RESUMEN
This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.
Asunto(s)
Clorfeniramina/química , Composición de Medicamentos/métodos , Antagonistas de los Receptores Histamínicos/química , Liposomas/química , Administración Tópica , Clorfeniramina/administración & dosificación , Liberación de Fármacos , Antagonistas de los Receptores Histamínicos/administración & dosificación , Estructura MolecularRESUMEN
In French Guiana, a French overseas region partly located in the Amazon, "Africanized" bees, a hybrid species of Brazilian bees known as "killer bees," have been observed since 1975. Since then, several cases requiring long hospitalization times have been described, allowing for a better understanding of the physiopathological mechanisms of this particular envenomation. Here, we report on a series of 10 cases of patients simultaneously attacked by hundreds of killer bees and immediately treated by a prehospital medical team already on site. Between 75 and 650 stingers were removed per victim. The reference treatment for anaphylaxis using intramuscular injection of epinephrine, vascular filling, and oxygen therapy was administered to all patients without delay. A clinical description was provided, and biological tests were performed immediately after the envenomation. We therefore observe the existence of a two-phase, medically well-controlled systemic toxic reaction. Thus, all our patients left the hospital after 44 hours of monitoring with no complications or sequelae, despite levels of intoxication described as potentially fatal elsewhere in the literature.
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Abejas/clasificación , Mordeduras y Picaduras de Insectos/epidemiología , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Animales , Antiinfecciosos Locales/administración & dosificación , Antiinfecciosos Locales/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Clorfeniramina/administración & dosificación , Clorfeniramina/uso terapéutico , Epinefrina/uso terapéutico , Guyana Francesa/epidemiología , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Mordeduras y Picaduras de Insectos/tratamiento farmacológico , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Oxígeno/uso terapéutico , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Solución Salina , Simpatomiméticos/administración & dosificación , Simpatomiméticos/uso terapéutico , Adulto JovenRESUMEN
A hybrid species of Brazilian bee has proliferated on the South American continent since 1956. We describe a "killer bee" swarm attack on a 2-year-old girl in French Guiana. The patient weighed 10 kg, and approximately hundreds of bees' stingers were removed, that is, 10 stings/kg. Our patient survived without long-term sequelae. The management of her condition required admission into intensive care for renal failure due to acute tubular necrosis and severe rhabdomyolysis. We emphasize the importance of early medical intervention, clinical surveillance, and biological monitoring at the hospital to prevent a toxic chain reaction that could prove fatal within 72 hours.
Asunto(s)
Lesión Renal Aguda/etiología , Venenos de Abeja/toxicidad , Abejas , Mordeduras y Picaduras de Insectos , Acetaminofén/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Animales , Preescolar , Clorfeniramina/administración & dosificación , Clorfeniramina/uso terapéutico , Femenino , Guyana Francesa , Furosemida/uso terapéutico , Glucocorticoides/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Mordeduras y Picaduras de Insectos/complicaciones , Prednisolona/uso terapéuticoRESUMEN
Catheter-related bladder discomfort (CRBD) associated with intraoperative urinary catheterization is a distressing symptom during recovery from anesthesia. Anticholinergics have been used to manage CRBD. Chlorpheniramine maleate (CPM) is a first-generation antihistamine, which also has anticholinergic effects. This study was undertaken to evaluate the efficacy of CPM in preventing CRBD. Seventy-six adults (19-65 years old) with American Society of Anesthesiologists physical status I, II, or III of either sex, undergoing elective ureteroscopic stone removal under general anesthesia were randomized into one of two groups (each n = 38). Group C (control) received a placebo, and group CPM received 8 mg of intravenous CPM before the induction of anesthesia. CRBD was assessed upon arrival in the post-anesthetic care unit at 0, 1, 2, and 6 h. The severity of CRBD was graded as none, mild, moderate, and severe. Tramadol was administered when the severity of CRBD was more than moderate. The incidence rate and overall severity of CRBD did not differ between the groups at any of the time points (Ñ > 0.05). The incidence of moderate CRBD was higher in group C than in group CPM only at 0 h (26.3% vs. 5.3%, Ñ = 0.025). However, fewer patients in the CPM group required rescue tramadol to relieve CRBD after surgery (31.6% vs. 60.5%, Ñ = 0.011). CPM administration before the induction of anesthesia had little effect on the incidence and severity of CRBD after surgery, but it reduced the administration of tramadol required to control CRBD postoperatively.
