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Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability.

Submicron emulsions containing pilocarpine as ion-pair with mono-dodecylphosphoric acid were prepared. Physical stability of these preparations was confirmed during 4 months of storage at 4 degrees C. Approximately 50% of the drug was found in the aqueous phase of emulsion separated using an ultrafiltration technique, while the rest was present in the oily phase and interphase. The miotic effect observed in rabbits after application of the ion-pair in aqueous solution or in submicron emulsion was the same; indicating that the drug distribution into the oily phase of the colloidal vehicle does not improve ocular bioavailability.

Animals↗

Secondary acute angle closure glaucoma: a complication of AIDS.

A 58-year-old man with advanced AIDS presented to the emergency department complaining of headache and decreased vision bilaterally. On evaluation, he was found to have intraocular pressures of 69 and 65 mm Hg. After topical treatment with miotics and apraclonidine, he was given intravenous acetazolamide (Diamox) and peripheral iridotomy was performed. The pressures did not improve significantly. Secondary acute angle closure glaucoma was diagnosed. Emergency physicians should consider this diagnosis when evaluating AIDS patients with visual complaints.

Acetazolamide↗

Chromatic visual phenomenon caused by a subluxed intraocular lens.

A 74-year-old man developed an unusual chromatic aberration as a complication of cataract extraction surgery with posterior chamber intraocular lens implantation. The patient could see the location and color of one of the haptics of the dislocated lens. His symptoms resolved with miotic therapy.

Aged↗

Phenylephrine and pilocarpine in the treatment of post-operative irido-corneal adhesion.

Following cataract surgery, entrapment of the iris within the surgical wound is often managed by intensive use of miotics. As the radial fibres stretch, only a small amount of fraction is exerted upon the entrapped iris. Application of a combination of phenylephrine and pilocarpine drops causes simultaneous contraction of the pupil sphincter and the radial muscle fibres. This study investigated the relative magnitude of forces induced in the iris periphery by pilocarpine and phenylephrine and the effectiveness of adding g. phenylephrine 10% to g. pilocarpine 4% drops in the treatment of postoperative irido-corneal adhesions. The investigation was divided into two parts. First, the forces induced in the iris periphery upon exposure to pilocarpine and phenylephrine were measured in 6 cadaver irises. The mean force was 27.5 +/- 5.7 x 10(-3) N for pilocarpine and 23.3 +/- 4.0 x 10(-3) N for phenylephrine. The combination of the two drugs produced a force of 54.2 +/- 6.6 x 10(-3) N (p < 0.05). In the second part of the study intensive pilocarpine 4% drops were administered to 17 patients who had iris-wound entrapment on the first post-operative day. Patients with persistent adhesion were commenced on intensive g. phenylephrine 10% and assessed after 90 minutes. Of the 17 patients, 6 responded to pilocarpine drops alone; in a further 7 the irido-corneal adhesion was released only by the addition of phenylephrine drops, and in 4 patients drops were ineffective in relieving the adhesion. This study indicates that addition of phenylephrine 10% to pilocarpine 4% drops enhances the effectiveness of pharmacological treatment of post-operative irido-corneal adhesion.

Cataract Extraction↗

[Long-term treatment of open-angle glaucoma with bupranolol eye drops (author's transl)].

In this study we examined the effect of Bupranolol eye drops on 10 patients with open-angle glaucoma. Treatment extended over six months. Bupranolol eye drops lowered intraocular pressure by about 15% over a prolonged period. Some patients needed treatment in combination with miotics. Visual acuity and visual fields remained constant. As a rule, Bupranolol was tolerated well by the patients

Adult↗

Iridocorneal adhesions in patients with the Marfan syndrome.

