Acetazolamide
Encyclopedia
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma
, epileptic seizures, Idiopathic intracranial hypertension
(pseudotumor cerebri), altitude sickness
, cystinuria
, and dural ectasia
. Acetazolamide is available as a generic drug
and is also a diuretic
.
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:
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 serum. 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 convulated tubules of kidney) resulting in a mild diuresis. 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. This effect can also be used for therapeutic correction of alkalosis seen in altitude sickness or other forms of respiratory alkalosis
.
. Acetazolamide decreases the formation of aqueous humor in the human eye
, resulting in lower intraocular pressure.
s and myoclonic seizures. It can be used in both episodic ataxia
types 1 and 2 (although the mechanisms are presumed to be different between the two).
In catamential epilepsy, an increase in seizure frequency around menses, acetazolamide can be an adjunct to an anti-seizure medication regimen to aid in decreasing seizure frequency around menses.
Acetazolamide is also used to decrease the production of cerebrospinal fluid
in idiopathic intracranial hypertension
and has shown efficacy in some forms of periodic paralysis
.
in individuals with Marfan's Syndrome.
by lowering blood pH and encourage respiration.
acetazolamide is sometimes taken prophylactically, anywhere between 125 milligrams (mg) to 1000 mg per day, starting a few days before going to higher altitudes. Such use is recommended for those ascending from sea level to 3000 meters (9800 feet) in one day, or for those ascending more than 600 meters (2000 feet) per day once above an altitude of 2500 meters (8200 feet). Also, prophylactic use is recommended for those with a significant history of acute mountain sickness.
Acetazolamide
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 increases the amount of oxygen in the blood. At high altitudes, climbers hyperventilate in response to lower oxygen levels. The hyperventilation results in reduced carbon dioxide (an acid) and a respiratory alkalosis
. The normal physiologic response to a respiratory alkalosis is for the kidneys to increase excretion of bicarbonate (a base) to compensate for the loss of carbon dioxide. This kidney response takes a few days, however acetazolamide in a sense accelerates this process by leading to a more rapid renal bicarbonate loss (metabolic acidosis
).
Note that acetazolamide is not an immediate fix for acute mountain sickness; it speeds up part of the acclimatization
process 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 to a lower elevation is considered to be mandatory unless other circumstances present greater danger.
Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of Acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.
Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from inhibitory effect of the therapeutic agent.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
of using this drug include numbness and tingling
in the fingers and toes, and taste
alterations (parageusia
), especially for carbonated drinks. Some may also experience blurred 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. Acetazolamide also causes metabolic acidosis
.
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, epileptic seizures, Idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension , sometimes called by the older names benign intracranial hypertension or pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases...
(pseudotumor cerebri), altitude sickness
Altitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...
, cystinuria
Cystinuria
Cystinuria is an inherited autosomal recessive disease that is characterized by the formation of cystine stones in the kidneys, ureter, and bladder.-Signs and symptoms:Cystinuria is a cause of persistent kidney stones...
, and dural ectasia
Dural ectasia
Dural ectasia is a widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level. It is one of the major manifestations of Marfan syndrome. It may cause low back pain, headaches and neurological signs such as weakness and loss of bowel and bladder function,...
. Acetazolamide is available as a generic drug
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
and is also a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
.
Mechanism of action
Acetazolamide is a carbonic anhydrase inhibitor. Medically it may be used to treat conditions of moderate to severe metabolic or respiratory alkalosis. It does this by interfering with bicarbonate (HCO3-) resorption in the kidneys, thereby re-acidifying the blood (and thus alkalinizing the urine).Carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
(CA) catalyzes the first part of the following reversible reaction
Reversible reaction
A reversible reaction is a chemical reaction that results in an equilibrium mixture of reactants and products. For a reaction involving two reactants and two products this can be expressed symbolically as...
, in which carbon dioxide (CO2) and water (H2O) are converted to carbonic acid (H2CO3) and vice-versa:
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 serum. 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 convulated tubules of kidney) resulting in a mild diuresis. 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. This effect can also be used for therapeutic correction of alkalosis seen in altitude sickness or other forms of respiratory alkalosis
Respiratory alkalosis
Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH...
.
Glaucoma
Acetazolamide has been used for the treatment of suffers of glaucomaGlaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
. Acetazolamide decreases the formation of aqueous humor in the human eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
, resulting in lower intraocular pressure.
Neurologic
In epilepsy, its main use is in absence seizureAbsence seizure
Absence seizures are one of several kinds of seizures. These seizures are sometimes referred to as petit mal seizures ....
s and myoclonic seizures. It can be used in both episodic ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
types 1 and 2 (although the mechanisms are presumed to be different between the two).