Asunto(s)
Clorfeniramina/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Dolor Postoperatorio/epidemiología , Ureteroscopía/efectos adversos , Cateterismo Urinario/efectos adversos , Urolitiasis/cirugía , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ureteroscopía/instrumentación , Ureteroscopía/métodos , Vejiga Urinaria/efectos de los fármacos , Cateterismo Urinario/instrumentación , Cateterismo Urinario/métodos , Catéteres Urinarios/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Acute urticaria is a common dermatological condition in emergency departments (EDs). The main therapy involves controlling pruritus with antihistamines. Although guidelines have promoted the use of corticosteroids in addition to H1 antihistamines, well-designed clinical trials evaluating this approach are scarce. METHODS: Adult ED patients with acute urticaria and a pruritus scoreâ¯>â¯5 on a visual analog scale (VAS) were randomized into three groups: (i) IV chlorpheniramine (CPM) treatment, (ii) IV CPM and IV dexamethasone (CPM/Dex) and (iii) IV CPM and IV dexamethasone with oral prednisolone as discharge medication for 5â¯days (CPM/Dex/Pred). The primary outcomes were self-reported pruritus VAS scores at 60â¯min after treatment. We also evaluated 1-week and 1-month urticaria activity scores for 7â¯days and adverse events. RESULTS: Seventy-five patients (25 per group) were enrolled. The VAS scores of all groups decreased, but no significant difference was found in the VAS scores at 60â¯min after treatment between patients in the CPM group (nâ¯=â¯25) and those who received both CPM and dexamethasone (nâ¯=â¯50). At the 1-week and 1-month follow-ups, active urticaria (indicated by the urticaria activity score at 7â¯days) was more prevalent in the CPM/Dex/Pred group (nâ¯=â¯25) than in the control group. CONCLUSIONS: The present study did not find evidence that adding IV dexamethasone improves the treatment of severe pruritus from uncomplicated acute urticaria. Oral corticosteroid therapy may be associated with persistent urticaria activity. Due to the lack of clinical benefits and the potential for side effects, using corticosteroids as an adjunctive treatment is discouraged.
Asunto(s)
Corticoesteroides/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Enfermedad Aguda , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Clorfeniramina/administración & dosificación , Dexametasona/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Tailandia , Resultado del Tratamiento , Escala Visual Analógica , Adulto JovenRESUMEN
INTRODUCTION: Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at the H1 receptor and prevent binding of histamine at the H1 receptor, thereby preventing allergic reactions. Molecules containing a triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with the H1 receptor. METHODS: Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe-432 subunits. A pharmacophore model, new 5-(4-substituted phenyl)-4-(phenylamino)-4-H-1,2,4-triazole-3- thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum. RESULTS: According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to easily penetrate cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others. CONCLUSION: Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum, taking chlorpheniramine maleate as a standard. Most of the compounds were found to possess better antihistamine activity.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1/farmacocinética , Receptores Histamínicos H1/metabolismo , Triazoles/farmacocinética , Animales , Clorfeniramina/administración & dosificación , Clorfeniramina/farmacocinética , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Absorción Gastrointestinal , Cobayas , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/síntesis química , Simulación del Acoplamiento Molecular , Triazoles/administración & dosificación , Triazoles/síntesis químicaRESUMEN
This is a case of a patient who presented with an urticarial rash 48 hours before developing symptoms of fever and a continuous cough. She subsequently developed angioedema of her lips and hands before testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Urticarial rashes occurring 48 hours before other symptoms of COVID-19 infection have been documented. This case demonstrates the importance of heightened awareness that not all urticarial rashes represent spontaneous urticaria and as a consequence, this may result in misdiagnosis and ultimately delayed diagnosis. This is the first reported case in the literature of urticaria with angioedema as a prodromal phenomenon of COVID-19.
