acetazolamide sodium

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acetazolamide

WordNet

1. a silvery soft waxy metallic element of the alkali metal group; occurs abundantly in natural compounds (especially in salt water); burns with a yellow flame and reacts violently in water; occurs in sea water and in the mineral halite (rock salt) (同)Na, atomic number 11

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1. ソジウム,ナトリウム(金属元素;化学記号はNa)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/07 03:42:13」(JST)

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Not to be confused with acetohexamide or methazolamide.

Acetazolamide

Systematic (IUPAC) name
N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
Clinical data
Trade names	Diamox
AHFS/Drugs.com	monograph
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	oral or intravenous
Pharmacokinetic data
Protein binding	70-90%
Metabolism	None
Biological half-life	2-4 hours
Excretion	Urine (90%)
Identifiers
CAS Number	59-66-5 Y
ATC code	S01EC01
PubChem	CID: 1986
IUPHAR/BPS	6792
DrugBank	DB00819 Y
ChemSpider	1909 Y
UNII	O3FX965V0I Y
KEGG	D00218 Y
ChEBI	CHEBI:27690 Y
ChEMBL	CHEMBL20 Y
PDB ligand ID	AZM (PDBe, RCSB PDB)
Chemical data
Formula	C4H6N4O3S2
Molecular mass	222.245 g/mol
SMILES O=S(=O)(c1nnc(s1)NC(=O)C)N
InChI 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) Y Key:BZKPWHYZMXOIDC-UHFFFAOYSA-N Y
Physical data
Melting point	258 to 259 °C (496 to 498 °F)
Y (what is this?)  (verify)

Acetazolamide, usually sold under the trade name Diamox in some countries, is a carbonic anhydrase inhibitor that is used for the medical treatment of glaucoma, epileptic seizure, idiopathic intracranial hypertension, altitude sickness, cystinuria, periodic paralysis, central sleep apnea, and dural ectasia. Acetazolamide is a diuretic, and it is available as a generic drug in the United States. Diamox is now available as Diamox Sequels in the United States since the original product is no longer made or sold there.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.

Medical uses

It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, centrencephalic epilepsy and in reducing intraocular pressure after surgery. It has also been used in the treatment of mountain sickness, Ménière's disease, increased intracranial pressure and neuromuscular disorders.

In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an adjunct in refractory epilepsy. It has been demonstrated in drug trials to relieve symptoms associated with dural ectasia in individuals with Marfan's Syndrome. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea. In the treatment of mountain sickness, acetazolamide forces the kidneys to excrete bicarbonate, the conjugate base of carbonic acid. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. As the body equates acidity of the blood to its CO2 concentration, artificially acidifying the blood fools the body into thinking it has an excess of CO2, and it excretes this imaginary excess CO2 by deeper and faster breathing, which in turn increases the amount of oxygen in the blood. Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up part of the acclimatization process which in turn helps to relieve symptoms.

It has also been used to prevent methotrexate-induced kidney damage by alkalinalizing one's urine, hence speeding up methotrexate excretion by increasing its solubility in urine.

Pregnancy and lactation

Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs. Despite this there is insufficient evidence from studies in humans to either support or discount this evidence. It is also excreted in breast milk and hence breastfeeding is advised against in mothers taking this drug.

Side-effects

Common adverse effects of acetazolamide include the following: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black feces, polyuria, kidney stones, metabolic acidosis and electrolyte changes (hypokalemia, hyponatremia). Whereas less common adverse effects include: Stevens-Johnson syndrome, anaphylaxis and blood dyscrasias.

Contraindications

Contraindications include:

• Hyperchloremic acidosis
• Hypokalemia (low blood potassium)
• Hyponatremia (low blood sodium)
• Adrenal insufficiency
• Impaired kidney function
• Hypersensitivity to acetazolamide or other sulfonamides.
• Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.

Interactions

It is possible that it might interact with:

• Amphetamines, due to the fact it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines.
• Other carbonic anhydrase inhibitors - potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity.
• Ciclosporin, may increase plasma levels of ciclosporin.
• Antifolates such as trimethoprim, methotrexate, pemetrexed and raltitrexed.
• Hypoglycemics, acetazolamide can both increase or decrease blood glucose levels.
• Lithium, increases excretion, hence reducing therapeutic effect.
• Methenamine compounds, reduces the urinary secretion of methenamines.
• Phenytoin, reduces phenytoin secretion, hence increasing the potential for toxicity.
• Primidone, reduces plasma levels of primidone. Hence reducing anticonvulsant effect.
• Quinidine, reduces urinary secretion of quinidine, hence increasing the potential for toxicity.
• Salicylates, potential for severe toxicity.
• Sodium bicarbonate, potential for kidney stone formation.
• Anticoagulants, cardiac glycosides, may have their effects potentiated by acetazolamide.

