アセタゾラミド

アセタゾラミド · ジアモックス · アセトアゾールアミド · グラウパックス · ジアカルブ · ドンモックス · アセタゾールアミド · ダイアモックス

https://huagongshe.com/ja/chemical/1986

識別子と物理属性

CAS No.	59-66-5
分子式	C4H6N4O3S2
平均分子量	222.3 g/mol
単同位体質量	221.98813205 g/mol
SMILES	CC(=O)Nc1nnc(S(N)(=O)=O)s1
InChIKey	BZKPWHYZMXOIDC-UHFFFAOYSA-N
PubChem CID	1986
ChEMBL	CHEMBL20
ChEBI	CHEBI:27690
EC No.	200-440-5
DTXSID	DTXSID7022544
現地名	アセタゾラミド

化学・物理的性質

XLogP	-0.3
極性表面積	152
水素結合供与体数	2
水素結合受容体数	7
回転可能結合数	2
重原子数	13
形式電荷	0
複雑度	297
医薬品	Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> AntiepilepticsPharmaceuticals -> Used in Switzerland
LogP（分配係数）	Log P= -0.45-0.26-0.25
臭い	ODORLESS
Color/Form	CRYSTALS FROM WATERWHITE TO FAINTLY YELLOWISH WHITE, CRYSTALLINE, POWDER
溶解度	less than 1 mg/mL at 72 °F (NTP, 1992)SPARINGLY SOL IN COLD WATERSLIGHTLY SOL IN ALCOHOLINSOL IN CHLOROFORM, DIETHYL ETHER, CARBON TETRACHLORIDESLIGHTLY SOL IN ACETONEReadily soluble in 1 N sodium carbonate solution.NH4OH (50mg/mL)、DMSO、メタノールに可溶、エタノールに微溶。<0.1 g/100 mL で 22 ºC
Human Drugs	Breast FeedingLactationMilk, HumanAnticonvulsantsAntiglaucoma AgentsCarbonic Anhydrase InhibitorsDiureticsFDA approved drugs -> Active ingredientPharmaceuticalsOphthalmological preparations > Miotics and antiglaucoma medicines
融点	496 to 498 °F (effervescence) (NTP, 1992)258-259 °C (EFFERVESCENCE)260.5 °C
Physical Description	Acetazolamide appears as white to yellowish-white fine crystalline powder. No odor or taste. (NTP, 1992)Solid
Stability/Shelf Life	SENSITIVE TO LIGHT
Dissociation Constants	7.2PKA: 7.2
Collision Cross Section	137.8 Å² [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID7022544]151.05 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]140.7 Å² [M+H]+ [CCS Type: TW
Other Experimental Properties	WEAK ACID
密度	1.610 (estimate)
屈折率	1.6270 (estimate)
貯蔵条件	2-8°C
pKa（酸解離定数）	7.2(at 25℃)
外観・状態	個体
色	ホワイトからオフホワイト
由来生物	synthetic
Merck	14,53
BRN	212994
BCS Class	4
安定性	吸湿性
InChI	1S/C4H6N4O3S2/c1-2(9)6-3-7-8-4(12-3)13(5,10)11/h1H3,(H2,5,10,11)(H,6,7,9)
InChIKey	BZKPWHYZMXOIDC-UHFFFAOYSA-N
SMILES	CC(=O)Nc1nnc(s1)S(N)(=O)=O
CAS データベース	59-66-5(CAS DataBase Reference)
NISTの化学物質情報	2-Acetylamino-1,3,4-thiadiazole-5-sulfonamide(59-66-5)
EPAの化学物質情報	Acetazolamide (59-66-5)

