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PubMed1990

Systemic effects of medications used to treat glaucoma.

Medications used to treat glaucoma can have clinically important systemic effects in some patients; these effects may not be recognized in elderly patients who have chronic medical problems and who are taking several systemic medications. Beta-blocking ophthalmic agents are generally safe, but can be absorbed systemically to induce bronchospasm, worsen heart block, decompensate congestive heart failure, or create central nervous system effects in some patients. Reports of adverse systemic effects from miotics, such as pilocarpine, are rare, although cardiovascular decompensation has been seen in patients with acute angle closure who were given excessive doses before surgery. Topical sympathomimetic agents such as epinephrine may increase ventricular extrasystoles and have, on occasion, caused severe hypertensive reactions. Nearly 50% of patients taking carbonic anhydrase inhibitors must discontinue their use because of various adverse constitutional and central nervous system symptoms. Although these drugs are not usually part of internal medicine regimens, they can produce adverse effects that mimic primary disease in nonocular organ systems.

Adrenergic beta-Antagonists↗

PubMed1999

Topical therapies for glaucoma: what family physicians need to know.

Medication classes historically used in the management of glaucoma include beta blockers, miotics, sympathomimetics and carbonic anhydrase inhibitors. Because topically applied medications are more site specific, they are preferred in the treatment of glaucoma. Compared with oral medications, topical agents are associated with a decreased incidence of systemic side effects. With topical administration, conjunctival and localized skin allergic reactions are relatively common, whereas severe reactions, including death, are rare. Recently introduced topical agents for glaucoma therapy include dorzolamide and brinzolamide, the first topical carbonic anhydrase inhibitors; brimonidine and apraclonidine, more ocular-specific alpha agonists; and latanoprost, a prostaglandin analog, which is a new class of glaucoma medication. Latanoprost has the unique side effect of increasing iris pigmentation. Like their predecessors, the newer agents lower intraocular pressure by a statistically significant degree. Preservation of visual field, the more substantial patient-oriented end point, continues to be studied.

Adrenergic beta-Antagonists↗

PubMed2003

[The medical treatment of glaucoma].

Chronic open angle glaucoma is a one of the leading causes of irreversible blindness. Elevated intraocular pressure is a major risk factor for the progression of this disease. At present, most patients suffering from open angle glaucoma have started medical therapy. The goal is to reduce the intraocular pressure to an individualized target pressure in an effort to delay the progression of damage to the optic nerve. Until a decade ago, topical beta-adrenergic antagonists, adrenergic agonists, miotics and oral carbonic anhydrase inhibitors comprised the common medications in use. In the past decade many new drugs have been introduced. These drugs exert less systemic side effects and are very effective in lowering the intraocular pressure and furthermore, are easier to comply with. These include: local carbonic anhydrase inhibitors, prostaglandin F2á analogues and á2 adrenergic selective agonists. Due to lack of consensus as to the initial medication of choice for the commencement of treatment, the traditional tendency to initiate treatment with a local beta adrenergic antagonist persists. This review attempts to familiarize the reader with the new arsenal of glaucoma medications.

Adrenergic Agonists↗

PubMed1991

Drug-related cataract.

Associations between drug therapy and development of lenticular changes have been documented in the literature. Drugs most frequently implicated include corticosteroids, phenothiazines, miotics, gold, amiodarone, and allopurinol. The reported clinical observations on these agents are described, and similarities and differences between these drugs in regard to location of opacities and possible pathogenesis are discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1989

Inhibitors of the arachidonic acid cascade in the management of ocular inflammation.

