Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study.

BACKGROUND: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. METHODS: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. RESULTS: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. CONCLUSIONS: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

Pretreatment of microneedles enhances passive transdermal administration of pilocarpine and pilocarpine-induced sweat production in humans.

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to âˆ¼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures.

PURPOSE: This study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy. METHODS: Eighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms' severity related to hyposalivation. RESULTS: All patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients' self-assessment, with a median duration of 12 months (range, 3-36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7-18 points) to 7 points (range 4-13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04). CONCLUSION: Pilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model / Ratas sem Status Epilepticus apresentam comportamento do tipo crise epiléptica na fase crônica do modelo experimental da Pilocarpina

Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

Cardioprotective effects of amiodarone in a rat model of epilepsy-induced cardiac dysfunction.

Cardiac dysfunction is one of the leading causes of death in epilepsy. The anti-arrhythmic drug, amiodarone, is under investigation for its therapeutic effects in epilepsy. We aimed to evaluate the possible effects of amiodarone on cardiac injury during status epilepticus, as it can cause prolongation of the QT interval. Five rat groups were enrolled in the study; three control groups (1) Control, (2) Control-lithium and (3) Control-Amio, treated with 150 mg/kg/intraperitoneal amiodarone, (4) Epilepsy model, induced by sequential lithium/pilocarpine administration, and (5) the epilepsy-Amio group. The model group expressed a typical clinical picture of epileptiform activity confirmed by the augmented electroencephalogram alpha and beta spikes. The anticonvulsive effect of amiodarone was prominent, it diminished (p < 0.001) the severity of seizures and hence, deaths and reduced serum noradrenaline levels. In the model group, the electrocardiogram findings revealed tachycardia, prolongation of the corrected QT (QTc) interval, depressed ST segments and increased myocardial oxidative stress. The in-vitro myocardial performance (contraction force and - (df/dt)max ) was also reduced. Amiodarone decreased (p < 0.001) the heart rate, improved ST segment depression, and myocardial contractility with no significant change in the duration of the QTc interval. Amiodarone preserved the cardiac histological structure and reduced the myocardial injury markers represented by serum Troponin-I, oxidative stress and IL-1. Amiodarone pretreatment prevented the anticipated cardiac injury induced during epilepsy. Amiodarone possessed an anticonvulsive potential, protected the cardiac muscle and preserved its histological architecture. Therefore, amiodarone could be recommended as a protective therapy against cardiac dysfunction during epileptic seizures with favourable effect on seizure activity.

Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE. A set of 119 genes with subtle-to-moderate impact predicted most forms of epilepsy with ~ 97% accuracy and characteristically mapped to upregulated homeostatic and downregulated synaptic pathways. The deconvolution of cellular proportions revealed opposing changes in diverse cell types. The proportion of nonneuronal cells increased whereas that of interneurons, except for those expressing vasoactive intestinal peptide (Vip), decreased, and pyramidal neurons of the cornu-ammonis (CA) subfields showed the highest variation in proportion. A probabilistic Bayesian-network demonstrated an aberrant and oscillating physiological interaction between nonneuronal cells involved in the blood-brain-barrier and Vip interneurons in driving seizures, and their role was evaluated insilico using transcriptomic changes induced by valproic-acid, which showed opposing effects in the two cell-types. Additionally, we revealed novel epileptic and antiepileptic mechanisms and predicted drugs using causal inference, outperforming the present drug repurposing approaches. These well-powered findings not only expand the understanding of TLE and seizure oscillation, but also provide predictive biomarkers of epilepsy, cellular and causal micro-circuitry changes associated with it, and a drug-discovery method focusing on these events.

Dilute pilocarpine test for diagnosis of Adie's tonic pupil.

