What Are the Different Glipizide Side Effects?

It is mainly used for patients with mild to moderate non-insulin-dependent patients whose diet control alone has not achieved good results. The effective rate of drug treatment is about 87%.

Chinese name: Glipizide
Foreign name: Glipizide

CAS number: 29094-61-9
Molecular formula: C21H27N5O4S
Molecular weight: 445.54

Introduction of Glipizide Compounds

Glipizide Basic Information

Chinese name: Glipizide

Chinese alias: 1-cyclohexyl-3- {4- [2- (5-methylpyrazine-2-amide) -ethyl] benzenesulfonyl} urea; Glipizide; Glipizide; Jebel; Disa tablets; Cyclopenzol; Glipizide; Youtangling; Loerba; Ruiyining; Ibida; Disa; Mepyda; Youdaling; Diuretic

English name: Glipizide

English alias: N- [2- [4-[[[[(Cyclohexylamino) carbonyl] amino] sulfonyl] phenyl] ethyl] 5-methylpyrazinecarboxamide; 1-cyclohexyl-3-((p- (2- (5-methylpyrazinecarboxamido) ethyl ) phenyl) sulfonyl) ure; exylurea; Glipizibe; glipizide (usp); Glucotrol; k4024; Melizide; N- (2- {4-[(cyclohexylcarbamoyl) sulfamoyl] phenyl} ethyl) -5-methylpyrazine-2-carboxamide; N -[2- [4- (cyclohexylcarbamoylsulfamoyl) phenyl] ethyl] -5-methyl-piperazine-2-carboxamide; Glibenese; Minidiab; Minodiab; Mitoneu; Glucotrol XL

CAS number: 29094-61-9

EINECS number: 249-427-6

Molecular formula: C ₂₁ H ₂₇ N ₅ O ₄ S

Molecular weight: 445.54

Exact mass: 445.17800

PSA: 138.53000

LogP: 4.33160

Glipizide physical and chemical properties

Density: 1.29g / cm ³

Melting point: 208-209 ° C

Refractive index: 1.597

Storage conditions: Store in a dry, closed container. Store in 20º

Properties: white or off-white crystalline powder. Odorless and almost odorless.

Solubility: slightly soluble in acetone, chloroform or dioxane, very slightly soluble in ethanol, almost insoluble in water; easily soluble in dilute sodium hydroxide solution.

Glipizide Safety Information

Customs Code: 29350009090

WGK Germany: 3

Danger category code: R21

Safety instructions: S24 / 25

RTECS number: YS7640000

Dangerous goods mark: Xi; Xn ^[1]

Glipizide uses

It is a good hypoglycemic agent for non-insulin-dependent (II) diabetes. This product is mainly used for patients with mild to moderate non-insulin-dependent patients who fail to achieve good results with diet control alone ^[1] .

Glipizide analysis method

Method name:

Determination of Glipizide-Neutralization Titration

Application:

This method uses titration to determine the content of glipizide.

This method is applicable to glipizide.

Method principle:

After adding dimethylformamide to the test product to dissolve it, add quinalidine red indicator solution, titrate with sodium methoxide titration solution (0.1mol / L) until the solution becomes blue, record the amount of sodium methoxide titration solution, calculate That's it.

Reagent:

1. Water (newly boiled to room temperature)

2. Sodium methoxide titration solution (0.1mol / L)

3. Quinalidine red indicator solution

Dimethylformamide

equipment:

Sample preparation:

1. Sodium methoxide titration solution (0.1mol / L)

Preparation: Take 150 mL of sewage methanol (water content below 0.2%), put it in a container cooled by ice water, and add 2.5 g of freshly cut sodium metal in portions. After it is completely dissolved, add anhydrous benzene (water content is 0.2%). Below) Make an appropriate amount to 1000 mL and shake well.

Calibration: Take about 0.4g of standard benzoic acid dried under reduced pressure in a phosphorus pentoxide dryer to constant weight, accurately weigh, add 15mL of anhydrous methanol to dissolve, add 5mL of anhydrous benzene and 1% thymol blue One drop of anhydrous methanol solution was titrated to blue with this solution, and the result of the titration was corrected with a blank experiment. Each 1mL of sodium methoxide titer is equivalent to 12.21mg of benzoic acid. According to the consumption of this solution and the amount of benzoic acid used, calculate the concentration of this solution, that is, it can be obtained.

