醋酸己脲（Urea acetate）

1、醋酸己脲（Urea acetate）Urea acetatename of drugAcetic acid ureaEnglish Name: AcetohexamideOther names: acetohexamide, acetohexamide, cyclohexyl benzene sulfonyl urea, acetyl cyclohexyl ethyl sulfonyl urea, acetohexamide, Acetohexamidum, Antrepar, Dimelin, Dimelor, Gamadiabet, U-14812clinical applicationF

2、or the treatment of adult type 2 diabetes mellitus (foreign data). * (1).pharmacology1. pharmacodynamics this medicine is the first generation of sulfonylurea oral hypoglycemic agents, by stimulating the synthesis of pancreatic tissue and release of endogenous insulin, thereby reducing blood sugar.

3、* (1). In addition, this drug also can increase the sensitivity and improve the insulin receptor on insulin by surrounding tissues and play a hypoglycemic effect. * * (1) sulfonylurea drugs combined with sulfonylurea receptor and pancreatic beta cells, thus inhibiting ATP dependent potassium channel

4、 (K-ATP), potassium efflux induced depolarization and activation of L type calcium channel, calcium influx stimulates insulin secretion. * (1) the sulfonylurea effects at the cellular level and glucose are similar, however, sulfonylureas only stimulate insulin in phase I (early secretory peak) relea

5、se, release of phase II (continuous insulin release) had no effect. * (1) the use of sulfonylureas after treatment, insulin levels increased, blood glucose decreased, insulin level decreased with the decrease of blood glucose, but still higher than the level before treatment. * (1).2. pharmacokineti

6、cs, this medicine can take effect within 3 hours after oral administration, and the efficacy of single dose is 12-24 hours. * (1) the oral bioavailability is better, the total protein binding rate of 65%-90%. * * (1) mainly in the liver by hydroxylation to produce active and inactive metabolites, th

7、e main metabolites were active hydroxyl cyclohexyl urea. * (1) * 80% drug excretion by the kidneys, the elimination half-life is 1.3 hours, renal failure elimination half-life, hydroxyl cyclohexyl urea elimination half-life is 6 hours, peritoneal dialysis can not remove the drug. * (1).matters needi

8、ng attention1. contraindications (1) allergic to the drug. (2) diabetic ketoacidosis patients. (all from overseas). (1).2., caution (1) in fever, infection, surgery, trauma and other stress state (should use insulin). (2) kidney, liver, pituitary, adrenal gland damage. (all from overseas). (1).3. dr

9、ugs on pregnancy affect the drug through the placenta, the animal experiments show that the drug can cause fetal malformations, maternal drug research is not sufficient, the US Food and Drug Administration (FDA) for classification of pregnancy safety of this drug is C. * (1).Study on the influence o

10、f the drug feeding lactating women 4. drugs is not sufficient, should be weighed after medication. * (2).5. the effect of the drug on the test value or diagnosis can interfere with the determination of serum creatinine (by SMAC, ASTRA, and ACA) by Jaffe method, and increase the level of creatinine.

11、* (1).6., before and after medication and medication should be checked or monitored, should regularly monitor blood sugar and glycosylated hemoglobin levels. * (1).adverse effectsadverse reactions abroad reference1. cardiovascular research thinks, the joint control of diabetes diet therapy using thi

12、s drug, and the single control diet or diet combined with insulin compared to accept treatment, factors of cardiovascular mortality increased about 2.5 times. * (1).The adverse reactions of the 2. metabolic endocrine system are common and severe hypoglycemia (available as tachycardia, sweating, palp

13、itations, tremor, headache, visual disorder, confusion, irritability, personality changes, seizures and coma), the data that the drug has little effect on lipid metabolism. * (1).3. genitourinary system may lead to urinary calculi. * (1).4. cases of liver cirrhosis and jaundice caused by liver cirrh

14、osis (jaundice, dark urine, light stool, bilateral thigh edema and tenderness of gastrocnemius muscle) are reported. * (1).5. common gastrointestinal nausea, abdominal distention, acid regurgitation (incidence rate of about 2.5%), often associated with the dose, with the reduction or treatment, the

