2 Pharmacopoeia standard sulfasalazine 2. 1 product name 2. 1. 1 Chinese name sulfasalazine
2. 1.2 Chinese Pinyin Yi Xian Zuo An
2. 1.3 English name acetazolamide
2.2 structural formula
2.3 molecular formula and molecular weight C4H6N4O3S2 222.25
2.4 source (name) and content (potency) this product is N(5 sulfamoyl 1, 3,4 thiadiazole 2- yl) acetamide. The content of C4H6N4O3S2 should be 98.0% ~ 102.0% based on dry product.
2.5 Properties This product is white needle-shaped crystal or crystalline powder; Odorless, slightly bitter.
This product is slightly soluble in boiling water, slightly soluble in water or ethanol, and almost insoluble in chloroform or ether; Soluble in ammonia solution.
2.6 Identification (1) Take about 0. 1g of this product, add sodium hydroxide test solution to dissolve it, add 10ml water and 1 drop phenolphthalein indicator solution, add dilute hydrochloric acid until pink disappears, and add a few drops of mercury nitrate test solution to form a white precipitate.
(2) Take about 0.2g of this product, put it in a test tube, add 65438 0 ml ethanol and 65438 0 ml sulfuric acid, and heat it to produce the aroma of ethyl acetate.
(3) The infrared absorption spectrum of this product should be consistent with the control spectrum (Figure 9 for infrared spectrum collection of drugs).
2.7 Check the acidity of 2.7. 1 Take this product 1.0g, add 50ml of hot water, shake well, let it cool, and determine it according to law (Appendix 6 h of Pharmacopoeia II, 20 10 edition). The pH value should be 4.0 ~ 6.0.
2.7.2 Take 1.0g as the clarity of alkaline solution, add 5ml 10% sodium hydroxide solution to dissolve, and the solution should be clarified.
2.7.3 Chloride take 2.0g of this product, add water 100ml, heat and dissolve, quickly cool, filter, take 25ml of filtrate, and check it according to law (Appendix VIII A of Pharmacopoeia II, 20 10 edition). Compared with the control solution made of 7.0ml standard sodium chloride solution, it shall not be thicker (0.065438+).
2.7.4 Sulfate: Take 2.0ml of filtrate remaining under the above chloride and check it according to law (Appendix VIII B of Pharmacopoeia II, 20 10 edition). Compared with the control solution made of standard potassium sulfate solution, it should not be more concentrated (0.04%).
2.7.5 Take 50mg of related substances, put it in a 100ml volumetric flask, add 80ml of water, heat it in a water bath at 80℃ for 5min, shake it evenly to dissolve it, let it cool, dilute it to scale with water, and shake it evenly as the test solution; Accurately measure 1ml, put it in a 100ml volumetric flask, dilute it to scale with water, and shake it well as a control solution. According to the test of high performance liquid chromatography (Pharmacopoeia 20 10, Appendix V D), octadecylsilane bonded silica gel was used as filler. 0.43% anhydrous sodium acetate solution-methanol-acetonitrile (95: 2: 3, pH adjusted to 4.0 0.05 with glacial acetic acid) was used as the mobile phase. The detection wavelength is 265 nm. The theoretical plate number is not less than 5000 calculated by sulfasalazine acetate peak. Take 20μl of control solution, inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the chromatographic peak of the principal component is about 20% of the full scale. Then accurately measure 20μl of the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram until the retention time of the principal component peak is twice. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than 0.5 times (0.5%) of the main peak area of the reference solution, and the sum of impurity peak areas shall not be greater than the main peak area of the reference solution (1.0%).
2.7.6 Weigh 5.0g of silver reduction product, moisten it with 5ml of absolute ethanol, add 125ml of water and 10ml of nitric acid, accurately add 5ml of silver nitrate titration solution (0.1mol/L), shake it evenly, keep it away from light for 30min, filter it with a vertical glass funnel, and use/. Add 5ml ammonium ferric sulfate indicator, and titrate with ammonium thiocyanate titration solution (0. 1mol/L) to the end point, and the consumption of ammonium thiocyanate titration solution (0. 1mol/L) should be no less than 4.8ml
2.7.7 loss on drying takes this product and dries it to constant weight at 105℃, and the weight loss shall not exceed 0.5% (Appendix VIII L of Pharmacopoeia II, 20 10).
