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1.
Medicine (Baltimore) ; 99(33): e21624, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872021

RESUMO

BACKGROUND: To investigate the efficacy and safety of compound glycyrrhizin (CG) combined with antihistamines in the treatment of chronic urticaria (CU). METHODS: We will use computers to search all databases including Medline, Embase, Pubmed, Web of Science and Cochrane Central Register of Controlled Trials and China's 4 databases: China National Knowledge Infrastructure Database, China Biomedical Literature Database, China Science Journal Database, and Wanfang Database. Find data from creation date to July 2020. In addition, we will manually search the list of medical journals as a supplement. The scope of the search included randomized controlled clinical studies related to CG combined with antihistamines for CU. The primary outcome is the disease activity control. Secondary outcomes include response rate, adverse events, and recurrence rates. The Cochrane RevMan V5.3 Deviation Assessment Tool will be used to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The average difference, standard mean difference, and binary data will be used to represent continuous results. RESULTS: This study will comprehensively review the existing evidence on CG combined with antihistamines for CU. CONCLUSION: This systematic review will provide a basis for judging the effectiveness and safety of CG combined with antihistamines in the treatment of CU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156153.


Assuntos
Ácido Glicirrízico/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Urticária/tratamento farmacológico , Quimioterapia Combinada , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/efeitos adversos , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
2.
Yakugaku Zasshi ; 140(5): 701-710, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378674

RESUMO

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Uso de Medicamentos/estatística & dados numéricos , Polimedicação , Prescrições/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/classificação , Transtornos Cognitivos/induzido quimicamente , Estudos Transversais , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Risco
3.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
4.
J Dtsch Dermatol Ges ; 17(11): 1141-1147, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31765087

RESUMO

BACKGROUND: Cholinergic urticaria (CholU) is a frequent type of chronic inducible urticaria. Symptomatic treatment with second-generation antihistamines (sgAH) is recommended by current guidelines as first-line therapy, but little is known about how patients with CholU are treated in real life and how they respond to treatment. AIM: To assess real-life treatment of CholU in German-speaking countries. METHODS: Patients with CholU (n = 111) took part in an online survey study that assessed their treatments and their treatment responses. RESULTS: Virtually all patients (97 %) had used antihistamines, 87 % of them sgAH; 23 % had also taken first-generation antihistamines (fgAH). The proportion of patients who benefited from standard-dosed antihistamine treatment was low (sgAH: 32 % vs. fgAH: 16 %), and side effects of sgAH and fgAH were comparable. Updosing of antihistamines had been tried by 66 patients (59 %) (most commonly [98 %, n = 65] with sgAH) and resulted in marginally better responses (sgAH: 38 % vs. fgAH: 32 %). Only very few patients had used other treatments, mostly corticosteroids (30 %) and omalizumab (5 %). CONCLUSIONS: SgAH were commonly used, but insufficient in about two thirds of CholU patients. Accordingly, improved use of third-line and fourth-line treatment options and development of better therapies for patients with CholU are needed.


Assuntos
Antagonistas dos Receptores Histamínicos/uso terapêutico , Urticária/tratamento farmacológico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Antialérgicos/uso terapêutico , Áustria , Doença Crônica , Feminino , Alemanha , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Suíça , Resultado do Tratamento , Adulto Jovem
5.
Kathmandu Univ Med J (KUMJ) ; 17(65): 14-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734672

