Acetazolamide: Difference between revisions
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{{Short description|Chemical compound}} |
{{Short description|Chemical compound}} |
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{{ |
{{Distinguish|acetohexamide|methazolamide}} |
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{{Use dmy dates|date= |
{{Use dmy dates|date=May 2024}} |
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{{Drugbox |
{{Drugbox |
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| verifiedrevid = 477238754 |
| verifiedrevid = 477238754 |
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| image = Acetazolamide.svg |
| image = Acetazolamide.svg |
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| width = 200 |
| width = 200 |
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| Drugs.com = {{drugs.com|monograph|acetazolamide}} |
| Drugs.com = {{drugs.com|monograph|acetazolamide}} |
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| pregnancy_AU = B3 |
| pregnancy_AU = B3 |
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| class = [[Carbonic anhydrase inhibitor]] |
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| legal_AU = S4 |
| legal_AU = S4 |
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| legal_CA = Rx-only |
| legal_CA = Rx-only |
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| legal_UK = POM |
| legal_UK = POM |
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| legal_US = Rx-only |
| legal_US = Rx-only |
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<!--Pharmacokinetic data--> |
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| IUPHAR_ligand = 6792 |
| IUPHAR_ligand = 6792 |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 59-66-5 |
| CAS_number = 59-66-5 |
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| PubChem = 1986 |
| PubChem = 1986 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=4 | H=6 | N=4 | O=3 | S=2 |
| C=4 | H=6 | N=4 | O=3 | S=2 |
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| smiles = NS(=O)(=O)c1nnc(s1)NC(=O)C |
| smiles = NS(=O)(=O)c1nnc(s1)NC(=O)C |
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<!-- Definition and medical uses --> |
<!-- Definition and medical uses --> |
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'''Acetazolamide''', sold under the trade name '''Diamox''' among others, is a medication used to treat [[glaucoma]], [[epilepsy]], [[ |
'''Acetazolamide''', sold under the trade name '''Diamox''' among others, is a medication used to treat [[glaucoma]], [[epilepsy]], [[acute mountain sickness]], [[periodic paralysis]], [[idiopathic intracranial hypertension]] (raised brain pressure of unclear cause), [[heart failure]] and to alkalinize urine.<ref name=AHFS2016/><ref>{{cite journal | vauthors = Smith SV, Friedman DI | title = The Idiopathic Intracranial Hypertension Treatment Trial: A Review of the Outcomes | journal = Headache | volume = 57 | issue = 8 | pages = 1303–1310 | date = September 2017 | pmid = 28758206 | doi = 10.1111/head.13144 | s2cid = 13909867 }}</ref> It may be used long term for the treatment of [[open angle glaucoma]] and short term for [[acute angle closure glaucoma]] until surgery can be carried out.<ref name=WHO2008/> It is taken [[Oral administration|by mouth]] or [[intravenous|injection into a vein]].<ref name=AHFS2016/> Acetazolamide is a first generation [[carbonic anhydrase]] inhibitor and it decreases the ocular fluid and [[osmolality]] in the eye to decrease intraocular pressure.<ref>{{cite book | vauthors = Scozzafava A, Supuran CT | title = Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications | chapter = Glaucoma and the Applications of Carbonic Anhydrase Inhibitors | series = Subcellular Biochemistry | volume = 75 | pages = 349–359 | date = 2014 | publisher = Springer | pmid = 24146387 | doi = 10.1007/978-94-007-7359-2_17 | isbn = 978-94-007-7358-5 }}</ref><ref>{{cite web|url=https://www.openanesthesia.org/acetazolamide_mechanism_of_action/|title=Acetazolamide: mechanism of action|website=www.openanesthesia.org|language=en-US|access-date=10 May 2017}}</ref> |
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<!-- Side effects and mechanisms --> |
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Acetazolamide came into medical use in 1952.<ref>{{cite book| vauthors = Sneader W |title=Drug Discovery: A History|date=2005|publisher=John Wiley & Sons|isbn=9780471899792|page=390|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA390|language=en|url-status=live|archive-url=https://web.archive.org/web/20161228195543/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA390|archive-date= |
Acetazolamide came into medical use in 1952.<ref>{{cite book| vauthors = Sneader W |title=Drug Discovery: A History|date=2005|publisher=John Wiley & Sons|isbn=9780471899792|page=390|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA390|language=en|url-status=live|archive-url=https://web.archive.org/web/20161228195543/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA390|archive-date=28 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Acetazolamide is available as a [[generic medication]].<ref name=AHFS2016/> |
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==Medical uses== |
==Medical uses== |
