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3.
Urol Int ; 107(10-12): 924-934, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37939691

RESUMO

INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. METHODS: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. RESULTS: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (-3.9, p < 0.001), IPSS-voiding (-2.0, p = 0.011), IPSS-total (-5.9, p < 0.001), IPSS-QoL (-3.9, p < 0.001), BII (-2.0, p < 0.001), Qmax (+3.1 mL/s, p < 0.001), Qmean (+1.9 mL/s, p = 0.005), post-void residual volume (-7.7 mL, p < 0.001), and PSA (-0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (-2.7, p < 0.001), IPSS-voiding (-1.3, p = 0.033), IPSS-total (-3.5, p < 0.001), IPSS-QoL (-1.1, p = 0.004), BII (-1.7, p = 0.006), Qmax (+1.0 mL/s, p = 0.006), and PSA (-0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (-1.3, p = 0.007), IPSS-total (-1.6, p = 0.034), IPSS-QoL (-1.1, p < 0.001), and BII (-2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. CONCLUSION: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.


Assuntos
Curcumina , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , gama-Ciclodextrinas , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida , Curcumina/uso terapêutico , Antígeno Prostático Específico , gama-Ciclodextrinas/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Antagonistas Adrenérgicos alfa/uso terapêutico , Suplementos Nutricionais , Resultado do Tratamento
4.
Am J Vet Res ; 84(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37253449

RESUMO

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.


Assuntos
Anestésicos , Bloqueio Neuromuscular , Propofol , gama-Ciclodextrinas , Masculino , Animais , Cães , Rocurônio/farmacologia , Sugammadex/farmacologia , Bloqueio Neuromuscular/veterinária , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico , Propofol/farmacologia , Androstanóis/farmacologia , Anestesia Geral/veterinária
6.
Minerva Anestesiol ; 89(3): 197-205, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326774

RESUMO

INTRODUCTION: In class B surgical facilities, where only oral or intravenous (IV) sedation is employed without the administration of volatile anesthetics, laryngospasm is among the most common airway complications. However, these facilities generally do not stock succinylcholine to avoid the cost of storing dantrolene for the treatment of malignant hyperthermia (MH). High dose IV rocuronium with sugammadex reversal has been suggested as an alternative to succinylcholine for airway emergencies. The aim of this paper was to evaluate the clinical utility, patient safety, and financial implications of replacing succinylcholine with rocuronium and sugammadex in lieu of stocking dantrolene in class B facilities. EVIDENCE ACQUISITION: A systematic review of the literature concerning neuromuscular blockade for airway emergencies in class B settings in adult patients was conducted. The MEDLINE and EMBASE databases were searched for published studies from January 1, 1990, to October 1, 2021. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the certainty of evidence. EVIDENCE SYNTHESIS: The search strategy yielded 1124 articles. After review, 107 articles were included, with 49 graded as "strong" evidence to provide recommendations for the posed questions. CONCLUSIONS: The use of succinylcholine in isolation without volatile agents has a low incidence of triggering MH. Laryngospasm is a common airway emergency that requires immediate treatment to avoid morbidity and mortality. Both succinylcholine and rocuronium-sugammadex provide adequate treatment of airway emergencies and rapid return of spontaneous ventilation, but succinylcholine has a superior economic and clinical profile.


Assuntos
Anestesia , Laringismo , gama-Ciclodextrinas , Adulto , Humanos , Succinilcolina , Sugammadex , Rocurônio , Dantroleno/uso terapêutico , Laringismo/tratamento farmacológico , Emergências , gama-Ciclodextrinas/uso terapêutico , Androstanóis
7.
J Allergy Clin Immunol Pract ; 11(2): 466-473.e5, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36108924

