Acetazolamide (extended-release capsule): Difference between revisions

Revision as of 21:02, 25 February 2014

Acetazolamide
DIAMOX SEQUELS^® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Acetazolamide
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

For patient information about Acetazolamide, click here. Synonyms / Brand Names: DIAMOX SEQUELS^®

Overview

Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, benign intracranial hypertension, altitude sickness, cystinuria, and dural ectasia. Acetazolamide is available as a generic drug and is also used as a diuretic.

FDA Package Insert

DIAMOX SEQUELS (acetazolamide) capsule, extended release

Mechanism of Action

Acetazolamide is a carbonic anhydrase inhibitor. It can be used for the medical treatment of moderate to severe metabolic or respiratory alkalosis. Acetazolamide does this by interfering with bicarbonate (HCO₃^-) reabsorption in the kidneys, thereby reacidifying the blood – hence alkalyzing the urine.

Carbonic anhydrase (CA) catalyzes the first part of the following reversible reaction in which carbon dioxide (CO₂) and water (H₂O) are converted to carbonic acid (H₂CO₃) and vice-versa (the second half happens spontaneously, favouring production of H⁺ + HCO₃^-):

CO₂ + H₂O <--^CA--> H₂CO₃ <--> H⁺ + HCO₃^-

In the kidney tubules, locally secreted hydrogen ions normally combine with filtered bicarbonate (HCO₃^-) to form carbonic acid (H₂CO₃). Carbonic acid in turn is normally acted upon by carbonic anhydrase, leading to formation of CO₂. As CO₂ rapidly leaves the tubules by diffusing across cell membranes, the above reaction normally runs shifted strongly to the left (i.e. reversed), and more bicarbonate can be continuously reabsorbed from the preurine. However, in the presence of acetazolamide, carbonic anhydrase is inhibited and carbonic acid levels build up. The inhibition of carbonic anhydrase in turn leads to a slowing of the reverse reaction and a decrease in the body's ability to reabsorb serum bicarbonate, resulting in urinary bicarbonate wasting. This leads to a decreased ability to exchange Na⁺ for H⁺ in the presence of acetazolamide (in proximal convoluted tubules of kidney) resulting in a mild diuresis.^[1] By contrast, the H⁺ that is also present in the lumen is reabsorbed via an alternative pathway along with Cl^-; it then passes into the bloodstream, leading to hyperchloremic metabolic acidosis.^[2] This effect can also be used for therapeutic correction of alkalosis seen in altitude sickness or other forms of respiratory alkalosis.

References

↑ Lippincott's Illustrated Reviews: Pharmacology, 4th edition page 428
↑ Renal and Electrolyte Disorders Schrier 1976: page 89

Template:Anticonvulsants Template:Antiglaucoma preparations and miotics Template:Diuretics

[1] Lippincott's Illustrated Reviews: Pharmacology, 4th edition page 428

[2] Renal and Electrolyte Disorders Schrier 1976: page 89

[1]

[2]

