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PubMed2000

Pilocarpine in the prevention of postirradiation xerostomia.

During radiation therapy to the head and neck region, salivary gland hypofunction commonly develops. The aim of our study was to evaluate whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction. Our results showed the pilocarpine-treated group to have a lower frequency of oral symptoms during the treatment than the placebo-treated group. Although salivary flow decreased in all patients, the pilocarpine-treated group had smaller flow reductions. No drug effect was observed in the glands that were completely irradiated. Thus, pilocarpine appeared to stimulate salivary tissues outside the radiation field.

Double-Blind Method↗
PubMed2000

Effects of L-arginine on prevention and treatment of lithium-pilocarpine-induced status epilepticus.

The effects of various doses of L-arginine, a nitric oxide substrate, on lithium-pilocarpine-induced seizures were studied in rats. Rats were implanted with chronic, stainless steel screw electrodes epidurally for electrocortical recordings. A control group received 3 mEq/kg LiCl (i.p.) and 24 h later 45 mg/kg pilocarpine HCl (i.p.). Two different experimental procedures were followed: (1) L-arginine was applied in doses of 100 mg/kg, 300 mg/kg or 500 mg/kg (i.p.), 30 min before pilocarpine injection; (2) 300 mg/kg, 500 mg/kg or 1000 mg/kg (i.p.) L-arginine was injected either 5 min or 30 min after the onset of status epilepticus (SE). L-arginine (300 mg/kg) injected 30 min before pilocarpine significantly reduced the percentage of SE, but did not change the latency to SE or 24-hour survival. These parameters were not significantly affected by the 100 mg/kg or 500 mg/kg dose of L-arginine. On the other hand, no dose of L-arginine that was applied after SE had begun, had any significant influence on the seizures. We concluded that L-arginine may prevent seizure activity in some but not all doses, and does not have any effect on the ongoing seizure activity.

Animals↗
PubMed1975

Quantitation of pilocarpine flux enhancement across isolated rabbit cornea by hydrogel polymer lenses.

The comparative effect on pilocarpine flux across rabbit cornea induced by two hydrogel polymer lenses containing equal doses was quantitated in a transport chamber. This closed system featured continuous flow of a tear analog but excluded variables of the internal eye influencing concentration. Flux induced by both lenses increased linearly with time. At 240 minutes total flux was a whole order greater than that induced by the same pilocarpine dose in free fluid. Analysis of pilocarpine in tear analog effluent showed the flux to be independent of the available dose retained in the hydrogel polymer lens, suggesting that corneal transport of pilocarpine to the aqueous may involve mediation by a carrier system.

Animals↗
PubMed2001

Randomized double blind, placebo-controlled study of pilocarpine administered during head and neck irradiation to reduce xerostomia.

PURPOSE: Pilocarpine hydrochloride administered during head and neck irradiation was evaluated for its ability to relieve xerostomia and its adverse effects. MATERIAL AND METHOD: A total of 60 head and neck cancer patients were enrolled in a randomized, double blind, placebo-controlled trial. Each patient had both parotid glands treated with a radiation dose of at least 50 Gy. Patients received jelly containing pilocarpine or placebo 5.0 mg (1 cc.) tid at meal times during radiation. Pilocarpine was administered beginning on the first day of radiation and continued until radiation was completed. Patients were evaluated for symptomatic relief by responding to questionnaires using a Visual Analogue Scale (VAS). Questionnaires measured relief of oral dryness, oral discomfort, difficulty in chewing and swallowing, speaking, and sleeping. Evaluation was conducted preradiation as a baseline, weekly during radiation and monthly until 6 months after radiation was completed. RESULTS: The baseline characteristics, disease and radiation technique including field arrangement and total dose, were not significantly different between the two groups. There was no statistically significant subjective difference in xerostomia, including oral dryness, oral discomfort, inability to chew and swallow, speak and sleep, during and postradiation between the two groups. The adverse effects were non-specific symptoms such as nausea, vomitting, dizziness, urinary frequency, palpitation, sweating and tearing. The adverse effects during radiation and postradiation were not significantly different between the two groups. CONCLUSION: It was concluded that pilocarpine hydrochloride administered during head and neck irradiation produced subjectively insignificant benefit in relieving xerostomia with acceptable side effects.

Aged↗
PubMedDate not supplied

[Effect of pilocarpine and cycloplegic substances on ophthalmic tone in healthy eyes and ones with glaucoma].