RESUMO

BACKGROUND: Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely among reports. OBJECTIVE: To determine maximal ST nonirritant concentrations (NICs) of NMBAs (cisatracurium, rocuronium, succinylcholine, and vecuronium), NMBA-reversal agents (neostigmine and sugammadex), and S-R-Cx in NMBA-tolerant and NMBA-naïve participants. METHODS: A single-center, prospective study between October 2019 and November 2021 of adult participants with or without a planned surgical procedure. The reference standard was tolerance of medication tested during a procedure (NMBA-tolerant group) before ST. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 5-7 increasing concentrations of 1 or more medications. All medications were reconstituted according to package insert instructions and diluted with 0.9% saline. A concentration was considered irritant when more than 5% of participants had a positive test per ST positivity criteria (wheal ≥3 mm than initial wheal and associated erythema of the same size or greater than wheal). We also compared our results with current guidelines. RESULTS: A total of 187 participants (78% NMBA-tolerant) underwent 7812 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT NICs (mg/mL): cisatracurium (0.02), rocuronium (0.05), succinylcholine (0.8), vecuronium (0.01), neostigmine (0.2), sugammadex (50), and S-R-Cx (sugammadex 7.14 + rocuronium 2). CONCLUSION: Our results suggest that SPT may be performed with undiluted stock concentrations. We confirm maximal IDT NICs for cisatracurium and rocuronium. We also propose that currently recommended maximal IDT NICs of succinylcholine, neostigmine, sugammadex, and S-R-Cx could be increased, whereas the maximal IDT NIC of vecuronium could be decreased compared with current guidelines and prior reports.


Assuntos
Bloqueio Neuromuscular , Bloqueadores Neuromusculares , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Adulto , Humanos , Sugammadex , Rocurônio , Brometo de Vecurônio , Neostigmina , gama-Ciclodextrinas/uso terapêutico , Succinilcolina , Estudos Prospectivos , Androstanóis , Bloqueio Neuromuscular/métodos
8.
J Med Chem ; 65(24): 16893-16901, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36480913

RESUMO

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico , Água
9.
Am J Case Rep ; 23: e937128, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36229945

RESUMO

BACKGROUND Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. CASE REPORT A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-of-four [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. CONCLUSIONS When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery.


Assuntos
Recuperação Demorada da Anestesia , Miastenia Gravis , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Acetilcolina , Acetilcolinesterase , Adulto , Androstanóis/farmacologia , Inibidores da Colinesterase/uso terapêutico , Feminino , Humanos , Miastenia Gravis/tratamento farmacológico , Neostigmina/farmacologia , Neostigmina/uso terapêutico , Rocurônio , Sugammadex , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
10.
J Clin Neurosci ; 104: 82-87, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35981464

RESUMO

OBJECTIVE: Sugammadex reversal of neuromuscular blocking agents (NMBAs) is usually performed postoperatively. A scarcity of literature exists exploring sugammadex use for timely neurological examination of neurosurgical patients. NMBAs, like rocuronium, are used in the Emergency Department during intubation and their unpredictable duration of action often impedes timely and accurate assessment of patient neurological status. We aim to explore the role of sugammadex in evaluating patients in need of acute neurosurgical care. METHODS: Retrospective assessment of patients presenting with traumatic brain injury or intracranial hemorrhage was conducted at our level 1 trauma center. Patients of interest were those for whom sugammadex reversal of rocuronium neuromuscular blockade, from intubating doses, was pursued to ensure timely neurologic assessment. Nine patients were identified for whom GCS pre-/post-sugammadex, rocuronium dosing, elapsed time between rocuronium administration and reversal, and clinical course data were retrieved. RESULTS: Arrival GCS was 5.2 ± 3.2, with intubation accomplished within 10 ± 2.5 min of presentation. Rocuronium dosing was consistent between patients, average single dose of 1.2 ± 0.3 mg/kg. Lingering neuromuscular blockade ranged from 28 to 132 min (87.3 ± 34.3 min). All patients exhibited a GCS of 3 T upon initial neurosurgical evaluation, prior to reversal. Post-reversal GCS rose to 6.0 T ± 2.2. Sugammadex facilitated more accurate clinical decision making in 8 of 9 patients, including prevention of unnecessary invasive procedures. Two of 9 patients were eventually discharged home or to a rehabilitation facility. CONCLUSIONS: Rocuronium neuromuscular blockade can linger beyond pharmacokinetic predictions, thus delaying timely and precise neurologic assessment. Our data suggests sugammadex may be a useful addition to the clinician's armamentarium for acute neurologic assessment in the neurosurgical population. Sugammadex may impact clinical decision-making in certain patients and allow for more informed decision-making by families and physicians alike. Prospective studies are needed to definitively assess the impact of sugammadex on outcomes in acute neurosurgical settings.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Androstanóis , Humanos , Bloqueio Neuromuscular/métodos , Estudos Retrospectivos , Rocurônio , Sugammadex , gama-Ciclodextrinas/farmacocinética , gama-Ciclodextrinas/uso terapêutico
11.
Drugs Aging ; 39(10): 749-761, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35934764