化学的特性

White Solid

安全性と法規制

GHS 分類	This chemical does not meet GHS hazard criteria for 0.7% (1 of 153) of reports.WarningH315 (90.2%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P264, P264+P265, P280, P302+P352, P305+P351+P338, P318, P321, P332+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 153 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Danger
規制情報	Hazard Traits - Developmental ToxicityAcetamide, N-5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.
その他の安全情報	IMAP assessments - Acetamide, N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-: Human health tier I assessment
火災危険	Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992)
健康有害性	SYMPTOMS: Symptoms of exposure to this compound may include paresthesias, "tingling" feeling in the extremities, some loss of appetite, polyuria, occasional drowsiness, confusion and photosensitivity. Other symptoms may include papular or erythematous skin eruptions, nausea, acidosis and blood dyscrasias. In addition it can cause acute transient myopia, malaise syndrome, which includes fatigue, anorexia, loss of weight, depression and loss of libidogastrointestinal distress, elevated blood urate, acute gouty arthritis skin rashes and hair loss or excess growth of hair.
FDA 要件	Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392).
反応性グループ	Amides and Imides
Reactivity Profile	A weak acid and a diazo derivative. Azo, diazo, azido compounds can detonate. This applies in particular to organic azides that have been sensitized by the addition of metal salts or strong acids. Toxic gases are formed by mixing materials of this class with acids, aldehydes, amides, carbamates, cyanides, inorganic fluorides, halogenated organics, isocyanates, ketones, metals, nitrides, peroxides, phenols, epoxides, acyl halides, and strong oxidizing or reducing agents. Flammable gases are formed by mixing materials in this group with alkali metals. Explosive combination can occur with strong oxidizing agents, metal salts, peroxides, and sulfides.
Air and Water Reactions	Insoluble in water.
Hazard Classes and Categories	Skin Irrit. 2 (90.2%)Reproductive toxicity - Category 1B
消火	Fires involving this chemical can be controlled with a dry chemical, carbon dioxide, or Halon extinguisher. (NTP, 1992)
応急処置	EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.
保管条件	Store between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.
非火災時の漏出対応	SMALL SPILLS AND LEAKAGE: If you spill this chemical, dampen the solid spill material with 5% ammonium hydroxide, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% ammonium hydroxide to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% ammonium hydroxide followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.
処分方法	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Personal Protective Equipment (PPE)	RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
相互作用	/ACETAZOLAMIDE/ POTENTIATES MERCURIAL DIURETICS /IN ANIMALS/.Concurrent use /of glucocorticoid corticosteroids, especially with significant mineralocorticoid activitymineralocorticoid corticosteroidsparenteral amphotericincorticotropin, especially prolonged therapeutic use/ with carbonic anhydrase inhibitors may result in severe hypokalemia and should be undertaken with cautionserum potassium concentrations and cardiac function should be monitored during concurrent use. /Carbonic anhydrase inhibitors/Concurrent use of corticosteroids or corticotropin with acetazolamide sodium may increase the risk of hypernatremia and/or edema because these medications cause sodium and fluid retentionthe risk with corticosteroids or corticotropin may depend on the patients's sodium requirement as determined by the condition being treated. /Acetazolamide sodium/The possibility should be considered that concurrent chronic use of corticosteroids or corticotropin with carbonic anhydrase inhibitors may increase the risk of hypocalcemia and osteoporosis because these medications increase calcium excretion. /Carbonic anhydrase inhibitors/For more Interactions (Complete) data for ACETAZOLAMIDE (16 total), please visit the HSDB record page.
有害作用	There is a broad range of general and specific adverse effects that acetazolamide use can induce. Fatigue, nausea, vomiting, abdominal pain, and diarrhea are common in patients. Other patients will experience paresthesia, black stools, decreased libido, tinnitus, and taste alteration. There are also reports of patients developing depression while using acetazolamide or developing a bitter or metallic taste. Less commonly, there is a risk of developing metabolic acidosis, hyponatremia, and hypokalemia. Kidney stones can also be seen but are uncommon. Occasionally, patients develop Stevens-Johnson syndrome, aplastic anemia, agranulocytosis, toxic epidermal necrolysis, or fulminant hepatic necrosis.
