RESUMO
A large number of studies have evaluated the efficacy of low-dose atropine in preventing or slowing myopic progression. However, it is challenging to evaluate the ocular safety from these studies. We aimed to evaluate the incidence of adverse events induced by atropine in children with myopia. We performed a systematic literature search in several databases for studies published until November 2022. The incidence of adverse events induced by atropine was pooled by a common-effect (fixed-effect) or random-effects model. Subgroup analyses were conducted according to drug doses, types of adverse events, and ethnicity. A total of 31 articles were ultimately included in the study. The overall incidence of adverse events for atropine was 5.9%, and the incidence of severe adverse events was 0.0%. The most commonly reported adverse events were photophobia (9.1%) and blurred near vision (2.9%). Other adverse events including eye irritation/discomfort, allergic reactions, headache, stye/chalazion, glare, and dizziness occurred in less than 1% of the patients. The incidence of atropine-induced adverse events varied depending on the drug doses. A lower dose of atropine was associated with a lower incidence of adverse events. There was no significant difference in the incidence of adverse events for low-dose atropine between Asian and White children. Our study suggests photophobia and blurred near vision are the most frequently reported adverse events induced by atropine. Low-dose atropine is safer than moderate- and high-dose atropine. Our study could provide a safe reference for ophthalmologists to prescribe atropine for myopic children.
Assuntos
Atropina , Miopia , Humanos , Criança , Atropina/efeitos adversos , Midriáticos/efeitos adversos , Fotofobia/induzido quimicamente , Incidência , Progressão da Doença , Miopia/tratamento farmacológico , Miopia/induzido quimicamente , Miopia/prevenção & controle , Soluções Oftálmicas/efeitos adversosRESUMO
Purpose: To report a case of a drug-induced anterior uveitis secondary to the use ofintracameral moxifloxacin.Case report: A 64-year-old Colombian male patient presented with severe ocular pain and photophobia in his left eye 15 days after cataract surgery. In the ophthalmology and glaucoma specialist evaluation, pigment dispersion in the anterior chamber and camerular angle, severe anterior segment inflammation, and elevated intraocular pressure were observed. Poor response to treatment for a suspected viral origin and exclusion of other possible etiologies, led to the conclusion of intracameral moxifloxacin induced anterior uveitis.Conclusion and importance: We present the second published case worldwide about anterior uveitis secondary to intracameral moxifloxacin, which may rarely cause hypertensive uveitis that may be confused with viral uveitis. This provides evidence on the importance of postoperative follow-up by the surgeon for an early referral and treatment of these cases.
Assuntos
Câmara Anterior/efeitos dos fármacos , Antibacterianos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Moxifloxacina/efeitos adversos , Uveíte Anterior/induzido quimicamente , Extração de Catarata , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Endoftalmite/prevenção & controle , Síndrome de Exfoliação/induzido quimicamente , Síndrome de Exfoliação/diagnóstico , Dor Ocular/induzido quimicamente , Dor Ocular/diagnóstico , Gonioscopia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/diagnóstico , Fotofobia/induzido quimicamente , Fotofobia/diagnóstico , Uveíte Anterior/diagnósticoRESUMO
BACKGROUND: Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice. METHODS: Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay. RESULTS: Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion. CONCLUSION: We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.
