Carbachol
Encyclopedia
Carbachol also known as carbamylcholine, is a drug
that binds and activates the acetylcholine receptor
. Thus it is classified as a cholinergic agonist
. It is primarily used for various ophthalmic
purposes, such as for treating glaucoma
, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e. eyedrops).
carbamate
and a positively charged quaternary ammonium compound. It is not well absorbed in the gastro-intestinal tract and does not cross the blood-brain barrier
. It is usually administered topical ocular or through intraocular injection. Carbachol is not easily metabolized by cholinesterase
, it has a two to 5 minute onset of action and its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration, benzalkonium chloride
is mixed in to promote absorption.
Carbachol is a parasympathomimetic that stimulates
both muscarinic
and nicotinic
receptors. In topical ocular and intraocular administration its principal effects are miosis
and increased aqueous humour
outflow.
In the cat
and rat
, carbachol is well-known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular
formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic
receptors (mAChRs).
, but it is also used during ophthalmic surgery. Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils during cataract
surgery.
Topical ocular administration is used to decrease intraocular pressure in people with primary open-angle glaucoma
. Intracellular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying if the normal emptying mechanism is not working properly.
In most countries carbachol is only available by prescription.
, is contraindicated in patients with asthma
, coronary insufficiency
, gastroduodenal ulcers
, and incontinence
. The parasympathomimetic action of this drug will exacerbate the symptoms of these disorders.
(they both act on the cholinergic system, increasing cholinergic transmission), but its toxicity is much weaker and it is easier to antagonize in overdose. When administered ocularly there is little risk of such effects, since the doses are much smaller (see topical vs systemic administration).
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
that binds and activates the acetylcholine receptor
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...
. Thus it is classified as a cholinergic agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. It is primarily used for various ophthalmic
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
purposes, such as for treating glaucoma
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...
, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e. eyedrops).
Chemistry and pharmacology
Carbachol is a cholineCholine
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
carbamate
Carbamate
Carbamates are organic compounds derived from carbamic acid . A carbamate group, carbamate ester, and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.-Synthesis:Carbamic acids are derived...
and a positively charged quaternary ammonium compound. It is not well absorbed in the gastro-intestinal tract and does not cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. It is usually administered topical ocular or through intraocular injection. Carbachol is not easily metabolized by cholinesterase
Cholinesterase
In biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...
, it has a two to 5 minute onset of action and its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration, benzalkonium chloride
Benzalkonium chloride
Benzalkonium chloride, also known as alkyldimethylbenzylammonium chloride and ADBAC, is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered alkyl chain lengths. This product is a nitrogenous cationic surface-acting agent belonging to the quaternary ammonium group...
is mixed in to promote absorption.
Carbachol is a parasympathomimetic that stimulates
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
both muscarinic
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
and nicotinic
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
receptors. In topical ocular and intraocular administration its principal effects are miosis
Miosis
Miosis is the constriction of the pupil of the eye to two millimeters or less...
and increased aqueous humour
Aqueous humour
The aqueous humour is a clear, gelatinous fluid similar to plasma, but containing low-protein concentrations. It is secreted from the ciliary epithelium, a structure supporting the lens. It is located in the space between the lens and the cornea...
outflow.
In the cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
and rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
, carbachol is well-known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular
Pons
The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...
formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
receptors (mAChRs).
Indications
Carbachol is primarily used in the treatment 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...
, but it is also used during ophthalmic surgery. Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils during cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
surgery.
Topical ocular administration is used to decrease intraocular pressure in people with primary open-angle glaucoma
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...
. Intracellular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying if the normal emptying mechanism is not working properly.
In most countries carbachol is only available by prescription.
Contraindications
Use of carbachol, as well as all other muscarinic receptor agonistsMuscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
, is contraindicated in patients with asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, coronary insufficiency
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
, gastroduodenal 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...
, and incontinence
Incontinence
Incontinence or Incontinent may refer to:*Fecal incontinence, the inability to control one's bowels*Incontinence *Incontinent , a 1981 album by Fad Gadget*Urinary incontinence, the involuntary excretion of urine...
. The parasympathomimetic action of this drug will exacerbate the symptoms of these disorders.
Overdose
The effects of a systemic overdose will probably be similar to the effects of a nerve agentNerve agent
Nerve agents are a class of phosphorus-containing organic chemicals that disrupt the mechanism by which nerves transfer messages to organs...
(they both act on the cholinergic system, increasing cholinergic transmission), but its toxicity is much weaker and it is easier to antagonize in overdose. When administered ocularly there is little risk of such effects, since the doses are much smaller (see topical vs systemic administration).
Further reading
- Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
- Canadian Pharmacists Association (2000). Compendium of pharmaceuticals and specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
- Carbachol (1998). MedlinePlus. Retrieved June 27, 2004, from http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202110.html
- Carbachol (2003). RxList. Retrieved June 27, 2004, from http://www.rxlist.com/cgi/generic2/carbachol.htm
- National Institute for Occupational Safety and Health. (2002). Choline, chloride, carbamate. In The registry of toxic effects of chemical substances. Retrieved June 27, 2004, from http://www.cdc.gov/niosh/rtecs/gad59f8.html
- Carbachol Chloride (2004). Hazardous Substances Data Bank. Retrieved July 16, 2004, from http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?hsdbb.htm (search carbachol).