Carbonic anhydrase inhibitors
Encyclopedia
Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress
the activity of carbonic anhydrase
. Their clinical use has been established as antiglaucoma
agents, diuretics, antiepileptics, in the management of mountain sickness
, gastric and duodenal ulcers
, neurological disorders, or osteoporosis
.
is an inhibitor of carbonic anhydrase
. It is used for glaucoma, epilepsy
(rarely), idiopathic intracranial hypertension
, and altitude sickness
. It can act as a mild diuretic by reducing NaCl and bicarbonate reabsorption in the proximal tubule. However, the distal segment partially compensates for the sodium loss, and the bicarbonaturia will produce a metabolic acidosis, further reducing the effect.
Methazolamide
is also a carbonic anhydrase inhibitor. It has a longer elimination half-life than acetazolamide and is less associated with adverse effects to the kidney
.
Dorzolamide
is a sulfonamide)
and topical carbonic anhydrase II inhibitor. It is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension
and who are insufficiently responsive to beta-blockers. Inhibition of carbonic anhydrase II in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.
Topiramate
is a weak inhibitor of carbonic anhydrase, particularly subtypes II and IV. It is a sulfamate-substituted monosaccharide
, related to fructose
. In the US, it is approved by the U.S. Food and Drug Administration (FDA) as an anticonvulsant
to treat epilepsy
and Lennox-Gastaut syndrome
, and also to treat migraine
headaches. In rare cases, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis
of clinical importance.
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
the activity of 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...
. Their clinical use has been established as antiglaucoma
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...
agents, diuretics, antiepileptics, in the management of mountain sickness
Mountain sickness
Mountain sickness can refer to:* Altitude sickness or acute mountain sickness, a pathological condition that is caused by acute exposure to low air pressure* Chronic mountain sickness, a disease that can develop during extended time living at altitude...
, gastric and duodenal ulcers
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
, neurological disorders, or osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
.
Types
AcetazolamideAcetazolamide
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...
is an inhibitor of 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...
. It is used for glaucoma, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
(rarely), 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 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...
. It can act as a mild diuretic by reducing NaCl and bicarbonate reabsorption in the proximal tubule. However, the distal segment partially compensates for the sodium loss, and the bicarbonaturia will produce a metabolic acidosis, further reducing the effect.
Methazolamide
Methazolamide
Methazolamide is a carbonic anhydrase inhibitor....
is also a carbonic anhydrase inhibitor. It has a longer elimination half-life than acetazolamide and is less associated with adverse effects to 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...
.
Dorzolamide
Dorzolamide
Dorzolamide is a carbonic anhydrase inhibitor. It is an anti-glaucoma agent and topically applied in the form of eye drops. This drug, developed by Merck, was the first drug in human therapy which resulted from structure-based drug design...
is a sulfonamide)
Sulfonamide (medicine)
Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
and topical carbonic anhydrase II inhibitor. It is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension
Ocular hypertension
Ocular hypertension is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss.Current consensus in ophthalmology defines normal introcular pressure as that between 10 mmHg and 21 mmHg...
and who are insufficiently responsive to beta-blockers. Inhibition of carbonic anhydrase II in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.
Topiramate
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
is a weak inhibitor of carbonic anhydrase, particularly subtypes II and IV. It is a sulfamate-substituted monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
, related to fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
. In the US, it is approved by the U.S. Food and Drug Administration (FDA) as an anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
to treat epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
and Lennox-Gastaut syndrome
Lennox-Gastaut syndrome
Lennox–Gastaut syndrome , also known as Lennox syndrome, is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life, and is characterized by frequent seizures and different seizure types; it is often accompanied by developmental delay...
, and also to treat migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
headaches. In rare cases, the inhibition of carbonic anhydrase may be strong enough to cause 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...
of clinical importance.