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PubMed1979

Comparison of the pupillary, refractive, and hypotensive effects of Ocusert-40 and pilocarpine eyedrops in the treatment of chronic simple glaucoma.

Twelve patients with chronic simple glaucoma were treated for 1 week with Ocusert-40, and the effects on the pupil, intraocular pressure, and refraction were measured. A comparison was made with the effects of pilocarpine eyedrop therapy in 8 of these patients. Both forms of pilocarpine treatment gave satisfactory control of intraocular pressure and both constricted the pupil to a similar degree shortly after initiation of treatment. During the week on Ocusert-40 the pupils redilated, so that 54% of the initial miosis remained after 7 days' wear. There was, however, considerable variability in the pupillary sensitivity to Ocusert-40 within and between eyes, and it is suggested that this may have been partly due to variable release rates of pilocarpine. Only minor decreases in visual acuity and refraction resulted from pilocarpine in either form. Seven of the 12 patients rejected Ocusert-40 because of discomfort or inability to retain the device.

Aged↗
PubMed2000

Effect of cataract extraction and posterior chamber lens implantation on outflow facility and its response to pilocarpine in Korean subjects.

AIM: To investigate the effect of the lens on outflow facility in Korean patients with cataracts. METHODS: Intraocular pressure was measured by Goldmann applanation tonometry in 42 patients with cataracts and outflow facility was determined by tonography preoperatively, before and after instillation of pilocarpine. All patients received clear corneal phacoemulsification and silicone foldable intraocular lens implantation within the capsular bag by one surgeon. Two months after surgery, slit lamp examination and gonioscopy were performed and intraocular pressure and outflow facility were again determined. Statistical analysis was carried out using the Student's paired t test. RESULTS: There were no anterior chamber reactions and no visible trabecular meshwork damage 2 months after surgery. Intraocular pressure 2 months after lens extraction decreased by a mean of 2.4 (SE 0.4) mm Hg (p<0.001) compared with the preoperative value; postoperative outflow facility with and without pilocarpine increased by 0.080 (0.019) microl/min/mm Hg (p<0.001) and 0.045 (0.014) microl/min/mm Hg (p<0.001), respectively, at 2 months compared with preoperative values. The facility response to pilocarpine after lens extraction, relative to the baseline value and preoperative response, increased by 10.7 (7.1)% which was not statistically significant (p>0.1). CONCLUSION: Lens extraction causes a reduction in intraocular pressure and an increase in outflow facility in Korean subjects. Pilocarpine causes an increase in outflow facility which persists after cataract extraction and posterior chamber lens implantation.

Adult↗
PubMed1975

Adrenal cortical secretion in response to pilocarpine in dogs with hypothalamic lesions.

Adrenal venous blood samples were collected from conscious and anesthetized dogs before and after an injection of pilocarpine and were analyzed for 17-hydroxycorticosteriods (17-OHCS). In conscious dogs the adrenal 17-OHCS secretion rate increased from a pre-injection secretion rate of 0.11 plus or minus 0.014 to 1.58 plus or minus 0.069 (mean plus or minus SE) mug/kg/min following an intravenous injection of pilocarpine (0.3 mg/kg); there was a return to the baseline level by 120 min. In anesthetized dogs a marked increase in adrenal 17-OHCS secretion was also observed, which was completely abolished by hypophysectomy A noticeable impairment of the adrenocortical response to pilocarpine was found to be produced by radio-frequency-current lesions of the anterior median eminence. A partial depression of the response was also observed in dogs with the anterior ventromedial hypothalamic lesions. Lesions destroying other hypothalamic areas were found to be without significant effect upon the adrenal cortical secretory response to pilocarpine.

17-Hydroxycorticosteroids↗
PubMed1997

Fluoride and pilocarpine reduce the risk of caries produced by chronic clomipramine treatment in rats.

