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PubMed1978

Factors determining the potency of cholinomimetic miotic drugs and their effect upon the light reflex in man.

1. Television pupillometry was used to measure the effect of six topically applied cholinomimetic drugs on the resting diameter and light reflex amplitude of the human pupil. Drug potency was obtained from dose response curves. 2. The tertiary amines arecoline, aceclidine and pilocarpine were considerably more effective miotics than the choline esters carbachol, methacholine and acetylcholine. 3. All the drugs which caused miosis also reduced light reflex amplitude proportionally. 4. The in vitro potency of these drugs was also measured on preparations of rabbit iris sphincter and guinea pig ileum. 5. Dose response relationships for pilocarpine in man and in vitro showed evidence of partial agonist activity on the rabbit iris only. 6. A comparison of the in vivo and in vitro results showed that three factors influenced the potency of topically applied miotics: accessibility to the iris; sensitivity to cholinesterase; and cholinoceptor agonist potency.

Adult↗
PubMed1980

Subsensitivity to cholinoceptor stimulation of the human iris sphincter in situ following acute and chronic administration of cholinomimetic miotic drugs.

1 Maximal pupillary miosis was obtained with single topical applications of 4 cholinomimetic drugs in therapeutic concentrations to normal human subjects. 2 When the pupil had recovered from the miosis, there remained a reduced light reflex response of 22.7% at 24 h after aceclidine, 18.0% at 31 h after pilocarpine, 10.3% at 48 h after physostigmine and 4.9% at 7 h after arecoline. 3 This reduced sensitivity to light was accompanied by an overshoot of the resting pupil diameter and, after aceclidine miosis, a reduced response to a second application of miotic. 4 Similar findings were observed in glaucoma patients following withdrawal of chronic pilocarpine therapy. 5 It is suggested that the slowly reversible after-effects of acute and chronic administration of cholinomimetic miotics can be explained by desensitization of iris sphincter cholinoceptors.

Adult↗
PubMed1997

Dilated, miotic-resistant pupil and laser iridotomy in primary angle-closure glaucoma.

We analyzed 22 eyes with primary angle-closure glaucoma that underwent initial laser iridotomy to determine which factors could lead to subsequent trabeculectomy. Twenty-two eyes were divided into two groups: (1) the eyes in which intraocular pressure (IOP) could be controlled by iridotomy and/or topical medication (iridotomy success group, 15 eyes) and (2) the eyes that underwent trabeculectomy to control IOP in spite of a patent opening (iridotomy failure group, 7 eyes). The clinical variables between the two groups were analyzed. Age, sex, visual field defect, presenting IOP and cup/disk ratio were not significantly different between the iridotomy success and failure groups. However, presence of peripheral anterior synechiae (PAS) greater than 50% was found more frequently in the iridotomy failure group as compared with the iridotomy success group (4/7 vs. 1/15, p = 0.02). Dilated, miotic-resistant pupils were observed only in the iridotomy failure group (4/7 vs. 0/15, p = 0.004). PAS greater than 50% and dilated, fixed pupils were observed in these same cases (4 eyes). Our results suggest that laser iridotomy may not be helpful in cases with dilated and miotic-resistant pupils with formation of extensive PAS.

Aged↗
PubMed1975

Miotic drugs, glaucoma, and retinal detachment.

It has been reported in the literature, and is the clinical impression of many ophthalmologists, that the use of miotic drugs and especially Phospholine Iodide increases the incidence of retinal detachment. A review of 1,000 cases of retinal detachment is reported with a breakdown of the percentage of patients who previously had glaucoma and the various drugs with which they had been treated prior to the development of their retinal detachments. The incidence of bilateral cases is also studied and conclusions are drawn as to whether or not there is any increased incidence of retinal detachment or in the bilaterality in patients who are on miotic medications.

Adult↗
PubMed1994

[Miotics and occlusion in the treatment of accommodative strabismus].

Antisuppressive occlusion is an intermittent occlusion prescribed in order to eliminate suppression. This way, the system of vergences is reactivated which results in a stabilisation of the position of the eyes and reduces asthenopic complaints. Miotics are used to treat a recent or intermittent convergent squint. Miotics can equally be used to remove positive glasses and to reduce a visible postoperative recurrence.