Assuntos
Transtornos de Enxaqueca , Fotofobia , Animais , Cafeína , Peptídeo Relacionado com Gene de Calcitonina , Endotelina-1/toxicidade , Camundongos , Fotofobia/induzido quimicamente , Peptídeo Intestinal VasoativoRESUMO
OBJECTIVE: A hallmark of migraine is photophobia. In mice, photophobia-like behavior is induced by calcitonin gene-related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. DESIGN: We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and acute CGRP injections in wild-type mice. Since the light/dark assay has historically been used to investigate anxiety-like responses in animals, we measured anxiety in a light-independent open field assay and asked if stimulation of a brain region, the periaqueductal gray, that induces anxiety would yield similar results to posterior thalamic stimulation. The hippocampus was used as an anatomical control to ensure that light-aversive behaviors could not be induced by the stimulation of any brain region. RESULTS: Optogenetic activation of neuronal cell bodies in the posterior thalamic nuclei elicited light aversion in both bright and dim light without an anxiety-like response in an open field assay. Injection of CGRP into the posterior thalamic region triggered similar light-aversive behavior without anxiety. In contrast to the posterior thalamic nuclei, optogenetic stimulation of dorsal periaqueductal gray cell bodies caused both light aversion and an anxiety-like response, while CGRP injection had no effect. In the dorsal hippocampus, neither optical stimulation nor CGRP injection affected light aversion or open field behaviors. CONCLUSION: Stimulation of posterior thalamic nuclei is able to initiate light-aversive signals in mice that may be modulated by CGRP to cause photophobia in migraine.
Assuntos
Comportamento Animal , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Optogenética , Fotofobia/etiologia , Núcleos Posteriores do Tálamo , Animais , Comportamento Animal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/administração & dosagem , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fotofobia/induzido quimicamente , Núcleos Posteriores do Tálamo/efeitos dos fármacosRESUMO
ABSTRACT: Spontaneous and pharmacologically provoked migraine attacks are frequently preceded by nonheadache symptoms called premonitory symptoms. Here, we systematically evaluated premonitory symptoms in migraine patients and healthy controls after glyceryl trinitrate (GTN) infusion. In women with migraine without aura (n = 34) and age-matched female controls (n = 24), we conducted systematically a semistructured interview assessing 21 possible premonitory symptoms every 15 minutes in the 5 hours after GTN infusion (0.5 µg/kg/min over 20 minutes). Migraine-like headaches occurred in 28/34 (82.4%) migraineurs (GTN responders). After GTN, 26/28 (92.9%) responders, 6/6 (100%) nonresponders, and 13/24 (54.2%) controls reported at least one possible premonitory symptom. Concentration difficulties (P = 0.011), yawning (P = 0.009), nausea (P = 0.028), and photophobia (P = 0.001) were more frequently reported by those migraineurs who developed a migraine-like attack vs healthy controls. Importantly, concentration difficulties were exclusively reported by those who developed a migraine-like attack. Thus, our findings support the view that GTN is able to provoke the naturally occurring premonitory symptoms and show that yawning, nausea, photophobia, and concentration difficulties are most specific for an impending GTN-induced migraine-like headache. We suggest that these symptoms may also be helpful as early warning signals in clinical practice with concentration difficulties exclusively reported by those who develop a migraine-like attack.
Assuntos
Transtornos de Enxaqueca , Bocejo , Estudos de Casos e Controles , Feminino , Humanos , Transtornos de Enxaqueca/induzido quimicamente , Nitroglicerina/efeitos adversos , Fotofobia/induzido quimicamenteRESUMO
PURPOSE: Pregabalin binds to the α2-δ1/α2-δ2 subunits of the voltage-gated L-type calcium channel (LTCC), which is expressed in rod/cone photoreceptor terminals. The purpose of this report was to describe electroretinographic abnormalities associated with pregabalin treatment. CASE PRESENTATION: This is an observational case report. A 49-year-old female reported photophobia and night blindness in her left eye after 10 months of pregabalin administration. One month after the symptoms, ophthalmic examinations were performed, which revealed good visual acuity and no remarkable fundus findings. However, full-field electroretinography (ERG) of the left eye revealed a decreased b-wave in rod ERG, a slightly decreased a-wave and severely decreased b-wave (negative ERG) in bright flash ERG, decreased a- and b-waves in cone ERG, and decreased b-waves in 30-Hz flicker ERG. These findings are similar to those seen in incomplete congenital stationary night blindness, whereas the right eye ERG showed normal responses, except for a square a-wave in cone ERG. The ERG gradually improved from 1 to 12 months after discontinuing pregabalin. Finally, b-waves in bright flash ERG and cone ERG responses largely recovered, but b-waves in rod ERG and a-waves in bright flash ERG only partially recovered in the left eye. The square a-wave recovered to normal in the right eye. CONCLUSIONS: This is the first report to indicate that ERG abnormalities might be associated with pregabalin treatment. Our results suggest that pregabalin may affect LTCC function via the α2-δ1/α2-δ2 subunits, which leads to defective synaptic transmission from rod/cone photoreceptors to bipolar cells.