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It is used in the treatment of [[glaucoma]], drug-induced [[edema]], heart failure-induced edema, [[epilepsy]] and in reducing intraocular pressure after surgery.<ref name = AMH/><ref name = TGA/> It has also been used in the treatment of [[altitude sickness]],<ref>{{cite journal | vauthors = Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP | title = Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis | journal = BMJ | volume = 345 | pages = e6779 | date = October 2012 | pmid = 23081689 | pmc = 3475644 | doi = 10.1136/bmj.e6779 }}</ref> [[Ménière's disease]], [[increased intracranial pressure]] and neuromuscular disorders.<ref name = MD/> |
It is used in the treatment of [[glaucoma]], drug-induced [[edema]], heart failure-induced edema, [[epilepsy]] and in reducing intraocular pressure after surgery.<ref name = AMH/><ref name = TGA/> It has also been used in the treatment of [[altitude sickness]],<ref>{{cite journal | vauthors = Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP | title = Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis | journal = BMJ | volume = 345 | pages = e6779 | date = October 2012 | pmid = 23081689 | pmc = 3475644 | doi = 10.1136/bmj.e6779 }}</ref> [[Ménière's disease]], [[increased intracranial pressure]] and neuromuscular disorders.<ref name = MD/> Acetazolamide is also used in the critical care setting to stimulate respiratory drive in patients with [[chronic obstructive pulmonary disease]] as an [[Off-label use|off-label]] indication.<ref>{{cite journal | vauthors = Heming N, Urien S, Faisy C | title = Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit? | journal = Critical Care | volume = 16 | issue = 4 | pages = 318 | date = August 2012 | pmid = 22866939 | doi = 10.1186/cc11323 | pmc = 3580678 | doi-access = free }}</ref> |
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In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.<ref name = AMH/><ref>{{cite journal | vauthors = Reiss WG, Oles KS | title = Acetazolamide in the treatment of seizures | journal = The Annals of Pharmacotherapy | volume = 30 | issue = 5 | pages = 514–519 | date = May 1996 | pmid = 8740334 | doi = 10.1177/106002809603000515 | s2cid = 25763746 }}</ref> Though various websites on the internet report that acetazolamide can be used to treat [[dural ectasia]] in individuals with [[Marfan |
In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.<ref name = AMH/><ref>{{cite journal | vauthors = Reiss WG, Oles KS | title = Acetazolamide in the treatment of seizures | journal = The Annals of Pharmacotherapy | volume = 30 | issue = 5 | pages = 514–519 | date = May 1996 | pmid = 8740334 | doi = 10.1177/106002809603000515 | s2cid = 25763746 }}</ref> Though various websites on the internet report that acetazolamide can be used to treat [[dural ectasia]] in individuals with [[Marfan syndrome]], the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication.<ref>{{cite web | vauthors = Ahn NU, Sponseller PD, Ahn UM, Nallamshetty L, Rose P, Buchowski J, Lemma M, Garrett E | date = July 2005 | work = SpineUniverse.com |title= Dural ectasia|url=http://www.spineuniverse.com/displayarticle.php/article922.html|archive-url=https://web.archive.org/web/20070926233505/http://www.spineuniverse.com/displayarticle.php/article922.html|archive-date=26 September 2007}}</ref><ref>{{cite book|date=2020| vauthors = Farzam K, Abdullah M | chapter = Acetazolamide | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK532282/ | pmid = 30335315 }}</ref> Several published cases of intracranial hypotension related to Marfan syndrome would warrant caution in using acetazolamide in these patients unless there is a clear indication, as it could lower intracranial pressure further.<ref>{{cite journal | vauthors = Cheuret E, Edouard T, Mejdoubi M, Acar P, Pienkowski C, Cances C, Lebon S, Tauber M, Chaix Y | title = Intracranial hypotension in a girl with Marfan syndrome: case report and review of the literature | journal = Child's Nervous System | volume = 24 | issue = 4 | pages = 509–513 | date = April 2008 | pmid = 17906865 | doi = 10.1007/s00381-007-0506-3 | s2cid = 5734726 }}</ref> 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]].<ref>{{cite journal | vauthors = Aurora RN, Chowdhuri S, Ramar K, Bista SR, Casey KR, Lamm CI, Kristo DA, Mallea JM, Rowley JA, Zak RS, Tracy SL | title = The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses | journal = Sleep | volume = 35 | issue = 1 | pages = 17–40 | date = January 2012 | pmid = 22215916 | pmc = 3242685 | doi = 10.5665/sleep.1580 }}</ref> |
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It has also been used to prevent [[methotrexate]]-induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in |
It has also been used to prevent [[methotrexate]]-induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine.<ref name = MD/><ref>{{cite journal | vauthors = Shamash J, Earl H, Souhami R | title = Acetazolamide for alkalinisation of urine in patients receiving high-dose methotrexate | journal = Cancer Chemotherapy and Pharmacology | volume = 28 | issue = 2 | pages = 150–151 | date = 1991 | pmid = 2060085 | doi = 10.1007/BF00689708 | s2cid = 375183 }}</ref> There is some evidence to support its use to prevent [[hemiplegic migraine]].<ref>{{cite journal | vauthors = Russell MB, Ducros A | title = Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management | journal = The Lancet. Neurology | volume = 10 | issue = 5 | pages = 457–470 | date = May 2011 | pmid = 21458376 | doi = 10.1016/S1474-4422(11)70048-5 | s2cid = 25823747 }}</ref> |
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=== Open-Angle Glaucoma === |