Accommodation, Ocular↗
PubMed2004

Miotic effect of brimonidine tartrate 0.15% ophthalmic solution in normal eyes.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.15% ophthalmic solution (Alphagan P) on pupil diameter in eyes of healthy adults under different luminance conditions. SETTING: Center for Refractive Surgery, Ophthalmology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA. METHODS: Using a Colvard pupillometer, the pupil diameter was measured in 15 eyes of 15 healthy adults under 3 luminance conditions (scotopic, mesopic, photopic). The luminance of the room was measured using the Minolta LS-110 Luminance Meter. Pupil diameter was remeasured using the same technique 30 minutes, 4 hours, and 6 hours after administration of 1 drop of brimonidine tartrate 0.15% ophthalmic solution. RESULTS: Under scotopic conditions (luminance 0.0 candelas [cd]/m(2)), the pupil diameter decreased by 1.0 mm or more in 100%, 87%, and 60% of eyes at 30 minutes, 4 hours, and 6 hours, respectively (P<.005); under mesopic conditions (luminance 0.2 cd/m(2)), in 93%, 73%, and 40% of eyes, respectively (P<.005); and under photopic conditions (luminance 150.2 cd/m(2)), in 73%, 87%, and 67% of eyes, respectively (P<.005). CONCLUSIONS: Brimonidine tartrate 0.15% ophthalmic solution produced a significant miotic effect under all 3 luminance conditions. The reproducible miotic effect under scotopic and mesopic conditions may help postoperative refractive patients who report night-vision difficulties related to a large pupil.

Adrenergic alpha-Agonists↗
PubMed2003

Respiratory and miotic effects of morphine in healthy volunteers when P-glycoprotein is blocked by quinidine.

AIM: Our objective was to evaluate whether P-glycoprotein inhibition after quinidine pretreatment results in modified central nervous effects of morphine. METHODS: Twelve healthy volunteers received 7.5 mg morphine as an intravenous infusion over a 3-hour period. In a randomized, double-blind, 2-way crossover fashion, subjects received either 800 mg quinidine or placebo 1 hour before the start of morphine administration. The miotic and respiratory depressive effects of morphine were assessed by means of pupillometry and the respiratory response to carbon dioxide rebreathing, respectively. Quinidine effects were assessed by electrocardiogram recordings. Plasma concentrations of morphine and its glucuronide metabolites were measured throughout the observation period of 5 hours. RESULTS: Morphine significantly reduced both the respiratory response to carbon dioxide and the pupil diameter. Throughout the observation period, quinidine had significant effects on the corrected QT interval (QTc increase of >60 milliseconds), indicating clinically relevant quinidine action. However, quinidine pretreatment did not enhance the respiratory depressive effects of morphine, nor did it alter the miotic effects of morphine to a statistically significant or clinically relevant extent. Plasma concentrations of morphine and its glucuronides were not significantly changed by quinidine pretreatment. CONCLUSIONS: Whereas morphine clearly produced miosis and respiratory depression, pretreatment with quinidine as an inhibitor of P-glycoprotein did not result in an enhancement of central nervous opioid effects in healthy volunteers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Tolerance to the miotic effect of sarin vapor in rats after multiple low-level exposures.

Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pupil size and cholinesterase activity in the eyes and blood. Male Sprague-Dawley rats were exposed to 4.0 mg/m3 of GB vapor for 1 h on each of 3 consecutive days. Pupil size and cholinesterase activities were determined at various points throughout the exposure sequence. The results demonstrate that multiple inhalation exposures to GB vapor produce a decrease in the miotic potency of GB in rats. This tolerance developed at a dose of GB that produced no overt signs of intoxication other than miosis. AChE and butyrylcholinesterase activity did not increase throughout the exposure sequence, suggesting that the tolerance cannot be attributed to a reduced inhibitory effect of GB. A decrease in the amount of GB present in the eye occurred after the third exposure. However, this change is insufficient to explain the tolerance, as there was no corresponding increase in AChE activity. Thus, the mechanism mediating the miotic tolerance observed after multiple inhalation exposures to the nerve agent GB remains uncertain, although several possibilities can be excluded based on the results of the present study.

Acetylcholinesterase↗
PubMed1988

Consensual pupillary responses to mydriatic and miotic drugs.

