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[PMID]:29320603
[Au] Autor:McTague A; Martland T; Appleton R
[Ad] Endereço:Molecular Neurosciences, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
[Ti] Título:Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.
[So] Source:Cochrane Database Syst Rev;1:CD001905, 2018 01 10.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs. This is an update of a Cochrane Review first published in 2002 and updated in 2008. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsant drugs used to treat any acute tonic-clonic convulsion of any duration, including established convulsive (tonic-clonic) status epilepticus in children who present to a hospital or emergency medical department. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Group's Specialised Register (23 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to 23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International Clinical Trials Registry Platform (ICTRP, 23 May 2017). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. MAIN RESULTS: The review includes 18 randomised trials involving 2199 participants, and a range of drug treatment options, doses and routes of administration (rectal, buccal, nasal, intramuscular and intravenous). The studies vary by design, setting and population, both in terms of their ages and also in their clinical situation. We have made many comparisons of drugs and of routes of administration of drugs in this review; our key findings are as follows:(1) This review provides only low- to very low-quality evidence comparing buccal midazolam with rectal diazepam for the treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690 children). However, there is uncertainty about the effect and therefore insufficient evidence to support its use. There were no included studies which compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants were shown to lead to similar rates of seizure cessation as intravenous anticonvulsants, e.g. intranasal lorazepam appears to be as effective as intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high-quality evidence) and intranasal midazolam was equivalent to intravenous diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality evidence).(3) Intramuscular midazolam also showed a similar rate of seizure cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105 children; low-quality evidence).(4) For intravenous routes of administration, lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality evidence. Furthermore, we found no statistically significant or clinically important differences between intravenous midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In general, intravenously-administered anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish intravenous access.(5) There is limited evidence from a single trial to suggest that intranasal lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160 children; moderate-quality evidence).(6) Adverse side effects were observed and reported very infrequently in the included studies. Respiratory depression was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of respiratory depression between the different anticonvulsants or their different routes of administration; but when pooled, three studies (439 children) provided moderate-quality evidence that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).Much of the evidence provided in this review is of mostly moderate to high quality. However, the quality of the evidence provided for some important outcomes is low to very low, particularly for comparisons of non-intravenous routes of drug administration. Low- to very low-quality evidence was provided where limited data and imprecise results were available for analysis, methodological inadequacies were present in some studies which may have introduced bias into the results, study settings were not applicable to wider clinical practice, and where inconsistency was present in some pooled analyses. AUTHORS' CONCLUSIONS: We have not identified any new high-quality evidence on the efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic convulsion that would inform clinical practice. There appears to be a very low risk of adverse events, specifically respiratory depression. Intravenous lorazepam and diazepam appear to be associated with similar rates of seizure cessation and respiratory depression. Although intravenous lorazepam and intravenous diazepam lead to more rapid seizure cessation, the time taken to obtain intravenous access may undermine this effect. In the absence of intravenous access, buccal midazolam or rectal diazepam are therefore acceptable first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion that has lasted at least five minutes. There is no evidence provided by this review to support the use of intranasal midazolam or lorazepam as alternatives to buccal midazolam or rectal diazepam.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Epilepsia Tônico-Clônica/tratamento farmacológico
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração por Inalação
Administração Oral
Administração Retal
Anticonvulsivantes/administração & dosagem
Criança
Diazepam/administração & dosagem
Seres Humanos
Injeções Intramusculares
Injeções Intravenosas
Lorazepam/administração & dosagem
Midazolam/administração & dosagem
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD001905.pub3


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[PMID]:28750059
[Au] Autor:Carballo-Diéguez A; Balán IC; Brown W; Giguere R; Dolezal C; Leu CS; Marzinke MA; Hendrix CW; Piper JM; Richardson BA; Grossman C; Johnson S; Gomez K; Horn S; Kunjara Na Ayudhya RP; Patterson K; Jacobson C; Bekker LG; Chariyalertsak S; Chitwarakorn A; Gonzales P; Holtz TH; Liu A; Mayer KH; Zorrilla C; Lama J; McGowan I; Cranston RD
[Ad] Endereço:HIV Center for Clinical and Behavioral Studies at New York State Psychiatric Institute and Columbia University, New York, NY, United States of America.
[Ti] Título:High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.
[So] Source:PLoS One;12(7):e0181607, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/administração & dosagem
Emtricitabina/administração & dosagem
Infecções por HIV/prevenção & controle
Tenofovir/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Administração Retal
Adolescente
Adulto
Estudos Cross-Over
Feminino
Géis
Homossexualidade Masculina
Seres Humanos
Masculino
Adesão à Medicação
Meia-Idade
Profilaxia Pré-Exposição
Pessoas Transgênero
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Gels); 99YXE507IL (Tenofovir); G70B4ETF4S (Emtricitabine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181607