The effects of chronic clomipramine treatment on the incidence of caries in the rat and their prevention by fluoride and pilocarpine were investigated. One hundred and twenty male Wistar rats were divided into six groups, five experimental groups, one control group and treated with 50 mg/kg/day of clomipramine, 10 ppm fluoride in drinking water, and 5 mg/kg/day of pilocarpine. All animals were infected with Streptococcus sobrinus 6715 and fed a cariogenic diet ad libitum for 42 days. Water and food consumption, weight gain, salivary flow rate, amylase activity, protein and fluoride concentration in saliva, and caries scores were determined in all animals. Whereas clomipramine significantly increased the fluoride and protein concentration in saliva, pilocarpine only decreased fluoride concentration. Animals treated with clomipramine developed 40% more sulcal caries than nontreated animals. Administration of fluoride (10 ppm) in drinking water and chronic oral administration of pilocarpine prevented the increased risk of developing caries associated with chronic treatment with clomipramine.

Administration, Oral↗
PubMed1997

Short-term effect of apraclonidine on intraocular pressure in glaucoma patients receiving timolol and pilocarpine.

A placebo-controlled, prospective study was undertaken to determine whether apraclonidine has an additive effect in eyes treated with timolol and pilocarpine. Twelve patients with primary open-angle glaucoma while on continuing therapy with timolol 0.5% twice daily and pilocarpine 4% four times a day in both eyes for 3 months were included in the study. A single drop of apraclonidine 1% or placebo was added to treatment with timolol and pilocarpine. Intraocular pressure (IOP) was measured on both days before a single drop of test medications in both eyes as well as 2, 4, 6, 8 and 12 h later. The fall in IOP with apraclonidine was significantly greater than with placebo at all time intervals (p < 0.05). This study suggests that apraclonidine provides an additive IOP-lowering effect to timolol and pilocarpine for at least 12 h after single-drop applications.

Administration, Topical↗
PubMed1994

Regulation of Clara cell 10 kD protein secretion by pilocarpine: quantitative comparison of nonciliated cells in rat bronchi and bronchioles based on laser scanning confocal microscopy.

Standard immunohistochemical techniques and laser scanning confocal microscopy were used to assess changes in the abundance of Clara cell 10 kD protein (CC10) within granules and endoplasmic reticulum of rat nonciliated cells after the administration of the secretagogue pilocarpine. Intracellular pools of CC10 were compared over time with time-matched controls at two airway levels, proximal bronchi and terminal bronchioles. Three zones of reflectance intensity (high, medium, and low), corresponding to different densities of CC10 were used to quantify changes in CC10 levels. We observed a shift in the abundance of CC10 from endoplasmic reticulum to granules 30 min after injection of pilocarpine. In addition, the depletion of granule-based CC10 occurred earlier in bronchial cells (30 min) than in bronchiolar cells (60 min). We also noted that the density of CC10 within the two cellular compartments remained steady even though the levels of CC10 dropped due to degranulation. Following degranulation, CC10 levels returned to near-control levels. In the absence of pilocarpine, the percentage of cell volume occupied by the granule-based CC10 indicated that two varieties of nonciliated cells exist in bronchial airways. However, administration of pilocarpine abolishes this difference in CC10 abundance. Our results demonstrate that bronchial cells respond sooner to the secretagogue than do their bronchiolar counterparts and/or possess biosynthetic capabilities that are more easily overwhelmed than those of the terminal bronchiolar cells. These differences suggest that proximal nonciliated cells are distinct from distal nonciliated cells.

Animals↗
PubMed1983

Volume and composition of pilocarpine- and isoproterenol-stimulated submandibular saliva of early postnatal rats.