We have compared the diagnostic ability of different concentrations of 0.125% and 0.0625% dilute pilocarpine for detecting denervation supersensitivity in unilateral Adie's tonic pupil. This retrospective, observational, case-control study involved 117 subjects, consisting of 56 patients with unilateral Adie's tonic pupil and 61 controls with other causes of unilateral dilated pupils. Subjects underwent the dilute pilocarpine test with one of the two concentrations, 0.125% or 0.0625%. Pupillary light reflex was recorded with a dynamic pupillometer at baseline and at 30-40 min after instilling one of the two concentrations of dilute pilocarpine. Diagnostic accuracy of two different concentrations of the dilute pilocarpine test, 0.125% group versus 0.0625% group, were compared by area under the receiver operating characteristic curve (AUC). Diagnostic ability of the dilute pilocarpine test for detecting denervation supersensitivity in unilateral Adie's tonic pupil was significantly better in the 0.0625% group than in the 0.125% group (AUC = 0.954 vs. 0.840, respectively, P = 0.047). In the 0.0625% group, the change in maximal pupil diameter of ≥ 0.5 mm after topical pilocarpine instillation showed 100% sensitivity and 82.8% specificity for detecting Adie's tonic pupil. This study confirmed that pupillary constriction with 0.0625% pilocarpine is better than 0.125% pilocarpine for detecting denervation supersensitivity in Adie's tonic pupil. Digital pupillometry is a reliable method for assessing denervation supersensitivity in Adie's tonic pupil.

Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits.

The present study was focused on investigating niosomal gels loaded with cholinergic drug; pilocarpine HCl, for prolonged precorneal residence time and improved bioavailability for glaucoma treatment. Pilocarpine HCl niosomes were prepared using various nonionic surfactants (span 20, span 60 and span 80), in the presence of cholesterol in different molar ratios by ether injection method. The selected formulations were incorporated into carbopol 934 and locust bean gum-based gels. TEM analysis confirmed that niosomes formed were spherical in shape and has a definite internal aqueous space with uniform particle size. Formulation F4 composed of span 60 and cholesterol (1:1) gave the highest entrapment (93.26 ± 1.75%) and slower release results after 8 hours (Q8h = 60.35 ± 1.87%) among other formulations. The in-vitro drug permeation studies showed that there was a prolonged release of drug from niosomal gels as compared to niosomes itself. Considering the in-vitro drug release, niosomal gel formulation G2 was the best among the studied formulations. The release data were fitted to an empirical equation, which indicated that the release follows non-Fickian diffusion mechanism. The stability study revealed that incorporation of niosomes in gel increased their stability than the niosome itself. No signs of redness, inflammation, swelling or increased tear production were observed over the study period for tested formulation by Draize's test. The intraocular pressure (IOP) lowering activity of G2 formulation showed relative bioavailability 2.64 times more than bioavailability of marketed Pilopine HS® gel. These results suggest that the niosomal gels containing pilocarpine HCl are promising ocular carriers for glaucoma treatment.

Cumulative effects of ciprofloxacin and pilocarpine on cytotoxicity and G0 phase arrest in hepatoma-derived Hep G2 cell line.

OBJECTIVES: Uncontrolled cell proliferation was caused by multiple deficient pathways that inhibition of one pathway may result to activate an alternative pathway. Therefore, combination of drugs which targeted multiple pathways could be beneficial to overcome drug resistance. Ciprofloxacin (CPF) cytotoxicity was widely investigated on cancer cell lines, and results revealed hepatoma-derived Hep G2 cells are relatively resistant. So, this study aimed to increase CPF cytotoxicity by rational design of a supplement which targeted Ca2+ homoeostasis as major hub in unchecked proliferation. METHODS: Cells were treated by CPF and/or pilocarpine (PILO), and cell cycle distribution, caspases activity and regulatory proteins were evaluated. KEY FINDINGS: MTT and flow cytometry analysis confirmed administration of CPF + PILO causes more cytotoxicity. CPF-exposed cells accumulated in S phase due to DNA damages while PILO + CPF imposed G0 stage arrest through cyclin D1 and P-Akt downregulation. Caspase 8 was activated in cells treated by CPF but accompaniment of PILO with CPF led to activation of caspase 9, 8 and 3 and ROS overproduction. CONCLUSIONS: Ciprofloxacin imposed mitochondrial-independent apoptosis while PILO + CPF caused mitochondrial-dependent and independent apoptosis simultaneously. Consequently, coadministration of PILO and CPF causes intense cytotoxic effects through targeting the mitochondria, DNA gyrase enzyme and other unknown mechanisms.

A Proline Derivative-Enriched Fraction from Sideroxylon obtusifolium Protects the Hippocampus from Intracerebroventricular Pilocarpine-Induced Injury Associated with Status Epilepticus in Mice.