Asunto(s)
Angioedema , Clorfeniramina/administración & dosificación , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Prednisona/administración & dosificación , Terfenadina/análogos & derivados , Urticaria , Angioedema/diagnóstico , Angioedema/etiología , Angioedema/fisiopatología , Antialérgicos/administración & dosificación , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Síntomas Prodrómicos , SARS-CoV-2 , Terfenadina/administración & dosificación , Resultado del Tratamiento , Urticaria/diagnóstico , Urticaria/etiología , Urticaria/fisiopatologíaRESUMEN
BACKGROUND: This study sought to assess the cutaneous (peripheral) analgesic effects of antihistamine chlorpheniramine, compared with the long-lasting local anesthetic bupivacaine. METHODS: After chlorpheniramine and bupivacaine were subcutaneously injected under the dorsal skin of the rats, the cutaneous analgesia effect was quantitatively evaluated by scoring the number to which the animal failed to react (cutaneous trunci muscle reflex). The quality and duration of chlorpheniramine and bupivacaine on infiltrative cutaneous analgesia were compared. RESULTS: We revealed that subcutaneous chlorpheniramine, as well as the local anesthetic bupivacaine elicited cutaneous analgesia in a dosage-dependent manner. Based on their ED50s (50% effective doses), the relative potency was found to be chlorpheniramine [1.13 (1.05-1.22) µmol] < bupivacaine [0.52 (0.46-0.58) µmol] (p < 0.01). When comparing the ED25s, ED50s and ED75s, full recovery time induced by chlorpheniramine was longer (p < 0.01) than that induced by bupivacaine. CONCLUSIONS: Our preclinical data demonstrated that both chlorpheniramine and bupivacaine dose-dependently provoked the cutaneous analgesic effects. Chlorpheniramine with a more prolonged duration was less potent than bupivacaine in inducing cutaneous analgesia.
Asunto(s)
Analgesia/métodos , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Clorfeniramina/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Administración Cutánea , Animales , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Inyecciones Subcutáneas , Masculino , Dimensión del Dolor/métodos , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.
Asunto(s)
Antialérgicos/administración & dosificación , Quitosano/administración & dosificación , Clorfeniramina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanopartículas/administración & dosificación , Rinitis Alérgica/tratamiento farmacológico , Administración Intranasal , Animales , Antialérgicos/química , Quitosano/química , Clorfeniramina/química , Femenino , Geles , Nanopartículas/química , Mucosa Nasal/anatomía & histología , Mucosa Nasal/química , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Conejos , OvinosRESUMEN
Centipede bites are a constant risk throughout tropical regions and have the rare potential for systemic side effects. We report a case of multiple centipede bites in South Sudan that was complicated by severe pain refractory to opioid analgesia and an unusual association with acute involuntary muscle contractions. Treatment with local anesthetic, antihistamines, and corticosteroids was effective. This report aims to add to the local literature; because of decades of internal conflict and poor infrastructure, reporting of health data from South Sudan is severely lacking. Further investigation into the pharmacological variation and activity of toxic peptides in centipede venom is recommended. As it stands, this case provides additional information on potential effects of centipede envenomation that should be useful to any healthcare providers preparing for the delivery of remote medical care throughout the Great Upper Nile region.
Asunto(s)
Venenos de Artrópodos/envenenamiento , Artrópodos , Mordeduras y Picaduras/tratamiento farmacológico , Adulto , Analgésicos Opioides/administración & dosificación , Anestésicos Locales/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Clorfeniramina/administración & dosificación , Fentanilo/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Humanos , Hidrocortisona/administración & dosificación , Lidocaína/administración & dosificación , Masculino , Personal Militar , Contracción Muscular/efectos de los fármacos , Dolor/tratamiento farmacológico , Prurito/tratamiento farmacológico , Sudán del SurRESUMEN