During the calibration of this liquid, care should be taken to prevent the interference of carbon dioxide and the volatilization of solvents, and it should be recalibrated before each use.

Storage: Keep in a closed container with a titration device to avoid contact with carbon dioxide and moisture in the air.

2. Quinalidine red indicator solution

Take 0.1 g of quinalidine red and dissolve by adding 100 mL of methanol, that is, obtained.

Steps:

Weigh precisely 0.4 g of the product, add 50 mL of dimethylformamide to dissolve it, add 1 drop of quinalidine red indicator solution, and use the sodium methoxide titration solution (0.1mol / L) to titrate the solution. The red color disappeared, and the titrated The results were corrected with a blank test, and the volume (mL) of the sodium methoxide titration solution was recorded. Each 1 mL of the sodium methoxide titration solution (0.1 mol / L) was equivalent to 44.55 mg of glipizide (C ₂₁ H ₂₇ N ₅ O ₄ S ), That's it.

Note 1: "Precise weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision weighing" means that the accuracy of the measured volume should conform to the national standard for the volume of the pipette. Precision requirements ^[2] .

Glipizide Pharmacopoeia Standard

[Source (name), content (potency)]

This product is 5-methyl-N- [2- [4-[[[(cyclohexylamino) carbonyl] amino] sulfonyl] phenyl] ethyl] -pyrazinecarboxamide. Calculated based on dry products, C ₂₁ H ₂₇ N ₅ O ₄ S should be 98.0% 102.0%.

[Character]

This product is white or off-white crystalline powder; odorless; almost odorless. This product is soluble in dimethylformamide, slightly soluble in acetone, chloroform, dioxane or methanol, very slightly soluble in ethanol, almost insoluble in water; easily soluble in dilute sodium hydroxide solution .

Melting point

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 203 to 208 ° C.

[Identification] Take about 50mg of this product, add 5ml of dioxane, heat in a water bath to dissolve, add 1% of 0.5% 2,4-dinitrofluorobenzene dioxane solution, boil for 2 to 3 minutes, the solution Bright yellow.

Take this product, add a phosphate buffer solution (pH 7.4) to make a solution containing about 25 g per 1 ml, and determine it by spectrophotometry (Appendix IVA). It has maximum absorption at the wavelengths of 222nm and 275nm.

(3) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 808).

[Inspection] Take the product, add chloroform-methanol (1: 1) to make a solution containing 20mg per 1ml, and use it as the test solution; take an appropriate amount and dilute with chloroform-methanol (1: 1). Each 1ml contains a solution of 0.1mg and 0.04mg, as the control solutions and ; another appropriate amount of 4- [2- (5-methylpyrazine-2-carboxamido) ethyl] benzenesulfonamide reference substance, Add chloroform-methanol (1: 1) to make a solution containing 0.1mg per 1ml, and use it as the reference solution solution . According to the thin layer chromatography (Appendix VB) test, draw 25l of each of the above four solutions, and point them on the same silica gel. GF254 thin-layer plate, using dichloromethane-carbon tetrachloride-ethyl acetate-anhydrous formic acid (40: 40: 20: 20) as a developing agent, after unfolding, dry.

View under UV light (254nm). If the test solution shows obvious impurity spots, it must not be deeper than the corresponding impurity spots of the reference solution ; if other impurity spots are displayed, not more than 3, one of the spots must not be deeper than the main spot of the control solution; The other spots must not be deeper than the main spots of the control solution.

Take the product after losing weight and dry it at 105 to constant weight, and the weight loss should not exceed 0.5% (Appendix L).

Take 1.0 g of the residue from the burning residue and inspect it according to law (Appendix N). The residual residue shall not exceed 0.1%.

The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected in accordance with the law (Appendix H Second Law). The content of heavy metal shall not exceed 20 parts per million.

[Content determination] Take about 0.4g of this product, weigh it accurately, add 50ml of dimethylformamide to dissolve, add 2 drops of quinalidine red indicator solution, and titrate with sodium methoxide titration solution (0.1mol / L) to the solution. The red color faded, and the results of the titration were corrected with a blank test. Each 1ml of sodium methoxide titration solution (0.1mol / L) is equivalent to 44.55mg of C ₂₁ H ₂₇ N ₅ O ₄ S ^[3] .

