Physostigminae Sulphas, B.P. Physostigmine Sulphate.
C30H44N6O8S = 648.482.
Physostigmine sulphate, (C15H21N3O2)2, H2SO4, a salt of the alkaloid physostigmine, may be prepared by adding sulphuric acid (10 per cent.) to a solution of physostigmine in ether, drop by drop, until separation of the crystalline sulphate ceases. The salt is collected and carefully dried at a temperature of about 40°. It is also official in the U.S.P. It occurs as a yellowish-white microcrystalline, very deliquescent, odourless powder, having a bitter taste, gradually becoming reddened on exposure to air and light, owing to formation of rubreserine, a product of oxidation, which is insoluble in ether, but soluble in chloroform and in carbon bisulphide. The aqueous solution, which is colourless at first, becomes pink on keeping, like the salt, and is neutral to litmus, or only very faintly acid. Heated to 130°, it becomes soft, and at 140° melts without decomposition. With gold chloride it produces a purple colour. With sulphuric acid alone the salt gives only a faint yellow colour, but with sulphuric acid containing a crystal of potassium iodate a light purple colour is produced, changing at once to yellowish-red.
Soluble in water (4 in 1), alcohol (2.5 in 1), soluble in chloroform, but not very soluble in ether.
Action and Uses.—The action of physostigmine on involuntary muscle and on secretory glands closely resembles that of pilocarpine. Applied to the eye, it causes great constriction of the pupil; the effect is local, and is due mainly to stimulation of the terminations of the third nerve; intra-ocular pressure is largely reduced as a result of the contraction. Other plain muscle is affected by physostigmine in much the same way; gastric movements are increased and vomiting may result, intestinal peristalsis is exaggerated with production of liquid motions, owing to the hurried passage of the intestinal contents; the bladder and uterine movements are augmented and the bronchioles constricted. All these effects are antagonised by atropine. A similar stimulation of the peripheral nerve-endings in glands, results in an increase of their secretions, especially in the case of the sudoriferous, salivary, mucous, and lachrymal glands. The action of physostigmine on the circulation is to slow the pulse and raise blood pressure. It depresses the central nervous system, causing muscular weakness and diminished reflexes. Very large doses excite motor nerve-endings, and so cause irregular twitchings. Physostigmine has been employed internally for its depressant action on the central nervous system in epilepsy, chorea, etc., but has not proved of much service. It is given hypodermically, 3/4 milligram (1/100 grain), every four hours, in acute tetanus, and in some abdominal conditions to obtain an action of the bowels, or to prevent the formation of adhesions after operation, by exciting peristalsis. In veterinary practice it is used as a hypodermic purgative. The chief use of physostigmine is for its action on the eye; under its influence the pupil commences to contract in five to fifteen minutes, reaches the maximum contraction in thirty minutes, and remains contracted for more than twelve hours. The muscles regulating accommodation are also affected, but they regain their normal condition in three to four hours. Physostigmine is employed to correct the dilatation caused by atropine, homatropine, or cocaine. It is used in glaucoma to decrease intra-ocular pressure, but whether this is brought about by lessening the secretion of fluid or by facilitating its escape is not yet clear. For ophthalmic use, Lamellae Physostigminae or 0.25 to 1 per cent. solutions in sterile distilled water are employed. Neutral solutions rapidly become pink in colour; this may be to a great extent avoided by dissolving the alkaloidal salt in a weak solution of boric acid (2 per cent.). The addition of sulphurous or hypophosphorous acid to solutions of physostigmine sulphate has been suggested in order to prevent this colouration; the use of such powerful deoxidising agents is unnecessary, and offers no advantage for the purpose over the weak acidity of the boric acid solution. For internal use the sulphate may be administered in pills, the salt being carefully triturated with milk sugar, and massed with glycerin, of tragacanth. In cases of poisoning by physostigmine the stomach, should be washed out with 0.2 per cent. solution of potassium permaganate, and atropine and strychnine administered hypodermically. The alkaloid physostigmine occurs in colourless or pale pink crystals, very slightly soluble in water, soluble in castor oil (1 in 100), and in melted soft paraffin (1 in 180). It is employed in the preparation of ointments and oily drops for application to the eye as myotics.
Dose.—1 to 3 milligrams (1/60 to 1/20 grain).
- Guttae Physostigminae, B.P.C.—PHYSOSTIGMINE EYE DROPS. Syn.—Guttae Eserinae; Eserine Eye Drops. 1 per cent.
- Physostigmine contracts the pupil and reduces intra-ocular tension. It is antagonistic to atropine. Solutions of physostigmine tend to become pink owing to slow oxidation of the salt. They should be preserved in amber bottles, and kept as much as possible from the air; the addition of boric acid largely prevents colouration, which also occurs less readily in the presence of cocaine.
- Guttae Physostigminae et Cocainae, B.P.C.—PHYSOSTIGMINE AND COCAINE EYE DROPS. Syn.—Guttae Eserinae et Cocainae; Eserine and Cocaine Eye Drops.
- Physostigmine sulphate, 0.25 per cent.; cocaine hydrochloride, 1 per cent.
- Lamellae Physostigminae B.P.—PHYSOSTIGMINE DISCS. Syn.—Lamellae Eserinae; Eserine Discs.
- Each disc weighs about 1 1/4 milligrams (1/50 grain) and contains 0.065 milligram (1/1000 grain) of physostigmine sulphate. These discs are used to diminish intra-ocular pressure, as in glaucoma, and to contract the pupil. Stronger discs, containing 1/250 or 1/500 grain, are also prepared.
- Oculentum Physostigminae, B.P.C.—PHYSOSTIGMINE EYE OINTMENT. Syn.—Oculentum Eserinae; Eserine Eye Ointment. 1 (alkaloid) in 500.
The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.