Assuntos
Bloqueadores dos Canais de Cálcio/efeitos adversos , Eletrorretinografia/efeitos dos fármacos , Cegueira Noturna/induzido quimicamente , Fotofobia/induzido quimicamente , Pregabalina/efeitos adversos , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Canais de Cálcio Tipo L , Adaptação à Escuridão , Feminino , Humanos , Pessoa de Meia-Idade , Cegueira Noturna/fisiopatologia , Fotofobia/fisiopatologia , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To compare the biocompatibility and subjective symptoms of four multipurpose solutions marketed in Palestine with hydrogel contact lenses. METHODS: 50 habitual soft contact lens wearers were recruited in this interventional crossover study. Subjects were asked to attend the optometry clinic five times. A new pair of hydrogel lenses (Bioxifilcon-B) were fitted each time. This pair was soaked randomly overnight in one of the following four-multipurpose solutions (NEOPLUS®, AvizorUnicaSensitive®, ReNuMultiPlus® and COMPLETERevitaLens®) which contain different disinfecting agents (PHMB, Phx, PAPB, and PQ-1+Alexidine, respectively), or non-preserved saline. At each visit, corneal staining, ocular redness and subjective symptoms were assessed. RESULTS: The percentage of corneal staining increased significantly (P≤0.050) after soaking the lenses with PHMB (86%), PAPB (64%) and Phx (32%) based-solutions. However, a non-significant increase was noticed after the use of PQ-1+Alexidine based solution (30%, P=0.083). Ocular redness evaluation showed a significant increase (P≤0.050) in limbal hyperemia after the use of all solutions, while bulbar redness was significantly increased after the use of biguanide-based solutions (P≤0.050). The subjective assessment analysis showed a non-significant change in comfort, dryness, photophobia and scratchiness (P≥0.050) at 2-h intervention using all solutions, except for the PHMB based solution which showed a significant change in subjective symptoms (P≤0.050). CONCLUSION: The combination of Bioxifilcon-B hydrogel contact lenses and solution containing PHMB, PAPB and Phx-disinfectants induced a significant increase in corneal staining after 2h of CL-wear with a higher severity when the PHMB-based solution was used, while the PQ-1+Alexidine-based solution did not. Only the PHMB-based solution triggered a significant change in subjective symptoms which might which suggests that it might be related to the severity of staining rather than the induction of staining.
Assuntos
Doenças da Túnica Conjuntiva/induzido quimicamente , Soluções para Lentes de Contato/efeitos adversos , Lentes de Contato Hidrofílicas , Doenças da Córnea/induzido quimicamente , Síndromes do Olho Seco/induzido quimicamente , Hiperemia/induzido quimicamente , Fotofobia/induzido quimicamente , Adolescente , Adulto , Doenças da Túnica Conjuntiva/diagnóstico , Doenças da Córnea/diagnóstico , Estudos Cross-Over , Síndromes do Olho Seco/diagnóstico , Feminino , Humanos , Hiperemia/diagnóstico , Masculino , Teste de Materiais , Fotofobia/diagnóstico , Adulto JovemRESUMO
PURPOSE: To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation. METHODS: Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented. RESULTS: Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2). CONCLUSIONS: Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.
Assuntos
Annona/toxicidade , Ceratite/induzido quimicamente , Infestações por Piolhos/tratamento farmacológico , Pediculus/efeitos dos fármacos , Administração Oftálmica , Adolescente , Adulto , Animais , Antibacterianos/uso terapêutico , Criança , Dor Ocular/induzido quimicamente , Dor Ocular/diagnóstico , Dor Ocular/tratamento farmacológico , Feminino , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Doenças do Aparelho Lacrimal/induzido quimicamente , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/tratamento farmacológico , Masculino , Ofloxacino/uso terapêutico , Fotofobia/induzido quimicamente , Fotofobia/diagnóstico , Fotofobia/tratamento farmacológico , Estudos Retrospectivos , Transtornos da Visão/induzido quimicamente , Transtornos da Visão/diagnóstico , Transtornos da Visão/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.