1. Three experiments were conducted to examine whether mydriatic or miotic drugs instilled into one eye have any effect on the diameter of the pupil of the untreated fellow eye, in healthy volunteers. 2. In Experiment 1, the effects of four subjects, using photography in an illuminated room to assess pupil diameter. The drug evoked a dose-dependent mydriasis in the index eye which was accompanied by a simultaneous dose-dependent miosis in the fellow eye. 3. In Experiment 2, the same method was used to assess pupil diameter as in Experiment 1. The effects of mydriatic (methoxamine and tyramine) and of miotic (pilocarpine) drugs instilled into the fellow eye, were studied on the sizes of pupillary responses to the same drugs instilled into the index eye. The presence of a mydriatic drug in the fellow eye resulted in a decrease in the size of the mydriatic responses in the index eye. 4. In Experiment 3, the effects of three concentrations of phenylephrine hydrochloride (0.15-0.60 M) and of three concentrations of pilocarpine hydrochloride (0.002-0.008 M), were studied in darkness using an infra-red binocular television pupillometer, in seven subjects. Phenylephrine evoked dose-dependent mydriasis and pilocarpine evoked dose-dependent miosis. The pupillary responses of the index eye were not accompanied by any changes in the diameter of the pupil of the fellow eye. 5. It is concluded that drug-induced mydriasis in the index eye is accompanied by a consensual miosis in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Uniocular miotic therapy.

The beneficial and harmful effects of 2% pilocarpine and 0.125% echothiophate iodide were evaluated on the prospective study of uniocular miotic therapy using the fellow eye as a control. Thirty primary open-angle glaucoma patients were treated with pilocarpine alone over a median time of 55 months. Twenty-nine similar patients were treated initially with echothiophate iodide and subsequently with pilocarpine over a median time of 54 months. Pilocarpine is cataractogenic but the changes are less marked and require more time than those induced by echothiophate iodide. In the combined group of 118 eves of 59 patients there were 11 optic disc changes and dix glaucomatous field defects. There was no difference in incidence between the treated and control eyes. The results suggest that one should be conservative in prescribing miotics, including pilocarpine alone, for patients suspected of having glaucoma.

Aged↗
PubMed1989

The putative and demonstrated miotic effects of prostaglandins in mammals.

The foregoing clearly indicates that there are tremendous differences in the responsiveness of the iris sphincters of different mammalian species to the miotic effects of PGs. The iris sphincter of cats and dogs contracts in response to PGF2 alpha, but not in response to other PGs, at concentrations that can be expected to occur under in vivo physiological conditions. In both of these species, PGF2 alpha, but none of the other PGs tested, yielded a dose-dependent full miosis when applied topically to intact eyes. Although in vivo studies are not available on bovine eyes, in vitro studies show that the isolated bovine iris sphincter exhibits a contractile response in the presence of several PGs, but that the threshold concentration for this response is about hundred-fold higher than the concentration of PGF2 alpha required to cause a similar or an even larger effect on feline or canine iris sphincters. Thus, in contrast to the feline iris, the bovine iris shows low sensitivity and low specificity, exhibiting responses to high concentrations of several PGs. In vivo and in vitro studies also are in full agreement that the iris sphincter of several other species, including rabbits and diurnal primates (rhesus and cynomolgus monkeys, baboons, and humans) do not exhibit similar miotic responses to any of the PGs that had been studied so far. It is difficult to summarize all these findings in a truly quantitative manner because the in vitro studies have used different experimental conditions, especially with respect to the inhibitors or precontracting agents used, while in vivo studies have differed with respect to the form of the PG used and in the mode of its administration. These differences, together with the lack in some instances of adequate descriptions of experimental conditions, must be borne in mind in any effort to compare the effects of PGs on the iris sphincter of different species. Nevertheless, because of the importance of obtaining at least a semi-quantitative picture of the extent of these species differences, the data derived from reports on in vivo studies of miosis have been tabulated in the chapter dealing with the effects of PGs on IOP (see Bito et al., 1989). Results extracted from some of the in vitro studies that have been reviewed in the previous sections are summarized in Table 1. The readers are urged to study the original publications and to bear in mind the problems described in the preceding sections that are encountered when trying to interpret the results presented by van Alphen et al. (1977).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1975

Malignant glaucoma" in an eye with no antecedent operation or miotics.

The diagnosis of malignant glaucoma was entertained preoperatively in a patient with no previous history of glaucoma surgery or use of miotics. The marked asymmetry in the anterior chamber depth and angle configuration between the two eyes was the significant clue. The findings at operation confirmed the diagnosis. The closure of the angle appeared to be due to retrovitreal fluid displacing the vitreous and the iris-lens diaphram forward.

Aged↗
PubMed1977

Malignant glaucoma induced by miotics postoperatively in open-angle glaucoma.