Glipizide Drug Description

Glipizide Classification

Endocrine System Drugs> Drugs for Diabetes and Islet Disease

Glipizide dosage form

1. Tablets: 5mg each;

2. Diabetic, tablet: 5mg;

3. Mepyda, tablet: 5mg;

4. Disha, tablet: 2.5mg;

5. You Da Ling, tablets: 5mg;

6. Ebida, capsule: 5mg;

7. Glipizide, capsules: 5mg.

Glipizide pharmacological effects

Glipizide is a second-generation sulfonylurea hypoglycemic agent, and has lipid-lowering and anticoagulant effects. Its hypoglycemic effect is rapid and strong, about 1000 times that of tolbutamide, and its effect is similar to that of glibenclamide. The mechanism of action is to stimulate the beta cells of the islets, increase insulin secretion, and also stimulate the islets of the islets to cause high blood glucose Suppressed. Its mode of action is similar to that of chlorpromide, with less toxic and side effects and no teratogenicity. In addition, some people think that glipizide still has the effect of inhibiting the breakdown of liver glycogen, promoting muscle utilization and glucose consumption; it may also change the response of insulin target tissues to insulin and enhance the effect of insulin through the action of the pancreas, so some patients Taking a single dose can effectively control blood sugar for up to 24 hours. Other literature reports that glipizide can correct the microvascular circulation disorder of early diabetes, reduce the plasma triacylglycerol level, accelerate the conversion of cholesterol to HDL in the body, and can also reduce the cohesion of platelets and improve the ability to break down and absorb fibrin. Therefore, it can resist platelet aggregation, slow down the formation of thrombus and endothelial damage in capillaries, and may have a certain prevention and treatment effect on microvascular diseases. The use of controlled release technology enables the drug to be slowly released to achieve a long-lasting hypoglycemic effect. The effect can be maintained for 24 hours, which can reduce fasting blood glucose and postprandial blood glucose ^[4] .

Glipizide Pharmacokinetics

After oral administration, the absorption in the gastrointestinal tract is complete and rapid, and a significant drop in blood glucose can be seen after 30 minutes. If taken with food, the absorption can be delayed by 30 to 40 minutes. The peak plasma drug concentration time is 1 to 2 hours. Above 10h. In the liver metabolism, its metabolites are inactive, the plasma half-life is 2 to 4 hours, and the plasma protein binding rate is 92% to 99%. 97% of the drug can be excreted within 24 hours, and all can be cleared within 3 days (72 hours), so there is no or very few adverse reactions due to accumulation due to hypoglycemia. Fast absorption, high bioavailability, and low dosage are the major characteristics of glipizide ^[4] .

Glipizide dosage

Take 2.5mg orally, once before breakfast or before breakfast and lunch, but also 1.25mg, 3 times a day, three meals before meals, and increase 2.5mg daily after 7 days if necessary.

Internal organs The general daily dose is 5 to 15 mg, and the maximum daily dose does not exceed 20 to 30 mg. 2.5mg of this product is equivalent to 0.5g of tolbutamide. Among the sulfonylurea drugs, this product has the fastest gastrointestinal absorption, and the highest efficacy time is most consistent with the peak blood glucose rise time after meals, so it has less chance of causing hypoglycemic reactions before meals, short half-life, and serious The risk of persistent hypoglycemia is less among sulfonylureas.

Other medication instructions are the same as tolbutamide. Patients who use other oral sulfonylurea hypoglycemic drugs should be observed for 1 to 2 weeks when switching to this product to prevent hypoglycemia. Take orally, 30 minutes before a meal, starting at 2.5 to 5 mg daily, once a day. Later, depending on the condition, the dose can be adjusted gradually to achieve satisfactory control of blood glucose concentration. When the daily dose is more than 10mg, it can be divided into 2 to 3 times, and the maximum daily dose does not exceed 30mg. Patients who use other oral sulfonylurea hypoglycemic drugs should be observed for 1 to 2 weeks when switching to this product to prevent hypoglycemia.

Glipizide adverse reactions and contraindications

A few patients may develop mild nausea and dizziness. Individual cases have hypoglycemia. The incidence of nausea, vomiting, diarrhea, abdominal pain, headache, etc., ranges from 1% to 2%, but the symptoms will disappear after continued treatment. Individual patients develop temporary rashes and occasionally hypoglycemia. If you drink alcohol while taking the medicine, flushing, palpitations and other reactions may occur. Glipizide is hepatotoxic and dose-dependent.