Assuntos
Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Sumatriptana/administração & dosagem , Vasoconstritores/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Hiperacusia/induzido quimicamente , Hiperacusia/diagnóstico , Hiperacusia/tratamento farmacológico , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/diagnóstico , Náusea/tratamento farmacológico , Manejo da Dor/métodos , Medição da Dor/métodos , Fotofobia/induzido quimicamente , Fotofobia/diagnóstico , Fotofobia/tratamento farmacológico , Sumatriptana/efeitos adversos , Resultado do Tratamento , Vasoconstritores/efeitos adversosRESUMO
Multiple eccrine hidrocystoma (EH) has been treated with topical atropine with variable results. However, in rare cases, anticholinergic side effects have been seen after the use of the topical form of this drug. We presented a 50-year-old woman who developed recent onset of visual disturbance and photophobia from 2 weeks prior. The diagnosis of topical atropine-induced bilateral mydriasis was made. We reported a recognized but often overlooked case of bilateral mydriasis caused by application of topical 1% atropine for treatment of multiple EH.
Assuntos
Atropina/efeitos adversos , Hidrocistoma/tratamento farmacológico , Antagonistas Muscarínicos/efeitos adversos , Midríase/induzido quimicamente , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Atropina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Fotofobia/induzido quimicamenteRESUMO
RATIONALE: Bilateral acute iris transillumination (BAIT) is a poorly-understood ocular syndrome in which patients present with acute iridocyclitis and pigmentary dispersion with or without ocular hypertension. The etiology of the disease remains unknown, though recent reports suggest an antecedent upper respiratory tract infection or systemic antibiotic administration may trigger the clinical syndrome. PATIENT CONCERNS: A 55-year-old female was referred for a second opinion regarding her bilateral ocular pain, photophobia, and ocular hypertension. Her medical history was notable for a diagnosis of pneumonia managed with oral moxifloxacin several weeks prior to her initial presentation. DIAGNOSES: Visual acuity was 20/40 with an intraocular pressure (IOP) of 30âmmHg in the affected eye despite maximal tolerated medical therapy. The patient had severe bilateral iris transillumination defects with posterior synechiae formation and 3+ pigment with rare cell in the anterior chamber. This constellation of findings was consistent with a diagnosis of BAIT. INTERVENTIONS: A peripheral iridotomy was placed, which mildly relieved the iris bowing, but did not affect the IOP or inflammatory reaction. The patient then underwent cataract extraction with posterior synechiolysis and ab interno trabeculotomy of the left eye with the Trabectome. OUTCOMES: The patient's IOP on the first post-operative day was 13âmmHg, and anterior chamber inflammation was noted to be significantly reduced at post-operative week 2. The patient was recently seen at a 1-year post-operative visit and her IOP remains in the low teens on a low-dose combination topical agent. LESSONS: Ophthalmologists should remain aware of the association between systemic fluoroquinolones and acute pigmentary dispersion that can progress to glaucoma. The Trabectome remains a viable option for management of pigmentary and uveitic glaucoma resistant to medical treatment.
Assuntos
Antibacterianos/efeitos adversos , Fluoroquinolonas/efeitos adversos , Glaucoma de Ângulo Aberto/induzido quimicamente , Glaucoma de Ângulo Aberto/cirurgia , Trabeculectomia/métodos , Extração de Catarata , Dor Ocular/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Moxifloxacina , Hipertensão Ocular/induzido quimicamente , Fotofobia/induzido quimicamente , Pneumonia Bacteriana/tratamento farmacológico , Trabeculectomia/instrumentaçãoRESUMO
The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (ß2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), ß2 adrenoceptor (3NYA) and Dopamine D3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.