The majority of active pharmaceutical ingredients (APIs) are bitter. Therefore, compliance can be a problem where adequate taste masking has not been achieved; this is most problematic in pediatrics. Taste masking is thus a key stage during pharmaceutical development with an array of strategies available to the formulation scientist. Solid oral dosage forms can be taste-masked quite simply by polymer coating, which prevents drug release in the mouth, without unwantedly impairing drug release further down the gastrointestinal tract. At the early stages of pharmaceutical development, an in vitro method for the assessment of taste masking is necessary given the lack of toxicological data preventing the use of human taste panels. Currently, there is no such tool allowing prediction of taste masking efficiency. In this study, drug dissolution in the context of aversive taste thresholds was proposed as a means to bridge this knowledge gap. Thus, a biorelevant buccal dissolution test was developed in which previously determined taste thresholds in vivo were used to evaluate taste masking efficiency: if drug release exceeded said thresholds, the formulation was deemed to be poorly taste-masked, and vice versa. This novel dissolution test was compared to the USP I (basket) dissolution test, and the biopharmaceutical implications of taste masking were also assessed by performing USP I (basket) dissolution testing in simulated gastric fluid (SGF). Chlorphenamine maleate, a model bitter BCS class 1 API, was layered onto sugar spheres and taste-masked using polymer coatings. An array of coating technologies were employed and assessed single blinded: two pH-independent water-insoluble coatings (Surelease:Opadry at 8, 12, and 16% weight gain and Opadry EC at 4, 6, and 8% weight gain) and a pH-dependent water-insoluble reverse-enteric coating (developmental fully formulated system based on Kollicoat Smartseal 100P at 10% weight gain). Both the biorelevant buccal and the USP I dissolution tests were capable of discriminating between both type and level of coating used. However, only the buccal dissolution test was able to provide absolute quantification of the level of taste masking achieved in the context of previously determined taste thresholds, while the USP I test merely provided a relative comparison between the different technologies assessed. When the release data from the buccal test were assessed in parallel to that in SGF, it was possible to predict in vitro optimized taste masking without compromising bioavailability. The fully formulated system based on Smartseal 100P was identified as the most effective coating and Surelease:Opadry the least effective. The developed methodology provides true insight for the formulator, enabling more informed patient-centric formulation decisions, better taste masking, and ultimately more effective medicines.
Asunto(s)
Composición de Medicamentos/métodos , Desarrollo de Medicamentos/métodos , Liberación de Fármacos , Gusto/fisiología , Administración Oral , Adolescente , Adulto , Animales , Celulosa/análogos & derivados , Celulosa/química , Clorfeniramina/administración & dosificación , Clorfeniramina/farmacología , Femenino , Voluntarios Sanos , Humanos , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , Ratas , Método Simple Ciego , Solubilidad , Azúcares/química , Adulto JovenRESUMEN
OBJECTIVE: Evaluate effects of a multisymptom tablet on cold and flu symptoms within 4 hours post-administration. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled study in adults with cold and flu symptoms. Eligible participants with at least moderate common cold or flu symptoms and symptom onset ≤ 48 hours before screening were assigned to a single multiple-active-ingredient tablet (containing paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, and chlorpheniramine maleate) or placebo tablet. Participants rated severity of each symptom (sore throat, headache, extremity pain, nasal congestion, sneezing, runny nose, and cough) from 0 (absent) to 3 (severe) at 15 and 30 minutes and 1, 2, 3, and 4 hours post administration. The total symptom score (TSS) was calculated as the sum of the individual symptom scores (primary endpoint). Participants rated global response to treatment on a scale from 0 (ineffective) to 4 (excellent). Adverse events (AEs) were recorded throughout. RESULTS: Of 53 participants randomized, 52 received active tablet (n = 25) or placebo tablet (n = 27). Change from baseline in TSS throughout the 4-hour post-administration period was similar between groups. An efficacy criterion of 30% decrease in TSS at assessment points was not met (range, -1.91 to 8.94%). There were also no significant differences between groups in mean symptom scores for individual symptoms or global response to treatment. Four non-serious treatment-emergent adverse events occurred. CONCLUSION: In this exploratory pilot study, a multisymptom cold and flu tablet was well tolerated but did not differ from placebo tablet with regard to onset of action following a single dose.â©.
