Carbachol

182.65

182.082199

3917459

200-127-3

8Y164V895Y

755919|32865

2811

DTXSID9022730

C47430

Hard prismatic crystals|White or faintly yellow crystals or crystalline powder

N07AB01|N - Nervous system|S - Sensory organs

29239000

52.3

-3.78

white crystalline

1.2798 (rough estimate)

210 °C (decomp)

H2O: 1.0 G/ML

Desiccate at RT

Oral-rat LD50: 40 mg/kg; Oral-Mouse LD50: 15 mg/kg

Thermal decomposition releases toxic nitrogen oxides and chloride fumes

Odorless or has a slight amine-like odor

Neutral to litmus (aqueous soln)

128 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hygroscopic|Ophthalmic soln of carbachol has a pH of 5-7; the commercially available intraocular injection has a pH of 6.5-7.5 /Soln/|Chlorocresol (0.025 to 0.1%) and chlorbutol (0.5%) were incompatible with a soln of carbachol (0.8%) and sodium chloride (0.69%), very slight precipitates forming on heating and increasing on standing. /Soln/|Incompatible with alkalies, iodine, and silver salts

Hygroscopic.

Carbamates

CARBACHOL CHLORIDE is a carbamate ester. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates.

II

6.1

UN 2811 6.1/PG 2

3

25-36/37/38

45-36/37/39-28A-26

GA0875000

T

The warehouse is low-temperature, ventilated and dry; stored separately from food materials

The aqueous soln is stable even when heated.

P264-P301 + P310

H300

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl carbachol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From Appendix A, Product Name Index/

When heated to decomposition, it emits very toxic fumes of chloride and nitrogen oxides. The aqueous solution is stable even when heated. (EPA, 1998)

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 200 companies from 2 notifications to the ECHA C&L Inventory.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

Avoid skin contact. (EPA, 1998)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Carbachol chloride is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.

most toxic

Acetylcholine and methacholine are hydrolyzed by acetylcholinesterase and their effects are markedly enhanced by the prior administration of anticholinesterase agents. The latter drugs produce only additive effects with the stable analogs, carbachol and bethanechol. The muscarinic actions of all the drugs of this class are blocked selectively by atropine, through competitive occupation of cholinergic receptor sites on the autonomic effector cells and on the secondary muscarinic receptors of autonomic ganglion cells.|When used in conjunction with topical epinephrine, topical timolol, and/or systemically admin carbonic anhydrase inhibitiors, the effect of miotics in lowering intraocular pressure may be additive. /Miotics/|Although the clinical importance has not been established, the miotic and/or ocular hypotensive effects of miotics reportedly may be antagonized by long-term topical or systemic corticosteroid therapy, systemic anticholinergics, antihistamines, meperidine, sympathomimetics, & tricyclic antidepressants ... .|Ophthalmic carbachol may be ineffective when administred following ophthalmic flubiprofen; the pharmacologic basis for this interference is not known.|Concurrent use of ... /ophthalmic belladona alkaloids or cyclopentolate/ may interfere with the antiglucoma action of carbachol; also concurrent use with carbachol counteracts the myrdiatic effects of these medications ... .

LD50 Mouse oral 5 mg/kg|LD50 Mouse iv 0.3 mg/kg

Analgesics, Non-Narcotic; Cardiotonic Agents; Cholinergic Agonists; Miotics; Muscarinic Agonists; Nicotinic Agonists; Parasympathomimetics|Acetylcholine, 1%, or carbachol, 0.01%, is used in cataract extractions and certain other surgical procedures on the anterior segment when it is desired to produce miosis rapidly; the action of acetylcholine is brief. For the chronic therapy of noncongestive, wide-angle glaucoma, carbachol (0.75 to 3.0%) has been employed.|Carbachol has been used in the treatment of postoperative intestinal atony and postoperative retention of urine, for which it has been given by subcutaneous injection ... or by mouth. It has also been used to stop supraventricular paroxysmal tachycardia when all other measures have failed. Carbachol has a miotic action and eye-drops ... have been used to lower intraocular pressure in glaucoma ... Even in comparatively late cases of sun blindness the symptoms could in many instances be alleviated ... by retrobulbar injection of carbachol.|Pilocarpine (or occasionally carbachol) is used to lower intraocular pressure in the emergency treatment of acute (congestive) angle-closure glaucoma prior to surgery.|For more Therapeutic Uses (Complete) data for CARBACHOL CHLORIDE (11 total), please visit the HSDB record page.