Assuntos
Encéfalo/efeitos dos fármacos , Quitosana/química , Portadores de Fármacos/química , Transtornos de Enxaqueca/tratamento farmacológico , Nanopartículas/química , Nistatina/química , Nistatina/farmacologia , Animais , Bradicinina/farmacologia , Encéfalo/metabolismo , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Asseio Animal/efeitos dos fármacos , Hiperalgesia/complicações , Masculino , Camundongos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/metabolismo , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Nistatina/metabolismo , Nistatina/uso terapêutico , Tamanho da Partícula , Fotofobia/induzido quimicamente , Fotofobia/complicações , Conformação Proteica , SoftwareRESUMO
Background The antibody-drug conjugate PF-06263507 targets the cell-surface, tumor-associated antigen 5T4 and consists of a humanized IgG1 conjugated to the microtubule-disrupting agent monomethylauristatin-F by a non-cleavable maleimidocaproyl linker. In this first-in-human, dose-finding trial (NCT01891669), we evaluated safety, pharmacokinetics, and preliminary antitumor activity of PF-06263507 in pretreated patients with advanced solid tumors, unselected for 5T4 expression. starting at 0.05 mg/kg, with 25, 56, and 95% dose increments, depending on observed dose-limiting toxicities (DLTs), applying a modified continual reassessment method. Results Twenty-six patients received PF-06263507 at 0.05 to 6.5 mg/kg. The first DLT, grade 3 photophobia, occurred at 4.34 mg/kg and two additional DLTs, grade 2 keratitis and grade 1 limbal stem cell deficiency (> 2-week dosing delay), at 6.5 mg/kg. The most common adverse events (AEs) were fatigue (38.5%), photophobia (26.9%), and decreased appetite, dry eye, nausea, and thrombocytopenia (23.1% each). No treatment-related grade 4-5 AEs were reported. Systemic exposure of PF-06263507 increased in a dose-related manner. At the maximum tolerated dose (MTD, 4.34 mg/kg), mean terminal half-life for PF-06263507 and unconjugated payload were ~6 and 3 days, respectively. Payload serum concentrations were substantially lower compared with PF-06263507. No objective responses were observed. Conclusions The MTD and recommended phase II dose were determined to be 4.34 mg/kg. Ocular toxicities accounted for the DLTs observed, as previously reported with monomethylauristatin-F payloads. Further studies are warranted to investigate clinical activity of this agent in patients with 5T4-expressing tumors.Trial registration ID: NCT01891669.
Assuntos
Anticorpos Monoclonais Humanizados , Antígenos de Neoplasias , Imunoconjugados , Glicoproteínas de Membrana/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Oligopeptídeos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos de Neoplasias/efeitos adversos , Antígenos de Neoplasias/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Ceratite/induzido quimicamente , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo , Oligopeptídeos/efeitos adversos , Oligopeptídeos/farmacocinética , Oligopeptídeos/uso terapêutico , Fotofobia/induzido quimicamente , Resultado do TratamentoRESUMO
INTRODUCTION: Glyceryl trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy. In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. METHODS: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl trinitrate on these behaviors in female rats was observed. RESULTS: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None of the three behavioral tests were altered by glyceryl trinitrate infusion. In the light-dark box, some batches of rats showed light sensitivity after treatment with glyceryl trinitrate but it could not be repeated in other batches of rats. DISCUSSION: We have investigated the stability towards repeated testing and the effect of i.v. glyceryl trinitrate infusion to awake rats in three behavioral assays. Of the assays evaluated, only light sensitivity was capable of detecting changes after glyceryl trinitrate infusion but, this was not repeatable. Thus, the infusion of a low dose glyceryl trinitrate to concious rats together with the chosen behavioral tests is not a robust setup for studying immediate GTN induced headache behavior in rats.