The N-methyl-(2S,4R)-trans-4-hydroxy-l-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 µg/1 µL icv, followed by the vehicle per os, po) and NMP-treated groups (Pilo 300 µg/1 µL icv, followed by 100 or 200 mg/kg po). The treatments started one day after the Pilo injection and continued for 15 days. The effects of NMP were assessed by characterizing the preservation of cognitive function in both the Y-maze and object recognition tests. The hippocampal cell viability was evaluated by Nissl staining. Additional markers of damage were studied-the glial fibrillary acidic protein (GFAP) and the ionized calcium-binding adaptor molecule 1 (Iba-1) expression using, respectively, immunofluorescence and western blot analyses. We also performed molecular docking experiments revealing that NMP binds to the γ-aminobutyric acid (GABA) transporter 1 (GAT1). GAT1 expression in the hippocampus was also characterized. Pilo induced cognitive deficits, cell damage, increased GFAP, Iba-1, and GAT1 expression in the hippocampus. These alterations were prevented, especially by the higher NMP dose. These data highlight NMP as a promising candidate for the protection of the hippocampus, as shown by the icv Pilo model.

Effect of Topical Pilocarpine on Choroidal Thickness in Healthy Subjects.

SIGNIFICANCE: This is a proof-of-concept study showing the possibility of pharmacological control for choroidal thickness using pilocarpine as an agent that causes 2 to 5% choroidal thinning in healthy eyes after the instillation. PURPOSE: The purpose of this article was to study the effect of instillation of 1% pilocarpine on choroidal thickness in healthy subjects. METHODS: Sixteen healthy individuals (seven males and nine females; mean ± standard deviation age, 25.8 ± 3.3 years) were included. All participants received optical coherence tomography to evaluate subfoveal choroidal thickness (SCT) and choroidal area on cross-sectional scan within 4-mm central area. Axial length was measured using optical biometry. Optical coherence tomography was performed before and after pilocarpine was instilled six times for a 75-minute period in one eye; the fellow eye was used as the control. Subfoveal choroidal thickness and choroidal area were measured by two masked graders in random fashion and averaged for analysis. RESULTS: After instillation of 1% pilocarpine, percentage SCT change in study and control eye was -3.3 ± 3.8% and 0.4 ± 3.2%, respectively (P = .03). Percentage change choroidal area in study and control eye was -2.3 ± 2.5% and 0.8 ± 3.3%, respectively (P < .001). There was a correlation between percentage SCT change and axial length (r = -0.56, P < .001), as well as between percentage SCT change and baseline SCT (r = 0.72, P < .001). CONCLUSIONS: Instillation of 1% pilocarpine causes a decrease of choroidal thickness, which is more substantial in eyes with short axial length and thick choroid.

Pilocarpine-induced status epilepticus reduces chemosensory control of breathing.

One of the possible causes of death in epilepsy is breathing disorders, especially apneas, which lead to an increase in CO2 levels (hypercapnia) and/or a decrease in O2 levels in arterial blood (hypoxemia). The respiratory neurons located in the ventral brainstem respiratory column are the main groups responsible for controlling breathing. Recent data from our group demonstrated respiratory changes in two experimental models of epilepsy, i.e. audiogenic epilepsy, and amygdala rapid kindling. Here, we aimed to evaluate respiratory changes in the classic model of temporal lobe epilepsy induced by intra-hippocampal injection of pilocarpine. Adult Wistar rats with stainless-steel cannulas implanted in the hippocampus region were used. The animals were submitted to pilocarpine injection (2.4 mg/µL, N = 12-15) or saline (N = 9) into the hippocampus. The respiratory parameters analyzed by whole-body plethysmography were respiratory rate (fR), tidal volume (VT) and ventilation (VE). Respiratory mechanics such as Newtonian airway resistance (Rn), viscance of the pulmonary parenchyma (G) and the elastance of the pulmonary parenchyma (H) were also investigated. No changes in baseline breathing were detected 15 or 30 days after pilocarpine-induced status epilepticus (SE). However, 30 days after pilocarpine-induced SE, a significant reduction in VE was observed during hypercapnic (7% CO2) stimulation, without affecting the hypoxia (8% O2) ventilatory response. We also did not observe changes in respiratory mechanics. The present results suggest that the impairment of the hypercapnia ventilatory response in pilocarpine-induced SE could be related to a presumable degeneration of brainstem respiratory neurons but not to peripheral mechanisms.