There are also reports of changes in taste caused by this product. This product has no serious adverse reactions, only about 1.5% of patients discontinued due to adverse reactions. 1.0% -3.0% of patients have a gastrointestinal reaction, and 1.4% of patients have a rash. Specifications: tablets: 5mg each. Most insulin-dependent diabetes mellitus, those with a tendency to ketosis. Patients with severe infection, liver and kidney dysfunction, and allergies to this product are disabled. Diabetic ketoacidosis, diabetic hyperosmolar coma, pregnant women, with liver, renal insufficiency, adrenal insufficiency and those who are allergic to this product are contraindicated.

Glipizide Drug Interactions

When this product is used in combination with sulfa drugs, salicylic acids, butamethin, indomethacin, biscoumarin, monoamine oxidase inhibitors, chloramphenicol, propranolol, carboxybenzamide, etc., it can strengthen the product. Hypoglycemic effect, induce hypoglycemic response. Chloramphenicol, coumarins, doxycycline, muscle relaxant fenyramidol, butepine, probenecid, and sulfamethoxazole can inhibit the metabolism and excretion of sulfonylureas and prolong the decline. The role of blood sugar. Salicylic acids, sulfonamides, and sulfonylureas compete for plasma protein binding. -adrenaline, monoamine oxidase inhibitors, salicylic acids and antidepressants, phencyclamine can inhibit glucose production, increase glucose oxidation, and stimulate insulin The secretion of these drugs can enhance the hypoglycemic effect of sulfonylureas. Sulfonylureas, especially chlorosulfuramide and tolbutamide, can inhibit the degradation of liver's alcoholase, leading to tachycardia, headache, angina pectoris and skin reactions.

Glipizide precautions

Those who are allergic to this product are prohibited. It is contraindicated in most patients with insulin-dependent diabetes mellitus, tendency to ketosis, severe infection, and liver and kidney dysfunction. This product has no serious adverse reactions, only about 1.5% of patients discontinued due to adverse reactions. 1.0% -3.7% of patients have gastrointestinal reactions, and 4% of patients have rash. Its hypoglycemic effect can be enhanced by salicylic acid, sulfonamides, biscoumarin, monoamine oxidase inhibitors, bute pine, ketamine, cyclophosphamide, probenecid, and also weakened by the following drugs, such as Adrenaline, corticosteroids, thiazide diuretics.

Glipizide poisoning

Glipizide (Pyrisulfazone, Mepidac) is a second-generation sulfonylurea oral hypoglycemic agent. The effect is basically the same as D-860, the oral absorption is fast and complete, the plasma half-life is 2 to 4 hours, the effect is maintained for 10 hours, 97% of the drug can be discharged within 1 day, there is no obvious accumulation effect, and it causes less hypoglycemic reaction. It is suitable for non-insulin-dependent mild and moderate diabetic patients who are unable to achieve good control by dietary control alone. The usual amount is 2.5mg, 2 ~ 3 / d, taken before meals. Adjust the dose according to blood sugar and urine sugar. Allergic reactions, liver damage and altered taste have been reported.

The processing points are the same as those of tolbutamide:

Clinical manifestations:

1. Gastrointestinal reactions such as abdominal distension, abdominal pain, anorexia, nausea, vomiting, and liver damage can occur during conventional medication.

2. Overdose can cause hypoglycemia.

3. Allergic reactions: itchy skin, erythema, urticaria, exfoliative dermatitis, leukopenia, agranulocytosis, thrombocytopenia, etc.

Key points for diagnosis:

There is a history of application of tolbutamide, and the above manifestations appear.

Treatment points:

1. Take sugar immediately when a hypoglycemic reaction occurs.

2. To reduce gastrointestinal reactions can be changed to take medicine after meals; starting from a small dose, the addition of antacids can reduce or prevent symptoms.

3. Immediately discontinue the drug when allergic reactions occur, and give anti-allergic treatment.

4. Liver toxicity occurs, and the drug can be stopped immediately to recover quickly; liver protection treatment can be given at the same time ^[5] .