毒性の概要	IDENTIFICATION: Acetazolamide is of synthetic origin. Acetazolamide exists as a white to faintly yellowish-white, odorless crystalline powder. Acetazolamide is very slightly soluble in water and only slightly soluble in ethanol (approx 750 g/l)it is practically insoluble in ether and chloroform. Uses: Preoperative management of closed-angle glaucoma, or as an adjunct in the treatment of open-angle glaucoma. Abnormal retention of fluid: drug-induced edema, obesity, and congestive cardiac failure. Epilepsy Metabolic alkalemia. Periodic paralysis HUMAN EXPOSURE: Patients with either acute or chronic overdosage with acetazolamide may show signs of dehydration with thirst, lethargy, confusion, poor skin turgor, and prolonged capillary refill time, but may have a paradoxical continued diuresis. Electrolyte abnormalities include hyponatremia, hypokalemia, and a non-anion gap hyperchloremic metabolic acidosis in the more than mild ingestion which may lead to further deterioration in mental status, production of seizures, electrocardiographic abnormalities, and arrhythmias. Prior renal insufficiency will lead to increased toxicity at a given dose. There are idiosyncratic reactions producing bone marrow suppression with hepatic and renal insufficiency. Acetazolamide may also precipitate in the renal tubules producing calculi with renal colic. Hypokalemia may lead to muscular weakness, hyporeflexia, and hypochloremic metabolic alkalosis. In geriatric patients, a chronic metabolic acidosis may lead to a chronic compensatory hyperventilation which increases pulmonary vascular resistance and decreases left ventricular function. This can be especially significant in patients on concurrent beta-blocker or calcium channel blocker therapy. The ventricular fibrillation threshold may then be reduced. Cardiac arrhythmias may occur due to potassium deficiency. Abuse or overdose may result in pancreatitis. Hyperglycemia, hyperuricemia, and hyperlipidemia may occur with acute overdose or in chronic use or abuse. Hypersensitivity reactions such as rash, photosensitivity, thrombocytopenia, and pancreatitis are rare. Contraindications: Renal hyperchloremic acidosis. Addison's disease and all types of suprarenal gland failure. Conditions where there is known depletion of sodium and potassium (at least until this is treated). Long-term administration is contraindicated in patients with chronic closed angle-closure glaucoma. Known sensitivity to sulfonamides. Acetazolamide should not be used to alkalinize urine following salicylate overdose since it may worsen metabolic acidosis. Acetazolamide is well absorbed from the gastrointestinal tract. Acetazolamide is distributed throughout body tissuesit concentrates principally in erythrocytes, plasma and kidneys and to a lesser extent in liver, muscles, eyes and the central nervous system. Acetazolamide does not accumulate in tissues. The drug crosses the placenta in unknown quantities. Acetazolamide is tightly bound to carbonic anhydrase and high concentrations are present in tissues containing this enzyme such as erythrocytes and the renal cortex. There is a small amount of irreversible binding to red cells. It is 70 to 90% bound to plasma protein. Acetazolamide is not metabolized. Acetazolamide is excreted unchanged by the kidneys via tubular secretion and passive reabsorption. There is no evidence of enterohepatic circulation although small amounts of unchanged drug are eliminated in the bile. Acetazolamide is a carbonic anhydrase inhibitor. Acetazolamide reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and water by noncompetitive, reversible inhibition of the enzyme carbonic anhydrase, thereby reducing the availability of these ions for active transport into secretions. One patient died of cholestatic jaundice after taking 13 g of acetazolamide in 26 days. In one patient, fatal bone marrow depression with leukopenia, thrombocytopenia, and anemia occurred after therapy with 500 mg of acetazolamide twice daily for 14 weeks. One case of renal failure (anuria) occurred in a patient after taking 500 mg of acetazolamide twice daily for 2 weeks. There have been no reports of congenital defects despite past widespread use though one women on 750 mg per day for glaucoma during the 1st and 2nd trimester had a baby with a sacrococcygeal teratoma but no causal link could be made. Teratogenicity tests in rats and mice showed the absence of fourth and fifth digits from the right forelimb in the offspring of rats and mice. There were no apparent lessions in the newborn of rabbits and monkeys. The drug crosses the placenta in unknown quantities. Potentially hazardous interactions: The effects of folic acid antagonists, oral hypoglycaemic agents and oral anticoagulants may be increased by acetazolamide. The urinary antiseptic effect of methenamine may be prevented by acetazolamide by keeping the urine alkaline. The alkalinization of the urine by acetazolamide can reduce the urinary excretion of many weak bases (including amphetamine, quinine, quinidine, and diethylcarbamazine) and thus enhance their pharmacological effects. In one patient taking phenytoin and acetazolamide drug-induced osteomalacia was reported. The more serious effects include blood disorders, skin toxicity and renal stone formation. Stevens-Johnson syndrome has not been reported. Symptomatic