@@ Line 1: / Line 1: @@
-{{Drugbox|
+__NOTOC__
-|IUPAC_name = ''N''-(5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl)-acetamide
-| image = Acetazolamide skeletal.svg
-| image2 = Acetazolamide 3D.png
-| CAS_number=59-66-5
-| ATC_prefix=S01
-| ATC_suffix=EC01
-| ATC_supplemental=
-| PubChem=1986
-| DrugBank=APRD00119
-| C = 4 | H = 6 | N = 4 | O = 3 | S = 2
-| molecular_weight = 222.248 g/mol
-| bioavailability=
-| metabolism = None
-| elimination_half-life=3 to 9 hours
-| excretion = [[Kidney|Renal]]
-| pregnancy_AU = B3
-| pregnancy_US = C
-| legal_US = Rx-only
-| legal_UK = POM
-| routes_of_administration= Oral, [[Intravenous therapy|IV]]
-}}
-{{SI}}
-{{CMG}}
+{{Acetazolamide}}
+{{CMG}}; {{AE}} {{SS}}
+'''''For patient information about Acetazolamide, click [[Acetazolamide (patient information)|here]].'''''
+{{SB}} DIAMOX SEQUELS<sup>®</sup>
+==Overview==
-==Overview==
 '''Acetazolamide''', sold under the trade name '''Diamox''', is a [[carbonic anhydrase]] inhibitor that is used to treat [[glaucoma]], [[epileptic seizure]]s, [[benign intracranial hypertension]], [[altitude sickness]], [[cystinuria]], and dural ectasia. Acetazolamide is available as a [[generic drug]] and is also used as a [[diuretic]].
+==Category==
-==Uses==
+Carbonic anhydrase inhibitors;Mountaineering and health;Anticonvulsants;Sulfonamides;World Health Organization essential
+medicines;Thiadiazoles;Amides;Cardiovascular Drugs
-===General===
+==FDA Package Insert==
-Acetazolamide is often used in the treatment of various diseases. For glaucoma sufferers, the drug decreases fluid formation in the [[eye]] resulting in lower intraocular pressure.  In epilepsy, its main use is in [[absence seizure]]s, with some benefit in other seizure syndromes. It is also used to decrease generation of [[cerebrospinal fluid]] in [[benign intracranial hypertension]] and has also shown efficacy in autosomal dominant hyperkalemic periodic paralysis.  It has also been demonstrated in drug trials to relieve symptoms associated with dural ectasia in indivduals with [[Marfan Syndrome]].
+====DIAMOX SEQUELS (acetazolamide) capsule, extended release====
-===Acute mountain sickness ===
+'''  [[Acetazolamide indications and usage|Indications and Usage]]'''
+'''| [[Acetazolamide dosage and administration|Dosage and Administration]]'''
+'''| [[Acetazolamide dosage forms and strengths|Dosage Forms and Strengths]]'''
+'''| [[Acetazolamide contraindications|Contraindications]]'''
+'''| [[Acetazolamide warnings and precautions|Warnings and Precautions]]'''
+'''| [[Acetazolamide adverse reactions|Adverse Reactions]]'''
+'''| [[Acetazolamide drug interactions|Drug Interactions]]'''
+'''| [[Acetazolamide use in specific populations|Use in Specific Populations]]'''
+'''| [[Acetazolamide overdosage|Overdosage]]'''
+'''| [[Acetazolamide description|Description]]'''
+'''| [[Acetazolamide clinical pharmacology|Clinical Pharmacology]]'''
+'''| [[Acetazolamide nonclinical toxicology|Nonclinical Toxicology]]'''
+'''| [[Acetazolamide clinical studies|Clinical Studies]]'''
+'''| [[Acetazolamide how supplied storage and handling|How Supplied/Storage and Handling]]'''
+'''| [[Acetazolamide patient counseling information|Patient Counseling Information]]'''
+'''| [[Acetazolamide labels and packages|Labels and Packages]]'''
-Acetazolamide is best taken [[prophylaxis|prophylactically]], anywhere between 125 milligrams (mg) to 500 mg per day, starting a few days before going to the higher altitude.  The drug forces the [[kidney]]s to excrete [[bicarbonate]], the [[conjugate base]] of [[carbonic acid]]. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. Acidifying the blood stimulates ventilation, which is beneficial during acclimatization.  Others only take it when [[symptom]]s begin to appear so they can tell whether the drug really has any benefits for them. Whereas some people have reported that it relieves mild cases of acute mountain sickness, it is best taken prophylactically.
+==Mechanism of Action==
+Acetazolamide is a [[carbonic anhydrase inhibitor]]. It can be used for the medical treatment of moderate to severe metabolic or respiratory alkalosis. Acetazolamide does this by interfering with [[bicarbonate]] (HCO<sub>3</sub><sup>-</sup>) reabsorption in the [[kidney]]s, thereby reacidifying the blood – hence [[alkali|alkalyzing]] the urine.
-Note that acetazolamide is not an immediate fix for acute mountain sickness; it speeds up [[acclimatization]] which in turn helps to relieve symptoms.  This may take up to a day or two, and requires waiting without any further rapid ascent.  It is often advisable to descend if even mild acute mountain sickness is experienced.  If serious sickness is encountered, descent is considered mandatory unless other circumstances present greater danger.