Marfan syndrome is an autosomal dominant connective tissue disorder characterized by skeletal, cardiovascular, and ocular anomalies. Ectopia lentis is the most common ocular manifestation. We report an ocular sign not previously described in Marfan syndrome, iridocorneal adhesions secondary to anterior lens subluxation. Three patients with the Marfan syndrome had iridocorneal adhesions on slit-lamp examination. One patient developed adhesions following treatment with pilocarpine. She underwent pars plana vitrectomy and lensectomy in both eyes due to progression of the iridocorneal adhesions. Treatment with miotics rotates the lens-iris diaphragm anteriorly and may contribute to the formation of such adhesions. The two other patients remained stable and did not received lensectomy or vitrectomy. Careful slit-lamp examination of the anterior segment should be conducted in patients with dislocated lenses.

Adolescent↗

Pluronic F127-based ocular delivery system containing biodegradable polyisobutylcyanoacrylate nanocapsules of pilocarpine.

The objectives of our study were to prepare a biodegradable polyisobutylcyanoacrylate (PIBCA) colloidal particulate system of pilocarpine, to incorporate it into a Pluronic F127(PF127)-based gel delivery system, and to evaluate its ability to prolong the release of pilocarpine. Polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) of pilocarpine were prepared by interfacial polymerization. Physicochemical characterization of the colloidal dispersion of PIBCA-NC of pilocarpine was performed by measuring drug loading, particle size analysis, and scanning electron microscopy. Results indicated that approximately 13.5% of pilocarpine was loaded onto the PIBCA-NC, the nanocapsules ranged from 370 to 460 nm, the distribution was narrow, and there was no significant effect of stirring speed on particle size. The PIBCA-NC dispersion of 1% pilocarpine alone (I) and after incorporation into the Pluronic F127 gel delivery system (II) were compared against 1% pilocarpine incorporated into a PF127 gel containing 5% methylcellulose (PF127MC) alone (III) by measuring the miotic response in the albino rabbit eye. Statistical analysis indicated a rank-order for both the duration and intensity of miosis of II > III >> I, with all differences being significant (p < 0.05). Thus, it appears that II increases the contact time of pilocarpine with the absorbing tissue in the eye, thereby improving ocular bioavailability. The PIBCA-NC of pilocarpine dispersed in the PF127MC gel delivery system has considerable potential for achieving a prolonged delivery for such drugs as pilocarpine and other more hydrophobic drugs.

Algorithms↗

Pupillary effects of alfentanil and morphine.

We have measured the onset and extent of the miotic effect of morphine and alfentanil in conscious patients. Forty unpremedicated ASA I and II patients were allocated randomly to four groups to receive either i.v. saline (control group), morphine 0.1 mg kg-1, alfentanil 4.0 micrograms kg-1 or a combination of these doses, and pupil diameters were measured for the next 30 min. There were no significant differences in the control diameters. In the opioid groups, a significant decrease in diameter (about 1 mm), occurred 4 min after administration of the drug and persisted throughout the study. The opioid groups behaved similarly for 25 min. After 10 min the mean diameter of the alfentanil group began to increase, but this did not reach statistical significance until after 25 min.

Adult↗

Alfentanil dose-response relationships for relief of postoperative pain.

The aim of this study was to characterize within-patient alfentanil dose-response curves for the relief of spontaneous postoperative pain and to test the closeness of relationships 1) between pain intensity and alfentanil analgesic requirements, and 2) between alfentanil requirements for analgesic and nonanalgesic (sedative and miotic) effects. The effects of alfentanil were studied in 23 patients after elective abdominal surgery. During a 40- to 60-min testing session, the patient received two intravenous (i.v.) injections of saline (placebo) and up to six 3-micrograms/kg increments of alfentanil at 5-min intervals. The patient rated the pain intensity with a visual analog scale, and in a subgroup of 15 patients the blinded observer rated patients' sedation and measured pupil diameter. Spontaneous postoperative pain was completely relieved in all patients with cumulative doses of alfentanil ranging from 6 to 8 micrograms/kg. The within-patient alfentanil dose-analgesic response curves were primarily quantal in nature: a precipitous decrease in pain intensity (representing > or = 2/3 of the total effect) after the injection of only one of the increments of alfentanil was observed in 15 of 23 patients. When the analgesic effect of alfentanil was presented as the collective response of a group of individuals, the quantal nature of the response was concealed by the wide interindividual variability of the response. No statistically significant relationship was noted between predrug pain intensity and the cumulative dose of alfentanil necessary to produce pain relief. A strong correlation was found between interpatient variabilities in the analgesic and sedative effects of alfentanil (r = 0.75, P < 0.002). At the same time, the relationship between alfentanil requirements for pain relief and that for pupil constriction did not demonstrate any significant correlation. The results suggest that, in a population of patients with postoperative pain, the intensity of spontaneous pain cannot be the primary factor determining the dose of alfentanil necessary for its relief.