Topical carbachol shares the toxic potentials of the direct-acting miotics, and the usual precautions of miotic therapy should be observed. The manufacturer states that intraocular carbachol does not produce the adverse effects of topically applied carbachol; bullous keratopathy and postoperative iritis following cataract extraction have been reported in some patients.|Corneal edema may occur if excessive amounts of carbachol are introduced into the anterior chamber or if the drug is used in patients with an already compromised endothelium, eg, Fuchs' dystrophy, corneal transplants, cataract surgery that requires more manipulation than usual.|It is recommended that carbachol should not be used as eye-drops in patients with a corneal abrasion as there may be excessive absorption. The sensitivity of asthmatic patients to carbachol bronchoconstriction was increased when inhalation of carbachol was preceded by maximum respiratory maneurvers.|Drugs of this class should be admin only by the oral or subcutaneous route for systemic effects; they are also used locally in the eye. If they are given intravenously or intramuscularly, their relative selectivity of action no longer holds, and the incidence and severity of toxic side effects are greatly increased. /Choline esters/|For more Drug Warnings (Complete) data for CARBACHOL CHLORIDE (10 total), please visit the HSDB record page.

Drugs that bind to and activate cholinergic receptors. (See all compounds classified as Cholinergic Agonists.)|A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS. (See all compounds classified as Analgesics, Non-Narcotic.)|Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). (See all compounds classified as Cardiotonic Agents.)|Agents causing contraction of the pupil of the eye. Some sources use the term miotics only for the parasympathomimetics but any drug used to induce miosis is included here. (See all compounds classified as Miotics.)

Topical carbachol penetrates intact corneal epithelium very poorly; combination with wetting agent ... greatly improves corneal penetration by the drug. ... Carbachol /is/ ... absorbed through intact skin.

Carbachol, which is an unsubstituted carbamyl ester, is totally resistant to hydrolysis by either acetylcholinesterase or nonspecific cholinesterases; its half-life is thus sufficiently long that it is distributed to areas of low blood flow.

The pharmacologic effects of all miotics are similar; they differ primarily in ocular and systemic absorption, duration of action and degree of effects. Acetylcholine, an endogenous mediator of nerve impulses, stimulates cholinergic receptors, resulting in muscarinic and nicotinic effects. The action of acetylcholine is transient. ... Pilocarpine, carbachol, and methacholine also directly stimulate cholinergic receptors; however, these drugs have a more prolonged duration of action (several hours) than does acetylcholine. There is some evidence that carbachol also has a weak anticholinesterase effect ... .|Miotics reduce intraocular pressure in normal and glaucomatous eyes. The mechanism of action of the drugs in lowering intraocular pressure has not been precisely determined. In patients with open-angle (chronic simple, noncongestive) glaucoma, the drugs facilitate aqueous humor outflow, apparently by causing contraction of the ciliary muscle and widening of the trabecular meshwork. ... Miotics decrease activity of extraocular muscles of convergence. ... Systemically absorbed miotics produce parasympathomimetic effects on various body systems. /Miotics/|/Carbachol acts/ ... with selectivity on the smooth muscle of the gastrointestinal tract ... Carbachol /also/ retains substantial nicotinic activity, particularly on autonomic ganglia. It is likely that both its peripheral and its ganglionic actions are due, in part, to the release of endogenous acetylcholine from the terminals of cholinergic fibers.|The choline esters /carbachol & bethanechol/ increase ureteral peristalsis, contract the detrusor muscle of the urinary bladder, increase the maximal voluntary voiding pressure, and decrease the capacity of the bladder. In addition, the trigone and external sphincter are relaxed. In animals with experimental lesions of the spinal cord or sacral roots, these drugs bring about satisfactory evacuation of the neurogenic bladder.|For more Mechanism of Action (Complete) data for CARBACHOL CHLORIDE (7 total), please visit the HSDB record page.

Highly toxic by mouth. (EPA, 1998)

Note: Carbachol chloride is a direct cholinergic agonist. Due to spontaneous vomiting, administration of syrup of Ipecac is unnecessary. Cathartics will usually not be needed. Signs and Symptoms of Acute Carbachol Chloride Exposure: Signs of symptoms of acute carbachol chloride exposure include the following: tearing, pinpoint pupils, salivation, flushing, sweating, hypothermia, shortness of breath, bronchospasm (choking), increased bronchial secretion, pulmonary edema, belching, abdominal pain, nausea, vomiting, diarrhea, involuntary urination and/or defication. Weakness, muscle cramps, vertigo, tremors, seizures, coma, bradycardia (slow heart rate), and cardiac arrest may also occur. Emergency Life-Support Procedures: Acute exposure to carbachol chloride may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to carbachol chloride. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Transport to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to carbachol chloride. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Remove and isolate contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas thoroughly with soap and water. 6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 7. Transport to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 4. Cathartics will usually not be needed. If charcoal stools are not observed, promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1 3/4 to 3-1/2 oz) is recommended for adults. 5. Transport to a health care facility. (EPA, 1998)

Atropine sulfate injection is used as an antidote to the systemic effects of carbachol.