adverse effects: Flushing, thirst, headache, drowsiness, dizziness, fatigue, irritability, excitement, paresthesias, ataxia, hyperpnoa and gastrointestinal disturbances have all been reported (Dollery). Oral ingestion is the usual means of exposure. There is no appreciable dermal absorption. There is no significant absorption or local irritation. ANIMAL/PLANT STUDIES: Numerous animal studies have demonstrated that the toxicity of acetazolamide was very low in the species studied (mouse, dog, rat, monkey).There have been reports of central nervous system (CNS) toxicity with coma. In addition, hyperchloremic metabolic acidosis and electrolyte disturbances are usually seen in acetazolamide overdose. Therefore, clinicians should rapidly obtain serum electrolyte levels (especially serum potassium) and arterial blood gas analysis. According to product labeling, there is no specific antidote to acetazolamidehence treatment is usually supportive. Bicarbonate administration can usually correct metabolic acidosis. Despite its plasma protein binding and high RBC distribution, acetazolamide may be dialyzable. Dialysis may be especially valuable in managing acetazolamide overdosage complicated with acute kidney injury.
Human Toxicity Excerpts	Serious toxic reactions to carbonic anhydrase inhibitors are infrequenthowever, these drugs are sulfonamide derivatives and, like other sulfonamides, may cause bone marrow depression, skin toxicity, and sulfonamide-like renal lesions and may cause allergic reactions in patients hypersensitive to sulfonamides. /Carbonic Anhydrase Inhibitors/Bone marrow depression manifested by aplastic anemia, thrombocytopenia or thrombocytopenic purpura, leukopenia, agranulocytosis, and hemolytic anemia has been reported with carbonic anhydrase inhibitors. Fatalities resulting from aplastic anemia have been reported following therapy with acetazolamide or methazolamide. In one patient, fatal bone marrow depression with leukopenia, thrombocytopenia, and anemia occurred after therapy with 500 mg of acetazolamide twice daily for 14 weeks.Hypersensitivity reactions common to all sulfonamide derivatives occur rarely in patients receiving carbonic anhydrase inhibitors. One patient died of cholestatic jaundice after taking 13 g of acetazolamide in 26 days. The jaundice was attributed to drug-induced hypersensitivity and hepatitis. Other hypersensitivity reactions which may occur include fever, rash and skin eruptions including exfoliative dermatitis and urticaria, and pruritus.One case of renal failure (anuria) occurred in a patient after taking 500 mg of acetazolamide twice daily for 2 weeks. The patient recovered after treatment of sodium bicarbonate (4 g orally initially, followed by 2 g every 6 hours) and forced fluids.For more Human Toxicity Excerpts (Complete) data for ACETAZOLAMIDE (7 total), please visit the HSDB record page.
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)AcetazolamidevMost-DILI-concern8Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015
Non-Human Toxicity Excerpts	IV INFUSION OF ACETAZOLAMIDE INTO DOGS DECR GLOMERULAR FILTRATION RATE @ ALL DOSE LEVELS.IV ADMIN OF ACETAZOLAMIDE 25 MG/KG INDUCED INCR OF CORTICAL OXYGEN TENSION IN RABBITS, ALSO ELEVATION OF LOCAL BLOOD FLOW IN CEREBRAL CORTEX. LENGTHENED SURVIVAL TIME OF MICE SUBMITTED TO ATMOSPHERIC DECOMPRESSION. NOT PROTECTIVE IN RATS UNDER ASPHYXIA.IN RHESUS MONKEYS, ACETAZOLAMIDE PRODUCED AN IMMEDIATE & SIGNIFICANT INCR IN CEREBRAL BLOOD FLOW, INCR IN ARTERIAL CO2 TENSION, & A DECR IN CEREBRAL OXYGEN CONSUMPTION.... Post-axial forelimb defects in mice and rats by feeding a diet containing 0.6% acetazolamide. The defect was specifically localized to the forelimb and the light side more often involved. Symmetric forelimb defects have been produced in the hamster. In monkeys, administration of 600 mg/kg for 3 to 6 embryonic days gave negative results.For more Non-Human Toxicity Excerpts (Complete) data for ACETAZOLAMIDE (6 total), please visit the HSDB record page.
Environmental Fate/Exposure Summary	No Data
Effects During Pregnancy and Lactation	◉ Summary of Use during Lactation
水環境危害等級（WGK）	2
TSCA 収載状態	TSCA listed
RTECS 番号	AC8225000
輸送番号（UN）	2811
毒性	LD50 oral in mouse: 4300mg/kg
税関コード	29350090
危険文句（R）	36/38-36/37/38
危険表示	Xi
安全措置（S）	26-36
危険等級	6.1Eye Irrit. 2Skin Irrit. 2
包装等級	III
貯蔵分類	11 - Combustible Solids
有害物質データ	59-66-5(Hazardous Substances Data)

用途

解説

アセタゾラミド，白色の結晶性粉末．分解点255 ℃．pKa 7.2．エタノール，水，エーテルに難溶，アルカリに可溶．炭酸脱水酵素阻害剤，利尿薬，妊娠中毒症，および緑内障治療薬として使用される．森北出版「化学辞典（第2版）

用途

炭酸脱水酵素阻害剤です。炭酸脱水酵素阻害作用を示します。

用途

炭酸脱水酵素阻害剤です。炭酸脱水酵素阻害作用を示します。

用途

医薬(炭酸脱水素酵素抑制剤)

説明

Acetazolamide is a weak diuretic with limited use in edema associated with cardiac insufficiency, glaucoma, minor epileptic attacks, and altitude sickness.

使用

Acetazolamide is used for epilepsy in the absence of attacks and also in conjunction with other antiepileptic drugs.

一般的な説明

White to yellowish-white fine crystalline powder. No odor or taste.

製法・合成法

純化方法

It is recrystallised from water. [Roblin & Clapp J Am Chem Soc 72 4890 1950, Beilstein 27 III/IV 8219.]