RESUMO

Background Acne vulgaris has considerable impact on physical and psychological health. Isotretinoin is considered most effective drug available for acne therapy but with limited acceptance because of its adverse effects. Antihistamine inhibits inflammatory mediators, Propionibacterium acne induced itching, reduction of squalene and sebum in sebocyte, reduces anxiety and further lessens hormonal derangement and inhibits mast cell induced fibrosis and scars. Clinical relevance is lacking in the use of antihistamine in the treatment of acne and its potential efficacy needs to be clarified. Objective To evaluate the efficacy and safety of combining isotretinoin and antihistamine compare to isotretinoin alone in patients with moderate to severe acne at week 12. Method One hundred patients with moderate to severe acne were included in this randomised, controlled comparative study. Fifty patients were treated with isotretinoin and 50 patients were treated with additional antihistamine, levocetirizine and assessment was done at baseline, 4, 8 and 12 weeks of treatment. Result At week 12, compared to isotretinoin only group, combination of isotretinoin and levocetirizine group showed more statistically significant decrease in score of global acne grading system (51.0 vs. 38.5%) and acne lesion counts (non-inflammatory lesion: 63.2 vs. 44.5%; inflammatory lesions: 75.9 vs. 62.7%; total lesions: 66.07 vs. 48.7%; all p< 0.05). Flaring up of acne occurred less frequently and adverse effects were more tolerable in levocetirizine group. Conclusion Use of antihistamine with isotretinoin provides synergic effect while minimizing the side effect of isotretinoin and greater clearance of the lesion and scars.


Assuntos
Acne Vulgar/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Isotretinoína/uso terapêutico , Acne Vulgar/complicações , Adolescente , Adulto , Cetirizina/efeitos adversos , Cetirizina/uso terapêutico , Cicatriz/etiologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/normas , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Isotretinoína/efeitos adversos , Masculino , Exame Físico , Resultado do Tratamento
6.
J UOEH ; 41(2): 145-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31292358

RESUMO

Constipation is very common and can be caused by adverse drug reactions as a result of many drugs. While the adverse effects of several medications such as opioids and anticholinergic agents are well established and well known, other commonly prescribed drugs, such as hypnotics, are less well understood. This review presents the results of an analysis of the relationship between constipation and drugs.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Constipação Intestinal/induzido quimicamente , Hipnóticos e Sedativos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Diuréticos/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Constipação Induzida por Opioides/etiologia , Parassimpatolíticos/efeitos adversos
7.
Br J Clin Pharmacol ; 85(10): 2255-2263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31269270

RESUMO

Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibular vertigo symptoms. Agents targeting the H1 and H3 receptors have been in clinical use for several decades as single agents. Nonetheless, effective management of vertigo proves elusive as many treatments largely address only associated symptoms, and with questionable efficacy. Additionally, the primary and limiting side effect of sedation is counterproductive to normal functioning and the natural recovery process occurring via central compensation. To address these issues, the timing of administration of betahistine, the mainstay H3 antihistamine, can be fine-tuned, while bioavailability is also being improved. Other approaches include antihistamine combination studies, devices, physical therapy and behavioural interventions. Recently demonstrated expression of H4 receptors in the peripheral vestibular system represents a new potential drug target for treating vestibular disorders. A number of novel selective H4 antagonists are active in vestibular models in vivo. The preclinical potential of SENS-111 (Seliforant), an oral first-in-class selective H4 antagonist is the only such molecule to date to be translated into the clinical setting. With an excellent safety profile and notable absence of sedation, encouraging outcomes in an induced vertigo model in healthy volunteers have led to ongoing clinical studies in acute unilateral vestibulopathy, with the hope that H4 antagonists will offer new effective therapeutic options to patients suffering from vertigo.


Assuntos
Antagonistas dos Receptores Histamínicos/administração & dosagem , Receptores Histamínicos H4/antagonistas & inibidores , Vertigem/tratamento farmacológico , Idoso , Animais , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Azetidinas/farmacologia , beta-Histina/administração & dosagem , beta-Histina/farmacologia , Agonistas dos Receptores Histamínicos/administração & dosagem , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/farmacologia , Receptores Histamínicos H4/metabolismo , Vertigem/fisiopatologia
8.
Dermatol Ther ; 32(4): e12993, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175673

RESUMO

Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross-sectional, single-center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as "complete response," 30-89% as "partial response" and <30% as "no significant response." Thirty-six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.