Abdomen↗

Management of intermittent esotropia.

Management of patients with intermittent esotropia having either normal or high accommodative convergence to accomodation (AC:A) ratios is discussed. Treatment should be based on liberal use of miotics to build up fusional reserves and use of hyperopic corrections or bifocals or both whenever specifically indicated. Divergent fusional reserve training is time-consuming and the cost/benefit ratio so low that most patients and doctors prefer the former treatment.

Accommodation, Ocular↗

The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma.

The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.

Adrenergic beta-Antagonists↗

Effect of prolonged and neonatal capsaicin treatments on the substance P immunoreactive nerves in the rabbit eye and spinal cord.

Substance-P (SP) immunoreactivity was demonstrated in the rabbit eye and spinal cord using monoclonal SP antibody and an indirect immunofluorescence technique. Norves containing SP immunoreactive material were found in the cornea, iris and ciliary body of which the iridic sphincter had the densest innervation. Neither prolonged subcutaneous treatment (up to 280 mg/kg) augmented by intracameral capsaicin injection nor neonatal treatment with drug 70 mg/kg eliminated this immunoreactivity, though both blocked the miotic effect of intracameral SP. It is concluded that capsaicin is not specific SP depleting agent but rather a neurotocic substance that affects noxious pathways and probably prevents the release of the SP retained by the nerve following the treatment used.

Animals↗

Long-term hypotensive effect of atenolol 4% eyedrops.

The effect of long-term application of 4% atenolol eye drops has been studied in patients with either glaucoma or ocular hypertension. In some patients who show a good initial response the ocular hypotensive effect gradually wears off with long-term use. This pattern of response appears to be more frequent in patients with pretreatment intraocular pressure of 25 mmHg, or greater. In combination with atenolol miotics or adrenaline show an additive effect.

Adult↗

Trabeculectomy: a review and 4-year follow-up.

Since the first attempt at glaucoma surgery in 1830 many surgical procedures have been devised and adopted depending on the understanding of the aetiology and pathogenesis of the disease. Trabeculectomy, the most recent drainage procedure for glaucoma, has become a widely used, effective, and safe method, particularly for chronic simple glaucoma. Up to 4 years' follow-up of 66 eyes (55 patients) is reported. The findings at 6 months, 1 year, 2 years, 3 years, and 4 years were in agreement with previous reports by other authors. The main postoperative complication was transient hyphaema. Of the total number of eyes, 7 needed miotic drops and 5 required further surgical procedures to control the intraocular pressure.

Adolescent↗

The effects of new topical treatments on management of glaucoma in Scotland: an examination of ophthalmological health care.