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Acetazolamide is used in the treatment of open-angle glaucoma. The carbonic anhydrase inhibitor is able to decrease ocular fluid and osmolality of the fluid in the humor of the eye and decrease intraocular pressure in the eye. The medication comes in the form of an oral tablet used for this indication. |
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===High altitude sickness=== |
===High altitude sickness=== |
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Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the [[kidney]]s to reabsorb [[bicarbonate]], the [[conjugate base]] of [[carbonic acid]]. Increasing the amount of bicarbonate excreted in the urine leads to acidification of the blood.<ref name="MD" /> Because the body senses CO<sub>2</sub> concentration indirectly via blood pH (increase in CO<sub>2</sub> causes a decrease in pH), acidifying the blood through decreased renal reabsorption of bicarbonate is sensed as an increase in CO<sub>2</sub>. This, in turn, causes the body to increase minute ventilation (the amount of air breathed per minute) in order to "breathe off" CO<sub>2</sub>, which in turn increases the amount of oxygen in the blood.<ref name="altorg">{{cite web |title=Altitude.org |year=2004 |url=http://www.altitude.org |access-date=2009 |
Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the [[kidney]]s to reabsorb [[bicarbonate]], the [[conjugate base]] of [[carbonic acid]]. Increasing the amount of bicarbonate excreted in the urine leads to acidification of the blood.<ref name="MD" /> Because the body senses CO<sub>2</sub> concentration indirectly via blood pH (increase in CO<sub>2</sub> causes a decrease in pH), acidifying the blood through decreased renal reabsorption of bicarbonate is sensed as an increase in CO<sub>2</sub>. This, in turn, causes the body to increase minute ventilation (the amount of air breathed per minute) in order to "breathe off" CO<sub>2</sub>, which in turn increases the amount of oxygen in the blood.<ref name="altorg">{{cite web |title=Altitude.org |year=2004 |url=http://www.altitude.org |access-date=5 June 2009 |url-status=live |archive-url=https://web.archive.org/web/20090208180452/http://altitude.org/ |archive-date=8 February 2009 }}</ref><ref name="Leaf_2007" /> Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up (or, when taking before traveling, forces the body to early start) part of the [[acclimatization]] process which in turn helps to relieve symptoms.<ref name="Acclimatization">{{cite journal | vauthors = Muza SR, Fulco CS, Cymerman A |title=Altitude Acclimatization Guide |journal=US Army Research Inst. Of Environmental Medicine Thermal and Mountain Medicine Division Technical Report |issue=USARIEM–TN–04–05 |year=2004 |url=http://archive.rubicon-foundation.org/7616 |url-status=usurped |archive-url=https://web.archive.org/web/20090423042451/http://archive.rubicon-foundation.org/7616 |archive-date=23 April 2009 |access-date=5 March 2009 }}</ref> Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for the first two days at altitude.<ref>{{cite web |url=http://who.int/ith/ITH_EN_2012_WEB_1.2.pdf |author=World Health Organization|title=International Travel and Health 2012|access-date=27 January 2017 |url-status=live |archive-url=https://web.archive.org/web/20170319214120/http://who.int/ith/ITH_EN_2012_WEB_1.2.pdf |archive-date=19 March 2017 }}</ref> |
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===Pregnancy and lactation=== |
===Pregnancy and lactation=== |
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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.<ref name = TGA/> Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence.<ref name = TGA/> |
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.<ref name = TGA/> Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence.<ref name = TGA/> |
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Limited data are available on the effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants.<ref>{{cite web|url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+489|publisher=[[National Institutes of Health]]|title=LactMed: Acetazolamide|access-date=2017 |
Limited data are available on the effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants.<ref>{{cite web|url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+489|publisher=[[National Institutes of Health]]|title=LactMed: Acetazolamide|access-date=10 October 2017|url-status=live|archive-url=https://web.archive.org/web/20171011072459/https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+489|archive-date=11 October 2017}}</ref> |
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==Side effects== |
==Side effects== |
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* [[Hypokalemia]] (low blood potassium) |
* [[Hypokalemia]] (low blood potassium) |
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* [[Hyponatremia]] (low blood sodium) |
* [[Hyponatremia]] (low blood sodium) |
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* [[Adrenal insufficiency]] |
* [[Adrenal insufficiency]] |
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* Impaired kidney function |
* Impaired kidney function |
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* Hypersensitivity to acetazolamide or other sulphonamides. |
* Hypersensitivity to acetazolamide or other sulphonamides. |
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It is possible that it might interact with:<ref name = TGA/> |
It is possible that it might interact with:<ref name = TGA/> |