The study was carried out on the eyes of patients (aged 20-75 eyes) without glaucoma and with primary open-angle glaucoma (POAG). A single instillation of 1 or 2% pilocarpin hydrochloride did not lead to a decrease of intraocular pressure (IOP) in the eyes without glaucoma. IOP fluctuations after pilocarpin instillations were accidental and as a rule were observed both in the treated and control eyes. Instillations of the same pilocarpin solutions significantly decreased IOP in the eyes with OAG in the majority of cases (in 76% in our study), which is apparently due to removal or decrease of the canalicular block. The results of relieving tonometric pilocarpin test should be taken account of in early diagnosis of glaucoma, but the diagnostic parameters of the test should be determined more precisely. After instillation of short-acting cycloplegic drugs (1% homatropin and 0.5% tropicamide) IOP did not change either in normal or POAG eyes. These drugs are recommended for dilatation of the pupil for ophthalmoscopy in patients with anterior chamber open angle glaucoma.

Adult↗
PubMed1976

[Acetylcholine in the bovine choroid and the cholinergic effect of pilocarpine].

In this study the authors have compared the cholinergic tone in a collection of bovine choroids after instillation of pilocarpine in the conjunctival fornix in one group using the opposite choroid from the same animal as a control. The tests for acetylcholine (ACh) were assayed on guinea-pig ileum. The choroidal nerves in the pilocarpinised eyes had an average level of 0,50 mug of ACh, the homologous choroidal nerves of the controls had an average level of 0,45 mug of standard ACh per 150 mg of tissue. The pilocarpine had been instilled in the conjunctival fornix as a 3 per cent aqueous solution of pilocarpine HCl, ten times three drops in intervals of three minutes. One hour after the last application the animals were sacrificed and the eyes enucleated. The authors discuss the clinica importance of the infiltration of pilocarpine into the choroid.

Acetylcholine↗
PubMedDate not supplied

[Acetylcholine in the bovine retina and the parasympathomimetic effect of pilocarpine].

Using titrations of acetylcholine (ACh) on guinea-pig ileum the authors have demonstrated that there is no significant statistical difference between the cholinergic activity of extracts of 150 mg of retinal tissue from pilocarpinised eyes (0.3 mug of ACh) and the activity of extracts from control eyes not subjected to pilocarpine (0.29 mug of ACh). The pilocarpine had been instilled into the bovine conjunctival sac at the rate of three drops of 3 p. 100 pilocarpine HCl ten times at intervals of three minutes. One hour after the last application the animals were killed and the eyes enucleated. The role of pilocarpine in the regulation of tissues in the posterior segment of the eye is discussed.

Acetylcholine↗
PubMedDate not supplied

Ultrasonic study to see the effect of topical pilocarpine and homatropine on anterior chamber depth in phakic cases.

Pilocarpine and Homatropine are the drugs having known effect on the depth of anterior chamber. The purpose of this study was to demonstrate the time of onset, peak effect and its duration of action as well as shallowing/deepening of the anterior chamber, after single instillation of pilocarpine 2% or homatropine bromide 2%, topically in one eye. Also we tried to see if there is any effect on the contralateral eye, due to systemic absorption of pilocarpine, homatropine after topical instillation of the drug in one eye. Pilocarpine causes a measurable shallowing of the anterior chamber with onset of effect with in 20 minutes and a peak in 60 minutes, the average narrowing being 0.26 mm. (range 0.20-0.29 mm.). Homatropine has a measurable deepening effect on the anterior chamber, due to axial flattening of the lens because of cycloplegia, with a range of 0.33 to 0.36 mm. In 70% of the cases the effect passes away with in 24 hours., but in 30% it comes to normal in 48 hours.

Adult↗
PubMed2000

Transtympanic pilocarpine in tinnitus.

In 48 patients who had neurosensory hypoacusia and whose main complaint was tinnitus, a 1% pilocarpine solution or a 2% carbachol Isopto solution was placed in the tympanic cavity by means of a No. 26 pencil-tipped lumbar puncture needle through the front quadrant of the eardrum. Patients were chosen without regard for age, gender, or topographical damage of the acoustic pathway. Evaluation of the drug's effect was performed audiometrically by masking with the minimum intensity of the pure sound or narrow band that most closely resembled the patients' own noises. The results of this medical therapy were positive and ranged from complete annulment to attenuation of the tinnitus, which was confirmed by audiometric masking 30 minutes after the intratympanic injection. These positive results reached 50% and would have been higher if the several cases submitted by accident insurance companies and cases of presbyacusia were discarded. The unsatisfactory element of the study was the short-term effect of the therapy, which usually lasted no more than 12-72 hours. Tinnitus reappeared in all patients at its original intensity. The best results involved the use of carbachol as compared with pilocarpine. The decision to replace pilocarpine with carbachol was based on the idea that the inhibitory cholinergic efferent pathways are damaged before the afferent pathways. The use of pilocarpine depends on efficient cholinergic functioning, as its activity is as an indirect agonist (i.e., to annul the cholinesterase enzyme).

Adult↗
PubMed2005

Molecular mechanism of bovine trabecular meshwork cells apoptosis induced by dexamethasone and protection by pilocarpine.