+[[Carbonic anhydrase]] (CA) catalyzes the first part of the following [[reversible reaction]] in which carbon dioxide (CO<sub>2</sub>) and water (H<sub>2</sub>O) are converted to carbonic acid (H<sub>2</sub>CO<sub>3</sub>) and vice-versa (the second half happens spontaneously, favouring production of H<sup>+</sup> + HCO<sub>3</sub><sup>-</sup>):
-==Side-effects==
+CO<sub>2</sub> + H<sub>2</sub>O <--<sup>CA</sup>--> H<sub>2</sub>CO<sub>3</sub>  <--> H<sup>+</sup> + HCO<sub>3</sub><sup>-</sup>
-Common [[Adverse drug reaction|side effects]] of using this drug include [[paresthesia|numbness and tingling]] in the fingers and toes, and [[taste]] alterations ([[parageusia]]), especially for carbonated drinks; both are usually due to mild [[hypokalemia]] (low [[potassium]] levels). Some may also experience blurred [[Visual perception|vision]] but this usually disappears shortly after stopping the medication.  Acetazolamide also increases the risk of developing calcium oxalate and calcium phosphate kidney stones. Everyone will experience more frequent [[urination]] as a result of using acetazolamide. One should drink more fluids than usual to prevent [[dehydration]] and [[headache]]s. Acetazolamide prolongs the effects of amphetamines and related drugs.
+In the kidney tubules, locally secreted hydrogen ions normally combine with [[Renal_physiology#Filtration|filtered]] bicarbonate (HCO<sub>3</sub><sup>-</sup>) to form carbonic acid (H<sub>2</sub>CO<sub>3</sub>). Carbonic acid in turn is normally acted upon by carbonic anhydrase, leading to formation of CO<sub>2</sub>. As CO<sub>2</sub> rapidly leaves the tubules by diffusing across cell membranes, the above reaction normally runs shifted strongly to the left (i.e. reversed), and more bicarbonate can be continuously reabsorbed from the preurine. However, in the presence of acetazolamide, carbonic anhydrase is inhibited and carbonic acid levels build up. The inhibition of carbonic anhydrase in turn leads to a slowing of the reverse reaction and a decrease in the body's ability to reabsorb serum bicarbonate, resulting in urinary bicarbonate wasting. This leads to a decreased ability to exchange Na<sup>+</sup> for H<sup>+</sup> in the presence of acetazolamide (in proximal convoluted tubules of kidney) resulting in a mild diuresis.<ref>Lippincott's Illustrated Reviews: Pharmacology, 4th edition page 428</ref> By contrast, the H<sup>+</sup> that is also present in the lumen is reabsorbed via an alternative pathway along with Cl<sup>-</sup>; it then passes into the bloodstream, leading to hyperchloremic metabolic acidosis.<ref>Renal and Electrolyte Disorders Schrier 1976: page 89</ref> This effect can also be used for therapeutic correction of alkalosis seen in altitude sickness or other forms of [[respiratory alkalosis]].
-==Contraindications==
-Acetazolamide should not be taken by individuals if:
-* They have [[sickle cell anemia]]
-* They are [[allergic]] to [[sulfa drug|sulfa]] medications
-* They are allergic to any carbonic anhydrase inhibitor
-* They have [[liver]] or [[kidney]] disease
-* They have [[adrenal gland]] failure (i.e. [[Addison's disease]])
-* They have [[diabetes]]
-* They are pregnant or nursing mothers
-==Myths Regarding the use of Acetazolamide in Patients with Mountain Sickness==
-===Acetazolamide covers up symptoms===
-Not so: Acetazolamide speeds up acclimatization which in turn helps to alleviate symptoms. However, if you still feel sick, you need to stop ascending immediately.
-===Acetazolamide prevents acute mountain sickness from getting worse===
-Not so: If your symptoms are not improving, continued ascent can lead to [[HAPE]] or [[HACE]].
-===Stopping the drug causes symptoms to worsen===
-Not so: Your body will just return to its own acclimatization rate. If you are already acclimatized, the drug will not change that fact.
 ==References==
+{{reflist|2}}
-* ''Going Higher: Oxygen Man and Mountains'' by Charles Houston, M.D., Fifth Edition, 2005. ISBN 0-89886-631-6.
+{{Anticonvulsants}}
-* ''Complete Guide to Prescription & Non-Prescription Drugs'' by H. Winter Griffen, M.D., Sixth edition, 1989. ISBN 0-89586-754-0.
+{{Antiglaucoma preparations and miotics}}
-* http://www.ismmed.org/np_altitude_tutorial.htm
+{{Diuretics}}
-* ''Dural Ectasia in the Marfan Spine: Symptoms and Treatment.'' November 27, 2006. http://www.spineuniverse.com/displayarticle.php/article922.html
-* ''Diamox - Quoted from the Physician's Desk Reference 1993'' http://www.climber.org/gear/diamox.html
 [[Category:Carbonic anhydrase inhibitors]]
-[[Category:Mountaineering]]
+[[Category:Mountaineering and health]]
 [[Category:Anticonvulsants]]
 [[Category:Sulfonamides]]
-{{Anticonvulsants}}
+[[Category:World Health Organization essential medicines]]
-{{Antiglaucoma preparations and miotics}}
+[[Category:Thiadiazoles]]
+[[Category:Amides]]
-[[ja:アセタゾラミド]]
+[[Category:Cardiovascular Drugs]]
-[[pl:Acetazolamid]]
+[[Category:Drugs]]
-[[pt:Acetazolamida]]
-[[ro:Acetazolamidă]]
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