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* [[Amphetamine]]s, because it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines. |
* [[Amphetamine]]s, because it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines. |
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* Other carbonic anhydrase |
* Other carbonic anhydrase inhibitors—potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity. |
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* [[Ciclosporin]], may increase plasma levels of ciclosporin. |
* [[Ciclosporin]], may increase plasma levels of ciclosporin. |
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* [[Antifolate]]s such as [[trimethoprim]], [[methotrexate]], [[pemetrexed]] and [[raltitrexed]]. |
* [[Antifolate]]s such as [[trimethoprim]], [[methotrexate]], [[pemetrexed]] and [[raltitrexed]]. |
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== Mechanism of action == |
== Mechanism of action == |
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[[File:4ITO2.png|thumb|right|250px|Carbonic anhydrase ([[Ribbon diagram|ribbon]]) complex with a sulfonamide inhibitor ([[Ball-and-stick model|ball-and-sticks]]) |
[[File:4ITO2.png|thumb|right|250px|Carbonic anhydrase ([[Ribbon diagram|ribbon]]) complex with a sulfonamide inhibitor ([[Ball-and-stick model|ball-and-sticks]])]] [[File:Proximal_convoluted_tubule.jpg|thumb|250px|Proximal convoluted tubule. Urinary space is on left.]] |
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Acetazolamide is a [[carbonic anhydrase inhibitor]], hence causing the accumulation of [[carbonic acid]].<ref name = MD>{{cite web|title=Acetazolamide|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|date=7 January 2014|access-date=10 April 2014|url=http://www.medicinescomplete.com/mc/martindale/current/ms-2301-x.htm| veditors = Brayfield A }}</ref> Carbonic anhydrase is an enzyme found in [[red blood cells]] and many other tissues that catalyses the following reaction:<ref>{{cite web|title=January 2004: Carbonic Anhydrase|work=RCSB PDB Protein Data Bank|date=January 2004|access-date=10 April 2014|url=http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/download/CarbonicAnhydrase.pdf| vauthors = Dutta S, Goodsell D |url-status=live|archive-url= https://web.archive.org/web/20130514071456/http://rcsb.org/pdb/education_discussion/molecule_of_the_month/download/CarbonicAnhydrase.pdf |archive-date=14 May 2013}}</ref> |
Acetazolamide is a [[carbonic anhydrase inhibitor]], hence causing the accumulation of [[carbonic acid]].<ref name = MD>{{cite web|title=Acetazolamide|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|date=7 January 2014|access-date=10 April 2014|url=http://www.medicinescomplete.com/mc/martindale/current/ms-2301-x.htm| veditors = Brayfield A }}</ref> Carbonic anhydrase is an enzyme found in [[red blood cells]] and many other tissues that catalyses the following reaction:<ref>{{cite web|title=January 2004: Carbonic Anhydrase|work=RCSB PDB Protein Data Bank|date=January 2004|access-date=10 April 2014|url=http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/download/CarbonicAnhydrase.pdf| vauthors = Dutta S, Goodsell D |url-status=live|archive-url= https://web.archive.org/web/20130514071456/http://rcsb.org/pdb/education_discussion/molecule_of_the_month/download/CarbonicAnhydrase.pdf |archive-date=14 May 2013}}</ref> |
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which has a [[Acid dissociation constant|pK<sub>a</sub>]] of 6.3.<ref name = chem>{{cite web|title=Carbonic Anhydrase 2|work=UC Davis Chemwiki|publisher=University of California| vauthors = Larsen D |access-date=10 April 2014|url=http://chemwiki.ucdavis.edu/@api/deki/pages/2479/pdf?stylesheet=default&deep=false&showtoc=false}}</ref> |
which has a [[Acid dissociation constant|pK<sub>a</sub>]] of 6.3.<ref name = chem>{{cite web|title=Carbonic Anhydrase 2|work=UC Davis Chemwiki|publisher=University of California| vauthors = Larsen D |access-date=10 April 2014|url=http://chemwiki.ucdavis.edu/@api/deki/pages/2479/pdf?stylesheet=default&deep=false&showtoc=false}}</ref> |
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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. A general side effect of carbonic anhydrase inhibitors is loss of potassium due to this function. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul breathing), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.<ref name="Leaf_2007">{{cite journal | vauthors = Leaf DE, Goldfarb DS | title = Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness | journal = Journal of Applied Physiology | location = Bethesda, Md. | volume = 102 | issue = 4 | pages = 1313–1322 | date = April 2007 | pmid = 17023566 | doi = 10.1152/japplphysiol.01572.2005 | url = |
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. A general side effect of carbonic anhydrase inhibitors is loss of potassium due to this function. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul breathing), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.<ref name="Leaf_2007">{{cite journal | vauthors = Leaf DE, Goldfarb DS | title = Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness | journal = Journal of Applied Physiology | location = Bethesda, Md. | volume = 102 | issue = 4 | pages = 1313–1322 | date = April 2007 | pmid = 17023566 | doi = 10.1152/japplphysiol.01572.2005 | s2cid = 5873210 | url = https://www.life.illinois.edu/ib/426/handouts/Diamox%20mechanism_review_2007.pdf | access-date = 8 December 2014 | url-status = live | archive-url = https://web.archive.org/web/20141213211909/http://www.life.illinois.edu/ib/426/handouts/Diamox%20mechanism_review_2007.pdf | archive-date = 13 December 2014 }}</ref> |