RESUMO

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Acetilcolina , Acetilcolinesterase , Idoso , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Humanos , Neostigmina/farmacologia , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , Complicações Pós-Operatórias/etiologia , Rocurônio , Sugammadex/farmacologia , Brometo de Vecurônio , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
12.
Br J Clin Pharmacol ; 88(8): 3760-3770, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35304924

RESUMO

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Adolescente , Adulto , Androstanóis/efeitos adversos , Humanos , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio , Sugammadex/farmacologia , Adulto Jovem , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
13.
Paediatr Anaesth ; 32(6): 706-715, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35212434

RESUMO

Allergic reactions are generalized hypersensitivity processes triggered by different antigenic stimuli, resulting in the end effect of mast cell degranulation and adverse physiologic effects. During the perioperative period, the most commonly identified agents include antibiotics, neuromuscular blocking agents (rocuronium and succinylcholine), chlorhexidine, and iodinated dyes for radiologic imaging. Sugammadex is a novel agent for the reversal of neuromuscular blockade achieved with rocuronium or vecuronium. Its unique mechanism of action, whereby it encapsulates and forms a one-to-one complex with rocuronium, has led to its anecdotal use as an adjunct in the treatment of anaphylactic and anaphylactoid reactions following rocuronium. The current manuscript discusses the potential use of sugammadex in the treatment of allergic reactions following the administration of rocuronium, reviews previous anecdotal reports of its use in these scenarios, and provides recommendations for future care.


Assuntos
Anafilaxia , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Androstanóis/efeitos adversos , Animais , Humanos , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio , Sugammadex/efeitos adversos , gama-Ciclodextrinas/uso terapêutico
14.
Carbohydr Polym ; 277: 118889, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893291

RESUMO

Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (Papp, 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUCAqueous humor, 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery.


Assuntos
Ciclodextrinas/uso terapêutico , Flurbiprofeno/uso terapêutico , Hidrogéis/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Poloxâmero/uso terapêutico , Rotaxanos/uso terapêutico , Uveíte Anterior/tratamento farmacológico , gama-Ciclodextrinas/uso terapêutico , Administração Oftálmica , Animais , Ciclodextrinas/administração & dosagem , Ciclodextrinas/química , Sistemas de Liberação de Medicamentos , Flurbiprofeno/administração & dosagem , Flurbiprofeno/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/química , Poloxâmero/administração & dosagem , Poloxâmero/química , Coelhos , Rotaxanos/administração & dosagem , Rotaxanos/química , gama-Ciclodextrinas/administração & dosagem , gama-Ciclodextrinas/química
15.
Molecules ; 26(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34641590

RESUMO

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and ß-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.