Assuntos
Comportamento Animal/efeitos dos fármacos , Luz , Atividade Motora/efeitos dos fármacos , Nitroglicerina/farmacologia , Vasodilatadores/farmacologia , Animais , Modelos Animais de Doenças , Ciclo Estral , Feminino , Infusões Intravenosas , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/fisiopatologia , Nitroglicerina/administração & dosagem , Fotofobia/induzido quimicamente , Fotofobia/psicologia , Ratos , Corrida , Vasodilatadores/administração & dosagemRESUMO
BACKGROUND: This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. METHODS: Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. RESULTS: The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. CONCLUSIONS: These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.
Assuntos
Comportamento Animal/efeitos dos fármacos , Transtornos de Enxaqueca/diagnóstico , Atividade Motora/efeitos dos fármacos , Nitroglicerina , Vasodilatadores , Animais , Modelos Animais de Doenças , Masculino , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Fotofobia/induzido quimicamente , Fotofobia/diagnóstico , Fotofobia/tratamento farmacológico , Ratos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Sumatriptana/farmacologia , Sumatriptana/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: The term «poppers¼ refers to products made of volatile alkyl nitrites used for recreational practices. CLINICAL CASE: 40 year old man reported blurred vision in both eyes and photophobia, and admitted regular use of «poppers¼. Best corrected visual acuity was 0.63/1 in both eyes. Bilateral yellowish vitelliform macular lesions were present in both eyes in the funduscopy, as well as a disruption of the IS/OS line in the optical coherence tomography. DISCUSSION: This is the first case of «poppers maculopathy¼ registered in Spain. Clinical findings and symptoms are similar to previous reported cases.
Assuntos
Drogas Ilícitas/efeitos adversos , Degeneração Macular/induzido quimicamente , Nitritos/efeitos adversos , Fotofobia/induzido quimicamente , Adulto , Infecções por HIV/complicações , Humanos , Lactente , Degeneração Macular/diagnóstico por imagem , Masculino , Oftalmoscopia , Espanha , Transtornos Relacionados ao Uso de Substâncias/complicações , Tomografia de Coerência ÓpticaRESUMO
OBJECTIVE: To describe the first case of sertraline-induced diplopia. METHOD: Medline and PubMed data search using the words sertraline, Zoloft, diplopia, double vision. A case summary of a patient who developed diplopia from sertraline. RESULT: This case describes a 34-year-old man who developed diplopia after treatment with sertraline. The diplopia resolved after discontinuation of sertraline and redeveloped upon rechallenge. CONCLUSION: Although incidences of diplopia caused by citalopram, another SSRI, have been described, to the best of our knowledge, this is the first reported case of sertraline-induced diplopia. More studies are needed to describe the full mechanism of action of sertraline-induced diplopia.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Diplopia/induzido quimicamente , Sertralina/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Diplopia/diagnóstico , Humanos , Masculino , Fotofobia/induzido quimicamente , Fotofobia/diagnóstico , Fotofobia/psicologia , Sertralina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Acuidade Visual/efeitos dos fármacosAssuntos
Dermatologia , Cefaleia/induzido quimicamente , Fotofobia/induzido quimicamente , Púrpura/induzido quimicamente , Envelhecimento da Pele/efeitos dos fármacos , Feminino , Cefaleia/diagnóstico , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Pessoa de Meia-Idade , Fotofobia/diagnóstico , Púrpura/diagnóstico , Envelhecimento da Pele/patologiaRESUMO
We report the case of a 65-year-old woman presenting with recurrent vomiting for 3 days. She had been previously diagnosed with an atrial septal defect and was on treatment with diuretics and digoxin for paroxysmal supraventricular tachycardia. The clinical examination was consistent with an atrial septal defect with severe pulmonary hypertension. Electrocardiography showed complete heart block with ST-segment changes suggestive of digitalis toxicity. Transthoracic echocardiography confirmed Eisenmengerisation. Serum digoxin levels were elevated. Following hospitalisation, she was diagnosed with photophobia when she persistently asked for ambient lighting to be switched off. Most interestingly, the patient kept reporting seeing little yellow men, which was how she perceived the attending doctors. Cessation of digoxin therapy led to progressive abatement of her symptoms.