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In the eye this results in a reduction in [[aqueous humour]].<ref name="TGA" /> |
In the eye this results in a reduction in [[aqueous humour]].<ref name="TGA" /> |
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In short, under normal conditions, the net effect of carbonic anhydrase in the urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate (HCO<sub>3</sub><sup>−</sup>) into the body. Another effect is excretion of Cl<sup>−</sup> as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na<sup>+</sup> into the body. |
In short, under normal conditions, the net effect of carbonic anhydrase in the urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate (HCO<sub>3</sub><sup>−</sup>) into the body. Another effect is excretion of Cl<sup>−</sup> as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na<sup>+</sup> into the body. |
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Thus, by disrupting this process with acetazolamide, urinary Na<sup>+</sup> and bicarbonate (HCO<sub>3</sub><sup>−</sup>) are increased, and urinary H<sup>+</sup> and Cl<sup>−</sup> are decreased. Inversely, serum Na<sup>+</sup> and bicarbonate (HCO<sub>3</sub><sup>−</sup>) are decreased, and serum H<sup>+</sup> and Cl<sup>−</sup> are increased. H<sub>2</sub>O generally follows sodium, and so this is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure.<ref name="pmid19948674">{{cite journal | vauthors = Koeppen BM | title = The kidney and acid-base regulation | journal = Advances in Physiology Education | volume = 33 | issue = 4 | pages = 275–281 | date = December 2009 | pmid = 19948674 | doi = 10.1152/advan.00054.2009 | url = http://d3qpq7e7yxjovl.cloudfront.net/content/ajpadvan/33/4/275 | url-status = dead | archive-url = https://web.archive.org/web/20160420042900/http://d3qpq7e7yxjovl.cloudfront.net/content/ajpadvan/33/4/275 | archive-date = |
Thus, by disrupting this process with acetazolamide, urinary Na<sup>+</sup> and bicarbonate (HCO<sub>3</sub><sup>−</sup>) are increased, and urinary H<sup>+</sup> and Cl<sup>−</sup> are decreased. Inversely, serum Na<sup>+</sup> and bicarbonate (HCO<sub>3</sub><sup>−</sup>) are decreased, and serum H<sup>+</sup> and Cl<sup>−</sup> are increased. H<sub>2</sub>O generally follows sodium, and so this is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure.<ref name="pmid19948674">{{cite journal | vauthors = Koeppen BM | title = The kidney and acid-base regulation | journal = Advances in Physiology Education | volume = 33 | issue = 4 | pages = 275–281 | date = December 2009 | pmid = 19948674 | doi = 10.1152/advan.00054.2009 | url = http://d3qpq7e7yxjovl.cloudfront.net/content/ajpadvan/33/4/275 | url-status = dead | archive-url = https://web.archive.org/web/20160420042900/http://d3qpq7e7yxjovl.cloudfront.net/content/ajpadvan/33/4/275 | archive-date = 20 April 2016 }}</ref> |
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==History== |
==History== |
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== Research == |
== Research == |
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Smaller clinical trials have also shown promising results in the treatment of [[ |
Smaller clinical trials have also shown promising results in the treatment of [[normal pressure hydrocephalus]] (NPH).<ref>{{cite journal | vauthors = Alperin N, Oliu CJ, Bagci AM, Lee SH, Kovanlikaya I, Adams D, Katzen H, Ivkovic M, Heier L, Relkin N | title = Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH | journal = Neurology | volume = 82 | issue = 15 | pages = 1347–1351 | date = April 2014 | pmid = 24634454 | doi = 10.1212/WNL.0000000000000313 | pmc = 4001191 }}</ref><ref>{{cite journal | vauthors = Ivkovic M, Reiss-Zimmermann M, Katzen H, Preuss M, Kovanlikaya I, Heier L, Alperin N, Hoffmann KT, Relkin N | title = MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic normal pressure hydrocephalus | journal = Fluids and Barriers of the CNS | volume = 12 | issue = 1 | pages = 9 | date = April 2015 | pmid = 25928394 | pmc = 4432506 | doi = 10.1186/s12987-015-0004-z | doi-access = free }}</ref><ref>{{cite journal |url=https://n.neurology.org/content/acetazolamide-treatment-normal-pressure-hydrocephalus |title=Acetazolamide in the treatment of Normal Pressure Hydrocephalus | journal = Neurology | vauthors = Gilbert GJ |date=18 May 2022|volume=82 |issue=15 |pages=1347–1351 |doi=10.1212/WNL.0000000000000313 |pmid=24634454 |pmc=4001191 |via=n.neurology.org}}</ref><ref>{{cite journal | vauthors = Aimard G, Vighetto A, Gabet JY, Bret P, Henry E | title = [Acetazolamide: an alternative to shunting in normal pressure hydrocephalus? Preliminary results] | journal = Revue Neurologique | volume = 146 | issue = 6–7 | pages = 437–439 | date = 21 May 1990 | pmid = 2399408 | url = https://pubmed.ncbi.nlm.nih.gov/2399408/ }}</ref><ref>{{ClinicalTrialsGov|NCT03779594|Acetazolamide for Treating NPH in Shunt-candidates Patients: an Open Label Feasibility Trial}}</ref> |
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== References == |
== References == |
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{{reflist}} |
{{reflist}} |
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== External links == |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/acetazolamide | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Acetazolamide }} |