At the present time, corticosteroids are still the most effective class of drugs for the treatment of ocular inflammation. However, since their prolonged use may result in severe ocular side effects, it would be therapeutically beneficial to develop nonsteroidal anti-inflammatory drugs that have similar or greater efficacy than steroids, but do not share their ocular side effects. Several currently available non-steroidal drugs have been used clinically as prophylactic or therapeutic agents for the following: 1. Prevention of pupillary constriction during intraocular surgery (cataract extraction). 2. Prevention of postoperative inflammation, i.e., incidence of anterior chamber cellular reaction and aqueous flare (breakdown of blood-aqueous barrier) and IOP rise following cataract surgery, intraocular lens implantation, and argon laser trabeculoplasty. 3. Prevention of contact lens induced corneal neovascularization. 4. Improvement of lens opacity (bendazac). 5. Prevention of cystoid macular edema following intraocular surgery. Treatment over long-term period may be effective; postoperative treatment is ineffective. 6. Prevention of conjunctival hyperemia. Some prophylactic ocular uses such as prevention of surgical miosis or postoperative fluorescein leakage have been reported to be successful. However, it is unclear whether the reported success reflected the pharmacological effects due to inhibition of the AA cascade - and hence, reflects the role of some eicosanoids in surgical miosis or postoperative fluorescein leakage - or reflect the effects of these drugs on unexplored physiological or pharmacological mechanisms. For example, pretreatment with flurbiprofen to prevent surgical miosis was based on the assumption that PGs are potent miotic agents in all mammals, including humans. It remains to be established however, whether the small reduction in the extent of pupillary miosis is due to prevention of PG synthesis by this drug or to the prevention of the synthesis of other AA products, such as prostacyclin and thromboxane or possibly to some entirely different mechanism. Prevention of post-surgical fluorescein leakage by prophylactic pre and/or post surgical treatment with a variety of nonsteroidal anti-inflammatory agents is also assumed to be due to inhibition of intraocular PG synthesis, although the possibility that it is due to prevention of the synthesis of prostacyclin or TxA2 has not been ruled out. Even more important, it has not been demonstrated that prevention of this post operative fluorescein leakage reflects the prevention or inhibition of true CME and associated loss of visual acuity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

PubMed1989

[Inhibition of acetylcholinesterase at pupil-related central nuclei by organophosphorus pesticide (fenthion)--an experimental study].

An organophosphorus pesticide (OP) inhibits acetylcholinesterase (AChE) of various organs, especially in cholinergically innervated organs. Pupil constriction is a major sign of an ocular symptom in the patient with acute OP intoxication, but the etiology is unknown. The present experiments were intended to elucidate a central mechanism of pupil size in which AChE and OP are involved. Fenthion (dimethyl 4-methylthion-m-tolyl phosphorothionate) of 5mg/day body weight) was subcutaneously administered dorsally in Wistar rats for 14 days consecutively in the longest group. Histochemical staining and microspectrophotometry were used to analyze the intensity of the AChE activity in the iris, the pretectal nucleus and Edinger-Westphal (EW) nucleus on the 2nd, 4th, 6th, 10th and 14th day of administration. The pupil was measured after 20 minutes of dark adaptation. The pupil constricted on the 6th day and most remarkably on the 10th day. The AChE activity in the iris decreased remarkably on the 4th day. Miosis was not seen on the 4th day. The AChE activity in the pretectal nucleus decreased remarkably on the 6th day. The AChE activity in the EW nucleus reduced gradually from the 6th day and 62% reduction of initial value was seen on the 14th day. Intense miosis was seen on the 10th day. In conclusion inhibition of AChE activity was detected first in the iris, thereafter in the pretectal nucleus and the EW nucleus in close correlation with the miotic pupil. Therefore, miosis associated with OP intoxicated patients may parallel the central inhibition of AChE in pupil-related centers.

Acetylcholinesterase↗

PubMed1988

Pigmentary dispersion syndrome and suspected low tension pigmentary glaucoma.

Recent evidence suggests that pigmentary dispersion syndrome is a result of the mechanical abrasion of the posterior iris surface and the anterior zonular fibers causing pigmentary release onto the ocular structures. Irreversible glaucomatous changes may be the result of the inability of the endothelial cells lining the trabecular beams to continue to phagocytize the release pigment. Glaucomatous field changes may occur despite low intraocular pressures and no clinically observable cupping. Visual field testing is indicated in any patient presenting with pigmentary dispersion syndrome since pressure spikes inducing nerve damage occur with stress, exercise, or prolonged mydriasis. Treatment may include miotics to prevent further abrasion rather than typical pressure-lowering medication.

Diagnosis, Differential↗

PubMed1982

[The effect of antiglaucoma drugs on the depth of the anterior chamber (I)].

The Authors have taken into account the most common effect of antiglaucomatous drugs on the depth of the anterior chamber. The modifications of the anterior chamber have been evaluated utilizing a Jaeger Pachymeter. The values were obtained before the drug instillation and an hour afterwards. The results are presented as the mean and standard deviation. Among the examined drugs, only miotics have brought about a notable decrease, whereas the others have shown no significant effects.

Adult↗

PubMed1984

[Neurotransmitter control of pupillary motoricity in man].