Pilocarpine Induced Behavioral and Biochemical Alterations in Chronic Seizure-Like Condition in Adult Zebrafish.

Epilepsy is a devastating neurological condition exhibited by repeated spontaneous and unpredictable seizures afflicting around 70 million people globally. The basic pathophysiology of epileptic seizures is still elusive, reflecting an extensive need for further research. Developing a novel animal model is crucial in understanding disease mechanisms as well as in assessing the therapeutic target. Most of the pre-clinical epilepsy research has been focused on rodents. Nevertheless, zebrafish disease models are relevant to human disease pathophysiology hence are gaining increased attention nowadays. The current study for the very first time developed a pilocarpine-induced chronic seizure-like condition in adult zebrafish and investigated the modulation in several neuroinflammatory genes and neurotransmitters after pilocarpine exposures. Seizure score analysis suggests that compared to a single dose, repeated dose pilocarpine produces chronic seizure-like effects maintaining an average seizure score of above 2 each day for a minimum of 10 days. Compared to the single dose pilocarpine treated group, there was increased mRNA expression of HMGB1, TLR4, TNF-α, IL-1, BDNF, CREB-1, and NPY; whereas decreased expression of NF-κB was upon the repeated dose of pilocarpine administration. In addition, the epileptic group demonstrates modulation in neurotransmitters levels such as GABA, Glutamate, and Acetylcholine. Moreover, proteomic profiling of the zebrafish brain from the normal and epileptic groups from LCMS/MS quantification detected 77 and 13 proteins in the normal and epileptic group respectively. Summing up, the current investigation depicted that chemically induced seizures in zebrafish demonstrated behavioral and molecular alterations similar to classical rodent seizure models suggesting the usability of adult zebrafish as a robust model to investigate epileptic seizures.

Low-dose Pilocarpine Spray to Treat Xerostomia.

Although pilocarpine hydrochloride tablets are currently indicated for the treatment of xerostomia, their adverse effects are frequently reported. The development of a new, low-dose pilocarpine solution for topical oral-cavity use is needed. This article discusses a few clinical trials to formulate a topical low-dose solution of pilocarpine hydrochloride for the treatment of xerostomia and presents two low dose, stable formulations of pilocarpine topical spray that can improve the patient's quality of life with minimal adverse effects.

Temporal Effects of 2% Pilocarpine Ophthalmic Solution on Human Pupil Size and Accommodation.

INTRODUCTION: First responders and those who work with organophosphate (OP) compounds can experience ocular symptoms similar to those caused by exposure to low levels of nerve agents. This study was designed to examine the efficacy of a safe, clinically available, simulant that reproduces ocular symptoms associated with low-level OP exposure. Among these ocular symptoms are a constriction of the pupils (miosis), decreased visual acuity, and changes in accommodation. MATERIALS AND METHODS: Volunteers aged 18-40 were assigned to groups receiving either a two-drop or three-drop dose of FDA approved 2% pilocarpine ophthalmic solution. Baseline visual performance measurements were taken before eye drop instillation and a timer was started following the first drop of pilocarpine. Once eye drops were administered, visual performance including distant and near vision, pupil size, and accommodation were measured every 5 minutes for 2 hours. RESULTS: Both groups experienced significant miosis in excess of 90 minutes. Visual acuity was significantly reduced because of accommodative changes. The three-drop group experienced longer lasting combined effects when compared to the two-drop group. CONCLUSIONS: 2% pilocarpine ophthalmic solution can safely simulate major ocular symptoms of OP exposure for behavioral research studies for at least 60 minutes.

Gellan gum and its methacrylated derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies.

Gellan gum was chemically modified by the reaction with methacrylic anhydride to produce derivatives with 6, 14 and 49% methacrylation. The structure and substitution degrees of these derivatives were confirmed by 1H NMR- and FTIR-spectroscopy. These derivatives are more hydrophobic compared to pristine gellan and form turbid solutions in water. In vitro study performed with formulations of sodium fluorescein containing gellan gum and its methacrylated derivatives indicated that methacrylation enhances their retention on bovine conjunctival mucosa. In vivo experiments with the formulations of pilocarpine hydrochloride containing gellan gum and methacrylated derivatives have demonstrated that all polymers enhance the drug effect significantly, but best performance is observed for the polysaccharide with 6% methacrylation.