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{{Antiglaucoma preparations and miotics}} |
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[[Category:World Health Organization essential medicines]] |
[[Category:World Health Organization essential medicines]] |
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[[Category:Ophthalmology drugs]] |
Latest revision as of 18:02, 9 December 2024
Clinical data | |
---|---|
Trade names | Diamox, Diacarb, others |
AHFS/Drugs.com | Monograph |
Pregnancy category |
|
Routes of administration | By mouth, intravenous |
Drug class | Carbonic anhydrase inhibitor |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Protein binding | 70–90%[1] |
Metabolism | None[1] |
Elimination half-life | 2–4 hours[1] |
Excretion | Urine (90%)[1] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
PDB ligand | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.400 |
Chemical and physical data | |
Formula | C4H6N4O3S2 |
Molar mass | 222.24 g·mol−1 |
3D model (JSmol) | |
Melting point | 258 to 259 °C (496 to 498 °F) |
| |
| |
(verify) |
Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, acute mountain sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), heart failure and to alkalinize urine.[2][3] It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out.[4] It is taken by mouth or injection into a vein.[2] Acetazolamide is a first generation carbonic anhydrase inhibitor and it decreases the ocular fluid and osmolality in the eye to decrease intraocular pressure.[5][6]
Common side effects include numbness, ringing in the ears, loss of appetite, vomiting, and sleepiness.[2] It is not recommended in those with significant kidney problems, liver problems, or who are allergic to sulfonamides.[2][4] Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication.[2] It works by decreasing the formation of hydrogen ions and bicarbonate from carbon dioxide and water.[2]
Acetazolamide came into medical use in 1952.[7] It is on the World Health Organization's List of Essential Medicines.[8] Acetazolamide is available as a generic medication.[2]
Medical uses
[edit]It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery.[9][10] It has also been used in the treatment of altitude sickness,[11] Ménière's disease, increased intracranial pressure and neuromuscular disorders.[12] Acetazolamide is also used in the critical care setting to stimulate respiratory drive in patients with chronic obstructive pulmonary disease as an off-label indication.[13]
In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.[9][14] Though various websites on the internet report that acetazolamide can be used to treat dural ectasia in individuals with Marfan syndrome, the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication.[15][16] Several published cases of intracranial hypotension related to Marfan syndrome would warrant caution in using acetazolamide in these patients unless there is a clear indication, as it could lower intracranial pressure further.[17] 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.[18]
It has also been used to prevent methotrexate-induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine.[12][19] There is some evidence to support its use to prevent hemiplegic migraine.[20]
High altitude sickness
[edit]Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the kidneys to reabsorb bicarbonate, the conjugate base of carbonic acid. Increasing the amount of bicarbonate excreted in the urine leads to acidification of the blood.[12] Because the body senses CO2 concentration indirectly via blood pH (increase in CO2 causes a decrease in pH), acidifying the blood through decreased renal reabsorption of bicarbonate is sensed as an increase in CO2. This, in turn, causes the body to increase minute ventilation (the amount of air breathed per minute) in order to "breathe off" CO2, which in turn increases the amount of oxygen in the blood.[21][22] Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up (or, when taking before traveling, forces the body to early start) part of the acclimatization process which in turn helps to relieve symptoms.[23] Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for the first two days at altitude.[24]
Pregnancy and lactation
[edit]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.[10] Despite this, there is insufficient evidence from studies in humans to either support or discount this evidence.[10]
Limited data are available on the effects of nursing mothers taking acetazolamide. Therapeutic doses create low levels in breast milk and are not expected to cause problems in infants.[25]
Side effects
[edit]Common adverse effects of acetazolamide include the following: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black stool, polyuria, kidney stones, metabolic acidosis and electrolyte changes (hypokalemia, hyponatremia).[9] Whereas less common adverse effects include Stevens–Johnson syndrome, anaphylaxis and blood dyscrasias.[9]
Contraindications
[edit]Contraindications include:[10]
- Hyperchloremic acidosis
- Hypokalemia (low blood potassium)
- Hyponatremia (low blood sodium)
- Adrenal insufficiency
- Impaired kidney function
- Hypersensitivity to acetazolamide or other sulphonamides.
- Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.
Interactions
[edit]It is possible that it might interact with:[10]
- Amphetamines, because 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 excretion of methenamines.
- Phenytoin, reduces phenytoin excretion, hence increasing the potential for toxicity.