Assuntos
Antineoplásicos/uso terapêutico , Celulose/uso terapêutico , Ciclodextrinas/uso terapêutico , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/uso terapêutico , Oxaliplatina/uso terapêutico , Células A549 , Motivos de Aminoácidos , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Celulose/química , Ciclodextrinas/química , Doxorrubicina/química , Portadores de Fármacos/química , Células Hep G2 , Humanos , Nanopartículas/química , Oxaliplatina/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/uso terapêutico , gama-Ciclodextrinas/química , gama-Ciclodextrinas/uso terapêutico
16.
Sci Prog ; 104(2): 368504211010629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33877942

RESUMO

The neuromuscular block state may affect the electroencephalogram-derived index representing the anesthetic depth. We applied an Anesthetic Depth Monitoring for Sedation (ADMS) to patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia, and evaluated the requirement of propofol according to the different neuromuscular block state. Adult patients scheduled to undergo laparoscopic cholecystectomy were enrolled and randomly assigned to either the moderate (MB) or deep neuromuscular block (DB) group. The UniCon sensor of ADMS was applied to monitor anesthetic depth and the unicon value was maintained between 40 and 50 during the operation. According to the group assignment, intraoperative rocuronium was administered to maintain proper neuromuscular block state, moderate or deep block state. The unicon value, electromyography (EMG) index, and total dose of propofol and rocuronium were analyzed. At similar anesthetic depth, less propofol was used in the DB group compared to the MB group (6.19 ± 1.36 in the MB mg/kg/h group vs 4.93 ± 3.02 mg/kg/h in the DM group, p = 0.042). As expected, more rocuronium were used in the DB group than in the MB group (0.8 ± 0.2 mg/kg in the MB group vs 1.2 ± 0.2 mg/kg in the DB group, p = 0.023) and the EMG indices were lower in the DB group than in the MB group, at several time points as follows: at starting operation (p < 0.001); at 15 (p = 0.019), 45 (p = 0.011), and 60 min (p < 0.001) after the initiation of the operation; at the end of operation (p = 0.003); and at 5 min after the administration of sugammadex (p < 0.001). At similar anesthetic depth, patients under the deep neuromuscular block state required less propofol with lower intraoperative EMG indices compared to those under the moderate neuromuscular block state during general anesthesia.


Assuntos
Bloqueio Neuromuscular , Propofol , gama-Ciclodextrinas , Adulto , Androstanóis , Anestesia Geral , Anestesia Intravenosa , Anestésicos Intravenosos , Humanos , Remifentanil , Rocurônio , gama-Ciclodextrinas/uso terapêutico
17.
J Pain Symptom Manage ; 62(2): 438-442, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33677073

RESUMO

In certain end-of-life scenarios, pharmacologic reversal of neuromuscular blockade may be indicated. However, given the depth of blockade frequently necessitated in the ICU setting, rapid reversal of neuromuscular blockade is generally not feasible with conventional reversal agents such as neostigmine that inhibit acetylcholinesterase. Sugammadex is a novel pharmacologic agent for the reversal of neuromuscular blockade that acts by directly encapsulating steroidal neuromuscular blocking agents and providing effective 1:1 binding of rocuronium or vecuronium. This unique mechanism of action is rapid and allows for complete reversal and recovery of neuromuscular function. We report the use of sugammadex to reverse neuromuscular blockade prior to compassionate extubation in three pediatric patients. Its clinical use in children is reviewed, potential applications in the palliative care arena discussed, and dosing algorithms presented.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Criança , Humanos , Rocurônio , Sugammadex , gama-Ciclodextrinas/uso terapêutico
18.
J Emerg Med ; 60(1): 44-53, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32962903