Submandibular saliva was collected from early postnatal rats by cannulation of the main excretory duct of individual glands after i.p. injections of pilocarpine (10 mg/kg body weight) or isoproterenol (10 mg/kg body weight). With this method of saliva collection, a secretory response to pilocarpine was observed at two wk of age. The average weight of 40 glands was 35.6 +/- 1.6 mg, and the average volume of saliva secreted in 60 min was 32 +/- 2.2 microliters. By three wk of age, the gland had approximately doubled in size (average weight of 39 glands = 61.9 +/- 3.1 mg), and the average total volume of saliva secreted in 60 min was more than three times larger (120.4 +/- 10.5 microliters) than that secreted by two-week-old rats. The relationship between electrolyte (Na+, K+, Ca++) and protein concentrations and rate of flow was similar to that observed in pilocarpine-stimulated adult saliva, and did not differ appreciably in the saliva of two- and three-week-old animals. A measurable secretory response to isoproterenol was observed at three wk of age when saliva was collected by duct cannulation. The average total volume of saliva secreted in 60 min was 48 +/- 3.1 microliters, and salivary Na+ and K+ concentrations, and their relationship to flow rate, were similar to those of isoproterenol-stimulated adult saliva. Saliva Ca++ and protein concentrations were also generally similar to those of isoproterenol-stimulated adult saliva. Total protein output (in 60 min) was 2 1/2 times greater in three-week-old rats with isoproterenol stimulation (compared to pilocarpine stimulation), but was significantly smaller than that of isoproterenol-stimulated adult glands. It is concluded that the submandibular gland of early postnatal rats is capable of secreting saliva in vivo following cholinergic and beta-adrenergic stimulation, and that this ability corresponds with the appearance of the corresponding autonomic receptors, but precedes cytodifferentiation. Ductal transport of electrolytes is well-developed at this stage of postnatal development, but fluid and protein output is smaller than in adult glands and requires full morphological maturation of acinar cells.

Animals↗
PubMed1998

A comparison of artificial saliva and pilocarpine in the management of xerostomia in patients with advanced cancer.

This was a crossover study comparing a mucin-based artificial saliva (Saliva Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.

Adult↗
PubMed1987

Effect of isoproterenol and forskolin on amylase release from parotid tissue after chronic pilocarpine administration in rats following ligation removal.

The influence of chronic pilocarpine administration on the recovery of the parotid gland from an obstruction was investigated by studying the amylase release induced by secretagogues in rats. Treatment with pilocarpine (5 mg/kg, daily for 7 days) increased amylase release induced by isoproterenol (10(-5) M) or forskolin (10(-5) M) in the parotid tissue of rats after the removal of a 7-day-duct ligation. However, there was no significant difference in the amylase activity of the parotid tissue between pilocarpine-treated rats and control rats. These results suggest that the accelerated recovery of amylase release from parotid tissue in rats chronically treated with pilocarpine may be due to the increased response of amylase release, rather than the increased accumulation of secretory materials in the cells; and furthermore, cyclic AMP-mediated events may be involved in the increased response of amylase release.

Amylases↗
PubMed2002

The contribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy.

The pilocarpine model of epilepsy in rats is characterised by the occurrence of spontaneous seizures (SRSs) during the chronic period that recur 2-3 times per week during the whole animal life. In a previous study on brain metabolism during the chronic period of the pilocarpine model it was possible to observe that, among several brain structures, the lateral posterior thalamic nuclei (LP) showed a strikingly increased metabolism. Some evidences suggest that the LP can participate in an inhibitory control system involved in the propagation of the seizures. The aim of the present study was to verify the role of LP in the expression and frequency of spontaneous seizures observed in the pilocarpine model. Ten adult male rats presenting SRSs were monitored for behavioural events by video system one month before and one month after LP ibotenic acid lesion. Another group of chronic epileptic rats (n=10) had the anteroventral thalamic nuclei (AV) lesioned by ibotenic acid. After the surgical procedure, the animals were sacrified and the brains were processed for histological analysis by the Nissl method. The LP group seizure frequency was 3.1+/-1.9 before ibotenic acid injection and showed an increase (16.3+/-7.2 per week) after LP lesion. No changes in SRSs frequency were observed in the AV group after ibotenic lesion in these nuclei. These results seem to suggest that LP play a role in the seizure circuitry inhibiting the expression of spontaneous seizures in the pilocarpine model.

Animals↗
PubMed1984

Lack of effect of pilocarpine on corneal epithelial wound healing.

The effect of a commercially available pilocarpine preparation on corneal epithelial healing rates was evaluated in rabbit eyes. Epithelial defects were created with filter paper discs soaked in n-heptanol. After creation of the defects, the corneas were stained with fluorescein and photographed using a Wratten blue filter. Follow-up examinations, drop administration, and photography were carried out every six hours for three days. Defect size was determined by computerized planimetry. The first phase of this study compared the effects of non-preserved saline and a commercially available methylcellulose preparation. The second phase compared a commercially available 2% pilocarpine preparation with 2% pilocarpine solution in non-preserved saline. We found that 2% pilocarpine had no significant effect on corneal epithelial healing rates.