A retrospective evaluation of systemic and/or topical pilocarpine treatment for canine neurogenic dry eye: 11 cases.

OBJECTIVE: To assess the response to topical and/or systemic pilocarpine in dogs with neurogenic dry eye. METHOD: Medical records of dogs diagnosed with dry eye between 2015 and 2018 were reviewed. Cases were excluded if STT values were decreased bilaterally, if dogs were lost to follow-up, or if surgical measures (parotid duct transposition) were undertaken within thirty days of presentation. Dogs were on treatment with topical pilocarpine (0.1%, every 6 hours) and/or oral pilocarpine (starting dose 2%, one drop per 10 kg every twelve hours). RESULTS: Eleven cases were included in the study, seven females and four males with mean age of 10 years. Seven cases had xeromycteria, two cases had facial nerve paralysis, and one case had Horner's syndrome. Seven cases (63.6%) had successful outcome following pilocarpine treatment, return to normal STT (15-25mm/minute), in an average of 24 ± 5.1 days. Of these cases, five had both systemic and topical treatment, one had just topical treatment, and one had just systemic treatment. The average time to normal tear production on treatment with topical pilocarpine ± systemic was 23 days (range 9-48 days). The number of systemic drops until a positive response varied between individuals from 0.8drops/10kg to 7drops/10kg. CONCLUSION: Pilocarpine treatment (topical ± systemic) is an effective therapy for unilateral dry eye disease in cases suspected to be neurogenic in origin. Most cases responded within 30 days. Side effects included topical irritation to the ophthalmic solution and systemic effects from oral pilocarpine, such as diarrhea and regurgitation.

Effect of topical pilocarpine on refractive surgery outcomes.

PURPOSE: To investigate the effect of topical pilocarpine on topical cycloplegia and on the results of refractive surgery. METHODS: The study included 100 eyes of 100 patients who underwent laser-assisted in situ keratomileusis. Group 1 comprised patients who wanted to undergo surgery on the same day after cycloplegic examination and were applied with 2% pilocarpine hydrochloride; group 2 comprised patients whose pupils spontaneously went into the natural position. Corneal thickness, mean refractive spherical equivalent (MRSE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), pupil diameter, pupil center shift and high-order aberrations (HOAs) were compared between the two groups. RESULTS: There were no statistically significant differences between the groups in respect of preoperative age, gender, corneal thickness, MRSE, UDVA and CDVA. The pupil diameter was not statistically significant between the groups. Pupil diameter after pilocarpine was not statistically significant when compared with the natural pupil diameter. There were no statistically significant differences in postoperative HOA between the two groups. CONCLUSIONS: The pupillary dilatation and the associated pupillary shift were reduced with pilocarpine. Postoperative refractive values and aberrations showed no difference between the groups.

Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation.

OBJECTIVES: Pilocarpine (PILO) and cevimeline (CEV) are muscarinic acetylcholine receptor agonists that stimulate salivary gland function. The aim of this investigation was to retrospectively run a head-to-head comparison for their effectiveness and frequency of adverse effects in patients with hyposalivation. METHODS: A retrospective chart review was conducted for patients seen at the Oral Medicine Clinic at Tufts University School of Dental Medicine (TUSDM) and was prescribed PILO or CEV. Patients' demographics, medical history/medication, stimulated salivary (SS), and unstimulated salivary (US) flow recorded at the initial visit and at 3- and 6-month follow-ups were collected. Changes in dosage/frequency, side effects, and drug discontinuation were also reported. RESULTS: A total of 110 patients' charts were reviewed. The majority of subjects (91%) were females with an average age of 61. At 3-month follow-up, the use of CEV showed significant improvement in SS compared to PILO (p = .033) but not in US (p = .10). At 6-month follow-up, there was no significant difference in SS or US between the two groups (SS: p = .09; US: p = .71). The use of PILO was associated with a higher proportion of adverse effects compared to CEV (p = .04). The overall adherence rate was significantly higher in the CEV group (p = .0056). CONCLUSIONS: The effectiveness of CEV and PILO is comparable. However, PILO seems to be associated with more reporting of side effects.