
2.2 Detection wavelength: 240 nm
2.3 column temperature: room temperature
Sample preparation:
1. Preparation of reference solution
Accurately weigh about 15mg of dexamethasone reference substance, put it in a 50mL volumetric flask, add 2mL of methanol to dissolve it, dilute it with mobile phase to scale, and shake it evenly to obtain the reference substance solution.
2. Preparation of test solution
Accurately weigh about 15mg of the test sample, put it in a 50mL volumetric flask, add 2mL of methanol to dissolve it, dilute it with mobile phase to scale, and shake it evenly to obtain the test sample solution.
Note: "Accurate weighing" means that the weighing should be accurate to one thousandth of the weighing. "Precise measurement" means that the accuracy of measuring volume should meet the accuracy requirements of volume pipette in national standards.
Operating steps: Accurately suck 10mL control solution and test solution respectively, inject them into high performance liquid chromatograph, measure the peak area of dexamethasone (C22H29FO5) at the wavelength of 240nm with ultraviolet absorption detector, and calculate its content.
References: China Pharmacopoeia, edited by National Pharmacopoeia Committee, Chemical Industry Press, 2005, Part II, p. 184.
5 Compatibility contraindications
edit
Dexamethasone (Figure 5)
Dexamethasone (Figure 5)
Compatibility of dexamethasone with calcium chloride, sulfadiazine sodium, tetracycline hydrochloride, oxytetracycline hydrochloride, diphenhydramine, chlorpromazine, promethazine, phenylethylamine, procaine hydrochloride, scopolamine hydrobromide, etc. It is easy to produce turbidity or precipitation, which makes the drug ineffective. Combined with furosemide and sodium salicylate can increase its toxicity.
1. When taken together with barbiturates, phenytoin and rifampicin, the metabolic promotion of this product is weakened.
2. Combine with salicylic acid drugs to increase their toxicity.
3. It can weaken the effect of anticoagulants and oral hypoglycemic agents, and the dosage should be adjusted.
4. Combined with diuretics (except potassium-preserving diuretics) can cause hypokalemia, so pay attention to the dosage.
5. Non-steroidal anti-inflammatory and analgesic drugs can strengthen the ulcer-causing effect of glucocorticoid. It can enhance the hepatotoxicity of acetaminophen. Amlumide can inhibit the function of adrenal cortex, accelerate the metabolism of dexamethasone and shorten its half-life by two times. When combined with amphotericin B or carbonic anhydrase inhibitor, hypokalemia can be aggravated, and the changes of blood potassium and cardiac function should be paid attention to. Long-term use with carbonic anhydrase inhibitors is prone to hypocalcemia and osteoporosis.
6. Combined with anabolic steroids, it can increase the incidence of edema and aggravate acne. Combined with antacid, it can reduce the absorption of prednisone or dexamethasone. Long-term use of anticholinergic drugs (such as atropine) will increase intraocular pressure. Tricyclic antidepressants can aggravate the mental symptoms caused by glucocorticoid.
Dexamethasone (Figure 6)
Dexamethasone (Figure 6)
7. When combined with hypoglycemic drugs such as insulin, the dosage of hypoglycemic drugs should be adjusted appropriately because it can increase the blood sugar of diabetic patients. Thyroid hormone can increase the metabolic clearance rate of glucocorticoid, so when thyroid hormone or antithyroid drugs are combined with glucocorticoid, the dose of the latter should be adjusted appropriately. Combined with contraceptives or estrogen preparations; It can strengthen the curative effect and adverse reaction of glucocorticoid. Combined with cardiac glycoside, digitalis toxicity and arrhythmia can be increased. Combined with potassium-expelling diuretics, it can cause severe hypokalemia and weaken sodium-expelling diuretic effect due to water and sodium retention.
8. Combined with ephedrine, it can enhance the metabolic clearance of glucocorticoid. Combined with immunosuppressants, it can increase the risk of infection and may induce lymphoma or other lymphoproliferative diseases. Glucocorticoids, especially prednisolone, can increase the metabolism and excretion of isoniazid in the liver, and reduce the blood concentration and curative effect of isoniazid.
9. Glucocorticoid can promote the metabolism of mexiletine in the body and reduce the blood drug concentration. Combined with salicylate, the concentration of salicylate in plasma can be reduced. Combined with growth hormone, it can inhibit the growth-promoting effect of the latter.
Six signs
edit
A glucocorticoid
A glucocorticoid
Indications are the same as prednisolone, mainly used for allergic and autoimmune inflammatory diseases. Such as connective tissue disease, severe bronchial asthma, dermatitis and other allergic diseases, ulcerative colitis, acute leukemia and malignant lymphoma. In addition, this drug is also used in the diagnosis of some adrenal cortical diseases-dexamethasone inhibition test. The product can also be used to prevent neonatal respiratory distress syndrome, reduce intracranial pressure, and diagnose and identify the cause of Cushing's syndrome. Because of its weak sodium retention effect, this product is usually not used as an alternative treatment for adrenocortical hypofunction. Dexamethasone acetate and dexamethasone sodium phosphate can also be used for intramuscular injection or injection into injured parts such as joint cavity and soft tissue.