15、symptoms can be reduced or even disappear. * (1).SixBlood can cause thrombocytopenia, white blood cells, granulocytes, hemolytic anemia, aplastic anemia, and whole blood cells. * (1).7. skin can be itching, erythema, urticaria, papules, less than 1% of the incidence, rash usually smaller, and good h

16、air in the face, neck, upper torso and proximal arm. * (1).drug interactionDrug drug interactions1. with acarbose, clofibrate, mebanazine, sulfa drugs (such as cotrimoxazole, sulfamethoxazole, sulfadiazine etc.), fluoroquinolones, azole antifungals, monoamine oxidase inhibitors, non steroidal anti-i

17、nflammatory drugs, eucalyptus, ginseng, plantain, grass, Saint John aloe, bitter gourd, glucomannan, lipoic acid combination, increase the risk of hypoglycemia, the combination should pay attention to blood glucose monitoring and dose adjustment. * (1).2., in combination with beta adrenergic blockad

18、e, hypoglycemia, hyperglycemia, hypertension may be related to beta blocking and altered glucose metabolism, and caution must be taken when combined. * (1).3. glucosamine may reduce the effect of anti diabetic drugs, the possible mechanism is inhibition of uptake of islet beta cell glucokinase and c

19、hange through competitive surrounding tissue for glucose, thus reduced insulin secretion, when combined with blood glucose monitoring. * (1).4. licorice can cause hypokalemia and aggravate glucose intolerance, thus reducing the effect of antidiabetic drugs and causing hyperglycemia. Both should be c

20、autious when combined. * (1).5. the use of liothyronine may cause hyperglycemia, the need to increase the amount of drug combination, should pay attention to blood glucose monitoring. * (1).6. rifabutin may increase the drug metabolism, the blood drug concentration decreased, weakened, the combinati

21、on should pay attention to adjust the dose. * (1).7. and Phil porphyrin combined with sodium may increase photosensitivity reactions, causing tissue damage, should be cautious when combined. * (1).8. and the combination of examination and substitution can reduce the efficacy of the test. * (1).Drug

22、alcohol / nicotine interaction1. this medicine may cause disulfiram like reaction, appear facial flushing, numbness, headache, dizziness, nausea, shortness of breath and discomfort during the treatment should avoid alcohol, or alcohol before taking aspirin and other antipyretic analgesics to relieve

23、 the reaction. * (1).2. alcohol may cause hypoglycemia or hyperglycemia by affecting gluconeogenesis, which should be noticed. * (1).directions for Administration1. because of the long half-life of sulfonylurea, it is necessary to monitor the blood sugar during the course of treatment. * (1).2., com

24、bined with weight control, can enhance the efficacy of this drug, the maximum amount of drugs can be reduced by 50%. * (1).usage and dosageusage, dosage, referenceAdultRoutine doseOral administration1. general usage: the starting dose is 250mg per day, before breakfast a single dose, if necessary, c

25、an be increased to 250-500mg within 5-7 days, the common dose is 250mg to 1.5g, the total amount of the day should not exceed 1.5g. When the total amount is not more than 1G, it can be given 1 times a day. When the dosage is 1.5g per day, it can be divided into 2, which is taken before breakfast and

26、 dinner. * (1).2. changed from insulin to this medicine: the usual starting dose is 250mg per day. (1) the dosage of insulin should be no more than 20U, and the insulin can be stopped directly and the medicine should be taken. (2) the dosage of insulin was 20-40U, and the dosage of insulin was decre

27、ased by 25%-30% every day or every other day. The curative effect was further reduced and the dosage of insulin was stopped. * (1).3. changed from other oral antidiabetic drugs to this medicine: (1) the dosage should be half of sulfonylurea. (2) the dose should be two times greater than that of sulfonylurea. * (1).Renal failure time doseThe drug is mainly excreted by the kidneys and has an increased risk of hypoglycemia in pa