PURPOSE: To study the molecular mechanism of trabecular meshwork cells apoptosis induced by dexamethasone and the protection of pilocarpine. METHODS: Determining mRNA expression with reverse transcription-polymerase chain protein expression with Western blots and the percentage of reaction (RT-PCR), apoptotic cells with fluorescent microscopy. RESULTS: Dexamethasone up-regulated Fas proteins and affected Bax, caspase-8 and caspase-9 proteins in an action of first decrease then increase. Pre -treatment with pilocarpine decreased the four proteins expression, which were increased by dexamethasone. Pilocarpine self could decrease pro-apoptotic factors Bax, caspase-8 and caspase-9 proteins expression. CONCLUSION: Fas/FasL pathway participated in apoptotic process induced by dexamethasone in trabecular meshwork cells and the process was probably related with both caspase-8 and caspase-9 pathways. Pilocarpine protected the cells against apoptosis through down-regulating Fas, Bax, caspase-8 and caspase-9 proteins expression.

Animals↗
PubMed1992

Effects of pilocarpine and tropicamide on blood-aqueous barrier permeability in man.

The time courses of changes in the effects of topical pilocarpine and tropicamide on the index of the blood-aqueous barrier permeability to plasma protein (Pin) were determined in normal volunteers. Before and after drug instillation in one eye, protein concentration in the anterior chamber (Ca) was determined from aqueous flare intensity with a laser flare-cell meter and from aqueous flow by fluorophotometry. The Pin was calculated from the Ca, plasma protein concentration, and aqueous flow. One percent pilocarpine produced a maximum increase of 21 +/- 10% in the Ca (mean +/- SEM, n = 10), no significant change in the aqueous flow (n = 5), and a maximum increase of 29 +/- 10% in the Pin (n = 10). Three percent pilocarpine produced a maximum increase of 55 +/- 11% in the Ca (n = 8), a maximum increase of 34 +/- 13% in the aqueous flow (n = 5), and a maximum increase of 74 +/- 18% in the Pin (n = 8). Tropicamide (0.4%) produced a maximum decrease of 17 +/- 7% in the Ca (n = 8), a maximum decrease of 15 +/- 11% in the aqueous flow (n = 8), and a maximum decrease of 24 +/- 13% in the Pin (n = 8). The results indicated that pilocarpine increased the blood-aqueous barrier permeability to plasma protein in a dose-dependent manner and that tropicamide reduced it.

Adult↗
PubMed1991

Effects of topical dihydroergocristine on intraocular pressure, aqueous humor dynamics and pupil diameter in conscious rabbits. A comparative study with timolol and pilocarpine.

This work comparatively studies the effects of dihydroergocristine, timolol and pilocarpine on intraocular pressure and pupil diameter in conscious rabbits. Intraocular pressure was measured by applanation tonometry and the pupil diameter by a photographic technique. In anesthetized rabbits, changes in tonographic facility of aqueous humor outflow and rate of aqueous humor formation were evaluated. Dihydroergocristine reduced the intraocular pressure more than timolol and much more than pilocarpine. The ocular hypotensive effect of dihydroergocristine was accomplished by a great reduction in aqueous humor formation, which surpasses the decrease in aqueous humor outflow, while timolol mainly reduced aqueous humor formation and pilocarpine increased aqueous humor outflow. Pupil diameter remained unchanged on dihydroergocristine, whereas timolol induced a slight mydriasis and pilocarpine provoked a clear myosis. Effects of dihydroergocristine might result in blockade of alpha-adrenoceptors in ciliary body, although available data about pretreatment with either metoclopramide or domperidone suggest that dopamine DA2-receptors might participate in ocular hypotensive effect of ergot derivatives.

Administration, Topical↗
PubMed1991

Aqueous humor pilocarpine and timolol levels after instillation of the single drug or in combination.

Aqueous humor levels of pilocarpine and timolol in rabbits after administration of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared with the concentrations found after instillation of a fixed combination of 0.5% timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min, 1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in individual aqueous samples by high-performance liquid chromatography. No statistically significant differences in either pilocarpine or timolol concentrations in aqueous humor were found at any time tested between the single-drug preparations and the combination.

Administration, Topical↗
PubMed1991

Effects of topical administration of 2.0% pilocarpine on intraocular pressure and pupil size in cats.

Effects of topical administration of a single dose of 2% pilocarpine on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and, diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was found to be 10.1 (+/- 0.5) mm. Topical treatment with pilocarpine resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 4 hours after treatment. Mean reduction of IOP was 15.2% in the treated eye and 9.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction in pupil diameter was 28.5% in the treated eye and 14.2% in the nontreated eye. Topically administered pilocarpine results in reduction of IOP and pupil diameter in treated and contralateral eyes, which supports the use of pilocarpine for treatment of glaucoma in cats.