A case of malignant glaucoma that developed in a patient with primary open-angle glaucoma is described. The malignant course was induced during the immediate postoperative period by the inadvertent use of miotics. The malignant course was successfully managed by osmotic agents, acetazolamide, cycloplegics, mydriatics, and topical steroids.

Female↗
PubMed1986

Thymoxamine: a miotic for intraocular use.

Thymoxamine hydrochloride can be used intraocularly to reverse phenylephrine or epinephrine mydriasis during intraocular surgery (0.2-0.5 ml of 0.01% or 0.02% solutions proved to be effective). No endothelial damage was found up to a dose of 1 ml of 0.02% thymoxamine in animal experiments using a physiologically buffered solution. Since stability is low in the buffered state, the final concentration has to be prepared at the time of surgery using a 0.5% solution and a phosphate buffer. Intracameral thymoxamine is a potent miotic during operations and can be helpful in extracapsular cataract surgery, keratoplasty, and repair of perforating injuries.

Animals↗
PubMed1979

Retinal detachments and topical ocular miotics.

There is increasing suspicion that topical ocular miotic therapy in selected persons may precipitate retinal detachments. This is a rare event and probably does not occur in patients free of retinal pathology. Data supporting a possible cause and effect relationship, obtained from the National Registry of Drug-Induced Ocular Side Effects, a survey of the Retina Society, medicolegal decisions, and a review of the literature, is presented.

Administration, Topical↗
PubMed1982

Miotics: side effects and ways to avoid them.

Pilocarpine, a parasympathomimetic drug used in the treatment of glaucoma, produces a variety of ocular and systemic adverse reactions. Ocular side effects include miosis, accommodative spasm, frontal headaches, twitching lids, conjunctival injection, cataractous changes, allergic reactions, iris cysts, retinal detachment, increased permeability of the blood-aqueous barrier, anterior chamber narrowing, and the potential for inducing an acute angle-closure attack. Systemic side effects include nausea, vomiting, tenesmus, abdominal spasm, salivation, lacrimation, sweating, pulmonary edema, and bronchial spasm. The systemic side effects can best be minimized initially through proper use of the medication and nasolacrimal occlusion. The Ocusert, a long-acting pilocarpine-incorporated ocular insert, is a recent advance in delivery technique that offers an adequate hypotensive action with fewer side effects. Pilopex is a promising new experimental pilocarpine polymer salt presently being studied in Israel. Photomydriasis, a process involving the use of a laser to enlarge miotic pupils also offers help for these patients. N-demethylated carbachol is a new parasympathomimetic drug currently under study for glaucoma therapy. Initial results show that it may have considerable ocular hypotensive action with fewer adverse effects.

Carbachol↗
PubMed1999

Miotic effect and irritation potential of pilocarpine prodrug incorporated into a submicron emulsion vehicle.

Pilocarpine prodrug, O,O'-dipivaloyl(1,2-ethylene) bispilocarpic acid diester, was introduced to a submicron emulsion vehicle in a dose equivalent to 0.5% pilocarpine base, and the formulation was studied in albino rabbits using miotic assay. Compared with pilocarpine HCl 0.5% solution delayed and prolonged miosis was observed after application of the prodrug emulsion. AUC(0-6 h) values for the prodrug emulsion and pilocarpine solution were 9252+/-1345 and 6845+/-1967%xmin, respectively. The prodrug was also administered twice daily for 5 days in the form of aqueous solution or submicron emulsion in order to study ocular irritation. Irritation potential of the prodrug was significantly reduced when submicron emulsion was used as a vehicle.

Animals↗
PubMed1979

Effects of epinephrine, benzalkonium chloride, and intraocular miotics on corneal endothelium.

Drugs formulated for use both inside and outside of the eye were tested for their potential toxic effects on the corneal endothelium. Commercially available epinephrine 1:1000 was toxic to the corneal endothelium, but solutions diluted fivefold caused no endothelial damage. The toxic agent was the sodium bisulfite 0.1% preservative. Benzalkonium chloride is highly toxic to corneal endothelium in its commonly used concentration of 0.01% and had to be diluted one thousand times to prevent endothelial damage. Ophthalmic medications for extraocular use should never be used intracamerally. Miotics commonly used in surgery during intraocular lens implantation are generally nontoxic to the cornea, though caution is advised in the use of carbachol in patients with preexisting endothelial disease and in patients having procedures in which substantial mechanical trauma to the endothelium may occur.

Animals↗