2.7.8 The residue on ignition shall not exceed 0.1%(Appendix VIII N, Part II of Pharmacopoeia 2010).
2.7.9 Take 0.50g of this product as heavy metal, and check it according to law (third method in Appendix VIII H of Pharmacopoeia II, 20 10), and the content of heavy metal shall not exceed 20 parts per million.
2.8 Content determination: Take about 0.2g of this product, weigh it accurately, add 400ml of boiling water, stir it to dissolve, let it cool, transfer it to a 1000ml volumetric flask, dilute it with water to scale and shake it evenly; Accurately measure 5ml, put it in a 100ml volumetric flask, add 10ml hydrochloric acid solution, dilute it to scale with water, shake it evenly, and measure the absorbance at the wavelength of 265nm by UV-Vis spectrophotometry (Appendix Ⅳ a of Pharmacopoeia II, 20 10 edition).
2.9 carbonic anhydrase inhibitors.
2. 10 storage and shading, sealed preservation.
2. 1 1 Preparation of sulfacetamide tablets
2. 12 Edition People's Republic of China (PRC) Pharmacopoeia 20 10 Edition
3 sulfacetamide instructions 3. 1 drug name sulfacetamide
3.2 English names of acetazolamide, acetamide, albox, diluran, diurramide, diamox and edemox.
3.3 Another name for acetazolamide and sulfacetamide; Acetamide; Acetazol sulfanilamide; Dammous; Acetylazo ammonia; De Marcos; Demax acetazolamide; acetazolamide
3.4 classification of drugs in circulatory system >: antihypertensive drugs > diuretic antihypertensive drugs
3.5 dosage form 1. Tablets: 250mg each;
2. Injection (powder): 500mg.
3.6 Pharmacological effects of sulfacetamide 1. Reduce intraocular pressure. Carbonic anhydrase exists in all tissues of the eye (such as retina, uvea and lens), and the amount of carbonic anhydrase in ciliary body is the largest. In glaucoma, the carbonic anhydrase activity of ciliary epithelium increases, which leads to excessive sodium bicarbonate, which increases the osmotic pressure, aqueous humor production and intraocular pressure of aqueous humor. Acesulfame K can inhibit the activity of carbonic anhydrase in ciliary epithelium, thus reducing the generation of aqueous humor (50% ~ 60%) and lowering the intraocular pressure of glaucoma patients. It is also believed that the antihypertensive effect of sulfacetamide is due to its decreasing the concentration of HCO-3 in plasma and increasing the concentration of plasma chloride, thus causing metabolic acidosis and reducing the blood alkali reserve.
2. Cardiogenic edema. Acesulfame can be used for cardiogenic edema, but not for renal and hepatic edema. Sulfoacetate can inhibit carbonic anhydrase in renal tubular epithelial cells, reduce the production of H+ and the reabsorption of Na+, and increase the excretion of Na+, water and bicarbonate, thus producing diuretic effect. However, sulfadiazine acetate has a weak diuretic effect (it has a good diuretic and antihypertensive effect on patients with eclampsia and edema), and it can produce drug resistance after long-term use. At present, diuretic alone is rarely used. Combined with mercury diuretic, acid-base imbalance caused by each other can be corrected.
3. Others: sulfacetamide can also reduce cerebrospinal fluid production and inhibit gastric acid secretion, and its mechanism may also be related to the inhibition of carbonic anhydrase. The antiepileptic mechanism of sulfacetamide is not clear.
3.7 Pharmacokinetics of sulfacetamide Oral absorption is easy, and the protein binding rate is high. After oral administration of 500mg, the intraocular pressure began to decrease at 1 ~ 1.5 h, and the blood concentration reached its peak at 2 ~ 4~6h, which was 12 ~ 27 μ g/ml. The duration of action is 4 ~ 6 h, and the half-life is 2~4h ~ 5.8 h: After oral administration of 500mg sustained-release capsules, the intraocular pressure starts to rise and fall 2 hours later, the peak time is 8 ~ 12 hours, the peak blood concentration is 6μg/ml, and the duration of action is 18 ~ 24 hours. Intraocular pressure began to decrease 2 minutes after intravenous injection of 500mg, and reached the peak of blood drug concentration at 65438±05min minutes, and the effect lasted for 4 ~ 5h hours. Whether oral or intravenous, 90% ~ 100% of the dose is excreted from the kidney within 24 hours, while only 47% of the sustained-release capsules are excreted within 24 hours.