Assuntos
Urticária Crônica/tratamento farmacológico , Doxepina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Adolescente , Adulto , Idoso , Estudos Transversais , Doxepina/efeitos adversos , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Turquia , Adulto Jovem
9.
CNS Drugs ; 33(3): 225-238, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30758782

RESUMO

BACKGROUND: Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea. METHODS: We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm. RESULTS: 19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1). CONCLUSION: Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Sialorreia/tratamento farmacológico , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Salivação/efeitos dos fármacos , Sialorreia/induzido quimicamente , Sialorreia/epidemiologia
11.
J Intensive Care Med ; 34(3): 183-190, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29699467

RESUMO

Delirium is a multifactorial entity, and its understanding continues to evolve. Delirium has been associated with increased morbidity, mortality, length of stay, and cost for hospitalized patients, especially for patients in the intensive care unit (ICU). Recent literature on delirium focuses on specific pharmacologic risk factors and pharmacologic interventions to minimize course and severity of delirium. While medication management clearly plays a role in delirium management, there are a variety of nonpharmacologic interventions, pharmacologic minimization strategies, and protocols that have been recently described. A PubMed search was performed to review the evidence for nonpharmacologic management, pharmacologic minimization strategies, and prevention of delirium for patients in the ICU. Recent approaches were condensed into 10 actionable steps to manage delirium and minimize medications for ICU patients and are presented in this review.


Assuntos
Delírio/prevenção & controle , Unidades de Terapia Intensiva , Analgésicos Opioides/efeitos adversos , Antagonistas Colinérgicos/efeitos adversos , Ritmo Circadiano , Delírio/terapia , Desprescrições , Remoção de Dispositivo , Di-Hidropiridinas/efeitos adversos , Deambulação Precoce , Família , Custos de Cuidados de Saúde , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Tempo de Internação , Manejo da Dor , Restrição Física , Fatores de Risco , Sono , Cateteres Urinários , Dispositivos de Acesso Vascular , Desmame do Respirador
12.
Forensic Sci Int ; 292: 50-60, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30292936

RESUMO

Drug-facilitated sexual assault (DFSA) is a sexual act in which the victim is unable to give or rescind consent due to intoxication with alcohol and/or drugs that have been self-administered (opportunistic DFSA) or covertly administered by the perpetrator (predatory DFSA). The drugs that are most commonly associated with DFSA are flunitrazepam and gamma-hydroxybutyric acid (GHB). They cause sedation and amnesia, are readily dissolved in beverages and are rapidly eliminated from the system. However, drugs such as amphetamine and cocaine, which are central nervous system (CNS) stimulants, have also been encountered in DFSA cases. This paper critically evaluates trend data from cohort studies, identifying drugs that have been detected in DFSA cases and reports on the differences in drugs used between opportunistic and predatory DFSA. This is the first time that a critical multifactorial review of drugs used in DFSA has been conducted. The pharmacology of each identified group of drugs is presented, showing why these compounds are of interest and used in the perpetration of DFSA. Furthermore, the pharmacology and mechanisms of action are described to explain how the drugs cause their effects. It is also apparent from this study that if meaningful data is to be exchanged between law enforcement agencies then it is necessary to agree on protocols for the collection of evidence and the drugs for which analysis should be performed and indeed on the analytical methods used.


Assuntos
Vítimas de Crime , Delitos Sexuais , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Barbitúricos/administração & dosagem , Barbitúricos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Cannabis/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/administração & dosagem , Cocaína/efeitos adversos , Relação Dose-Resposta a Droga , Toxicologia Forense , Meia-Vida , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/efeitos adversos
14.
J Drugs Dermatol ; 17(8): 873-879, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30124726

