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Edrophonium Chloride(BAN, Rinn)

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Edrophonium Chloride(BAN, Rinn) 630 Antimyasthenics cause the muscarinic symptoms of overdosage may be 2. Newsom-Davis J. Myasthenia gravis and the Lambert-Eaton Edrophonium Chloride (BAN, rINN) suppressed leaving only the more serious nicotinic effects (fas- myasthenic syndrome. Prescribers’ J 1993; 33: 205–212. ciculation and paralysis of voluntary muscle). 3. Sanders DB, et al. A randomized trial of 3,4-diaminopyridine in Cloruro de edrofonio; Edrofonio chloridas; Edrofonium-chlorid; Lambert-Eaton myasthenic syndrome. Neurology 2000; 54: Edrofoniumklorid; Edrofoniumkloridi; Edrofonyum Klorür; Edro- 603–7. Pharmacokinetics phonii chloridum; Édrophonium, chlorure d’. Ethyl(3-hydroxy- Ambenonium chloride is poorly absorbed from the gastrointesti- 4. Boerma CE, et al. Cardiac arrest following an iatrogenic 3,4- phenyl)dimethylammonium chloride. nal tract. It does not appear to be hydrolysed by cholinesterases. diaminopyridine intoxication in a patient with Lambert-Eaton myasthenic syndrome. J Toxicol Clin Toxicol 1995; 33: 249–51. Эдрофония Хлорид Uses and Administration Multiple sclerosis. Amifampridine has been tried in the man- C10H16ClNO = 201.7. Ambenonium is a quaternary ammonium compound that is a re- agement of multiple sclerosis (p.892). In a crossover study1 in- CAS — 312-48-1 (edrophonium); 116-38-1 (edrophonium versible inhibitor of cholinesterase activity with actions similar volving 36 patients with multiple sclerosis, amifampridine given chloride). to those of neostigmine (p.632), but of longer duration. Ambeno- in a dosage of up to 100 mg daily improved symptoms of leg nium chloride is given orally in the treatment of myasthenia weakness to a greater extent than placebo but paraesthesia and gravis (p.629) in usual doses of 5 to 25 mg three or four times abdominal pain which occurred in most patients were dose-lim- daily, adjusted according to response. It may be of value in pa- iting in some. A systematic review2 of the use of aminopyridines CH3 tients who cannot tolerate neostigmine or pyridostigmine. for symptomatic management of multiple sclerosis was unable to + Preparations come to any conclusion, and commented on the problem of pub- HO N CH3 − lication bias in this area. Cl Proprietary Preparations (details are given in Part 3) 1. Bever CT, et al. Treatment with oral 3,4-diaminopyridine im- CH3 Cz.: Mytelase; Fr.: Mytelase; Gr.: Mytelase; Hung.: Mytelase; Pol.: Mytela- proves leg strength in multiple sclerosis patients: results of a ran- se; Swed.: Mytelase; USA: Mytelase. domized, double-blind, placebo-controlled, crossover trial. Neu- rology 1996; 47: 1457–62. Pharmacopoeias. In Eur. (see p.vii), Int., Jpn, and US. 2. Solari A, et al. Aminopyridines for symptomatic treatment in Ph. Eur. 6.2 (Edrophonium Chloride). A white or almost white multiple sclerosis. Available in The Cochrane Database of Sys- crystalline powder. Very soluble in water; freely soluble in alco- Amifampridine (rINN) tematic Reviews; Issue 4. Chichester: John Wiley; 2002 (ac- cessed 15/02/06). hol; practically insoluble in dichloromethane. A 10% solution in Amifampridina; Amifampridinum; 3,4-Diaminopyridine. Pyridine- water has a pH of 4.0 to 5.0. Protect from light. 3,4-diamine. USP 31 (Edrophonium Chloride). A white odourless crystalline Амифампридин powder. Soluble 1 in 0.5 of water and 1 in 5 of alcohol; insoluble Distigmine Bromide (BAN, rINN) in chloroform and in ether. A 10% solution in water is practically C H N = 109.1. 5 7 3 BC-51; Bispyridostigmine Bromide; Bromuro de distigmina; colourless and the pH is between 4.0 and 5.0. CAS — 54-96-6. Distigmiinibromidi; Distigminbromid; Distigmine, Bromure de; ATC — N07XX05. Distigmini Bromidum; Hexamarium Bromide. 3,3′-[N,N′-Hex- Adverse Effects, Treatment, and Precau- ATC Vet — QN07XX05. amethylenebis(methylcarbamoyloxy)]bis(1-methylpyridinium tions bromide). As for Neostigmine, p.631. Дистигмина Бромид N Interactions C22H32Br2N4O4 = 576.3. CAS — 15876-67-2. As for Neostigmine, p.632. ATC — N07AA03. NH2 ATC Vet — QN07AA03. Uses and Administration NH2 Edrophonium is a quaternary ammonium compound that is a reversible inhibitor of cholinesterase activity. It Profile CH CH has actions similar to those of neostigmine (p.632) but Amifampridine has similar actions and uses to fampridine HC O N N O CH its effect on skeletal muscle is claimed to be particular- (p.631) but is reported to be more potent in enhancing the release N (CH ) N 2Br ly prominent. It has a rapid onset but short duration of of acetylcholine from nerve terminals. It is used in the Eaton- O O Lambert myasthenic syndrome (below) and other myasthenic action. In patients with myasthenia gravis, there is im- conditions. It has been tried in multiple sclerosis and in botulism. mediate subjective improvement and muscle strength There have been isolated reports of seizures and amifampridine Pharmacopoeias. In Jpn. increases. This effect usually lasts only for about 5 to is therefore contra-indicated in patients with epilepsy. Adverse