- Primidone, reduces plasma levels of primidone. Hence reducing anticonvulsant effect.
- Quinidine, reduces urinary excretion 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
[edit]Acetazolamide is a carbonic anhydrase inhibitor, hence causing the accumulation of carbonic acid.[12] Carbonic anhydrase is an enzyme found in red blood cells and many other tissues that catalyses the following reaction:[26]
- H2CO3 ⇌ H2O + CO2
hence lowering blood pH, by means of the following reaction that carbonic acid undergoes:[27]
- H2CO3 ⇌ HCO3− + H+
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. A general side effect of carbonic anhydrase inhibitors is loss of potassium due to this function. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul breathing), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.[22]
In the eye this results in a reduction in aqueous humour.[10]
Bicarbonate (HCO3−) has a pKa of 10.3 with carbonate (CO32−), far further from physiologic pH (7.35–7.45), and so it is more likely to accept a proton than to donate one, but it is also far less likely for it to do either, thus bicarbonate will be the major species at physiological pH.
Under normal conditions in the proximal convoluted tubule of the kidney, most of the carbonic acid (H2CO3) produced intracellularly by the action of carbonic anhydrase quickly dissociates in the cell to bicarbonate (HCO3−) and an H+ ion (a proton), as previously mentioned. The bicarbonate (HCO3−) exits at the basal portion of the cell via sodium (Na+) symport and chloride (Cl−) antiport and re-enters circulation, where it may accept a proton if blood pH decreases, thus acting as a weak, basic buffer. The remaining H+ left over from the intracellular production of carbonic acid (H2CO3) exits the apical (urinary lumen) portion of the cell by Na+ antiport, acidifying the urine. There, it may join with another bicarbonate (HCO3−) that dissociated from its H+ in the lumen of the urinary space only after exiting the proximal convoluted kidney cells/glomerulus as carbonic acid (H2CO3) because bicarbonate (HCO3−) itself can not diffuse across the cell membrane in its polar state. This will replenish carbonic acid (H2CO3) so that it then may be reabsorbed into the cell as itself or CO2 and H2O (produced via a luminal carbonic anhydrase). As a result of this whole process, there is a greater net balance of H+ in the urinary lumen than bicarbonate (HCO3−), and so this space is more acidic than physiologic pH. Thus, there is an increased likelihood that any bicarbonate (HCO3−) that was left over in the lumen diffuses back into the cell as carbonic acid, CO2, or H2O.
In short, under normal conditions, the net effect of carbonic anhydrase in the urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate (HCO3−) into the body. Another effect is excretion of Cl− as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na+ into the body.
Thus, by disrupting this process with acetazolamide, urinary Na+ and bicarbonate (HCO3−) are increased, and urinary H+ and Cl− are decreased. Inversely, serum Na+ and bicarbonate (HCO3−) are decreased, and serum H+ and Cl− are increased. H2O generally follows sodium, and so this is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure.[28]
History
[edit]An early description of this compound (as 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide) and its synthesis has been patented.[29]
Research
[edit]Smaller clinical trials have also shown promising results in the treatment of normal pressure hydrocephalus (NPH).[30][31][32][33][34]
References
[edit]- ^ a b c d "Diamox Sequels (acetazolamide) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 10 April 2014.
- ^ a b c d e f g "Acetazolamide". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
- ^ Smith SV, Friedman DI (September 2017). "The Idiopathic Intracranial Hypertension Treatment Trial: A Review of the Outcomes". Headache. 57 (8): 1303–1310. doi:10.1111/head.13144. PMID 28758206. S2CID 13909867.
- ^ a b World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 439. hdl:10665/44053. ISBN 9789241547659.
- ^ Scozzafava A, Supuran CT (2014). "Glaucoma and the Applications of Carbonic Anhydrase Inhibitors". Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications. Subcellular Biochemistry. Vol. 75. Springer. pp. 349–359. doi:10.1007/978-94-007-7359-2_17. ISBN 978-94-007-7358-5. PMID 24146387.
- ^ "Acetazolamide: mechanism of action". www.openanesthesia.org. Retrieved 10 May 2017.
- ^ Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 390. ISBN 9780471899792. Archived from the original on 28 December 2016.
- ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
- ^ a b c d Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- ^ a b c d e f "Product Information Diamox Acetazolamide Tablets" (PDF). TGA eBusiness Services. Aspen Pharma Pty Ltd. 25 February 2005. Archived from the original on 4 November 2016. Retrieved 10 April 2014.
- ^ Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP (October 2012). "Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis". BMJ. 345: e6779. doi:10.1136/bmj.e6779. PMC 3475644. PMID 23081689.
- ^ a b c d Brayfield A, ed. (7 January 2014). "Acetazolamide". Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 10 April 2014.
- ^ Heming N, Urien S, Faisy C (August 2012). "Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit?". Critical Care. 16 (4): 318. doi:10.1186/cc11323. PMC 3580678. PMID 22866939.
- ^ Reiss WG, Oles KS (May 1996). "Acetazolamide in the treatment of seizures". The Annals of Pharmacotherapy. 30 (5): 514–519. doi:10.1177/106002809603000515. PMID 8740334. S2CID 25763746.
- ^ Ahn NU, Sponseller PD, Ahn UM, Nallamshetty L, Rose P, Buchowski J, et al. (July 2005). "Dural ectasia". SpineUniverse.com. Archived from the original on 26 September 2007.
- ^ Farzam K, Abdullah M (2020). "Acetazolamide". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID 30335315.
- ^ Cheuret E, Edouard T, Mejdoubi M, Acar P, Pienkowski C, Cances C, et al. (April 2008). "Intracranial hypotension in a girl with Marfan syndrome: case report and review of the literature". Child's Nervous System. 24 (4): 509–513. doi:10.1007/s00381-007-0506-3. PMID 17906865. S2CID 5734726.
- ^ Aurora RN, Chowdhuri S, Ramar K, Bista SR, Casey KR, Lamm CI, et al. (January 2012). "The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses". Sleep. 35 (1): 17–40. doi:10.5665/sleep.1580. PMC 3242685. PMID 22215916.
- ^ Shamash J, Earl H, Souhami R (1991). "Acetazolamide for alkalinisation of urine in patients receiving high-dose methotrexate". Cancer Chemotherapy and Pharmacology. 28 (2): 150–151. doi:10.1007/BF00689708. PMID 2060085. S2CID 375183.
- ^ Russell MB, Ducros A (May 2011). "Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management". The Lancet. Neurology. 10 (5): 457–470. doi:10.1016/S1474-4422(11)70048-5. PMID 21458376. S2CID 25823747.
- ^ "Altitude.org". 2004. Archived from the original on 8 February 2009. Retrieved 5 June 2009.
- ^ a b Leaf DE, Goldfarb DS (April 2007). "Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness" (PDF). Journal of Applied Physiology. 102 (4). Bethesda, Md.: 1313–1322. doi:10.1152/japplphysiol.01572.2005. PMID 17023566. S2CID 5873210. Archived (PDF) from the original on 13 December 2014. Retrieved 8 December 2014.
- ^ Muza SR, Fulco CS, Cymerman A (2004). "Altitude Acclimatization Guide". US Army Research Inst. Of Environmental Medicine Thermal and Mountain Medicine Division Technical Report (USARIEM–TN–04–05). Archived from the original on 23 April 2009. Retrieved 5 March 2009.
{{cite journal}}
: CS1 maint: unfit URL (link) - ^ World Health Organization. "International Travel and Health 2012" (PDF). Archived (PDF) from the original on 19 March 2017. Retrieved 27 January 2017.
- ^ "LactMed: Acetazolamide". National Institutes of Health. Archived from the original on 11 October 2017. Retrieved 10 October 2017.
- ^ Dutta S, Goodsell D (January 2004). "January 2004: Carbonic Anhydrase" (PDF). RCSB PDB Protein Data Bank. Archived (PDF) from the original on 14 May 2013. Retrieved 10 April 2014.
- ^ a b Larsen D. "Carbonic Anhydrase 2". UC Davis Chemwiki. University of California. Retrieved 10 April 2014.
- ^ Koeppen BM (December 2009). "The kidney and acid-base regulation". Advances in Physiology Education. 33 (4): 275–281. doi:10.1152/advan.00054.2009. PMID 19948674. Archived from the original on 20 April 2016.
- ^ US 2554816, Clapp Jr JW, Roblin RO, "Heterocyclic sulfonamides and metyhods of preparation thereof", published 1951-05-29, assigned to American Cyanamid Company
- ^ Alperin N, Oliu CJ, Bagci AM, Lee SH, Kovanlikaya I, Adams D, et al. (April 2014). "Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH". Neurology. 82 (15): 1347–1351. doi:10.1212/WNL.0000000000000313. PMC 4001191. PMID 24634454.
- ^ Ivkovic M, Reiss-Zimmermann M, Katzen H, Preuss M, Kovanlikaya I, Heier L, et al. (April 2015). "MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic normal pressure hydrocephalus". Fluids and Barriers of the CNS. 12 (1): 9. doi:10.1186/s12987-015-0004-z. PMC 4432506. PMID 25928394.
- ^ Gilbert GJ (18 May 2022). "Acetazolamide in the treatment of Normal Pressure Hydrocephalus". Neurology. 82 (15): 1347–1351. doi:10.1212/WNL.0000000000000313. PMC 4001191. PMID 24634454 – via n.neurology.org.
- ^ Aimard G, Vighetto A, Gabet JY, Bret P, Henry E (21 May 1990). "[Acetazolamide: an alternative to shunting in normal pressure hydrocephalus? Preliminary results]". Revue Neurologique. 146 (6–7): 437–439. PMID 2399408.
- ^ Clinical trial number NCT03779594 for "Acetazolamide for Treating NPH in Shunt-candidates Patients: an Open Label Feasibility Trial" at ClinicalTrials.gov