Asunto(s)
Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Antitusígenos/administración & dosificación , Clorfeniramina/administración & dosificación , Resfriado Común/tratamiento farmacológico , Dextrometorfano/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Gripe Humana/tratamiento farmacológico , Descongestionantes Nasales/administración & dosificación , Seudoefedrina/administración & dosificación , Acetaminofén/efectos adversos , Administración Oral , Adulto , Analgésicos no Narcóticos/efectos adversos , Antitusígenos/efectos adversos , China , Clorfeniramina/efectos adversos , Resfriado Común/diagnóstico , Resfriado Común/virología , Dextrometorfano/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Descongestionantes Nasales/efectos adversos , Satisfacción del Paciente , Proyectos Piloto , Seudoefedrina/efectos adversos , Inducción de Remisión , Comprimidos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The landscape of thin films is continuously evolving as an attractive self-administration mean to drive patient compliance. This work reports incorporation of drugs into various polymeric compositions using spin coating technology to screen amorphous solid dispersion film formation for buccal applications. Polarized light microscopy and differential scanning calorimetry were used for characterization. Physical stability was assessed after films storage at 0% RH/25°C for 6 months. Chlorpheniramine maleate, theophylline, and famotidine were used as model drugs and mixed with Opadry amb II® or Kollicoat IR®. Acryl-EZE II® or Zein was also used as surface (design I) or surface and base polymers (design II). Of all the drug-Opadry combinations, only chlorpheniramine was amorphously dispersed up to 25% (w/w). In contrast, Kollicoat IR® resulted in amorphous dispersions of all the tested drugs, suggesting that it has a better solubilization capacity. Drugs prepared in design II achieved higher in vitro release compared to respective design I, indicating that lower content of Acryl-EZE II® or Zein can decrease drug release over 3 h. It has been also revealed that Zein could improve physical stability of the aged theophylline solid-dispersed films. Release kinetics of model drugs were satisfactory when described by first-order kinetics, facilitated through anomalous transport of both diffusion and polymer swelling.
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Sistemas de Liberación de Medicamentos/métodos , Polímeros/química , Administración Bucal , Broncodilatadores/administración & dosificación , Broncodilatadores/química , Clorfeniramina/administración & dosificación , Clorfeniramina/química , Liberación de Fármacos , Famotidina/administración & dosificación , Famotidina/química , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/química , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/química , Humanos , Polivinilos/química , Solubilidad , Teofilina/administración & dosificación , Teofilina/química , Zeína/químicaRESUMEN
We describe 2 patients who developed anaphylactic shock after sugammadex administration during anesthesia. Both had no history of prior sugammadex administration. The serum tryptase concentrations were elevated after the allergic reaction. Basophil activation testing 1 month after the events was positive for sugammadex in 1 patient, and negative in the other. However, it was positive for light-exposed sugammadex solution in both patients, suggesting a possible allergic reaction to a denatured compound of sugammadex generated by light exposure of the sugammadex solution.
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Anafilaxia/inmunología , Luz/efectos adversos , Sugammadex/efectos adversos , Anciano , Anafilaxia/inducido químicamente , Anafilaxia/tratamiento farmacológico , Anestesia/efectos adversos , Basófilos/citología , Clorfeniramina/administración & dosificación , Clorfeniramina/uso terapéutico , Femenino , Humanos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Adulto JovenRESUMEN
This study investigated the influence of the histamine H1 receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H1 receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H1 receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.
Asunto(s)
Dolor Abdominal/fisiopatología , Dolor Abdominal/terapia , Clorfeniramina/administración & dosificación , Clorfeniramina/farmacología , Electroacupuntura , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/farmacología , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Pirilamina/administración & dosificación , Pirilamina/farmacología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Dolor Abdominal/inducido químicamente , Ácido Acético/efectos adversos , Animales , Combinación de Medicamentos , Masculino , Ratones Endogámicos ICR , Dimensión del DolorRESUMEN
BACKGROUND: Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK's National Poisons Information Service. METHODS: Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.
Asunto(s)
Sobredosis de Droga/epidemiología , Fármacos Gastrointestinales/envenenamiento , Centros de Control de Intoxicaciones , Ranitidina/envenenamiento , Factores de Edad , Preescolar , Clorfeniramina/administración & dosificación , Clorfeniramina/envenenamiento , Bases de Datos Factuales , Domperidona/administración & dosificación , Domperidona/envenenamiento , Composición de Medicamentos , Sobredosis de Droga/diagnóstico , Femenino , Fármacos Gastrointestinales/administración & dosificación , Humanos , Incidencia , Lactante , Masculino , Metoclopramida/administración & dosificación , Metoclopramida/envenenamiento , Omeprazol/administración & dosificación , Omeprazol/envenenamiento , Ranitidina/administración & dosificación , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, Cmax was similar across age groups, although it tended to occur earlier in the youngest group. AUC was â¼15% to 30% higher in the oldest age group. As expected, CLo and Vz /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t1/2,z existed (â¼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar Cmax and AUC.
