Carbachol

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Carbachol(Carbastat, Carboptic, Isopto Carbachol, Miostat), also known

as carbamylcholine, 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 V-series nerve agents if a
massive overdose is administered (as may occur following industrial and
shipping accidents) and therefore constitutes a risk to human health. 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.[1]
Chemistry and pharmacology
Carbachol is a choline carbamate and a positively charged quaternary
ammonium compound.[2] 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.[2] 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.[2]
Carbachol is
a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.
[2] In topical ocular and intraocular administration its principal effects
are miosis and increased aqueous humour outflow.[2]
In the cat and rat, carbachol is well known for its ability to induce rapid eye
movement (REM) sleep when microinjected into the pontine reticularformation.
Carbachol elicits this REM sleep-like state via activation of postsynaptic
muscarinic cholinergic receptors (mAChRs).[2]
A recent review indicates that carbachol is a strong promoter of ICCactivity,
which is mediated through the calcium-activated chloride channel, anoctamin
1.[3]
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.[2] 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 if the normal emptying mechanism
is not working properly.
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.[2][4]
Contraindications
Use of carbachol, as well as all other muscarinic receptor agonists, is
contraindicated in patients with asthma, coronary insufficiency,
gastroduodenal ulcers, and incontinence. The parasympathomimeticaction 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 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).[5]
References

1. "40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous

Substances and Their Threshold Planning Quantities" (PDF) (July 1, 2008
ed.). Government Printing Office. Retrieved October 29, 2011.
2. "Carbachol". PubChem Compound. Retrieved 6 March 2014.
3. Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (February
2012). "Anoctamins and gastrointestinal smooth muscle excitability". Exp.
Physiol. 97 (2): 200–
206. doi:10.1113/expphysiol.2011.058248. PMC 3272164 
. PMID 22002868.
4. "Carbachol generics". ndrugs. Retrieved 6 March 2014.
5. Richard A. Harvey; Pamela C. Champe, eds. (2009). Lippincott's Illustrated
Review: Pharmacology (4th ed.). Lippincott Williams & Wilkins.
p. 49. ISBN 978-0781771559.

External links

 RxList.com - Carbachol
 International Carbachol brands and dosage forms
 PMC overdose case reports (humans)