Pilocarpine side effects

As is usual with hydrophilic matrices, the effect is greatest immediately after instillation and diminishes with time. The approach does allow for only a single administration per day, as opposed to a four times daily eye drop application, and a choice of night-time administration diminishes patient-perceived pilocarpine side effects, such as initial miosis and induced myopia. 

Pre-soaked hydrophilic SCLs, as compared with an eye drop, extend the time that the dissolved drug will continue to be effective. For instance, SCLs pre-soaked in a 2% pilocarpine solution and placed on the cornea can maintain a significant reduction in lOP for almost 24 h." However, 90% of the drug is desorbed within a half hour, and the increase in the pulse necessary to achieve a full day s hypotensive therapy produces significant pilocarpine side-effects, such as increased miosis and myopia. 

Initial attempts to treat AD using direct cholinergic agonists were limited by low efficacy and side-effect issues (140—142). Thus trials using RS-86 (25), oxotremorine [70-22-4] (26), arecoline [63-75-2] (27), and pilocarpine [92-32-7] (28) to treat AD were equivocal (Eig. 5). However, the identification of multiple subtypes of muscarinic receptors has stimulated a search for subtype specific muscarinic agonists which may limit side effects while increasing efficacy. 

Carbachol stimulates the same muscarinic receptor as pilocarpine and also inhibits acetylcholinesterase, the enzyme that metabolizes acetylcholine. Carbachol is more potent than pilocarpine, but it causes more accommodation spasm and brow ache and may also cause anterior uveitis. Carbachol is rarely used today because of the side-effect profile. 

The oral cholinergic agonists pilocarpine and cevimeline are used for patients with combined dry eye and dry mouth (e.g., Sjogren s syndrome) or severe dry eye. By binding to muscarinic receptors, the cholinergic agonists may increase tear production. Excessive sweating is a common side effect with pilocarpine and may limit its use (Table 60-10). 

Q58 Patients receiving pilocarpine eye drops should be advised that driving at night may be affected. Administration of pilocarpine may cause blurred vision, headache and brow ache as side-effects. 

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 generation of cholinomimetics, such as arecoline, bethanecol and pilocarpine, were not designed for the treatment of AD and the results of the early clinical trials were consistently disappointing. In addition to their poor bioavailability and short duration of action, any therapeutic benefits were limited by their cholinergic side effects. The second generation of muscarinic... 

Pilocarpine is commerciaUy available in a carbomer gel vehicle.The 4% pilocarpine gel is packaged in a 3-5-g tube similar to ophthalmic ointments. A practical advantage of this sustained delivery system is the once-daily dosage regimen, with the drug usuaUy administered at bedtime. Minor side effects include superficial corneal haze, which may occur after long-term use (>8 weeks), and superficial pimctate keratitis, which can affect almost one-half the treated patients but usually resolves spontaneously. 

Controlling the release of medication at the site of action is often desirable, especially for compounds that are absorbed rapidly through mucous membranes or are removed rapidly from the site of action. The approach normally reduces the systemic side effects of the agent. The application of this approach can be illustrated with the Progestasert and Pilocarpine Ocusert dosage forms. 

E Due to her concomitant disease states, AK should avoid beta-blockers, adrenergic agents, and sulfa medications. Pilocarpine is not a good choice for AK due to its bothersome local side effects. Latanoprost is a good initial choice for AK due to its convenient once daily dosing and mild local and systemic side effects. 

Topical miotic agents are historically important glaucoma medications but are less commonly used today. Miotics lower lOP by causing muscarinic-induced contraction of the ciliary muscle, which facilitates aqueous outflow. They do not affect aqueous production. Multiple miotic agents have been developed. Pilocarpine and carbachol are cholinomimetics that stimulate muscarinic receptors. Ecbotbiopbate (Phospholine iodide) is an organophosphate inhibitor of acetylcholinesterase it is relatively stable in aqueous solution and, by virtue of its quaternary ammonium structure, is positively charged and poorly absorbed. The usefulness of these medicines is lessened by their numerous side effects and the need to use them three to four times a day. 

Pilocarpine is administered orally in 5-10-mg doses given three times daily for the treatment of xerostomia that follows head and neck radiation treatments or that is associated with Sjogren s syndrome, an autoimmune disorder occurring primarily in women in whom secretions, particularly salivary and lacrimal, are compromised. Side effects typify cholinergic stimulation, with sweating being the most common complaint. Bethanechol is an oral alternative that produces less diaphoresis. Cevimeline (evoxac) has activity at M muscarinic receptors, such as those on lacrimal and salivary... 

Pilocarpine is marketed as tablets (Salogen), an ophthalmic solution, and gel. It penetrates the eye well and is the miotic of choice for open-angle glaucoma and to terminate acute angle closure attacks. It also is used for the treatment of xerostomia (dryness of the mouth) caused by radiatioh therapy of the head and neck, Sjogren s syndrome, or as a side effect of some psychotropic drugs. 

Wang, H., Lu, Y. and Chen, H. Z. (2003) Differentiating effects of anisodamine on cognitive amelioration and peripheral muscarinic side effects induced by pilocarpine in mice. Neurosci. Lett. 344, 173-176. 

In clinical studies the Oeuserl system has been shown to lower intra-ocular pressure, the main (and sight threatening) symptom of glaucoma, for periods up to one week (a.47). Furthermore, there were fewer side effects associated with this system and patient compliance was improved in comparison with the conventional pilocarpine eye drop formulation. One disadvantage of the Ocusert system was the discomfort to some patients and potential retention problems within the eye (a.43). 

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