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Antialérgicos/farmacocinética , Bromofeniramina/farmacocinética , Clorfeniramina/farmacocinética , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Administración Oral , Adolescente , Antialérgicos/administración & dosificación , Antialérgicos/efectos adversos , Bromofeniramina/administración & dosificación , Bromofeniramina/sangre , Niño , Preescolar , Clorfeniramina/administración & dosificación , Clorfeniramina/sangre , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/sangre , HumanosRESUMEN
Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk. Results We identified 248 subjects, including 13 (5.2%) with infusion-related reactions (grade 1 in five [2.0%], grade 2 in seven [2.8%], and grade 4 in one [0.4%]). The incidence of these reactions in cetuximab combination regimens, each employing an H1-receptor antagonist, using a higher dose of dexamethasone (13.2 mg) was not significantly lower compared with those using 6.6 mg DEX (2.4% vs 8.3%, respectively; p = 0.43). Twelve patients experienced infusion-related reactions associated with the first cetuximab administration, and one reaction occurred after the third administration. Conclusions The incidence of infusion-related reactions was lower compared with those of previous studies. Dexamethasone combined with an H1-receptor antagonist was useful for preventing allergic responses. The incidence of infusion-related reactions was not lower with 13.2 mg dexamethasone, and 6.6 mg DEX prevented infusion-related reactions.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Cetuximab/efectos adversos , Clorfeniramina/administración & dosificación , Dexametasona/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Adulto , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Cetuximab/administración & dosificación , Femenino , Humanos , Hipersensibilidad/prevención & control , Incidencia , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Premedicación , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The relationship between anaphylaxis and cardiovascular events has been reported in the past. While skin and respiratory symptoms are usually the most common and the first to appear, cardiovascular complications play a key role and represent the leading cause of death in anaphylaxis. METHODS: We report 3 episodes of atrial fibrillation triggered by anaphylaxis. Allergy and cardiology studies were performed. In both patients, the etiological agent was identified: Anisakis simplex hypersensitivity and food allergy. RESULTS: The heart is the source and target of chemical mediators released during an allergic reaction. In the heart, there are plenty of mast cells, and they are predominantly located around the coronary adventitia and in close contact with small vessels in the muscle wall. The release of mediators can influence ventricular function, heart rate, and coronary artery tone. Anaphylaxis can trigger any kind of arrhythmia. In these cases, the very interesting point of discussion was: which should be first, treating anaphylaxis or cardiac events? The other controversial point was the use of epinephrine, the first line of treatment for anaphylaxis. Recommendations about epinephrine in cardiac patients during an anaphylactic event are still a major dilemma. CONCLUSIONS: We emphasize the importance of the priority of establishing protocols between cardiologist and allergist in treatment of cardiac complications during anaphylaxis, and we warn about the correct diagnosis of arrhythmias in anaphylaxis in order to treat them as soon as possible, to prevent other consequences and complications.
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Anafilaxia/complicaciones , Atenolol/administración & dosificación , Fibrilación Atrial/etiología , Clorfeniramina/administración & dosificación , Epinefrina/uso terapéutico , Hipersensibilidad a los Alimentos/complicaciones , Metilprednisolona/uso terapéutico , Urticaria/complicaciones , Actinidia/efectos adversos , Actinidia/inmunología , Administración Intravenosa , Adulto , Anciano de 80 o más Años , Anafilaxia/tratamiento farmacológico , Anafilaxia/etiología , Animales , Anisakis/inmunología , Anisakis/parasitología , Antiarrítmicos/administración & dosificación , Antiarrítmicos/inmunología , Antiarrítmicos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Arachis/efectos adversos , Arachis/inmunología , Atenolol/inmunología , Atenolol/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Clorfeniramina/uso terapéutico , Quimioterapia Combinada , Epinefrina/administración & dosificación , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Hipersensibilidad a los Alimentos/etiología , Gadiformes/inmunología , Gadiformes/parasitología , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Hipodermoclisis , Masculino , Metilprednisolona/administración & dosificación , Urticaria/etiología , Urticaria/inmunologíaRESUMEN
The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6-11s) and more than 95% dissolution in 5min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.