Administration, Topical↗
PubMed1991

Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia).

We studied the effects of pilocarpine hydrochloride, a para-sympathomimetic agent, on major salivary gland output and subjective responses in 31 patients with salivary hypofunction. Pilocarpine hydrochloride (5-mg capsules, three times daily) was given for 5 months and a placebo was randomly assigned for 1 month in a double-blind fashion. Objective measurements of major salivary gland output, subjective impressions of oral moisture, treatment-related side effects, and a number of physiologic measures were assessed monthly. Pilocarpine significantly increased salivary output in 21 of the 31 patients. Subjective improvement in the feeling of oral dryness, speaking, chewing, and swallowing were reported by 27 individuals. Side effects, while common, generally were mild and tolerable. There were no significant alterations in cardiovascular or other physiologic measures. We conclude that pilocarpine is an effective and safe treatment for salivary gland hypofunction and xerostomia in selected patients. The increase in major gland output provides beneficial natural secretions and relief of oral dryness.

Adolescent↗
PubMed1990

Modulation of rat salivary carbonic anhydrase by pilocarpine.

Carbonic anhydrase (CA) from pilocarpine-treated (1.5 mg/kg body weight; i.p.) rat saliva was purified by inhibitor affinity chromatography. The purified CA contained Mr 42000 and 39000 proteins on sodium dodecyl sulfate polyacrylamide gel electrophoresis. In addition to the erythrocyte isozyme (Mr 30000), salivary gland CA from rats without pilocarpine stimulation contained Mr 39000 and 33000 proteins and that from rats with pilocarpine stimulation also contained Mr 42000 protein. The 42000Da and 39000Da proteins bound to concanavalin A and were cleaved by endo-beta-N-acetylglucosaminidase F to become 39000Da and 33000Da proteins. These results suggest that, under the influence of pilocarpine, salivary gland cells synthesize a new glycoprotein, Mr 42000, via N-linked glycosylation of a 39000Da glycoprotein, which is the only secretory glycoprotein in the unstimulated salivary gland and is produced by N-linked glycosylation of a 33000Da polypeptide.

Animals↗
PubMed1990

[Decrease in intraocular pressure following administration of the local carbonic anhydrase inhibitor (MK-927)--comparison of the effect with pilocarpine].

We studied the effect of a single dose of the local carbonic anhydrase inhibitor, MK-927, on lowering IOP in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension and compared it with the effect of pilocarpin in 9 patients. Following a washout of any glaucoma medication of 3 to 14 days, a diurnal IOP curve was performed. Two to seven days later one eye received a single drop of 2% MK-927 while the other eye received placebo and the diurnal IOP curve was repeated. MK-927 treated eyes showed a peak mean IOP change of 10.5 mmHg (33.1%) occurring at 4.5 h postmedication. In nine eyes treated with pilocarpin 1% q.d., the mean reduction of the mean IOP was 7.0 mmHg (22.1%) compared to no treatment. The same eyes showed a mean reduction of mean IOP of 6.1 mmHg (18.9%) following a single dose of MK-927. In contrast, the mean reduction of the maximal IOP treated with pilocarpin was 7.3 mmHg (25.8%) and 10.2 mmHg (34.2%) following MK-927. Considering the IOP lowering of MK-927 shown here, the possibility of a topically effective glaucoma therapy by local carbonic anhydrase inhibitor seems to be established. The IOP lowering effect of MK-927 appears to be similar to that of pilocarpin 1%.

Carbonic Anhydrase Inhibitors↗
PubMed1989

Effects of 4% pilocarpine gel on normotensive and glaucomatous canine eyes.

A 4% pilocarpine gel applied topically to eyes was evaluated in glaucomatous Beagles and normotensive Miniature Schnauzers to determine its efficacy in reducing intraocular pressure (IOP) and to assess any side effects. Pilocarpine gel significantly (P less than 0.05) reduced IOP for 24 hours after treatment, compared with baseline (pre-drug) values, untreated fellow eyes, and placebo-treated eyes. The IOP remained significantly lower (P less than 0.05) during 3 treatment days, as well as the first 2 days after treatment. The pupil sizes were significantly smaller (P less than 0.01) in all treated dogs after the first administration of pilocarpine, compared with baseline values, untreated eyes, and placebo-treated eyes. The subsequent pilocarpine gel administrations induced significant miosis (P less than 0.01), compared with baseline values, but the extent of miosis and duration were significantly less (P less than 0.01) as the number of treatments increased. Conjunctival irritation and blepharospasm were observed mainly in the first 2 days of treatment and were minimal after subsequent applications. There was no contralateral effect on IOP or pupil size, compared with baseline values and placebo-treated eyes.

Animals↗