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[PMID]:28570663
[Au] Autor:Pais R; Omosun Y; He Q; Blas-Machado U; Black C; Igietseme JU; Fujihashi K; Eko FO
[Ad] Endereço:Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America.
[Ti] Título:Rectal administration of a chlamydial subunit vaccine protects against genital infection and upper reproductive tract pathology in mice.
[So] Source:PLoS One;12(6):e0178537, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, we tested the hypothesis that rectal immunization with a VCG-based chlamydial vaccine would cross-protect mice against heterologous genital Chlamydia trachomatis infection and Chlamydia-induced upper genital tract pathologies in mice. Female mice were immunized with a C. trachomatis serovar D-derived subunit vaccine or control or live serovar D elementary bodies (EBs) and the antigen-specific mucosal and systemic immune responses were characterized. Vaccine efficacy was determined by evaluating the intensity and duration of genital chlamydial shedding following intravaginal challenge with live serovar E chlamydiae. Protection against upper genital tract pathology was determined by assessing infertility and tubal inflammation. Rectal immunization elicited high levels of chlamydial-specific IFN-gamma-producing CD4 T cells and humoral immune responses in mucosal and systemic tissues. The elicited immune effectors cross-reacted with the serovar E chlamydial antigen and reduced the length and intensity of genital chlamydial shedding. Furthermore, immunization with the VCG-vaccine but not the rVCG-gD2 control reduced the incidence of tubal inflammation and protected mice against Chlamydia-induced infertility. These results highlight the potential of rectal immunization as a viable mucosal route for inducing protective immunity in the female genital tract.
[Mh] Termos MeSH primário: Vacinas Bacterianas/administração & dosagem
Infecções por Chlamydia/prevenção & controle
Chlamydia trachomatis/imunologia
[Mh] Termos MeSH secundário: Administração Retal
Animais
Anticorpos Antibacterianos/biossíntese
Infecções por Chlamydia/imunologia
Feminino
Imunidade Celular
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bacterial); 0 (Bacterial Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178537


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[PMID]:28502682
[Au] Autor:Greuter L; Weil AG; Hildebrandt G; Surbeck W
[Ad] Endereço:Department of Neurosurgery, Cantonal Hospital St. Gallen, Switzerland.
[Ti] Título:Intrarectal Anesthesia in Neurosurgery.
[So] Source:World Neurosurg;104:158-160, 2017 Aug.
[Is] ISSN:1878-8769
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the early days of modern neurologic surgery, the inconveniences and potential dangers of general anesthesia by chloroform and ether using the so-called "open-drop technique" led to the quest for alternative methods of anesthesia. This became all the more necessary, since patient positioning and the surgical arrangements often hindered the use of a drop bottle. One approach to solve this problem was intrarectal ether application. The present article aims to shed light on this original, less well-known anesthesia technique in the neurosurgical field.
[Mh] Termos MeSH primário: Administração Retal
Anestesia Local/história
Éter/administração & dosagem
Éter/história
Neurocirurgia/história
[Mh] Termos MeSH secundário: História do Século XIX
História do Século XX
Internacionalidade
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0F5N573A2Y (Ether)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


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[PMID]:28438026
[Au] Autor:Johnson PN; Nguyen A; Neely SB; Johnson M
[Ad] Endereço:1 University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA.
[Ti] Título:Intramuscular Lorazepam for Status Epilepticus in Children With Complex Medical and Physical Disabilities.
[So] Source:Ann Pharmacother;51(8):656-662, 2017 Aug.
[Is] ISSN:1542-6270
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A protocol was developed to achieve status epilepticus (SE) resolution: step 1, intramuscular (IM) lorazepam; step 2, repeat IM lorazepam; step 3, rectal diazepam. OBJECTIVE: The primary objective was to identify the number of patients with SE resolution after step 1. Secondary objectives included categorization of mean number of IM doses per episode and patient factors associated with SE resolution. METHODS: This was a retrospective study of patients <21 years old with complex medical and physical disabilities admitted over 5 years. For analysis, IM dosing was categorized as high dose (>0.05 mg/kg/dose) and low dose (≤0.05 mg/kg/dose). A generalized linear mixed-model regression was used to assess the relationship with SE resolution at step 1 and patient characteristics. RESULTS: A total of 44 patients were included (n = 162 episodes). SE resolution was noted in 68.5% of episodes after step 1. Models were stratified by gender to present odds of SE resolution at step 1 versus step 2/3. For women, no covariate was significant. For men, the odds of SE resolution at step 1 were 14.9 times higher in those receiving 2 versus 4 maintenance antiepileptics, adjusting for covariates. Additionally, odds of resolution at step 1 was 3.1 times higher for high-dose versus low-dose lorazepam in males, adjusting for covariates, but was not statistically significant. CONCLUSIONS: SE resolution was noted in 68.5% after step 1. Unadjusted, females had a higher odds of SE resolution at step 1 than males. In males, high-dose lorazepam had higher odds of SE resolution at step 1 than low-dose lorazepam, though not significantly different.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Anticonvulsivantes/uso terapêutico
Lorazepam/administração & dosagem
Lorazepam/uso terapêutico
Estado Epiléptico/complicações
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Retal
Adolescente
Adulto
Criança
Pré-Escolar
Diazepam/administração & dosagem
Diazepam/uso terapêutico
Relação Dose-Resposta a Droga
Esquema de Medicação
Feminino
Hospitalização
Seres Humanos
Injeções Intramusculares
Modelos Lineares
Masculino
Razão de Chances
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1177/1060028017706522