Effects, Treatment, and Precautions 15 minutes, after which time the typical signs and Congenital myasthenia. Congenital or hereditary myasthenia As for Neostigmine, p.631. The anticholinesterase action of symptoms return; because of its brief action the drug is is a heterogeneous group of rare disorders associated with vari- distigmine, and hence its adverse effects, may be prolonged, and not suitable for the routine treatment of myasthenia ous defects in neuromuscular transmission including presynaptic if treatment with atropine is required it should be maintained for gravis. impairment of acetylcholinesterase release, postsynaptic abnor- at least 24 hours. Distigmine may stimulate uterine contractions mality of acetylcholine receptors, or a deficiency of acetylcho- and UK licensed product information has advised that it should Edrophonium chloride is used in myasthenia gravis linesterase.1 Symptoms may be similar to those of myasthenia be avoided in pregnancy. (p.629) both diagnostically and to distinguish between gravis (p.629) but there are no immunological abnormalities. Al- Interactions under- or over-treatment with other anticholinesteras- though some forms may respond to anticholinesterases, therapy As for Neostigmine, p.632. es. is usually unsatisfactory. Experience in 16 patients2 has suggest- ed that amifampridine used alone or with anticholinesterases Pharmacokinetics • The usual diagnostic procedure is to inject 2 mg in- may be of benefit. Clinical improvement was seen in 5 of 11 pa- Distigmine is poorly absorbed from the gastrointestinal tract. travenously and, if no adverse reaction occurs within tients with congenital myasthenia who were given amifamprid- 30 to 45 seconds, to continue with the injection of a Uses and Administration ine as part of a placebo-controlled study; 3 of the 11 responded further 8 mg. In the UK the recommended total dose 3 Distigmine is a quaternary ammonium compound that is a re- to placebo. There have also been reports of benefit from the use for children is 100 micrograms/kg, one-fifth of the of quinidine sulfate in patients with the slow-channel congenital versible inhibitor of cholinesterase activity with actions similar myasthenic syndrome.4 to those of neostigmine (p.632) but more prolonged. Maximum dose being given initially, followed 30 seconds later inhibition of plasma cholinesterase occurs 9 hours after a single by the remainder if no adverse effects develop; the 1. Engel AG. Congenital myasthenic syndromes. Neurol Clin North intramuscular dose, and persists for about 24 hours. Am 1994; 12: 401–37. BNFC suggests that this dose may be given to those 2. Palace J, et al. 3,4-Diaminopyridine in the treatment of congen- Although it is rarely used, distigmine bromide may be given oral- aged from 1 month to 12 years. In the USA a total ital (hereditary) myasthenia. J Neurol Neurosurg Psychiatry ly with short-acting parasympathomimetics for the treatment of 1991; 54: 1069–72. myasthenia gravis (p.629); patients being treated with parasym- dose of 5 mg for children weighing less than 34 kg 3. Anlar B, et al. 3,4-Diaminopyridine in childhood myasthenia: pathomimetics tend to prefer pyridostigmine. The initial dose is and 10 mg for heavier children is recommended, double-blind, placebo-controlled trial. J Child Neurol 1996; 11: 5 mg daily before breakfast, increased at intervals of 3 to 4 days with one-fifth of the dose being given initially fol- 458–61. if necessary to a maximum of 20 mg daily; children may be giv- lowed by increments of 1 mg every 30 to 45 sec- 4. Harper CM, Engel AG. Quinidine sulfate therapy for the slow- en up to 10 mg daily according to age. channel congenital myasthenic syndrome. Ann Neurol 1998; 43: onds; the recommended total dose for infants is 480–4. Distigmine is one of several drugs that have been used in the pre- 500 micrograms. vention and treatment of postoperative gastrointestinal atony Eaton-Lambert myasthenic syndrome. Daily doses of up (see Decreased Gastrointestinal Motility, p.1694). It has also When intravenous injection is difficult edrophonium to 100 mg of amifampridine by mouth have been found1 to be been used in postoperative urinary retention (p.2180), al- chloride may be given by intramuscular injection; effective in the treatment of both the motor and autonomic defi- though it has been superseded by catheterisation. A dose of the usual dose in adults is 10 mg while children be- cits of patients with Eaton-Lambert syndrome (p.629). A usual 500 micrograms of distigmine bromide was injected intramuscu- low 34 kg in weight may be given 2 mg and heavier starting dose of 10 mg given three or four times daily increasing larly about 24 to 72 hours after surgery and repeated at intervals if necessary to a maximum of 20 mg given five times daily has of 1 to 3 days until normal function was restored. Alternatively it children 5 mg; a suggested dose for infants is 0.5 to been used.2 However, some workers have recommended limit- has been given orally in a dose of 5 mg daily thirty minutes be- 1 mg given intramuscularly or subcutaneously.
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