The pupillary responses to different agonists and antagonists of the sympathetic and parasympathetic systems have been studied in normal volunteers. The eyedrops were instilled unilaterally and the responses were evaluated by measuring the changes in diameter of the pupils (in millimeters). All the eyedrops induced an unilateral response on the instilled side. The mydriatic substances (phenylephrine, thropamide, tyramine) showed an evident and lasting action. Phenylephrine 1% was found to be a threshold dose to acquire the mydriatic effect. The beta blocking agent (timolol) induced a short mydriatic response, while methaproterenol did not change the pupillary diameter. Clonidine caused an unilateral mydriasis. The alpha blocking agent and the parasympathetic system stimulation agent induced miotic effects The results are discussed with particular reference to the possible mechanism of the pupillary response to timolol and clonidine.

Clonidine↗

PubMed1982

[Preliminary study of the topical use of thymoxamine].

In this work the Authors have tried to show the efficacy of TMX, as a miotic drug, and to find out the lowest concentration which can give the best results with the minor complications. Seven patients, in whom TMX was instilled in both eyes at 0.50%, 1%, 2% concentrations, were studied. A mydriatic was instilled before in the right eye, in order to obtain mydriasis whereas the left eye served as control. The 0.5% concentration was as efficacious as 1% and 2% ones, but had less side-effects.

Administration, Topical↗

PubMed1981

Serotonin nerve endings and regulation of pupillary diameter.

On the basis of the effects caused by 5-6-dihydroxytryptamine (5-6-DHT) on the serotonin nerve endings (chronic degeneration with depletion of the mediator), the eventual existence of serotoninergic fiber regulating pupillary diameter (PD) and intraocular pressure (IOP) was studied from a functional point of view. For the miotic effect found after administration of 5-6-DHT in rabbit, not accompanied by any change in the IOP, the hypothesis of a coparticipation of the serotoninergic fibers in the regulation of the PD is proposed, thus sustaining the concept that both PD and IOP respond to mechanisms of autonomous control. A phenomenon of receptorial supersensitivity to serotonin after the lesion of the nerve endings, dependent on 5-6-DHT, was also encountered.

5,6-Dihydroxytryptamine↗

PubMed1995

Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 4. Chlorpromazine hydrochloride.

The potentiality of interaction of chlorpromazine hydrochloride (CPZ) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry, vapour pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between CPZ and beta-CD. The continuous variation method was used to elucidate the stoichiometry of such interaction by spectrophotometric as well as vapour pressure measurements. Both types of data revealed the formation of a 1:1 complex. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The enthalpy and entropy of interaction were evaluated and the results indicate that the interaction is exothermic. The CPZ/beta-CD complex was prepared, lyophilized and photochemical stability of the drug, its physical mixture with beta-CD as well as the prepared complex was investigated at different pH-values in presence of different buffer systems. The results revealed that the stability of the drug is greatly improved in presence of beta-CD and the great dependency of stability on the pH of the solution is decreased in presence of beta-CD. The partition coefficient of CPZ and its complex with beta-CD was determined. The data reveal a higher p.c. of the complex compared to the parent drug. The effect of beta-CD on the bioavailability of CPZ was investigated by measuring the miotic response intensity in volunteers receiving a single oral dose of the drug, drug/beta-CD physical mixture or complex. The results revealed a distinct improvement of the biological performance of CPZ by beta-CD as evidenced by an increased intensity of drug action and its duration as well as augmenting its bioavailability without affecting the time for maximum effect.

Adult↗

PubMed1996

[An experimental study on corneal collagen shield vehicle for delivery of pilocarpine].

OBJECTIVE: The study was designed to clarify the role of corneal collagen shield made in China as a drug vehicle for the delivery of pilocarpine in different ways. METHODS: 80 eyes of New Zealand white rabbits were randomly divided into three groups, corneal collagen shield immersed with pilocarpine, corneal collagen shield with topical application of pilocarpine and synthetic collagen pilocarpine shield. At 0.5, 1, 3 and 6 hours after the delivery, the aqueous concentrations of pilocarpine and the pupillary sizes of all the eyes were measured. RESULTS: This study showed that shortly after the delivery of pilocarpine in the 3 groups, in spite of difference in ways of its delivery, its aqueous concentrations reached a relatively high level and maintained for more than six hours, the shield acting as a temporary "drug source". The aqueous pharmacokinetics of corneal collagen shield for pilocarpine delivery was consistent with the first-order kinetics and it was confirmed by the observations of miotic response. CONCLUSIONS: The corneal collagen shield made in China is a fine vehicle for drug delivery.