Animals↗
PubMed1985

Pilocarpine concentrations in aqueous humor following single drop application. I. Effect of soft contact lenses.

Following single drop instillation of pilocarpine, drug levels in individual aqueous humor samples of rabbits were determined by high-performance liquid chromatography and correlated with changes in pupillary diameter and intraocular pressure (IOP). Application of higher concentrations of pilocarpine resulted in higher drug levels but these differences were neither statistically significant nor consistently proportional to the strength applied. Maximum miosis occurred between 30 and 60 minutes and the maximum fall in IOP occurred between 1 and 2 hours. The influence of contact lenses with varying water content and thickness upon intraocular penetration of pilocarpine was studied. Contact lenses did not affect 30-minute concentrations of pilocarpine in aqueous humor. Although two-hour levels were significantly lower with contact lenses, miosis and IOP at these time periods were comparable with and without lenses. Neither water content nor thickness appreciably influenced miosis and IOP.

Animals↗
PubMed1989

The toxic effects of pilocarpine gel and drops on rabbit cornea.

Pilocarpine drops and gel were applied daily for 3 months to rabbit cornea to determine their cytotoxic effects. The corneas were examined clinically with slit lamp biomicroscopy and histologically with scanning and transmission electron microscopy. The gel-treated corneas developed edema and desquamation of the superficial epithelial layers. Vacuoles, swollen mitochondria and amorphous deposits were detected in the basal epithelial layers. The drop-treated corneas developed endothelial cell damage characterised by cytoplasmic vacuoles, swelling and degeneration of the intracellular organelles. The study confirms the clinical impression that pilocarpine gel can produce anterior corneal damage. The toxic effect of pilocarpine gel on the corneal endothelium was much less than the effect produced with pilocarpine drops.

Administration, Topical↗
PubMed1999

Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma. Italian Latanoprost Study Group.

PURPOSE: To compare intraocular pressure (IOP) after adding either latanoprost or pilocarpine to timolol treatment or switching to latanoprost monotherapy in glaucomatous eyes in which IOP was inadequately controlled with timolol. METHODS: This 6-month randomized study comprised 148 patients with primary open-angle or pseudoexfoliation glaucoma, which was inadequately controlled with topical beta-adrenergic antagonists. After a 2- to 4-week run-in period with timolol 0.5% twice daily, patients were assigned in randomized fashion to three study groups: one group received add-on therapy of latanoprost 0.005% once daily, the second group received add-on therapy of pilocarpine 2% three times daily, and the third group switched to latanoprost 0.005% once daily. Mean diurnal IOP was measured at baseline and after 3 and 6 months of treatment. RESULTS: At 6 months, 128 patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups. Adding latanoprost to timolol treatment reduced diurnal IOP by 6.1+/-0.3 mmHg (-28%), adding pilocarpine to timolol treatment reduced diurnal IOP by 4.2+/-0.3 mmHg (-19%), and switching from timolol to latanoprost monotherapy reduced diurnal IOP by 5.5+/-0.3 mmHg (-25%). CONCLUSION: A significantly greater reduction in diurnal IOP was achieved after addition of latanoprost than after addition of pilocarpine in patients in whom IOP was not adequately controlled with timolol alone. Further, the results of this study indicate that a switch to latanoprost monotherapy can be attempted before combination treatment is initiated.

Adolescent↗
PubMed1998

Acute and chronic structural effects of pilocarpine on monkey outflow tissues.