3.8 indications of sulfacetamide 1. Treating various types of glaucoma and reducing intraocular pressure before anti-glaucoma and some intraocular surgery are effective auxiliary drugs to control the increase of intraocular pressure in various types of glaucoma in a short period of time.
2. Used for cardiogenic edema. It is also used for brain edema and can reduce the production of cerebrospinal fluid.
3. Treating peptic ulcer can inhibit gastric acid secretion.
4. Try the seizure.
5. It can also be used to treat acute mountain sickness and juvenile myoclonic epilepsy.
6. Hypochloric alkalemia and hypokalemic periodic paralysis in heart failure.
3.9 Contraindications of sulfasalazine 1. Allergic to sulfasalazine or other carbonic anhydrase inhibitors, sulfonamides and thiazide diuretics.
2. Adrenal failure and hypoadrenocortical function.
3. Hyponatremia and hypokalemia.
4. Severe liver and kidney dysfunction.
5. Perchloric acid poisoning.
6. Heart failure.
7. Have a history of urinary calculi.
8. Patients with chronic non-congestive angle-closure glaucoma.
3. 10 Precautions 1. (1) diabetes; (2) Pulmonary infarction or emphysema.
2. Effects of drugs on the elderly: Elderly patients are more prone to drug resistance after long-term use, and are prone to metabolic acidosis and hypokalemia.
3. Effect of drugs on pregnancy: Animal experiments have proved that giving rodents 10 times the normal dose of adult sulfacetamide has a high teratogenic rate, so pregnant women should not use sulfacetamide, especially in the first three months of pregnancy.
4. The influence of drugs on the test value or diagnosis: (1) can interfere with GlennNelson's absorption, leading to false positive results in urine 17 hydroxysteroid determination; (2) Urine can be alkalized for urine protein determination (such as bromophenol blue test, etc.). ) has a false positive result; (3) It can increase the concentration of blood ammonia, serum bilirubin and urine urobilinogen; (4) Blood glucose concentration and urine glucose concentration can be increased, but non-diabetic patients are not affected; (5) It can increase plasma chloride concentration and decrease serum potassium concentration.
5. Check or monitor before and after medication: For glaucoma patients: (1) The intraocular pressure should be measured every day during acute attack, and the intraocular pressure should be measured regularly during chronic period, and the vision and visual field should be checked regularly; (2) After the intraocular pressure is controlled, the dosage should be adjusted according to the type of glaucoma and the change of iris and cornea angle, and the appropriate anti-glaucoma surgery should be selected. (3) Patients with advanced open-angle glaucoma, congenital glaucoma and need to postpone anti-glaucoma surgery who still can't control their intraocular pressure by using mydriatic or timolol eye drops combined with sulfacetamide, besides taking potassium salt, they should also record the 24-hour intraocular pressure curve, vision, visual field, blood pressure, hemogram and urine routine before treatment, so as to evaluate the curative effect and find possible adverse reactions during treatment.
6. Patients who can't tolerate sulfonamides or other sulfonamides derivative diuretics can't tolerate sulfasalazine.
7. For angle-closure glaucoma, after the use of sulfasalazine in acute stage, in principle, the appropriate anti-glaucoma surgery should be selected according to the iris and cornea angle and tonogram, otherwise the decrease of intraocular pressure will give people the illusion of safety, thus further developing the angle adhesion and delaying the operation opportunity.
8. Some people who can't tolerate the adverse reactions of sulfasalazine or who are ineffective after taking sulfasalazine for a long time can switch to other carbonic anhydrase inhibitors (such as diclofenac).
9. In order to prevent the occurrence of renal complications, in addition to the general prevention principles of sulfonamides, potassium salts and magnesium salts should be added, and patients with hypercalciuria should enter a low-calcium diet.
