Pilocarpine systemic effects

The adverse effects of pilocarpine are caused by the induction of miosis. The contraction of the ciliary muscle causes the lens to displace forward, which can lead to accommodation spasm, myopia, and brow ache. Pupillary constriction can also affect night vision. Pilocarpine should be avoided in patients with severe myopia, as it increases the risk of developing retinal detachment. Systemic effects may occur at higher concentrations and include, nausea, vomiting, diarrhea, and bradycardia. 

All five muscarinic receptor subtypes have been detected in the central nervous system. The roles of Mx through M3 have been analyzed by means of experiments in knockout mice. The Mx subtype is richly expressed in brain areas involved in cognition. Knockout of Mx receptors was associated with impaired neuronal plasticity in the forebrain, and pilocarpine did not induce seizures in Mx mutant mice. The central nervous system effects of the synthetic muscarinic agonist oxotremorine (tremor, hypothermia, and antinociception) were lacking in mice with homozygously mutated M2 receptors. Animals lacking M3 receptors, especially those in the hypothalamus, had reduced appetite and diminished body fat mass. 

The safety profile and efficacy of 2% dorzolamide hydrochloride (Trusopt) eye-drops have been evaluated. It was as effective as pilocarpine 2% and its ocular hypotensive efficacy was comparable with that of betaxolol 0.5%. The patients reported less interference with quahty of life with dorzolamide than pilocarpine, particularly in regard to limitations in their ability to drive, read, and perform moderate activities. Long-term use was not associated with important electrolyte disturbances or the systemic effects commonly observed with oral carbonic anhydrase inhibitors (1-3). 

AK Mitra, TJ Mikkelson. (1982). Ophthalmic solution buffer systems. I. The effect of buffer concentration on the ocular absorption of pilocarpine. Int J Pharm 10 219-229. 

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... 

Ocular effects Carefully examine the fundus prior to initiating therapy with pilocarpine. An association of ocular pilocarpine use and retinal detachment in patients with preexisting retinal disease has been reported. The systemic blood level that is associated with this finding is not known. 

Potentially severe adverse effects can result from systemic administration of cholinomimetic drugs, and none should be administered by intramuscular or intravenous injection. If significant amounts of these drugs enter the circulation, nausea, abdominal cramps, diarrhea, salivation, hypotension with reflex tachycardia, cutaneous vasodilation, sweating, and bronchoconstric-tion can result. Pilocarpine can cross the blood-brain barrier and affect cognitive function. Even the topical application of cholinomimetics to the eyes can present... 

Acetylcholine acts at two different types of cholinergic receptors [see (1) and (2) in Fig. 2.5]. Muscarinic receptors bind ACh as well as other agonists (muscarine, pilocarpine, bethanechol) and antagonists (atropine, scopolamine). There are at least five different types of muscarinic receptors (M1-M5). All have slow response times. They are coupled to G proteins and a variety of second messenger systems. When activated, the final effect can be to open or close channels for K, Ca ", or CL (Bonner, 1989). Nicotinic receptors are less abundant than the muscarinic type in the CNS. They bind ACh as well as agonists such as nicotine or an-... 

Loucas, S. P. and H. M. Haddad. 1972. Solid-state ophthalmic dosage systems in effecting prolonged release of pilocarpine in the cul-de-sad. Pharm. Sci61 985-986. 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

The first nanoparticulate delivery system studied was Piloplex, consisting of pilocarpine ionically bound to poly(methyl)methacrylate-acrylic acid copolymer nanoparticles [44], Klein et al. [1,98] found that a twice-daily application of Piloplex in glaucoma patients was just as effective as three to six instillations of conventional pilocarpine eye drops. However, the formulation was never accepted for commercialization due to various formulation-related problems, including the nonbiodegradability, local toxicity, and difficulty of preparing a sterile formulation [208],... 

An example of a degradable matrix system is the pilocarpine-containing inserts formulated by Saettone et al. [148]. Pilocarpine nitrate and polyacrylic acid were incorporated into a matrix containing polyvinyl alcohol and two types of hydroxy-propyl methylcellulose. It was shown that all inserts significantly increased the pharmacological effect (miotic response) compared to a solution of pilocarpine nitrate. 

Pilocarpine is a widely studied peripheral stimulant of the parasympathetic system (101). It is used topically as a myotic to counteract the mydriatic effect of atropine and other parasympatholytic drugs. It has clinical value in the treatment of glaucoma when used as eye drop solutions ranging from 0.5 to 10% in concentration (102). Pilocarpine is reported to stimulate the growth of hair and therefore was employed in hair lotions (1). Internally, it was used as a diaphoretic in the treatment of nephritis (103). 

---