Glipizide Expert Reviews

Glipizide is mostly used in patients with type 2 diabetes who cannot be controlled with diet therapy. After oral administration, the blood glucose decreases, 23% when fasting, and 28% after meals. In long-term application, the blood glucose stabilizes at about 1 to 2 weeks. Lower levels, different reports of clinical efficacy, ranging from 80% to 97%, are related to patient age and disease duration. According to foreign reports, the effective rate is 75% for those over 60 years of age, and only 62% for those under 60 years of age. The course of treatment is less than 3 years, and the effect is better, but the treatment for 4 to 6 years is still effective, and only a few fail. . It was also reported that glipizide was used to treat 104 patients with type 2 diabetes, and the total effective rate was 85.6%, of which 70 cases were markedly effective and had good hypoglycemic effect, and the incidence of adverse reactions was low. They were widely used in clinical practice. Is currently one of the commonly used drugs for the treatment of type 2 diabetes sulfonylureas. Glipizide's sustained-release preparation maintains the effect for 24 hours and requires only oral administration once a day. The patient is well tolerated and has a significant hypoglycemic effect, which can effectively reduce fasting and postprandial blood glucose. It is an ideal drug for diabetes patients to control blood glucose ^{[ 4]} .

Glipizide finished drug

Glipizide Glipizide capsules

This product is a sulfonylurea antidiabetic drug, which is effective for most patients with type 2 diabetes, can reduce fasting and postprandial blood glucose, and reduce glycated hemoglobin (HbAlc) by 1% to 2%. These drugs mainly stimulate islet b cells to secrete insulin, but the prerequisite is that islet b cells also have a certain function of synthesizing and secreting insulin. Its mechanism is to specifically bind to the sulfonylurea receptor on the b cell membrane, thereby closing the K ⁺ channel, causing a change in membrane potential, opening the Ca ²⁺ channel, and increasing intracellular Ca ²⁺ to promote insulin secretion. There are also extrapancreatic effects, including improving insulin resistance in peripheral tissues (such as liver, muscle, and fat). The content of this product is a white powder, which disintegrates quickly in water ^[6] .

Glipizide Glipizide tablets

Taken orally, the dosage should be measured regularly and urine glucose and blood glucose levels vary from person to person. The general recommended dose is 2.5-20 / day, and those who fail to take diet therapy 30 minutes before meals; start 2.5-5, and then increase or decrease the dose according to the blood glucose and urine glucose conditions, and each increase or decrease is 2.5-5.0. The daily dose is more than 15:00, and it is divided into 2-3 times before meals. Those who have used other oral sulfonylurea hypoglycemic drugs: Stop using other sulfonylurea drugs after 3 days of rechecking blood glucose and start using this drug. Gradually increase the dose from 5 until the desired therapeutic effect is achieved. 30 ^[7] .

Glipizide Glipizide Controlled Release Tablets

This product is a sulfonylurea antidiabetic drug, which is effective for most patients with type 2 diabetes, can reduce fasting and postprandial blood glucose, and reduce glycated hemoglobin (HbAlc) by 1% to 2%. These drugs mainly stimulate islet cells to secrete insulin, but the prerequisite is that islet cells also have a certain function of synthesizing and secreting insulin. Its mechanism is to specifically bind to the sulfonylurea receptor on the -cell membrane, thereby closing the K + channel, causing a change in membrane potential, opening the Ca ²⁺ channel, and increasing the intracellular Ca2 + to promote insulin secretion. There are also extrapancreatic effects, including improving insulin resistance in peripheral tissues (such as liver, muscle, and fat).

This product is a glipizide controlled release tablet designed according to a special gastrointestinal treatment system (GITS). It is wrapped in a semipermeable membrane and contains glipizide and non-pharmacologically active ingredients that absorb water. The tablets swell after absorbing water, and glipizide is released from small holes made by laser. After 2 hours of oral administration, the active ingredient (glipizide) started to be released stably, which can be maintained for about 8 hours, and the release rate gradually decreased after that, until about 16 hours after taking the drug. Glipizide has a half-life of about 2.5 to 4 hours, which is gradually absorbed into the intestine. It can maintain a stable blood concentration within 24 hours after taking the drug. After 5 mg orally, the average blood concentration can reach 50 ng within 24 hours. / ml or more. Take your medication once a day to control your blood sugar throughout the day. After taking the drug for 5 days, the blood concentration reaches steady state, and it takes 6 to 7 days for elderly patients to reach steady state ^[8] .