RESUMO

BACKGROUND: Toreforant is a selective histamine H4 receptor antagonist. H4 receptor activation may play a role in immune-mediated inflammation in psoriasis. OBJECTIVE: To evaluate Toreforant efficacy and safety in patients with moderate-to-severe psoriasis. METHODS: Biologic-naïve patients were to be treated (30, 60, or 3 mg Toreforant or placebo) for 12 weeks and followed through week 16. In this adaptive-design study, assignments were guided by interim analyses. Primary and major secondary efficacy endpoints, evaluated using Bayesian analyses, were the proportions of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline and achieving Investigator's Global Assessment (IGA) of cleared (0) or minimal (1), respectively, at week 12. RESULTS: Per interim analyses results, patients were randomized to 30 (n = 30) or 60 mg (n = 26) Toreforant or placebo (n = 6). The estimated mean difference in the PASI 75 response rate at week 12 from the posterior distributions compared to placebo was 14.1% (95% credible interval [CI], -0.1% to 30.9%) and 8.9% (95% CI, -5.0% to 24.3%) with 30 and 60 mg Toreforant, respectively. The posterior probabilities of 30 and 60 mg Toreforant inducing a greater response rate than placebo were 97.4% and 90.3%, respectively; neither met the 97.5% predefined success criterion. Results for the IGA 0/1 endpoint were similar. Toreforant was generally safe and well tolerated. No deaths, serious or opportunistic infections, active tuberculosis, or malignancies were reported. CONCLUSIONS: Toreforant efficacy at 30 and 60 mg was greater than placebo but did not meet predefined success criterion. J Drugs Dermatol. 2018;17(8):873-879.


Assuntos
Antagonistas dos Receptores Histamínicos/uso terapêutico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Receptores Histamínicos H4/antagonistas & inibidores , Índice de Gravidade de Doença , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Nasofaringite/diagnóstico , Resultado do Tratamento
15.
Ann Allergy Asthma Immunol ; 121(5): 568-574, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30102965

RESUMO

BACKGROUND: Data from preclinical and clinical studies support the evaluation of histamine 4 receptor antagonists in the treatment of asthma. Toreforant is a selective histamine 4 receptor antagonist that could be effective in patients with eosinophilic asthma. OBJECTIVE: To evaluate the efficacy and safety of toreforant in patients with eosinophilic, persistent asthma that was inadequately controlled despite current treatment. METHODS: In this phase 2a, multicenter, randomized, double-blinded, parallel-group, placebo-controlled, proof-of-concept study, 162 eligible patients were randomized (1:1) to placebo or 30 mg of toreforant once daily through week 24 and followed for 4 weeks. The primary end point was change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16. Secondary end points included change from baseline at week 16 in postbronchodilator percent-predicted forced expiratory volume in 1 second, Asthma Control Questionnaire scores, weekly averages of Daytime and Nighttime Asthma Diary Symptom Scores, and weekly average of number of puffs in a day that rescue medication was used. RESULTS: There was no significant difference between groups in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at week 16 (difference in least-square means -0.19%; 95% confidence interval -3.01 to 2.64; P = .90). Similarly, there were no significant differences between groups at week 16 in changes from baseline in the secondary end points (P ≥ .30). Toreforant was generally well tolerated. No deaths or serious adverse events were reported at any time point. CONCLUSION: Toreforant, at the dose tested, failed to provide therapeutic benefit in this population of patients with uncontrolled, eosinophilic, persistent asthma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01823016.


Assuntos
Asma/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Receptores Histamínicos H4/antagonistas & inibidores , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Resultado do Tratamento , Estados Unidos
16.
Br J Clin Pharmacol ; 84(12): 2836-2848, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30152527