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[PMID]:28298192
[Au] Autor:Wan J; Ren Y; Zhu Z; Xia L; Lu N
[Ad] Endereço:Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People's Republic of China.
[Ti] Título:How to select patients and timing for rectal indomethacin to prevent post-ERCP pancreatitis: a systematic review and meta-analysis.
[So] Source:BMC Gastroenterol;17(1):43, 2017 Mar 15.
[Is] ISSN:1471-230X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively prevents this complication; however, the data are limited. We performed a systematic review and meta-analysis to clarify the applications for rectal indomethacin. METHODS: A systematic search was performed in June 2016. Human prospective, randomized, placebo-controlled trials that compared rectally administered indomethacin with a placebo for the prevention of post-ERCP pancreatitis (PEP) were included. A meta-analysis was performed using a random-effects model to assess the outcomes (PEP) using Review Manager 5.0. RESULTS: Seven randomized controlled trials met the inclusion criteria (n = 3013). The overall incidence of PEP was significantly lower after prophylactic administration of rectal indomethacin than after administration of the placebo (RR, 0.58, 95% CI, 0.40-0.83; P = 0.004). A subgroup analysis was performed for rectal indomethacin administration compared to a placebo in high-risk patients (RR, 0.46; 95% CI, 0.32-0.65; P < 0.00001) and average-risk patients (RR, 0.75; 95% CI, 0.46-1.22; P = 0.25) and for administration before ERCP (RR, 0.56; 95% CI, 0.39-0.79; P = 0.001) and after the procedure (RR, 0.61; 95% CI, 0.26-1.44; P = 0.26). CONCLUSIONS: This meta-analysis indicated that prophylactic rectal indomethacin is not suitable for all patients undergoing ERCP but it is safe and effective to prevent PEP in high-risk patients. In addition, rectal indomethacin administration before ERCP is superior to its administration after ERCP for the prevention of PEP.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/administração & dosagem
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos
Indometacina/administração & dosagem
Pancreatite/prevenção & controle
Pré-Medicação/métodos
[Mh] Termos MeSH secundário: Doença Aguda
Administração Retal
Adulto
Idoso
Colangiopancreatografia Retrógrada Endoscópica/métodos
Feminino
Seres Humanos
Masculino
Meia-Idade
Pancreatite/etiologia
Seleção de Pacientes
Ensaios Clínicos Controlados Aleatórios como Assunto
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1186/s12876-017-0599-4


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[PMID]:28215778
[Au] Autor:He XK; Sun LM
[Ad] Endereço:Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University Medical School, Hangzhou, China; Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
[Ti] Título:Does rectal indomethacin prevent post-ERCP pancreatitis in average-risk patients?
[So] Source:Gastrointest Endosc;85(3):687, 2017 Mar.
[Is] ISSN:1097-6779
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Indometacina
Pancreatite
[Mh] Termos MeSH secundário: Administração Retal
Anti-Inflamatórios não Esteroides
Colangiopancreatografia Retrógrada Endoscópica
Seres Humanos
Risco
Fatores de Risco
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


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[PMID]:28215777
[Au] Autor:Barkin JA; Souto EO; Barkin JS
[Ad] Endereço:Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA.
[Ti] Título:Rectal indomethacin should be used routinely in all patients for prevention of post-ERCP pancreatitis.
[So] Source:Gastrointest Endosc;85(3):687-688, 2017 Mar.
[Is] ISSN:1097-6779
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Indometacina
Pancreatite
[Mh] Termos MeSH secundário: Administração Retal
Anti-Inflamatórios não Esteroides
Colangiopancreatografia Retrógrada Endoscópica
Seres Humanos
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