In catamential epilepsy, an increase in seizure frequency around menses, acetazolamide can be an adjunct to an anti-seizure medication regimen to aid in decreasing seizure frequency around menses.
Acetazolamide is also used to decrease the production of cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
in idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension , sometimes called by the older names benign intracranial hypertension or pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases...
and has shown efficacy in some forms of periodic paralysis
Periodic paralysis
Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind...
.
Marfan's syndrome
It's been demonstrated in drug trials to relieve symptoms associated with dural ectasiaDural ectasia
Dural ectasia is a widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level. It is one of the major manifestations of Marfan syndrome. It may cause low back pain, headaches and neurological signs such as weakness and loss of bowel and bladder function,...
in individuals with Marfan's Syndrome.
Central sleep apnea
Off-label uses include acetazolamide as a conjunction drug to merely assist patients with central sleep apneaSleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
by lowering blood pH and encourage respiration.
Acute mountain sickness
To reduce the incidence of Acute Mountain SicknessAltitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...
acetazolamide is sometimes taken prophylactically, anywhere between 125 milligrams (mg) to 1000 mg per day, starting a few days before going to higher altitudes. Such use is recommended for those ascending from sea level to 3000 meters (9800 feet) in one day, or for those ascending more than 600 meters (2000 feet) per day once above an altitude of 2500 meters (8200 feet). Also, prophylactic use is recommended for those with a significant history of acute mountain sickness.
Acetazolamide
Acetazolamide
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...
forces the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s to excrete bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
, the conjugate base of carbonic acid
Carbonic acid
Carbonic acid is the inorganic compound with the formula H2CO3 . It is also a name sometimes given to solutions of carbon dioxide in water, because such solutions contain small amounts of H2CO3. Carbonic acid forms two kinds of salts, the carbonates and the bicarbonates...
. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. Acidifying the blood stimulates ventilation, which increases the amount of oxygen in the blood. At high altitudes, climbers hyperventilate in response to lower oxygen levels. The hyperventilation results in reduced carbon dioxide (an acid) and a respiratory alkalosis
Respiratory alkalosis
Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH...
. The normal physiologic response to a respiratory alkalosis is for the kidneys to increase excretion of bicarbonate (a base) to compensate for the loss of carbon dioxide. This kidney response takes a few days, however acetazolamide in a sense accelerates this process by leading to a more rapid renal bicarbonate loss (metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
).
Note that acetazolamide is not an immediate fix for acute mountain sickness; it speeds up part of the acclimatization
Acclimatization
Acclimatisation or acclimation is the process of an individual organism adjusting to a gradual change in its environment, allowing it to maintain performance across a range of environmental conditions...
process 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 to a lower elevation is considered to be mandatory unless other circumstances present greater danger.
Congestive Heart Failure
For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (five mg per kg). If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day.Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of Acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.
Drug-Induced Edema
Recommended dosage is 250 to 375 mg of Acetazolamide once a day for one or two days, alternating with a day of rest.Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from inhibitory effect of the therapeutic agent.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Side-effects
Common side effectsAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
of using this drug include numbness and tingling
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
in the fingers and toes, and taste
Taste
Taste is one of the traditional five senses. It refers to the ability to detect the flavor of substances such as food, certain minerals, and poisons, etc....
alterations (parageusia
Parageusia
Parageusia is the medical term for a bad taste in the mouth.One common form of parageusia is a metallic taste of food. This can be a side effect of several medications, such as acetazolamide, eszopiclone, zopiclone, metronidazole, or etoposide....
), especially for carbonated drinks. Some may also experience blurred vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
but this usually disappears shortly after stopping the medication. Acetazolamide also increases the risk of developing calcium oxalate
Calcium oxalate
Calcium oxalate is a chemical compound that forms needle-shaped crystals, known in plants as raphides. A major constituent of human kidney stones, the chemical is also found in beerstone, a scale that forms on containers used in breweries...
and calcium phosphate kidney stones. Everyone will experience more frequent urination
Urination
Urination, also known as micturition, voiding, peeing, weeing, pissing, and more rarely, emiction, is the ejection of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urination is under voluntary control...
as a result of using acetazolamide. One should drink more fluids than usual to prevent dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s. Acetazolamide prolongs the effects of amphetamines and related drugs. Acetazolamide also causes metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
.
Contraindications
Acetazolamide should not be taken by individuals if:- They have sickle cell anemia
- They are allergic to sulfa medications
- They are allergic to any carbonic anhydrase inhibitor
- They have liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
or kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
disease - They have adrenal glandAdrenal glandIn mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
failure (i.e. Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
) - They are pregnant or are nursing mothers