BACKGROUND: The management of glaucoma has been changed in the past decade by the introduction of new drugs. The impact of these changes on clinical care of patients was examined by examining operation and prescribing rates for glaucoma in four geographical areas of Scotland for the years 1994 to 1999. METHODS: A retrospective analysis of national health statistics: primary care prescribing data, hospital derived operation rates, consultant numbers, optometrist numbers, and eye test data, expressed by estimated population at risk of glaucoma. The outcome measures were prescribing volume and cost for glaucoma medications, and operation rates, corrected for population estimated to be at risk of glaucoma (PEG), for trabeculectomy, for Scotland as a whole, and for four geographical "regions" (north east, south east, central, and south west Scotland). RESULTS: Prescribed items per 1000 population estimated to have glaucoma (PEG) increased by 24.9% between 1994 and 1999. This was above the general increase in prescribing in Scotland (17.8%). This increase varied in the four health regions evaluated (14.3% to 31.9%). Prescribing of topical beta blockers increased little (6.4%), but there was a large increase in the use of new products (topical prostaglandins, carbonic anhydrase inhibitors, and alpha(2) agonists), at the expense of miotics (47.7% fall), and older sympathomimetics. This change in prescribing pattern was accompanied by a 61.5% increase in cost (range 42.2% to 73.4% in the four regions). New drugs accounted for more than half of total glaucoma expenditure in 1999. Operation rates (corrected for PEG) fell by 45.9% (range 43.1 to 58.6%) between 1994 and 1999. Other indicators suggested increased activity in ophthalmic areas (for example, cataract operations, eye tests, numbers of optometrists and ophthalmic surgeons all increased). Within north east Scotland operation rates decreased and prescribing increased less than in other regions, both from lowest regional baseline in 1994. CONCLUSIONS: The introduction of new drug classes has had dramatic effects on the prescribing of glaucoma treatments. There has been a decline in older treatments and an increase in new agents, which has been associated with a large reduction in operation rates for glaucoma in Scotland over 6 years. Comparison of prescribing and operation data indicates regional differences in healthcare delivery for glaucoma.

Administration, Topical↗

Bupranolol, a beta 1- and beta 2-blocker, causes constriction of the pupil in men.

Two out of three normal eyes tested with frequent instillation of 30 microliters of drops of 0.5% bupranolol, a beta 1 + beta 2 blocking drug with some intrinsic sympathomimetic and local anesthetic activity, showed a miotic effect of the order of a 25% reduction of pupil area, as estimated by an open-loop iris-videorecorder. A slight contralateral effect was also observed. Blocking by the drug of tonic inhibitory beta-adrenergic activity on the sphincter muscle of the pupil is postulated.

Adrenergic Fibers↗

[Preparation and testing of buffered eye drops containing pilocarpine chloride with timolol maleate].

BACKGROUND/AIM: In glaucoma therapy beta-blocator, timolol-maleate, is the first-line medicine of selection, whereas a miotic, pilocarpine chloride, is one of the oldest medicines used for the treatment of this illness. They are applied as eye drops. In order to achieve a better therapeutic effect and improve life quality of the ill, we produced and tested eye drops formulations based on combining pilocarpinechloride and timolol maleate in buffers of diferent pH values. METHODS: Following the general pharmacopoeial eye drops preparation regulation, we prepared formulations, of solution type, of pilocarpine chloride and timolol maleate combination, of pilocarpine choloride alone and of timolol maleate alone. A modified phosphate buffer according to Sorensen at 7.4, 7.7 and 8.0 pH values was used as a solvent. The quality of the produced formulations was examined using physical and physico-chemical methods and biological tests. Following pharmacopoeial regulations, we examined clarity, pH value and sterilty. Pilocarpine chloride level was determined by means of ion-par (High Performance Liguid Chromatography) RP-HPLC method, whereas UV/VIS absorption spectrophotometry was used for determining the level of both timolol maleate, and timolol. RESULTS: Results showed that monocomponent and combined preparations complied with the regulation demands. With the increase in the pH value of the solution pilocarpine chloride level decreased in relation to its initial content, whereas timolol level showed a tendency of moderate increase. CONCLUSION: Magistrally prepared pilocarpine chloride eye drops with timolol maleate have satisfied all the required conditions for an ophtalmological preparation. A modified phosphate buffer according to Sorensen at 7.4 pH value proved to be the most optimal solvent.

Adrenergic beta-Antagonists↗