Mechanism of action

Carbonic anhydrase complex with a sulfonamide inhibitor.

Acetazolamide is a carbonic anhydrase inhibitor, hence causing the accumulation of carbonic acid Carbonic anhydrase is an enzyme found in red blood cells that catalyses the following reaction:

hence lowering blood pH, by means of the following reaction that carbonic acid undergoes:

which has a pK_a of 6.3.

In the eye this results in a reduction in aqueous humour.

The mechanism of diuresis involves the proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation, increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.

References

UpToDate Contents

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• 1. 腫瘍崩壊症候群：予防および治療 tumor lysis syndrome prevention and treatment
• 2. 利尿剤の作用機序 mechanism of action of diuretics
• 3. Chapter 3A：近位尿細管輸送の細胞モデル chapter 3a cell model for proximal transport
• 4. 急性高山病および高地脳浮腫 acute mountain sickness and high altitude cerebral edema
• 5. 代謝性アルカローシスの治療 treatment of metabolic alkalosis

English Journal

• Pharmacologic Approaches to Electrolyte Abnormalities in Heart Failure.

• Grodin JL1.
• Current heart failure reports.Curr Heart Fail Rep.2016 Aug;13(4):181-9. doi: 10.1007/s11897-016-0295-7.
• Electrolyte abnormalities are common in heart failure and can arise from a variety of etiologies. Neurohormonal activation from ventricular dysfunction, renal dysfunction, and heart failure medications can perturb electrolyte homeostasis which impact both heart failure-related morbidity and mortali
• PMID 27278221

• Novel Mutations in the Nonselective Sodium Leak Channel (NALCN) Lead to Distal Arthrogryposis with Increased Muscle Tone.

• Karakaya M1, Heller R1, Kunde V2, Zimmer KP3, Chao CM3, Nürnberg P4, Cirak S1.
• Neuropediatrics.Neuropediatrics.2016 Aug;47(4):273-7. doi: 10.1055/s-0036-1584084. Epub 2016 May 23.
• Distal arthrogryposis (DA) is a feature in genetically and clinically heterogeneous groups of disorders. Mostly myopathic and neurogenic defects have been described, but many patients remain without genetic diagnosis. We are elaborating on the clinical presentation of neonatal cases with DA who carr
• PMID 27214504

• Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

• de Groot T1, Sinke AP1, Kortenoeven ML1, Alsady M1, Baumgarten R2, Devuyst O3, Loffing J4, Wetzels JF5, Deen PM6.
• Journal of the American Society of Nephrology : JASN.J Am Soc Nephrol.2016 Jul;27(7):2082-91. doi: 10.1681/ASN.2015070796. Epub 2015 Nov 16.
• To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alka
• PMID 26574046

Japanese Journal

• Reinvestigation of Drugs and Chemicals as Aquaporin-1 Inhibitors Using Pressure-Induced Hemolysis in Human Erythrocytes

• Yamaguchi Takeo,Iwata Yohei,Miura Shingo [他],Kawada Kazumasa
• Biological and Pharmaceutical Bulletin 35(11), 2088-2091, 2012
• … So, using this method we reinvestigated the functions as AQP1 inhibitors of drugs and chemicals such as acetazolamide, sodium nitroprusside, tetraethylammonium ions (TEA+), and dimethylsulfoxide (DMSO). … The values of hemolysis at 200 MPa were almost unaffected by acetazolamide or sodium nitroprusside, decreased by TEA+, and increased significantly by DMSO. …
• NAID 130001872270

• The role of sodium/hydrogen exchange in the teratogenic response to acetazolamide

• Scott Jr. William J.,Bell Sheila M.,Schreiner Claire M.
• Congenital anomalies 41(1), 76-82, 2001-03
• NAID 110002785796

• Effects of KW-3902 (8-(Noradamantan-3-yl)-1,3-dipropylxanthine), an Adenosine A_1-Receptor Antagonist, on Urinary Excretions of Various Electrolytes in Rats

• NAGASHIMA Ken,KARASAWA Akira
• Biological & pharmaceutical bulletin 19(7), 940-943, 1996-07-15
• … We examined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A_1-receptor antagonist, on urine volume and urinary excretions of various electrolytes in saline-loaded rats, as compared with those of furosemide, trichlormethiazide (TCM), acetazolamide and amiloride. … KW-3902 at doses of 0.001-1 mg/kg (p.o.) significantly increased urine volume and excretions of sodium, calcium, magnesium, chloride and bicarbonate. …
• NAID 110003641296

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acetazolamide sodium

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