Animals↗

PubMed1976

[The fellow eye in acute angle-closure glaucoma (author's transl)].

With 5 years after the acute angle-closure glaucoma of an eye, in the fellow eye the same disease developed in only 15% of cases, but in 42% of cases in spite of the preventive miotic therapy a chronic angle-closure glaucoma developed unnoticed by the patients. Hence preventive iridectomy is suggested in the fellow eye.

Glaucoma↗

PubMed1998

[Bioactivity and effect of a mixture of pilocarpine and lysine on the pupil and intraocular pressure in rabbits].

Based on experiments with rabbit eyes (strain New Zealand white) the authors submit evidence that the metabolite which is formed as a result of interaction of 2% pilocarpine and L-lysine 2 HCl.2H2O has a significantly greater and more rapid effect on the development of miosis than 2% pilocarpine alone. The amino acid lysine does not have a miotic effect. The authors explain the bioactivity of the new metabolite, its effect during the development of miosis and reduction of intraocular pressure. They emphasize a greater and more rapid bioactivity of the new metabolite as compared with pilocarpine. These results provide evidence that during treatment of primary glaucoma it is important to consider not only the effect on reduction of intraocular pressure but also physiological processes which develop in tissue structures after administration of different chemotherapeutic agents.

Animals↗

PubMed1979

Upward transtentorial herniation: seven cases and a literature review.

Seven cases of upward transtentorial herniation occurred. In each patient, coma with reactive, miotic pupils, asymmetrical or absent caloric responses, and decerebrate posture indicated brain-stem compression. In this setting, the development of unequal, then midposition, fixed pupils signaled midbrain failure from upward herniation. Vertebral angiography showed upward displacement of the superior cerebellar arteries. Results of autopsy confirmed the existence of grooving of the vermis by the tentorial margins and, in one case, of anterior displacement and distortion of the midbrain. In five of 45 reported cases of upward herniation, the conditions were diagnosed antemortem. Instances of cerebellar hematoma and tumor predominated. In at least seven patients, performance of ventriculography may have precipitated herniation. Clinical details were provided in only nine patients and did not separate upward herniation from brain-stem compression. Cerebellar ischemic infarct found in one of our patients is a rarely reported cause of upward herniation.

Adult↗

PubMed1998

Effects of H-7 on the iris and ciliary muscle in monkeys.

OBJECTIVES: To determine the effects of H-7 on (1) iris and ciliary muscles (CMs) in living monkeys; (2) isolated monkey CM strips; (3) actomyosin contractility in cultured Swiss 3T3 cells. METHODS: (1) Pupillary diameter (calipers) and accommodation (refractometer) in living monkeys were measured after topical, intracameral, or intravitreal administration of H-7 followed by systemic pilocarpine hydrochloride. (2) Pilocarpine-induced contraction of isolated monkey CM strips following administration of H-7 was measured in a perfusion chamber. (3) Actomyosin contractility in Swiss 3T3 cells cultured on thin silicone rubber film was determined by measuring cell-induced film wrinkles before and after administration of H-7. RESULTS: Topical H-7 prevented anesthesia-induced miosis but did not affect resting refraction. Intracameral or intravitreal H-7 dilated the pupil and inhibited miotic but not accommodative responses to pilocarpine. H-7 inhibited pilocarpine-induced contraction of isolated monkey CM strips and reduced Swiss 3T3 cell contraction. CONCLUSIONS: H-7 inhibits actin-based contractility in non-muscle cells and in monkey iris sphincter and CM. Under our in vivo experimental conditions, the effect on the iris predominates over that on the CM.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1976

Unilateral afferent pupillary defects in asymmetric glaucoma.

Unilateral relative afferent pupillary defects are associated with unilateral prechiasmal lesions affecting the retinomesencephalic pathway. Five patients with unilateral or asymmetric glaucoma and relative afferent pupillary defects are presented. The lack of descriptions of relative afferent pupillary defects in unilateral glaucoma may be explained by the frequency with which these patients are treated with miotics, the association of trauma, and the presence of anatomic alterations of the iris. It is important to distinguish unilateral afferent pupillary defects in glaucoma from those associated with other neuro-ophthalmic disorders that require more invasive diagnostic procedures.

Adult↗