Systemic reactions after chronic topical application of /some/ ... miotics to the eye or intraocular injection of acetylcholine or carbachol are rare and usually occur only with very frequent admin. ... Adverse systemic effects of miotics result from parasympathetic stimulation and the most common effects, especially in children, include nausea, vomiting, diarrhea, abdominal pain, and intestinal cramps.|A 58-yr-old man developed esophageal rupture 2 hr after a subcutaneous injection of carbachol to relieve urinary retention.|A report of life-threatening attacks of profuse sweating, intestinal cramps ... defecation, hypothermia, hypotension, and bradycardia in a 36-yr-old man due to carbachol intoxication /was recorded/. A 10-yr-old boy had died following similar attacks associated with repeated carbachol ingestion.|The most common ... effects of miotic therapy are painful ciliary or accommodative spasm, blurred vision or myopia, and poor vision in dim light. ... Other adverse effects ... include ciliary or conjunctival congestion, lacrimal passage stenosis, twitching of the eyelids, stinging, burning, lacrimation, ocular or brow pain, headache, photophobia ... /Miotics/|Tests of 0.01% solution introduced into the anterior chamber of eyes of human beings ... have shown no significant irritating or injurious action, but prompt miotic effect.

Carbachol

Commercially available ophthalmic solutions contain benzalkonium chloride as preservative and wetting agent. ... Preparations: Ophthalmic - Injection, for intraocular use only 100 ug/ml (0.01%) Miostat Intraocular. Solution: 0.75%, Isopto Carbachol (with benzalkonium chloride; viscous); 1.5%, Isopto Carbachol (with benzalkonium chloride; viscous); 2.25%, Isopto (with benzalkonium chloride: viscous); 3% Isotop Carbachol (with benzalkomum chloride; viscous).|Eyedrops: APF has carbachol 750 mg, sodium chloride 700 mg, benzalkonium chloride soln 0.02 ml, disodium edetate 50 mg. Water for injections to 100 ml ... Another formula: carbachol 800 mg, anhydrous dextrose 5 g, chlorhexidine acetate 5 mg. Water for injection to 100 ml ...|Carbachol intraocular soln is a sterile soln of carbachol in an aqueous medium. It contains not less than 90.0% & not more than 115.0% of the labeled amt of Carbachol. It contains no preservatives or antimicrobial agents.

Ethanaminium, 2-[(aminocarbonyl)oxy]-N,N,N-trimethyl-, chloride (1:1): ACTIVE

Dissolve about 400 mg of carbachol ... in a mixture of 10 ml of glacial acetic acid & 10 ml of mercuric acetate test soln. Add 2 drops of crystal violet test soln, and titrate with 0.1 N perchloric acid volumetric soln. Perform a blank determination, & make any necessary correction. Each ml of 0.1 N perchloric acid is equivalent to 18.27 mg of carbachol.|/To prepare the assay soln/ dilute ... /a/ measured vol of Carbachol Ophthalmic Soln ... with water to obtain a soln containing about 100 ug of carbachol per ml. ... Determine the absorbances of the solutions from the assay prepn and the std prepn in 1-cm cells at the wavelength of max absorbance at about 590 nm, with a suitable spectrophotometer, against blank. Calculate the quantity ... in each ml of soln ... /Ophthalmic soln/|By using NMR spectroscopy, carbachol can be assayed in commercial ophthalmic soln with a minimum of steps and reagents, and with a high degree of accuracy. The sample was freeze-dried to a powder which was first mixed with acetamide, the internal standard, and then dissolved in MeOH. An aliquot of the soln was evaporated to dryness, the residue dissolved in D2O, the soln mixed with the reference standard, and the spectrum recorded. The quantity of carbachol in the dosage form was calculated from the integral value at approx 3.27 ppm (carbachol) and approx 2.01 ppm (acetamide). The mean recovery value for carbachol added to synthetic formulations was 100.0%.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients