Análisis de las prescripciones nuevas al alta de un Servicio de Urgencias Hospitalario. Impacto en la seguridad y eficiencia / Analysis of new prescriptions at discharge in an Emergency Deparment. Impact on drug safety and efficiency

Objetivo: Analizar las prescripciones nuevas al alta del Servicio de Urgencias Hospitalario: perfil de utilización, grado de adecuación a la Guía Farmacoterapéutica del hospital (GFT), calidad de la prescripción y estimación de costes.Método: Estudio descriptivo transversal. Las variables incluyeron número de medicamentos prescritos, si se hizo según Denominación Oficial Española, financiación por el Sistema Nacional de Salud, adecuación a la GFT y existencia de alternativa más económica. También se comprobó la cumplimentación de datos básicos y coste de las prescripciones.Resultados: En un total de 1.252 episodios hubo 2.152 prescripciones nuevas al alta. Del total de prescripciones, se adecuaron a la Guía Farmacoterapéutica del hospital el 78,0% y estaban financiadas el 88,9%. Los fármacos más comunes fueron: paracetamol metamizol, ibuprofeno, dexketoprofeno y omeprazol. La cumplimentación deficitaria de la prescripción comprometió la dispensación en 231 prescripciones (10,7%). En 20 presentaciones se concentra el 57,5% del gasto y el 73% del ahorro. Extrapolando los resultados a las prescripciones de un año se obtiene que el gasto farmacéutico sería de 1.161.608,8€, esperándose una reducción en 370.846,2€ tras la adecuación a la guía o de 571.323,3€ añadiendo la entrega de medicación. Conclusiones: Las prescripciones nuevas al alta se concentran en un número bajo de medicamentos. Actuar sobre los mismos permite un amplio margen de mejora económico y aumenta la seguridad. Evitar la prescripción de medicamentos no financiados y garantizar la entrega de la medicación al alta en el Servicio de Urgencias, son otro de las puntos de mejora identificados. (AU)

Objective: To analyze the new prescriptions at discharge from the Emergency Department: utilization profile, degree of adaptation to the Pharmacotherapeutic Guide, quality of the prescription and cost estimation.Method: Cross-sectional descriptive study. The variables included the number of prescribed medications, if it was done according to the Spanish Official Denomination, financing by the National Health System, adaptation to the Pharmacotherapeutic Guide and the existence of a cheaper alternative. The completion of basic data and cost of prescriptions was also checked.Results: A total of 1,252 episodes received 2,152 prescriptions with a mean of 2.1 per episode. Out of them 78% were adapted to the hospital pharmacotherapeutic guide and 88.9% financed drugs. Most common drugs were: acetaminophen, metamizole, ibuprofen, desketoprofen and omeprazole. The deficit filling of the prescription compromised the dispensation in 231 prescriptions (10.7%). In 20 drugs, 57.5% of spending and 73.0% of saving were concentrated. Extrapolating the results to the prescriptions of one year, it is obtained that the expense would be €1,161,008.8, expecting for a reduction in €370,846.2 after adaptation to the guide or € 571,323.3 by adding the medication delivery strategy.Conclusions: New prescriptions at discharge are concentrated in a low number of medications. Acting on them allows a wide margin of economic improvement and increases security. Avoiding the prescription of non-financed medicines and guaranteeing the delivery of the medication upon discharge from the Emergency Department are another of the points of improvement identified. (AU)

Arginine-rich peptides are blockers of VR-1 channels with analgesic activity.

Vanilloid receptors (VRs) play a fundamental role in the transduction of peripheral tissue injury and/or inflammation responses. Molecules that antagonize VR channel activity may act as selective and potent analgesics. We report that synthetic arginine-rich hexapeptides block heterologously expressed VR-1 channels with submicromolar efficacy in a weak voltage-dependent manner, consistent with a binding site located near/at the entryway of the aqueous pore. Dynorphins, natural arginine-rich peptides, also blocked VR-1 activity with micromolar affinity. Notably, synthetic and natural arginine-rich peptides attenuated the ocular irritation produced by topical capsaicin application onto the eyes of experimental animals. Taken together, our results imply that arginine-rich peptides are VR-1 channel blockers with analgesic activity. These findings may expand the development of novel analgesics by targeting receptor sites distinct from the capsaicin binding site.

Three-dimensional reconstruction of scleral cold thermoreceptors of the cat eye.

Sensory endings that respond to local cooling were identified electrophysiologically in the cat's sclera. Functionally identified scleral thermal fibers were then used to analyze the structural characteristics of cold receptor endings. Four Adelta units sensitive to controlled cooling of their scleral receptive fields were recorded. The receptive areas were mapped, demarcated with pins and examined electron microscopically using extensive three-dimensional reconstructions. The supporting tissue within the receptive areas of cold units consisted of dense collageneous tissue with a small number of blood vessels that were either veins or capillaries. Adelta nerve fibers were found within these tissue blocks presumably corresponding with cold sensitive fibers. Small nerves and single nerve fibers devoid of a perineurium were found in all parts of the tissue, only occasionally passing a blood vessel. The terminal portions showed axonal swellings all along the unmyelinated segment filled with mitochondria, glycogen particles, and some vesicles. About 30% of the terminal axonal membrane is not covered by Schwann cells. In the unmyelinated distal portion, the mitochondrial content ranged from 0.012 to 0.038 microm(3) mitochondrial volume per microm(2) nerve fiber membrane. In comparison with sensory endings in the cat's knee joint, cold receptors in the cat sclera showed many similarities in their three-dimensional structure with polymodal nociceptor endings of the knee joint but contain less mitochondria. This suggests that cold sensory endings do not require specialized cellular processes for the transduction of cold stimuli, as is the case for multimodal transduction and sensitization in the terminal portion of polymodal nociceptors.

Reduction by antiinflammatory drugs of the response of corneal sensory nerve fibers to chemical irritation.

PURPOSE: Nonsteroidal antiinflammatory drugs (NSAIDs) have been applied topically to reduce ocular pain caused by corneal injury or anterior segment surgery. The authors investigated whether the analgesic effects of the NSAIDs diclofenac, indomethacin, and flurbiprofen and of the calcium channel antagonist diltiazem on corneal pain are mediated by a reduction of nerve activity in corneal polymodal nociceptive fibers. METHODS: Impulse activity of single A-delta and C corneal nerve fibers was recorded from the ciliary nerves of anesthetized cats. Polymodal units were identified by their response to both touching with the Cochet-Bonnet esthesiometer and to acidic stimulation with 30-second pulses of 80% or 98.5% CO2 or 60 microl of 10 mM acetic acid, applied to the corneal receptive area. Ongoing impulse activity, firing responses to CO2 or acetic acid, and mechanical threshold of single fibers were recorded before and at various times (5 to 90 minutes) after topical application of 0.1% sodium diclofenac, 0.03% sodium flurbiprofen, 0.1% indomethacin, and 0.045% diltiazem hydrochloride or of their vehicles. RESULTS: Indomethacin, diclofenac, and flurbiprofen, in decreasing order of potency, gradually reduced the mean frequency of the impulse response of corneal polymodal nerve fibers evoked by CO2 stimuli. The progressive increase of ongoing activity, observed in vehicle-treated eyes after repeated CO2 stimulation was also prevented by NSAIDs. Diltiazem also attenuated the response to CO2 for a shorter period of time and with a faster time course. The mechanical threshold of corneal polymodal fibers was not affected by treatment with any of these drugs. CONCLUSIONS: Indomethacin, diclofenac, and flurbiprofen, as well as the calcium antagonist diltiazem, diminish the responsiveness of corneal polymodal nociceptors to chemical stimuli. This appears to be caused, in part, by a direct effect of these drugs on the excitability of polymodal nerve endings, but also by an inhibition by NSAIDs of the formation of cyclooxygenase products such as prostaglandins, thus reducing the enhanced responsiveness of nociceptors caused by local release of arachidonic acid metabolites from injured cells.

Stimulation of the cervical sympathetic nerves increases intraocular pressure.

PURPOSE: To test the hypothesis that a moderate electrical stimulation of the cervical sympathetic nerves in rabbits can increase intraocular pressure (IOP). METHODS: Electrical stimulations of the cervical sympathetic nerves were performed in anesthetized and conscious rabbits. Intraocular pressure, pupil size, and concentrations of aqueous humor components were monitored. RESULTS: In urethane-anesthetized rabbits, stimulations of 5 V and 1 ms at 2.5 Hz for 1 hr and then at 20 Hz for 2 hr caused a short inhibition of IOP decrease and a prolonged mydriasis. Concentrations of norepinephrine (NE), neuropeptide Y (NPY), and cyclic AMP (cAMP) in aqueous humor were elevated. Aqueous humor protein concentration was not changed. In rabbits anesthetized with ketamine, chlorpromazine, and pentobarbital, electrical stimulations with the same parameters caused prolonged increases in IOP and pupil size. Aqueous humor NE and cAMP concentrations increased, while NPY and protein concentrations did not change. When the stimulations were set at 5 Hz for 3 hr under this anesthesia, the increase of IOP and mydriasis persisted. However, only the NE concentration increased. In conscious rabbits, stimulations of 5 V and 1 ms at either 5 Hz or 20 Hz were delivered from a portable stimulator for 4 hr, starting 2 hr before the onset of the dark. Stimulations at 5 Hz caused an increase in IOP in the light phase. The circadian IOP elevation in the dark phase persisted. When 20 Hz was used, a transient fall in IOP was observed, and the circadian IOP elevation was eliminated. Aqueous humor NE concentration doubled in conscious rabbits receiving electrical stimulations at 5 Hz for 1 hr. CONCLUSIONS: A moderate electrical stimulation of the cervical sympathetic nerves can increase IOP in anesthetized rabbits and in conscious rabbits in the light phase.

Endogenous circadian rhythm of basal pupil size in rabbits.

PURPOSE: The authors examined the circadian change of basal pupil size in light-dark entrained normal rabbits and in entrained rabbits with unilaterally decentralized ocular sympathetic nerves. The pattern of the circadian pupillary rhythm was compared with the circadian patterns of intraocular pressure (IOP) and body temperature in the same rabbits. METHODS: Adult male New Zealand albino rabbits were entrained to a daily 12-hour light-12-hour dark cycle. Using an infrared camera recording system, basal pupil sizes in seven entrained rabbits were videotaped under a constant dark environment at 1-hour intervals for 24 hours. Hourly IOP and rectal temperature in the same rabbits were measured separately under both the regular light-dark cycle and constant dark. In 10 entrained rabbits that underwent unilateral transection of the cervical sympathetic trunk, measurements of pupil size and IOP in constant dark were performed. RESULTS: In normal rabbits, a smaller basal pupil size in the subjective light phase and a consistently larger pupil size in the subjective dark phase were observed. Notably, pupil size increased sharply at the beginning of the subjective dark phase and peaked shortly. Circadian rhythms of IOP and body temperature were present under the regular light-dark cycle and in constant dark. As did pupillary enlargement, IOP rose sharply at the beginning of the subjective dark phase and peaked shortly thereafter. Body temperature, however, increased gradually and peaked in the late subjective dark phase. In rabbits with unilaterally decentralized ocular sympathetic nerves, the circadian rhythm of pupil size was present only in the intact eye. In addition, the circadian IOP elevation in the decentralized eye was reduced significantly. CONCLUSIONS: In light-dark entrained rabbits, basal pupil size changes in a circadian pattern and peaks at the beginning of the dark phase. The circadian pupillary rhythm disappears after ocular sympathetic decentralization. There are similar characteristics in the circadian rhythm of IOP. The increase of basal pupil size in the early dark phase is not related to the nocturnal increase of body temperature.

Effects of chronic sympathetic stimulation on corneal wound healing.

To explore the possibility that adrenergic fibers influence epithelial wound healing in the rabbit cornea, chronic electrodes were implanted in the left cervical sympathetic nerve, and symmetrical wounds were produced on the corneal epithelium of both eyes by means of n-heptanol. Continuous sympathetic stimulation was applied to awake, unrestrained animals during the wound-healing process (2-3 days) by use of a portable stimulator that delivered 1 ms, 3-Hz electric pulses at an amplitude necessary to evoke mydriasis. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. In stimulated corneas, the epithelial migration rate was smaller (36.9 +/- 6.2 microns/hr) than in control corneas (49.4 +/- 5.4 microns/hr), the differences being significant (P < 0.05). Significant differences in wound closure times between stimulated (53.2 +/- 6.8 hr) and control (41.3 +/- 5.5 hr) corneas were also observed. These results suggest a modulatory influence of corneal adrenergic fibers on the processes that follow epithelial injury of the cornea.

Chronic stimulation of ocular sympathetic fibers in unanesthetized rabbits.

The goal of this study was to devise a technique to implant permanent electrodes in the cervical sympathetic trunk, to stimulate the ocular adrenergic fibers for periods of hours or days in awake, unrestrained rabbits. Electrodes were made of a silver wire soldered to a multistranded wire and enclosed in silicone. Two of these electrodes were wrapped around the preganglionic sympathetic nerve, their leads emerging through a hole in the back of the neck. Success of the procedure was confirmed by the mydriasis elicited by electrical stimulation of the nerve following surgery; threshold voltages for the pupillary response varied between 5-10 volts. In eight rabbits, suprathreshold sympathetic stimulation was performed on the following days by means of a portable stimulator using increasing frequencies (1, 3, 5, 8, and 10 Hz) during a 20-hr period. Dilation of the ipsilateral pupil and vasoconstriction in the ear, measured by the fall in temperature of the ear's surface, was observed as long as stimulation was maintained. Both effects were proportional to the frequency of stimulation. Maximal mydriasis was obtained at 8 Hz, whereas full vasoconstriction was elicited with 5 Hz. Intraocular pressure, measured in 10 rabbits with a Perkins tonometer at the end of a 24-hr stimulation period, did not differ from pre-stimulation values. It was concluded that chronic stimulation of the sympathetic nerve allows to maintain known levels of adrenergic activity in the eye, and may be a useful method to study the actions of the adrenergic system on various ocular functions in unanesthetized animals.

Sensations evoked by selective mechanical, chemical, and thermal stimulation of the conjunctiva and cornea.

PURPOSE: To study the sensations evoked by selective mechanical, chemical, and thermal stimulation of the conjunctiva and compare them with those elicited by similar stimulation of the cornea. METHODS: Six young subjects participated in the study. Using a gas esthesiometer, selective mechanical (air puffs at flows from 0 to 264 ml/min), chemical (0--80% CO(2) in air), and thermal (air at temperatures from -10 degrees C to +80 degrees C) stimulation was performed on the center of the cornea and on the temporal conjunctiva. The intensity, degree of irritation, stinging and burning pain components, and thermal characteristics of the evoked sensation were evaluated after each stimulus in separate, 10-cm continuous visual analogue scales (VASs). The ability of the subjects to identify the quality of the stimulus applied to the cornea and the conjunctiva was also studied. RESULTS: The subjective intensity and thermal components (cooling or warming) of the sensation reported after mechanical, chemical, and heat stimulation were similar in the conjunctiva and cornea, although lower VAS scores were always reported in the conjunctiva for the irritation and the stinging and burning pain components. In the cornea, stimulation with low temperatures was perceived as a cooling sensation with an irritative component. In the conjunctiva, cooling was perceived as a purely cold sensation. Subjects showed similar discrimination capability in the cornea and the conjunctiva for the various types of stimuli. CONCLUSIONS: Sensations evoked in the cornea by selective mechanical, chemical, and heat and cold stimulation always presented an irritation component. In the conjunctiva, stimuli of the same intensity are always perceived as less irritating than in the cornea. Cold and other non-noxious subqualities of sensation can be evoked in the conjunctiva.

Effects of capsaicin on corneal wound healing.

This study examined whether the depletion of neuropeptides from sensory nerve terminals induced by capsaicin modifies the healing rate of experimental corneal wounds in adult rabbits. Capsaicin (33 or 3.3 mM solutions) was administered topically and/or by a single retrobulbar injection to one eye while the fellow eye, treated with the vehicle, served as a control. After 1-3 weeks of treatment, an epithelial wound was made in the center of the cornea of both eyes with n-heptanol. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. Combined treatment with 33 mM retrobulbar and 3.3 mM topical capsaicin for 3 weeks induced a significant delay in epithelial migration rates and in wound closure times (P less than 0.05). Topical or retrobulbar capsaicin alone for 3 weeks and combined treatment lasting only 1 week were not sufficient to modify wound healing times. The substance P antagonist, spantide (3 mM), applied topically for 1-3 weeks before or immediately after corneal wounding was also ineffective in changing wound closure rates. These findings suggest that the delayed wound healing observed after prolonged treatment with capsaicin could be due to a sustained depletion of neuropeptides from corneal sensory endings, supporting the hypothesis that trophic effects of sensory nerves on corneal epithelium are, at least in part, mediated by neuropeptides contained in peripheral nerve terminals.

Measurement of corneal sensitivity to mechanical and chemical stimulation with a CO2 esthesiometer.

PURPOSE: To develop an instrument to measure corneal sensitivity. Mechanical stimulation was performed with increasing air flow. Chemical stimulation consisted of local pH decreases induced by a mixture of air and CO2 at different concentrations. METHODS: Air and 98.5% CO2 were mixed with an electronic, proportional-direction control valve to obtain gas mixtures from 0% to 80% CO2. The regulated outflow of gas was carried to a probe mounted on a slit lamp holder, where it was warmed and its CO2 concentration monitored. An electronic valve directed gas pulses of controlled duration to the cornea. Corneal stimulation was performed in 17 young human subjects. The intensity of the experienced sensation was recorded in a continuous visual analog scale (VAS). To obtain threshold values and intensity-response curves, 3-second pulses were applied. For mechanical stimulation, air pulses of increasing flow were used. For chemical stimulation, gas mixtures of increasing CO2 concentration at subthreshold flow and CO2 in stepped increases of 5% was applied. RESULTS: Mechanical and chemical stimulation of the cornea evoked a brief sensation of irritation. Mechanical threshold (flow values) varied among subjects but were reproducible within each subject and were higher with warmed air. The magnitude of the sensation increased proportionally to the flow of air. The mean chemical stimulation threshold (CO2 concentration) was 25% +/- 3%. Increases in CO2 concentration from 10% to 80% augmented proportionally the intensity of the evoked sensation. CONCLUSIONS: The gas esthesiometer, which combines variable air flow and CO2 concentrations, permits application to the cornea of mechanical stimuli of controlled force and pH reductions of increasing magnitude. This instrument may be useful in a separate exploration of mechanical and chemical sensitivity of the cornea in human subjects.

Reduction of capsaicin-induced ocular pain and neurogenic inflammation by calcium antagonists.

PURPOSE: To examine whether blockade of chemosensitivity of corneal nociceptors by Ca2+ antagonists decreases pain and irritation induced by capsaicin. METHODS: In adult rabbits, the number of lid-squeezing movements and the degree of palpebral opening, miotic response, and conjunctival vasodilation evoked by a bilateral instillation of 30 microliters of capsaicin (33 mM) were measured at different times (up to 5 hours) after the drug. Irritative responses to capsaicin in eyes pretreated with diltiazem, verapamil, or nifedipine were compared with those that received only the vehicle. Protein content in aqueous humor was also measured at the end of the experiment. RESULTS: Diltiazem at doses of 1 to 28 mM, administered 15 minutes before the application of capsaicin, significantly decreased scratching movements, conjunctival hyperemia, closure of the eye, and elevated aqueous protein concentration induced by capsaicin; however, it did not significantly reduce miosis. Nifedipine (2.8 and 10 mM) diminished the number of scratching movements but not other inflammatory parameters, whereas verapamil (2.8 and 10 mM) was totally ineffective in attenuating ocular signs of irritation produced by capsaicin. CONCLUSIONS: These results suggest that by lowering capsaicin-induced neural activity in nociceptive terminals, diltiazem decreases pain and neurogenic inflammation and may be useful as both an analgesic and an antiinflammatory agent in the eye.

Effects of oleoresin capsicum pepper spray on human corneal morphology and sensitivity.

PURPOSE: To examine the potential harmful effects on corneal structure, innervation, and sensitivity of a spray containing the neurotoxin capsaicin (oleoresin capsicum, OC). METHODS: Ten police officers who volunteered for the study were exposed to OC. Clinical signs were assessed. Corneal sensitivity was measured using a Cochet-Bonnet or a noncontact esthesiometer that provides separate measurements of mechanical, chemical, and thermal sensitivity. Tear fluid nerve growth factor (NGF) was measured. Corneal cell layers and subbasal nerves were examined by in vivo confocal microscopy. The subjects were examined before application and 30 minutes, 1 day, 1 week, and 1 month after OC exposure. RESULTS: OC spray produced occasional areas of focal epithelial cell damage that healed within 1 day. Each eye showed conjunctival hyperemia and in two subjects, mild chemosis. All except one eye had unchanged best corrected visual acuity (BCVA). A transient decrease (day 1) of mechanical sensitivity was observed with the Cochet-Bonnet esthesiometer. With the gas esthesiometer, mechanical sensitivity remained below normal values for 7 days. Chemical sensitivity to CO2 was high for as much as 1 day and decreased below normal 1 week later, whereas sensitivity to cold was unaffected. Two subjects had measurable tear NGF that increased after exposure. Basal epithelial cell morphology suggested temporary corneal epithelial swelling, whereas keratocytes, endothelial cells, and subbasal nerves remained unchanged. CONCLUSIONS: Although OC causes immediate changes in mechanical and chemical sensitivity that may persist for a week, a single exposure to OC appears harmless to corneal tissues. The changes are possibly associated with damage of corneal nerve terminals of mainly unmyelinated polymodal nociceptor fibers.

Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type).

PURPOSE: To describe the corneal abnormalities and to measure different modalities of corneal sensitivity in corneal lattice dystrophy type II (familial amyloidosis, Finnish type, also known as gelsolin-related amyloidosis and originally as Meretoja syndrome). METHODS: Twenty eyes of 20 patients were examined by in vivo confocal microscopy and noncontact gas esthesiometry. RESULTS: Pleomorphism of, and dense deposits between or posterior to, the basal epithelial cells were frequently observed, as well as a reduction of long nerve fiber bundles in the subbasal nerve plexus. The anterior stroma was altered in most cases, with fibrosis and abnormal extracellular matrix. In 15 corneas, thick anterior and midstromal filaments, corresponding to lattice lines, and in 11 corneas, thin undulated structures were observed. The average mechanical sensitivity threshold of 12 subjects was increased, and in the remaining 8 subjects there was no response, even to the highest intensity of stimuli used. Three patients did not respond to CO(2), 11 to heat, and 2 to cold, but those patients who responded had normal thresholds. Patients with more long nerve fiber bundles per confocal microscopic image had better mechanical and cold sensitivity than patients with fewer nerve fiber bundles. CONCLUSIONS: Lattice lines seem to be related to amyloid material and not to corneal nerves. However, the subbasal nerve density appears reduced, which results mainly in a decrease in mechanical and, to a lesser extent, thermal sensitivity. The location of stromal filaments and undulated structures changes with increasing age.

Autosomal recessive cornea plana: in vivo corneal morphology and corneal sensitivity.

PURPOSE: Autosomal recessive corneal plana (RCP) is a rare corneal anomaly with unknown pathogenesis and a high incidence in Finland. The aim was to examine corneal sensitivity and the morphology of different corneal layers and subbasal nerves in RCP patients. METHODS: Three patients with a diagnosed autosomal recessive cornea plana were examined. Corneal sensitivity to different modalities of stimulation was tested in four corneas using noncontact esthesiometry. Tissue morphology of three corneas was evaluated, and in two corneas thickness of corneal layers was measured using in vivo confocal microscopy. RESULTS: Corneas of RCP patients appear to have mechanosensory, polymodal, and cold-sensitive nerve terminals. RCP patients had normal sensation thresholds for chemical, heat, and cold stimulation but a high threshold for mechanical stimulation. Their capacity to discriminate increasing intensities of stimulus was reduced, except for cold stimuli. Thickness of the epithelial layer was reduced, whereas total corneal and stromal thicknesses were slightly reduced or close to normal values. In all cases Bowman's layer was absent. Subbasal nerves had abnormal branching patterns. The arrangement of anterior keratocytes was altered, showing clustered and irregularly shaped nuclei. Increased backscattering of light in confocal microscopy through focusing (CMTF) profiles was observed throughout the stroma. Epithelial and endothelial cells appeared to be regular in shape. CONCLUSIONS: The present study revealed qualitative and quantitative alterations in corneal sensitivity, cellular morphology, and the thickness of corneal layers in RCP patients.

In vivo cAMP level in rabbit iris-ciliary body after topical epinephrine treatment.

PURPOSE: The present study estimates the in vivo cyclic AMP (cAMP) level in the rabbit iris-ciliary body after topical treatment with epinephrine. METHODS: Epinephrine 1% was applied unilaterally to pigmented rabbits. At selected time points between 10 min and 6 hr, a 2.5-mm diameter iris-ciliary body, in the treated eye, was irradiated with 2 J diode laser (2 W for 1 sec). Instant heat generated by the irradiation deactivated the cellular enzymes used in the synthesis and degradation of cAMP. Rabbits were sacrificed immediately, and samples of the iris-ciliary body were isolated from the irradiated area, the non-irradiated area, and from the contralateral, untreated eye. Levels of cAMP in these samples and in the aqueous humor were determined by radioimmunoassay. Further experiments were performed in rabbits pretreated with an alpha 2-adrenergic antagonist, yohimbine, and a beta-adrenergic antagonist, timolol, 30 min before the epinephrine treatment. Unilateral laser photocoagulation of the iris-ciliary body was performed at 10 min and 1 hr after the epinephrine treatment. RESULTS: The cAMP level in the photocoagulated iris-ciliary body did not change in parallel to the change in the aqueous humor. An increase of aqueous humor cAMP was observed for 6 hr. However, a reduction of cAMP level in the photocoagulated iris-ciliary body was observed at 1 hr after the epinephrine treatment. In yohimbine-pretreated rabbits, the reduction of cAMP level in the photocoagulated iris-ciliary body was absent. Pretreatment with timolol had no effect. CONCLUSIONS: These observations suggest that, at 1 hr after the epinephrine treatment, the cellular signal via the alpha 2-adrenergic receptors in the iris-ciliary body, which reduces the intracellular cAMP level, is stronger than that via the beta-adrenergic receptors.

Irritation of the anterior segment of the eye by ultraviolet radiation: influence of nerve blockade and calcium antagonists.

The aim of this investigation was to determine the influence on anterior segment inflammation elicited by UV radiation, of ocular denervation and pharmacological blockade of sensory nerve fibers with capsaicin, tetrodotoxin and calcium antagonists. Both eyes of pigmented rabbits were exposed for 5 min to UV radiation (254 nm); 24 h later, inflammatory signs were evaluated by biomicroscopy of the corneal epithelium, the stroma and the endothelium and scored from 0 to 4. Conjunctival vasodilation and miosis were also assessed. Two weeks before UV exposure, a group of rabbits received a retrobulbar injection of ethanol or of 1% capsaicin. Intact, capsaicin-treated and alcohol-denervated animals were treated topically, prior to UV exposure, with tetrodotoxin (0.78 mM) and the calcium antagonists diltiazem (1-28 mM) and nifedipine (10 mM). UV radiation produced at 24 h signs of corneal irritation, conjunctival hyperemia, miosis and elevated protein content of the aqueous humor. Retrobulbar injection of 99% alcohol or 1% capsaicin did not diminish significantly the inflammation of tissues directly exposed to UV radiation, although extension of inflammatory signs to unaffected areas was prevented. Pre-treatment of normal and denervated eyes with diltiazem attenuated UV-induced eye irritation signs at concentrations of 10 mM or over. The effect was less pronounced with tetrodotoxin and was not obtained with nifedipine. These findings suggest that the contribution of a neurogenic mechanism to anterior segment inflammation induced by UV exposure is modest. They also show that high concentrations of diltiazem, but not of nifedipine, effectively reduced inflammation of the anterior segment of the eye evoked by UV radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Corneal trophism and sensitivity changes after penetrating keratoplasty]. / Variaciones en el trofismo y la sensibilidad corneal tras la queratoplastia penetrante.

PURPOSE: To evaluate in the rabbit eye the changes in mechanical sensitivity and trophic function of the corneal epithelium after the denervation consecutive to circular trephinations of the peripheral cornea, similar to those produced by penetrating keratoplasty. METHODS: Complete trephination (8 mm diameter) with rotation of corneal button (PK) was performed in 12 eyes. Non-penetrating trephination, affecting 2/3 of the corneal depth, was made in a group of 12 eyes (NPK). A separate group of 16 nonoperated eyes served as control. Mechanical corneal sensitivity was measured with the Cochet-Bonnet esthesiometer (No. 12 filament). Trophic function of the corneal epithelium was assessed by determining the healing rate of epithelial wounds performed with n-heptanol. RESULTS: Three months after surgery, sensitivity in the center of the cornea was significantly reduced in both PK and NPK eyes (240+/-0 mg/S and 179+/-20 mg/S, respectively) when compared with control (88+/-10 mg/S, p<0.001). The ability of denervated corneas to regenerate corneal epithelial defects was similar in both, operated and non-operated eyes. Also, no differences were found between PK and NPK eyes. CONCLUSIONS: Results suggest that three months after corneal graft, throphic maintenance of the epithelium remains unaffected in spite of the significant hypoesthesia recorded at this time. Further experiments are needed to analyze the interaction between corneal epithelial cells and the trigeminal neurons innervating the cornea