Parasympathomimetics direct

Parasympathomimetics (direct acting) Pilocarpine Carbachol Increase aqueous outflow Miosis, accommodative spasm, constriction of visual field, retinal tears, cataracts, periorbital pain, precipitation of angle[Pg.76]

In rats, we know that tolerance does not occur to parasympathomimetic effects of LSD at a time when sympathomimetically mediated and behavioral effects show tolerance. Apart from the postreserpine LSD-induced pupillary changes, such differential effects in man are not known. We know also that the bradycardia in unrestrained rats (19) converts readily to a tachycardia, and assertions that LSD elevates blood pressure or pulse in man should be viewed as reactivity rather than a direct effect. 

The muscle fibres of the ciliary bodies are innervated by the mrd or oculomotor nerve. As explained above, when these fibres contract they allow the lens to take up its natural shape. Direct stimulation of the Illrd nerve therefore produces accommodation for near objects. Parasympathomimetic drugs have a similar action, whereas atropine paralyses this effect and so accommodates the lens for seeing distant objects. 

Acetylcholine (ACh) is too rapidly hydrolyzed and inactivated by acetylcholinesterase (AChE) to be of any therapeutic use however, its action can be mimicked by other substances, namely direct or indirect parasympathomimetics. 

The choline ester, carbachol, activates M-cholinoceptors, but is not hydrolyzed by AChE. Carbachol can thus be effectively employed for local application to the eye (glaucoma) and systemic administration (bowel atonia, bladder ato-nia). The alkaloids, pilocarpine (from Pilocarpus jaborandi) and arecoline (from Areca catechu betel nut) also act as direct parasympathomimetics. As tertiary amines, they moreover exert central effects. The central effect of muscarinelike substances consists of an enlivening, mild stimulation that is probably the effect desired in betel chewing, a widespread habit in South Asia. Of this group, only pilocarpine enjoys therapeutic use, which is limited to local application to the eye in glaucoma... 

Pharmacology Direct-acting miotics are parasympathomimetic (cholinergic) drugs which duplicate the muscarinic effects of acetylcholine. When applied topically, these drugs produce pupillary constriction, stimulate ciliary muscles, and increase aqueous humor outflow facility. With the increase in outflow facility, there is a decrease in lOP. Topical ophthalmic instillation of acetylcholine causes no discernible P.1248... 

Basic Pharmacology of the Directly Acting Parasympathomimetic Drugs... 

The mechanism of action of certain directly acting parasympathomimetic drngs shall now be discussed in the sections below ... 

The action of muscarine (16) and acetylcholine on smooth muscle is very similar muscarine is a potent parasympathomimetic drug (Antkowiak and Antkowiak, 1991). The term muscarinic activity is used to describe the direct peripheral action on cholinergic receptors in smooth muscles of the gastrointestinal tract, eye, exocrine glands, and heart (Wang and Joullie, 1984). Much early experimental work with muscarine is unreliable, as many of the materials used were impure. 

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