10. For kidney calculi patients (mainly containing calcium), sulfacetamide can induce or aggravate the disease. If abdominal cramps and hematuria occur, stop taking the medicine immediately.
1 1. Drink plenty of water during taking, and take potassium salt for a long time, which is not suitable for combination with calcium, iodine and broad-spectrum antibiotics.
12. Patients with cor pulmonale, heart failure, Addison syndrome, liver failure, metabolic acidosis, edema with hypokalemia should not use it. Not suitable for patients with chronic non-congestive angle-closure glaucoma.
13. sulfadiazine acetate can cause myopia, loss of eye accommodation, lens displacement, retinal edema and other symptoms, and should be stopped in time.
3. Adverse reactions of11sulfacetamide. Serious adverse reactions of sulfacetamide rarely occur in short-term and intermittent use in ophthalmology. Some adverse reactions are caused by sulfanilamide derivatives, and some adverse reactions are dose-related.
1. Common numbness and tingling in limbs, nausea, loss of appetite, lethargy, weight loss, depression, metallic taste, diarrhea and polyuria.
2. Occasional hearing loss, temporary myopia and sulfanilamide rash occurred after the first medication.
3. Rare exfoliative dermatitis, neutropenia or aplastic anemia.
4. Long-term medication can aggravate symptoms such as hypokalemia, hyponatremia, electrolyte disorder, metabolic acidosis, and renal complications (such as renal colic, lithiasis, sulfanilamide crystals, nephrotic syndrome, etc. ). Long-term use will cause abnormal sensation, gastrointestinal dysfunction, loss of appetite, lethargy, fatigue and temporary myopia. Long-term use of potassium is easy to cause hypokalemia, so potassium salt should be supplemented in time. The medicine can reduce uric acid excretion, and it is reported that gout is aggravated during treatment. For patients with diabetic nephropathy, renal function can be rapidly reduced. After long-term medication, urine is alkaline, calcium phosphate crystals are easy to precipitate, and kidney calculi appears, and sometimes acute renal failure may occur. Adverse reactions of sulfonamides can also occur, such as rash, crystallized urine, agranulocytosis, aplastic anemia and platelet deficiency.
3. Usage and dosage of 1 2 sulfacetamide1. Oral: (1) open angle glaucoma: the first dose is 250mg, 1 ~ 4 times, once a day. The maintenance dose should be determined according to the patient's reaction to the drug. Try to control the intraocular pressure with a small dose, generally 250mg each time, twice a day, which can control the intraocular pressure within the normal range. (2) Secondary glaucoma and preoperative intraocular pressure reduction: 250mg each time, twice a day; (3) Acute cases: the first dose was doubled to 500mg, and then the maintenance dose was changed to 125 ~ 250 mg, every 4 hours 1 time; (4) Treatment of cardiogenic edema: 250~500mg each time, daily 1 time, with the best effect after breakfast; (5) Treatment of brain edema: 250mg each time, 2-3 times a day; (6) Treatment of peptic ulcer: 500mg each time, 3 times a day, 3 weeks for 1 course of treatment, and the pain disappeared in 7 ~ 9 days. During the medication, 2g sodium bicarbonate, sodium citrate 1g, potassium bicarbonate 1g, magnesium oxide 1.5g and water 1500 ~ 2000ml can be added daily to prevent water-electrolyte disorder. Prevention of familial periodic paralysis: adults take 250 ~ 750 mg every day, divided into 2 ~ 3 times.
2. Intravenous injection: For patients with acute glaucoma rescue and partial nausea and vomiting that hinder oral administration, 500mg sulfacetamide can be injected intravenously or intramuscularly, or 250mg sulfacetamide can be injected alternately intravenously and intramuscularly. For some patients with acute glaucoma, the above dose can be used repeatedly within 2 ~ 4 hours, but the continuous treatment should be changed to oral dose according to the patient's condition.
3. intramuscular injection: intravenous injection.
4. Children: (1) Oral: anti-glaucoma, 5 ~ 10 mg/kg or 300 ~ 900 mg/m2 daily, taken in batches. (2) Intravenous injection: for the treatment of acute glaucoma, intravenous injection is usually performed according to body weight, with a dose of 5 ~ 10 mg/kg each time and every 6 hours 1 time. (3) intramuscular injection: see intravenous injection.