RESUMO

AIM: A Phase 1 study was performed to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the selective histamine H4 receptor antagonist SENS-111, an oral small molecule. METHODS: One hundred healthy subjects were randomized in a placebo-controlled, double-blind study evaluating single-ascending doses (SAD; 100-500 mg) and multiple-ascending doses (MAD; 50-150 mg day-1 , 4 days; 200-250 mg day-1 , 7 days). Effects of SENS-111 on nystagmus and vertigo induced by modified caloric tests were measured in the MAD studies. Population PK and PK/PD models were developed using a nonlinear mixed-effects approach. RESULTS: SENS-111 was well tolerated with mild to moderate events. No sedation was reported. A maximal tolerated dose was not reached. Dose-proportional increases in concentrations were seen up to 200 mg and more than dose-proportional thereafter, with mean half-life between 24 and 56 h. The caloric test induced mild but measurable vertigo and nystagmus with large intra/inter-individual variation for all parameters. SENS-111 did not significantly impact nystagmus but significantly improved latency of vertigo appearance/disappearance, duration and European Evaluation of Vertigo questionnaire parameters vs. baseline. A two-compartment model with first-order absorption, distribution and elimination best fit the data. PK/PD indirect modelling applied to vertigo duration and latency of appearance indicated maximum activity between 100 and 500 ng ml-1 plasma concentrations, corresponding to 100 and 200 mg day-1 , which are appropriate for clinical efficacy evaluations in vestibular diseases. CONCLUSIONS: SENS-111 is a well-tolerated first-in-class H4 receptor antagonist with acceptable PK for oral daily dosing. PK/PD modelling determined plasma concentrations and doses for efficacy studies in patients with vertigo symptoms.


Assuntos
Azetidinas/efeitos adversos , Testes Calóricos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Pirimidinas/efeitos adversos , Receptores Histamínicos H4/antagonistas & inibidores , Adolescente , Adulto , Azetidinas/farmacocinética , Azetidinas/farmacologia , Método Duplo-Cego , Voluntários Saudáveis , Antagonistas dos Receptores Histamínicos/farmacocinética , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Vertigem/tratamento farmacológico , Adulto Jovem
17.
Expert Rev Clin Immunol ; 14(9): 771-780, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30113236

RESUMO

INTRODUCTION: Acid suppressant medications (ASMs), such as proton pump inhibitors and histamine-2 receptor antagonists, are used often and throughout the lifespan. These medications have been linked to the development of a variety of allergic diseases. Areas covered: This review discusses prior studies investigating the association between acid ASM exposure and the development of allergic diseases. We performed a thorough literature search to identify potentially relevant studies for inclusion. In summary, exposure to these medications prenatally, in childhood and in adulthood, may increase the risk of allergic diseases. The current evidence is limited by primarily observational study design and potential bias and confounding. The mechanism of action is not yet known, but there are several proposed theories. Expert commentary: There is a growing body of evidence to support that exposure to acid ASMs increases the risk of developing allergic diseases. Further research is needed to not only clarify this relationship but to define the potential mechanism of action. If further research confirms these observations, we believe that could warrant changes in the patterns of prescribing and use of acid ASMs.


Assuntos
Antialérgicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Refluxo Gastroesofágico/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/efeitos adversos , Hipersensibilidade/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Adulto , Antialérgicos/uso terapêutico , Viés , Fatores de Confusão Epidemiológicos , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Hipersensibilidade/etiologia , Gravidez , Inibidores da Bomba de Prótons/uso terapêutico , Risco
18.
Osteoporos Int ; 29(10): 2163-2170, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30046925

RESUMO

Despite their anticholinergic side effects, first-generation antihistamines are widely prescribed to elderly patients. A systematic review was conducted to synthesize real-world evidence. First-generation antihistamine use is considerably associated with an increased risk of injurious falls or fracture among the elderly. INTRODUCTION: First-generation antihistamines are considered potentially inappropriate for elderly patients owing to anticholinergic side effects. We aimed to determine whether elderly patients taking antihistamines are at increased risk of injurious falls or fracture. METHODS: We identified studies in MEDLINE, EMBASE, and several local databases through November 2016. Observational studies on the association between antihistamine use and the risk of injurious falls or fracture were selected. Quality of the studies and the level of evidence were assessed. The random-effects model was employed for meta-analysis, and heterogeneity was examined based on I-square and Cochrane's Q test. Subgroup analyses were performed when the heterogeneity among studies could not be explained. RESULTS: From 473 identified studies, five (three case-control studies, one cohort study, and one case-crossover study) were included in our analysis based on eligibility criteria. First-generation antihistamine use showed significantly increased risk of injurious falls or fracture (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.49-2.76, heterogeneity: p = 0.41, I2 = 0%). Studies including antihistamines of all generations or containing no generation information were dealing with falls during hospitalization. Among these studies, the association was statistically significant without heterogeneity (OR 2.89, 95% CI 1.71-4.89, heterogeneity: p = 0.42, I2 = 0%). Due to the small number of studies included and unadjusted results, meaningful interpretation based on subgroup analysis was limited. CONCLUSIONS: First-generation antihistamine use is considerably associated with increased risk of injurious falls or fracture among the elderly. Clinicians need to exercise caution when prescribing first-generation antihistamines to elderly patients.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Ferimentos e Lesões/etiologia , Idoso , Uso de Medicamentos/estatística & dados numéricos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Medição de Risco/métodos , Ferimentos e Lesões/epidemiologia
19.
Otolaryngol Clin North Am ; 51(5): 897-908, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29914725

