Miotic Agents

Miotic agents, miotica (from Greek meioo-I diminish), are substances that constrict the pupil. Miosis - pupil constriction - can occur either through nerve influences (excitation of the oculomotorii system, paralysis or paresis of the cervical sympathetic nerve system) or through humoral pathways. Thus, there are indications that insulin, as well as thyroid gland substances, maintain the tone of the sphincter pupillae, being antagonists of adrenaline; furthermore, it is indicated that potassium salts, and especially strontium and barium salts, can increase the tone of the iris muscles; but since the circular muscles are stronger than the radial ones, the result is pupil constriction. Pupil constriction is observed in the following main cases: during accommodation of the eye for near objects; thus, when objects are brought closer by approximately 30.5 cm, accommodative miosis occurs; under the action of light on the eye - light reflex miosis; miosis under the action of morphine, in the stage of deep chloroform anesthesia, during physiological sleep is explained either by direct increase in the tone of the oculomotorii center or, more likely, indirectly - through weakening of nerve inhibitory influences on this center; further, miosis occurs from local action on the iris of substances like muscarine, physostigmine and partially nicotine (e.g., in humans and some animals, nicotine in the first phase of its action - excitation of autonomic nerve ganglia, e.g., gangl. ciliare, can cause miosis). The greatest use in ophthalmology has been made of pilocarpine, physostigmine, partially arecoline; muscarine and nicotine are not used. The point of physiological application of pilocarpine (see Mydriatic agents) is the myoneural intermediate substance between the oculomotor nerve and the circular fibers of the iris, as well as the ciliary body; this is proven by the fact that pilocarpine excites these muscles even after degeneration of the oculomotor nerve fibers. Arecoline acts similarly to pilocarpine, but stronger; the mechanism of action is the same; a 1/2% solution of it causes maximum pupil constriction. Locally on the conjunctiva, arecoline often has an irritating effect. Interesting literary indications (Bennhold, Rauptstein) show that by combining pilocarpine (exciter of the sphincter) and cocaine (exciter of the dilator), i.e., with active simultaneous excitation of both the sympathetic and oculomotor systems, it is possible to obtain so-called "balanced", "functionally neutral" solutions in terms of action on the pupil (in the authors' experiments, these were: 1% cocaine solution and 0.4% pilocarpine solution). Besides pupil constriction, pilocarpine and arecoline, as well as physostigmine, increase accommodation, resp. cause spasm of it; this is explained by contraction of the ciliary muscle, whereby the Zinn's ligament, in which the lens is enclosed, is relaxed; the latter, due to its elasticity, assumes a more convex, resp. optically more refractive form. Furthermore, physostigmine, pilocarpine and arecoline usually after a transient increase decrease intraocular pressure; the mechanism of the latter action is that due to thinning of the iris, the angle between it and the cornea increases and thereby the Fontana space becomes freer, through which the outflow of lymph from the internal media of the eye mainly occurs; with existing increased intraocular pressure, this action of pilocarpine (as well as arecoline and physostigmine) is an important therapeutic moment. After the action of pilocarpine ceases, in the "after-effect" phase, instead of increased tone of the sphincter, a temporary paresis of it occurs. Atropine, being a stronger antagonist and having the same points of application, can already in small doses eliminate the above-mentioned actions on the eye of both pilocarpine and arecoline. The mechanism of action of physostigmine on the eye is more complex and has not yet been fully elucidated. Indeed, the pupil under the influence of physostigmine constricts; this constriction can be weakened by the use of atropine, but disappears only from very large doses of atropine. On the other hand, the pupil dilation caused by atropine can, although not completely, be weakened by physostigmine. Most authors believe that physostigmine acts on the endings of the oculomotor nerve, and not on the myoneural substance; furthermore it apparently increases the excitability of the muscle tissue itself of both the sphincter and the ciliary muscle. The observed increase in accommodation and decrease in intraocular pressure is explained by the above-mentioned mechanism. After the action of physostigmine has already ended, the increased excitability of the iris muscles and ciliary body remains for some time. A more significant decrease in intraocular pressure with physostigmine is explained by some as constriction of intraocular vessels.-When using all miotic agents and especially with physostigmine, miosis is observed, explained by spasm of accommodation and setting the eye to the nearest point of clear vision.-The main application in the treatment of eye diseases of M. s. is found in glaucoma; sometimes they are used in the treatment of iris synechiae, alternating with mydriatic agents. In the prodromal period of glaucoma, systematic use of 1% pilocarpine in the form of eye drops is recommended. For an attack of acute glaucoma, more strongly acting physostigmine (=eserine) in 1% solution or 1-2% arecoline is prescribed, up to 5-6 times a day, even during the night. It is believed that the strongest effect is achieved by using the so-called Vicherkevich mixture: Physostigm. salicylici, 0.05-1; Pilocarpini hydrochlor. 0.2; Cocainihydrochlorici 0.03, Dionini 0.2, Aq. destill. 10.0, Sol. Adrenalini 1:1000 gtt. X-XV. By adding cocaine and dionin, their local anesthetic action is expected; dionin in particular has the ability to enhance lymph circulation; adrenaline reduces hyperemia. The following preparations are usually used as M. s.: Arecolini hydrobromicum, Physostigmini salicylicum, Physostigmini sulfuricum and Pilocarpini hydrochloricum.