3. 13 drug interaction 1. Combined with adrenocorticotropic hormone, glucocorticoid and mineralocorticoid, it can lead to severe hypokalemia and osteoporosis. When combined with the above drugs, attention should be paid to monitoring blood potassium concentration and cardiac function.
2. When combined with amphetamine, anticholinergic drugs (especially atropine) and quinidine, alkaline urine can be formed, thus reducing the excretion of sulfasalazine and aggravating the adverse reactions of sulfasalazine.
3. Because sulfacetamide can cause hyperglycemia and urine sugar, the dosage of antidiabetic drugs should be adjusted when combined with antidiabetic drugs (such as insulin).
4. Combination with phenobarbital, carbamazepine or phenytoin sodium can increase the incidence of osteomalacia.
5. Combination with digitalis glycoside can improve the toxicity of digitalis and lead to hypokalemia.
6. Combined with mannitol or urea, it can enhance the effect of lowering intraocular pressure and increase urine output.
3. 14 expert comment: sulfacetamide is a carbonic anhydrase inhibitor, belonging to sulfonamides derivatives. By inhibiting carbonic anhydrase in ciliary body cells, the formation of carbonic acid and HCO 3- is reduced, and the formation of aqueous humor is reduced due to osmotic pressure, thus reducing intraocular pressure. Clinically, it is often used with mydriatic drugs or other intraocular pressure lowering drugs. It is often used for all kinds of glaucoma and patients with hypotension before intraocular surgery and delayed anterior chamber formation after surgery.
4 sulfacetamide poisoning sulfacetamide (sulfacetamide) is a carbonic anhydrase inhibitor. Inhibit carbonic anhydrase in renal tubular epithelial cells, reduce the formation of H+ and HC03, slow down the exchange of Na+ and H+, reduce the reabsorption of Na+, and increase the excretion of Na+, K+, H2O and HC03, thus promoting diuresis. Sometimes it can be used to treat brain edema and mild cardiogenic edema.
This medicine inhibits carbonic anhydrase in ciliary body cells, reduces aqueous humor production and reduces intraocular pressure, so it is mainly used to treat glaucoma. Also used as an antiepileptic drug. Oral LD50 >: 1.0g/kg, LD50: 2g/kg. This drug was completely excreted from the kidney within 24 hours, and there was no accumulation. The common dose of oral glaucoma and brain edema is 0.25g 1 ~ 2/d each time, which mainly damages the central nervous system, blood system, liver and kidney. [ 1]
4. 1 The clinical manifestations of adverse reactions are as follows [2]:
Central nervous system.
Occasionally numbness and tingling in face and limbs, lethargy, fatigue, weakness, dizziness, disorientation, depression, myasthenia, delayed paralysis, ataxia, etc.
2. Digestive system
Anorexia, nausea, vomiting, dry mouth, thirst and diarrhea. There may be gastric ulcer, gastrointestinal bleeding, cholestatic jaundice; The drug can induce hepatic encephalopathy in patients with liver cirrhosis.
3. Blood system
Produce bone marrow suppression, granulocytopenia, leukopenia, thrombocytopenic purpura, hemorrhage, megaloblastic anemia, aplastic anemia and so on.
4. Urinary system
Frequent micturition, polyuria, urine sugar, anuria, hematuria, crystallized urine and urinary calculi, kidney calculi's disease and renal colic.
5. Others
Slow heart rate, hyperglycemia and hyperuricemia aggravate gout, abnormal liver function, deafness, temporary myopia, increased serum bilirubin, increased excretion of calcium, potassium, magnesium and sodium, and increased chlorine concentration, leading to hypokalemia and hyperchloric acidosis.
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4.2 Treatment of sulfadiazine acetate poisoning treatment points for [3]:
1. Stop taking the medicine immediately.
2. Replenish fluids and potassium, correct dehydration and acidosis, and maintain the balance of water and electrolyte.
3. If there is bone marrow suppression, glucocorticoid, vitamin B6, inosine and nucleotide tablets can be used. It's all for me. I need several small blood transfusions.
4. If allergic reaction occurs, give anti-allergic treatment.