RESUMO

Nasal obstruction is a common, and potentially debilitating, problem. It is caused by a combination of structural factors and/or mucosal swelling/inflammation. The medical treatment of nasal obstruction is aimed at decreasing mucosal inflammation and edema and is generally guided by the underlying cause. Several different drug classes are commonly used in the treatment of nasal obstruction, each with different indications, and pros and cons to their use. This article discusses the most commonly used therapies for nasal obstruction. Current evidence on the efficacy and side effect profile of each therapy is reviewed.


Assuntos
Corticosteroides/administração & dosagem , Antagonistas dos Receptores Histamínicos/administração & dosagem , Descongestionantes Nasais/administração & dosagem , Obstrução Nasal/tratamento farmacológico , Administração Intranasal , Administração Tópica , Corticosteroides/efeitos adversos , Quimioterapia Combinada , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Descongestionantes Nasais/efeitos adversos , Obstrução Nasal/etiologia , Resultado do Tratamento
20.
J Acquir Immune Defic Syndr ; 79(1): 83-91, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29781879

RESUMO

OBJECTIVE: The aging HIV population has increased comorbidity burden and consequently non-antiretroviral medication utilization. Many non-antiretroviral medications have known neurocognitive-adverse effects ("NC-AE medications"). We assessed the cognitive effects of NC-AE medications in HIV+ and HIV- women. METHODS: One thousand five hundred fifty-eight participants (1037 HIV+; mean age 46) from the Women's Interagency HIV Study completed a neuropsychological test battery between 2009 and 2011. The total number of NC-AE medications and subgroups (eg, anticholinergics) were calculated based on self-report. Generalized linear models for non-normal data were used to examine the cognitive burden of medications and factors that exacerbate these effects. RESULTS: HIV+ women reported taking more NC-AE medications vs. HIV- women (P < 0.05). NC-AE medication use altogether was not associated with cognitive performance. However, among NC-AE medication subgroups, anticholinergic-acting medications, but not opioids or anxiolytics/anticonvulsants, were negatively associated with performance. HIV status moderated the association between these NC-AE medication subgroups and performance (P's < 0.05). HIV-serostatus differences (HIV- < HIV+) in global, learning, fluency, and motor function were greatest among women taking >1 anticholinergic medications. HIV-serostatus differences in performance on learning and psychomotor speed were also greatest among women taking 1 or more anxiolytics/anticonvulsants and 1 or more opioids, respectively. CONCLUSIONS: HIV+ women have increased cognitive vulnerabilities to anticholinergic, anxiolytic/anticonvulsant, and opioid medications. Potential synergy between these medications and HIV may explain some HIV-related cognitive impairments. It may be important clinically to consider these specific types of medications as a contributor to impaired cognitive performance in HIV+ women and assess the cost/benefit of treatment dosage for underlying conditions.


Assuntos
Disfunção Cognitiva/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Adulto , Analgésicos Opioides/efeitos adversos , Ansiolíticos/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antidepressivos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Comorbidade , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Infecções por HIV/complicações , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Testes Neuropsicológicos
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