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[PMID]:28181835
[Au] Autor:Din FU; Choi JY; Kim DW; Mustapha O; Kim DS; Thapa RK; Ku SK; Youn YS; Oh KT; Yong CS; Kim JO; Choi HG
[Ad] Endereço:a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.
[Ti] Título:Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration.
[So] Source:Drug Deliv;24(1):502-510, 2017 Nov.
[Is] ISSN:1521-0464
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/administração & dosagem
Camptotecina/análogos & derivados
Carcinoma de Células Escamosas/tratamento farmacológico
Portadores de Fármacos
Lipídeos/química
Nanopartículas
Poloxâmero/química
Temperatura de Transição
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Retal
Animais
Antineoplásicos Fitogênicos/sangue
Antineoplásicos Fitogênicos/química
Antineoplásicos Fitogênicos/farmacocinética
Camptotecina/administração & dosagem
Camptotecina/sangue
Camptotecina/química
Camptotecina/farmacocinética
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/patologia
Preparações de Ação Retardada
Composição de Medicamentos
Feminino
Seres Humanos
Hidrogéis
Masculino
Camundongos Nus
Nanomedicina
Transição de Fase
Ratos Sprague-Dawley
Solubilidade
Tecnologia Farmacêutica/métodos
Carga Tumoral/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Delayed-Action Preparations); 0 (Drug Carriers); 0 (Hydrogels); 0 (Lipids); 106392-12-5 (Poloxamer); 7673326042 (irinotecan); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.1080/10717544.2016.1272651


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[PMID]:28156169
[Au] Autor:Moawad FA; Ali AA; Salem HF
[Ad] Endereço:a Department of Pharmaceutics , Faculty of Pharmacy, Beni-Suef University , Beni-Suef , Egypt.
[Ti] Título:Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: preparation, in vitro and in vivo performance.
[So] Source:Drug Deliv;24(1):252-260, 2017 Nov.
[Is] ISSN:1521-0464
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The purpose of the current study was to develop tizanidine HCl (TIZ; a myotonolytic agent used for treatment of spasticity) loaded nanotransfersomes intended for rectal administration, aiming to bypass the hepatic first-pass metabolism. TIZ-loaded nanotransfersomes were prepared by thin-film hydration method followed by characterization for various parameters including entrapment efficiency, vesicle diameter, in vitro release and ex vivo permeation studies. Transfersomal formulation composed of phosphatidylcholine and Tween 80 at a weight ratio of (85:15) gave a satisfactory results. It exhibited encapsulation efficiency of 52.39%, mean diameter of 150.33 nm, controlled drug release over 8 h and good permeation characteristics. Optimum formula was then incorporated into Pluronic-based thermoreversible gel using hydroxypropyl methylcellulose (HPMC) as a mucoadhesive polymer. Pharmacokinetic study was performed by rectal administration of transfersomes-loaded in situ gel to rabbits and compared with oral drug solution and rectal TIZ in situ gel. The pharmacokinetic study revealed that the transfersomal formulation successively enhanced the bioavailability of TIZ by about 2.18-fold and increased t to about 10 h as compared to oral solution. It can be concluded that encapsulation of TIZ into nanotransfersomes can achieve a dual purpose of prolonged TIZ release and enhanced bioavailability and so may be considered as a promising drug delivery system for the treatment of spasticity.
[Mh] Termos MeSH primário: Clonidina/análogos & derivados
Géis/administração & dosagem
Géis/química
[Mh] Termos MeSH secundário: Administração Retal
Animais
Disponibilidade Biológica
Química Farmacêutica/métodos
Clonidina/administração & dosagem
Clonidina/química
Clonidina/farmacocinética
Portadores de Fármacos/química
Sistemas de Liberação de Medicamentos/métodos
Géis/farmacocinética
Derivados da Hipromelose/química
Masculino
Nanopartículas/administração & dosagem
Nanopartículas/química
Tamanho da Partícula
Permeabilidade
Fosfatidilcolinas/química
Poloxâmero/química
Polissorbatos/química
Coelhos
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Gels); 0 (Phosphatidylcholines); 0 (Polysorbates); 106392-12-5 (Poloxamer); 3NXW29V3WO (Hypromellose Derivatives); 6AI06C00GW (tizanidine); MN3L5RMN02 (Clonidine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170302
[Lr] Data última revisão:
170302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1080/10717544.2016.1245369



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