7 doses
edit
Tablets: 0.75mg/ tablet. Start with 0.75~3mg/ time, 2~4 times/day, maintain 0.5 ~ 0.75 mg/d, dexamethasone injection 2.5mg/ 1ml, 5mg/ml. 5~ 10mg/ time, 1~2 times/day. Intramuscular injection or intravenous drip of 500 ml of 5% glucose solution. Ointment: 0.05%
Oral: 1 day 0.75 ~ 6 mg, divided into 2 ~ 4 times. The maintenance dose of 1 day is 0.5 ~ 0.75 mg. Intramuscular injection (dexamethasone acetate injection), 1 time 8 ~ 16 mg, 1 time interval 2-3 weeks. Intravenous drip (dexamethasone sodium phosphate injection), 2 ~ 20 mg each time, or as directed by the doctor. Anti-inflammatory and anti-allergic, 65438+ 0.5 ~ 3 mg per day, once in the morning or twice in the afternoon. Mainly used as emergency medicine for critical diseases, treating various inflammations and allergic reactions. The anti-inflammatory, anti-allergic and anti-toxic effects are stronger than those of prednisone, and the side effects of water and sodium retention are less, which can be intramuscular injection or intravenous drip.
Intramuscular injection (dexamethasone acetate injection): 8- 16mg once every 2-3 weeks. Intravenous drip (dexamethasone sodium phosphate injection), 2-20mg each time, or as directed by the doctor. Reference of time pharmacology medication method: Long-term medication should simulate the law of natural hormone secretion. Take 3/4 or the whole dose at 7 am. Dexamethasone tablet 0.75mg, dexamethasone sodium phosphate injection υ 1ml:2mgυ 1ml:5mg. Dexamethasone ointment or cream 0.05 ~ 0. 1%. Oral administration, 0.75-6mg per day, divided into 2-4 times, with a maintenance amount of 0.5-0.75mg per day at 1 to make up the whole amount. Do not use medicine after 1 point.
8 Adverse reactions
edit
urticaria
urticaria
Glucocorticoids, such as dexamethasone, have no obvious adverse reactions in the application of physiological dose replacement therapy, and most of the adverse reactions occur in the application of pharmacological dose, which is closely related to the course of treatment, dose, drug type, usage and route of administration. Common adverse reactions are as follows:
1. Long-term use can cause the following side effects: face and posture, weight gain, edema of lower limbs, purple stripes, bleeding tendency, poor wound healing, acne, menstrual disorder, ischemic necrosis of humerus or femoral head, osteoporosis and fracture (including vertebral compression fracture and pathological fracture of long bone), muscle weakness, muscle atrophy, hypokalemia, gastrointestinal irritation (nausea)
2. Patients may have mental symptoms: euphoria, excitement, delirium, anxiety, disorientation or inhibition. Mental symptoms include people who are prone to chronic wasting diseases and people who have mental disorders in the past.
3. Infection is the main adverse reaction of adrenocortical hormone. Mainly fungi, tuberculosis, staphylococcus, Proteus, Pseudomonas aeruginosa and various herpes viruses.
4. Glucocorticoid withdrawal syndrome. Sometimes patients have dizziness, fainting tendency, abdominal pain or backache, low fever, loss of appetite, nausea, vomiting, muscle or joint pain, headache, fatigue and weakness after stopping taking the drug. If careful examination can rule out adrenal hypofunction and recurrence of primary disease, it can be considered as glucocorticoid dependence syndrome.
Disorder of substance metabolism and water and salt metabolism Long-term and large-scale application of glucocorticoids can cause disorder of substance metabolism and water and salt metabolism, resulting in adrenocortical syndrome, such as edema, hypokalemia, hypertension, diabetes, skin thinning, full moon face, buffalo back, centripetal obesity, hirsutism, acne, myasthenia gravis, muscular atrophy, etc., which generally do not need special treatment and can subside automatically after stopping taking drugs. But the recovery of myasthenia is slow and incomplete. Measures such as low salt, low sugar and high protein diet and adding potassium chloride can alleviate these symptoms. In addition, glucocorticoid can delay the wound healing of trauma patients by inhibiting the synthesis of protein. In children, it can lead to negative nitrogen balance by inhibiting the secretion of growth hormone, thus affecting growth and development.
