Carbachol

Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. 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., eye drops).

Carbachol produces effects comparable to those of sarin if a massive overdose is administered (as may occur following industrial and shipping accidents) and therefore it is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.<ref name="gov-right-know">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">Template:Cite book</ref>

Chemistry and pharmacology

Carbachol is a choline carbamate and a positively charged quaternary ammonium compound.<ref name="PubChem">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name="PubChem" /> Carbachol is not easily metabolized by cholinesterase, it has a 2 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.<ref name="PubChem" />

Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.<ref name="PubChem" /> In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.<ref name="PubChem" />

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).<ref name="PubChem" />

A recent review indicates that carbachol is a strong promoter of ICC activity, which is mediated through the calcium-activated chloride channel, anoctamin 1.<ref name="pmid22002868">Template:Cite journal</ref>

Synthesis

Carbachol may be prepared in a 2 step process beginning with the reaction of 2-chloroethanol with urea to form a 2-chloroethyl-carbamate, which is then quaternised by a reaction with trimethylamine.

Indications

Carbachol is primarily used in the treatment of glaucoma, but it is also used during ophthalmic surgery.<ref name="PubChem" /> 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. Intraocular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying to treat the condition of underactive bladder.<ref>Template:Cite journal</ref>

In most countries carbachol is only available by prescription. Outside the United States, it is also indicated for urinary retention as an oral (2 mg) tablet.<ref name="PubChem" /><ref name="ndrugs">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Contraindications

Use of carbachol, as well as all other muscarinic receptor agonists, is contraindicated in patients with asthma, coronary insufficiency, gastroduodenal ulcers, and incontinence.Template:Fact The parasympathomimetic action of this drug will exacerbate the symptoms of these disorders.Template:Fact

Overdose

The effects of a systemic overdose will probably be similar to the effects of a nerve agent (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 versus systemic administration).<ref name="Lippencott's">Template:Cite book</ref>

External links

• {{#invoke:citation/CS1|citation

|CitationClass=web }}