PURPOSE: Determine the effects of supraclinical topical doses of pilocarpine on the structure of the trabecular meshwork (TM), ciliary muscle (CM), and ciliary processes in monkeys. METHODS: Cynomolgus monkeys received topical pilocarpine hydrochloride doses of 1 to 2 mg unilaterally once or twice daily for 1 to 211 days. Both eyes were examined by light and electron microscopy. RESULTS: After 1 dose, the TM was expanded and the flow pathways open. Some elastic anterior CM tendons were disconnected from the muscle tips and/or the tips themselves were disrupted; macrophage-like cells accumulated in these regions. In eyes that had long-term treatment, scar tissue at the muscle tips and disruption of myofibrils within muscle cells indicated regions of previous disconnection. Most collagen tendons inserting into the peripheral cornea were unaffected. With increasing treatment duration in younger monkeys, there was anteroposterior shortening of Schlemm's canal, TM densification due to collapse, and increased cellularity in the subendothelial region of Schlemm's canal. TM densification and Schlemm's canal shortening were not found in older monkeys, implicating posterior movement of the elastic young limbal region induced by strong CM contraction, rather than pilocarpine toxicity. In the ciliary body we found vasodilation, Greeff's vesicles, and blood-aqueous barrier breakdown in the anterior ciliary processes and vasodilation, edema, and round-cell infiltration in the posterior pars plana. CONCLUSIONS: Large pilocarpine doses induce morphologic changes in the monkey anterior segment, likely consequent to intense CM contraction. Changes in the TM and Schlemm's canal are seen only in young monkeys, apparently owing to mechanical deformation of the elastic limbal region.

Animals↗
PubMed1975

Pilocarpine delivery by hydrophilic lens in the management of acute glaucoma.

Patients with acute closed-angle glaucoma were treated with a hydrophilic contact lens saturated in 1, 4, or 8 per cent. pilocarpine or bt intensive 4 per cent. pilocarpine drops. The greatest hypotensive response was produced by the 1 per cent. presoaked lens and increased strength of soaking solution gave reduced response. Intensive drops gave the least response. In vitro studies show that the lens is effectively saturated after 2 hrs' soaking holds c. 700 mug. pilocarpine and yields almost all of the contained pilocarpine after 2 hrs' elution. The method of lens preparation is described and pharmaceutical studies confirm a shelf life of 4 months in a domestic refrigerator.

Acetazolamide↗
PubMed1979

The effects of topical pilocarpine on the morphology of the outflow apparatus of the baboon (Papio cynocephalus).

The morphology of the outflow system of the baboon (Papio cynocephalus) was studied by light microscopy and transmission electron microscopy in tissue from eyes treated with topical pilocarpine. In one group of five animals the intraocular pressure (IOP) was maintained at 18 mm /g in both the experimental and the control eye of each baboon for the duration of the experiment. The endothelial meshwork was more distended, and there was a significantly greater number of giant vacuoles in the lining endothelium of Schlemm's canal in the pilocarpine-treated eyes than in the corresponding controls. However, in another series of animals, IOP was not maintained, and the differences between the treated and untreated eyes was much less striking. There appeared to be little evidence that the increase in vacuolation was produced by the direct action of pilocarpine on the endothelium of Schlemm's canal; more likely, it was a consequence of an increased passage of fluid through the drainage system. In addition, we have been able to show that (1) the mode of primary fixation can produce partial reversal of the pilocarpine effect and (2) the mechanical manipulation which is required to determine outflow facility has a deleterious effect on the morphology of the outflow tissues.

Animals↗
PubMed2000

Pharmacological effects of pilocarpine on rabbit ciliary artery.

PURPOSE: A disturbance in ocular blood flow is an important factor in the pathogenesis of visual damage caused by glaucoma. We investigated the innervation of the ciliary artery, important to blood flow in the optic nerve head, and the effects of pilocarpine thereon. METHODS: Ciliary arteries were prepared from rabbit eyes and mounted in a myograph system. The effects of electrical nerve stimulation and pilocarpine on the isolated rabbit ciliary artery were investigated using isometric tension recording methods. RESULTS: Electrical field stimulation evoked contraction of the ciliary artery, which was inhibited by pretreatment with 10 microM bunazosin. Electrical field stimulation also evoked relaxation when the ciliary artery was pre-contracted by 10 microM histamine in the presence or absence of endothelium. This relaxation was inhibited by pretreatment with 10 microM N(G)-nitro-L-arginine methylester (L-NAME). Pilocarpine administration produced a dose-dependent muscle relaxation that was abolished by treatment with L-NAME, 1 aeM atropine, or denudation of the endothelium. CONCLUSIONS: Results indicate that the rabbit ciliary artery is innervated by at least two different types of nerves, adrenergic nerves, which evoke contraction and nerve fibers that cause an endothelium-independent release of nitric oxide (NO). Pilocarpine relaxation of this muscle was dependent on the endothelium and NO synthesis.

Animals↗