Glucocorticoid can inhibit the immune function of the body and has no antibacterial effect, so long-term application can often induce or aggravate the infection, which can spread the potential infection focus in the body or rekindle the static infection focus, especially for patients with decreased original resistance, such as nephrotic syndrome, tuberculosis, aplastic anemia and so on. Because patients often feel good about themselves when taking glucocorticoids, it masks the symptoms of infection development. Therefore, before deciding to take long-term treatment, they should check their bodies to eliminate potential infection, be vigilant in the application process, use effective antibacterial drugs when necessary, and pay special attention to the prevention and treatment of potential tuberculosis lesions.
Gastrointestinal complications can stimulate the secretion of gastric acid and pepsin, inhibit the secretion of gastric mucus and reduce the resistance of gastric mucosa, so it can induce or aggravate peptic ulcer, and glucocorticoid can also cover up the initial symptoms of ulcer, leading to sudden bleeding, perforation and other serious complications, which should be paid attention to. Long-term use will aggravate gastric or duodenal ulcer. This side effect is more likely to occur when combined with other drugs with gastric irritation (such as aspirin, indomethacin and butazolamide). A few patients can induce pancreatitis or fatty liver.
Long-term use of glucocorticoids to treat cardiovascular complications can lead to sodium and water retention and elevated blood lipids, which can induce hypertension and atherosclerosis.
Osteoporosis and vertebral compression fracture Osteoporosis and vertebral compression fracture are serious complications of glucocorticoid treatment for patients of all ages. Ribs and vertebrae have high beam-column structures and are usually the most seriously affected. This may be related to glucocorticoid inhibiting osteoblast activity, increasing calcium and phosphorus excretion, inhibiting intestinal calcium absorption and increasing the sensitivity of bone cells to parathyroid hormone. If osteoporosis occurs, the drug must be stopped. D (To prevent and treat osteoporosis, vitamin D, calcium salt and anabolic steroids from protein should be supplemented.
The chemical structure of dexamethasone is that fluorine atom is introduced into the 9α position of prednisolone B ring and methyl group is introduced into the 16α position of D ring; 9α fluoride and 16α methyl significantly enhanced its anti-inflammatory activity, while 16α methyl significantly reduced the side effects of dexamethasone in water and sodium retention. The clinical bioequivalent dose ratio of dexamethasone to prednisolone is 0.75:5, and the biological half-life is 36-54 hours, which belongs to long-acting glucocorticoid.
Dexamethasone, like other glucocorticoids, has pharmacological effects such as anti-inflammatory, anti-endotoxin, immunosuppression, anti-shock and stress response, so it is widely used in various departments to treat many diseases, such as autoimmune diseases, allergies, inflammation, asthma, dermatology and ophthalmology. Dexamethasone sodium phosphate injection is an indispensable first-aid medicine to save dying patients. In recent ten years, clinicians have used dexamethasone sodium phosphate to treat and prevent drug allergy caused by various Chinese and western medicines and to treat fever caused by viral cold, so that the clinical dosage of dexamethasone has increased year by year. So far, China has become the largest dexamethasone market in the world.
If taken in large quantities, it is easy to cause diabetes and class library syndrome. Long-term use is more likely to cause mental symptoms and psychosis. If you have a hypothetical history and a history of mental illness, it is best not to use it. Patients with ulcer, thrombophlebitis, active pulmonary tuberculosis and intestinal anastomosis should not use it or use it with caution. For other precautions, please refer to the "Application Precautions" of this kind of drugs. Specification: 1. Demisone acetate tablets: 0.75 mg per tablet. Dexamethasone sodium phosphate injection: 1mg( 1ml), 2mg( 1ml) and 5mg( 1ml) respectively.
Glucocorticoid dexamethasone, commonly known as "skin opium", is a banned ingredient in cosmetics. When consumers use cosmetics containing dexamethasone, their skin will feel obviously better at first, but long-term use will not only lead to dependence, but also lead to dermatitis and even various diseases.
9 related data
edit
No. :MFCD00064 136
EINECSno。 : 200-003-9
RTECS number: TU3980000
I don't know : 206665 1
PubChemNo。 : 24893536
Molar refractive index: 100.23
Molar volume (m3/mol): 296.2
Isotonic specific volume (90.2 k): 8 12.3.
Surface tension (dyne/cm): 56.5
Polarity (10-24cm3): 39.73
Preparation method of 10
edit
A new process for producing dexamethasone 2 1- hydroxy compound includes the following steps: using intermediate 2 1- acetate as substrate, using appropriate amount of methanol containing 0- 10% chloroform as solvent for semi-dissolution, using alkali as catalyst for hydrolysis reaction, neutralizing with acetic acid after the reaction is complete, concentrating the reaction solution to an appropriate volume under reduced pressure, cooling and filtering. This process can shorten the production cycle, improve the quality and yield of 2 1- hydroxy compound, and reduce the impurity oil in 2 1- hydroxy compound.