RESUMO

BACKGROUND: Sugammadex is a medication newly available to many emergency physicians. It effectively, and within minutes, reverses neuromuscular blockade in patients who have received rocuronium or vecuronium. The role of sugammadex for the reversal of neuromuscular blockade after rapid sequence intubation in the emergency department (ED) is evolving, and limited emergency medicine-specific literature exists. OBJECTIVE: This narrative review evaluates the role of sugammadex for the reversal of neuromuscular blockade in the ED. DISCUSSION: The basic pharmacology, duration of action, adverse effects, and important medication and disease interactions specific to sugammadex are well described. Case reports suggest sugammadex can reverse neuromuscular blockade to facilitate an urgent, neurologic examination by an emergency physician or consultant. Multiple case reports of failure to improve airway patency with the use of sugammadex, even when neuromuscular blockade is completely reversed, and concern for added difficulty of definitive airway management in a patient with spontaneous movement suggest that sugammadex should largely be omitted from failed or difficult airway management strategies. Instead, it is important to focus on the ability to oxygenate and ventilate, including progression to surgical airway or jet ventilation if needed. CONCLUSION: Sugammadex is an effective, rapid reversal agent for rocuronium and has the potential use to facilitate an urgent neurologic examination shortly after administration of rocuronium. Its routine inclusion in a failed or difficult emergency airway is not supported by available literature.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Androstanóis/farmacologia , Androstanóis/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , Sugammadex/farmacologia , Sugammadex/uso terapêutico , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
19.
BMC Anesthesiol ; 19(1): 160, 2019 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-31421671

RESUMO

BACKGROUND: Myasthenia gravis (MG) is a challenge for anesthesia management. This report shows that the use of rocuronium-sugammadex is not free from flaws and highlights the importance of cholinesterase inhibitors management and neuromuscular block monitoring in the perioperative period of myasthenic patients. CASE PRESENTATION: Myasthenic female patient submitted to general balanced anesthesia using 25 mg of rocuronium. Under train-of-four (TOF) monitoring, repeated doses of sugammadex was used in a total of 800 mg without recovery of neuromuscular blockade, but TOF ratio (TOFR) was stabilized at 60%. Neostigmine administration led to the improvement of TOFR. CONCLUSIONS: Although the use of rocuronium-sugammadex seems safe, we should consider their unpredictability in myasthenic patients. This report supports the monitoring of neuromuscular blockade as mandatory in every patient, especially the myasthenic ones.


Assuntos
Bloqueio Neuromuscular/métodos , Monitoração Neuromuscular , Rocurônio/uso terapêutico , Sugammadex/uso terapêutico , Adulto , Inibidores da Colinesterase/uso terapêutico , Feminino , Humanos , Miastenia Gravis , Neostigmina/uso terapêutico , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas/uso terapêutico
20.
Medicine (Baltimore) ; 97(15): e0428, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29642212

RESUMO

RATIONALE: In patients with oropharyngeal and nasopharyngeal bleeding, blood aspiration can make airway management difficult and lead to severe pulmonary complications. PATIENT CONCERNS: A 44-year-old male patient with recurrent epistaxis underwent surgery for hemostasis. The patient aspirated blood through the endotracheal tube when he hiccupped during the surgery. DIAGNOSIS: The patient was diagnosed with blood aspiration after intraoperative fiberoptic bronchoscopy revealed a blood clot and viscous mucus in the airways, but no sign of active bleeding. INTERVENTIONS: Tracheobronchial suctioning and irrigation with normal saline was performed through the bronchoscope to remove the aspirated blood clot. Prior to emergence from anesthesia, sugammadex was administered to induce complete neuromuscular recovery and enable the patient to cough up any blood remaining in the airways. OUTCOMES: The patient was successfully extubated and fully recovered with no complications. LESSONS: Blood aspiration due to oropharyngeal or nasopharyngeal bleeding can be diagnosed and treated by tracheobronchial suctioning via fiberoptic bronchoscopy. In addition, sugammadex can enable patients to recover spontaneous breathing, facilitate extubation, and enable patients to cough up any blood remaining in the airways.


Assuntos
Sangue , Broncoscopia/métodos , Epistaxe/complicações , Epistaxe/cirurgia , Hemostasia Cirúrgica , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/terapia , Aspiração Respiratória/etiologia , Aspiração Respiratória/terapia , gama-Ciclodextrinas/uso terapêutico , Adulto , Humanos , Complicações Intraoperatórias/diagnóstico , Masculino , Aspiração Respiratória/diagnóstico , Sucção , Sugammadex
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