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1.
Int. braz. j. urol ; 48(5): 742-759, Sept.-Oct. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394384

ABSTRACT

ABSTRACT Introduction: The efficacy of alpha-blockers as medical expulsive therapy (MET) is well established. However, it is not known which of the three most commonly used alpha-blockers (tamsulosin, alfuzosin and silodosin) is the most efficacious. With this study we aimed to assess the efficacy of the three commonly used alpha-blockers as MET for distal ureter stones. Materials and Methods: For this review, we searched multiple databases such as PubMed/Medline, Scopus, Embase, OviD SP, CINAHL, and web of science to identify all the relevant randomized studies comparing the efficacy of tamsulosin, alfuzosin, and silodosin. Preferred reporting items for systematic reviews for network meta-analysis (PRISMA-NMA) were followed while conducting this review and the study protocol was registered with PROSPERO (CRD42020175706). Results: In this review, 31 studies with 7077 patients were included. Compared to placebo all the treatment groups were more effective for both stone expulsion rate (SER) and stone expulsion time (SET). For both SER and SET, silodosin had the highest SUCRA (94.8 and 90.4) values followed by alfuzosin (58.8 and 64.9) and tamsulosin (46.2 and 44.5). The incidence of postural hypotension was similar with all the drugs, whereas, the incidence of retrograde ejaculation was significantly higher for silodosin. Overall confidence for each comparison group in this review ranged from "very low" to "moderate" according to the CINeMA approach. Conclusion: Among the three commonly used alpha-blockers silodosin is the most efficacious drug as MET for lower ureter stones followed by alfuzosin and tamsulosin.

2.
Rev. colomb. anestesiol ; 50(3): e501, July-Sept. 2022. graf
Article in English | LILACS | ID: biblio-1388937

ABSTRACT

Abstract Pheochromocytomas are neuroendocrine tumors capable of synthetizing, storing and releasing catecholaminergic hormones that may lead to lifethreatening hemodynamic instability. The COVID-19 pandemic has increased the risks and perioperative complexity of the patients undergoing pheochromocytoma-associated adrenalectomy. This article discusses the use of adenosine for the management of hypertensive crisis during this intervention, as well as the need to individualize the suitable timing for surgery after recent COVID-19 infection. This article discusses the case of a patient with a finding of right adrenal incidentaloma; further studies determined a metanephrines secreting pheochromocytoma. Following hospital admission for preoperative optimization, the eve of the procedure the patient developed an acute myocardial infarction and subsequently SARS-CoV-2 symptomatic infection. Intraoperatively, hypertensive peaks were managed with continuous adenosine perfusion. The patient was discharged after 48 hours. Preoperative optimization positively influences the intraoperative management of patients with pheochromocytoma. The intraoperative use of adenosine allows for adequate and safe control of hypertensive crises. Each situation must be individualized in patients pending surgery, with a recent COVID-19 infection.


Resumen Los feocromocitomas son tumores neuroendocrinos capaces de sintetizar, almacenar y liberar hormonas catecolaminérgicas que pueden provocar inestabilidad hemodinámica con compromiso vital. La pandemia por COVID-19 ha aumentado los riesgos y la complejidad perioperatoria de los pacientes sometidos a adrenalectomía por feocromocitoma. Describimos el uso de adenosina para manejar las crisis hipertensivas durante esta intervención, así como establecer la necesidad de individualizar el momento quirúrgico idóneo tras infección reciente por COVID-19. Presentamos el caso de un paciente con hallazgo de incidentaloma suprarrenal derecho cuya ampliación de estudio se orientó como feocromocitoma secretor de metanefrinas. Tras ingreso hospitalario para optimización preoperatoria, el día previo al procedimiento presentó un infarto agudo de miocardio y posteriormente una infección sintomática por SARS-CoV-2. Intraoperatoriamente se manejaron los picos hipertensivos con perfusión continua de adenosina. Tras 48 horas recibió el alta hospitalaria. La optimización preoperatoria influye positivamente en el manejo intraoperatorio de los pacientes con feocromocitoma. El uso intraoperatorio de adenosina permite un adecuado y seguro control de las crisis hipertensivas. En pacientes pendientes de cirugía con infección reciente por COVID-19 se requiere individualizar cada situación.

3.
Horiz. meÌüd. (Impresa) ; 22(1): e1355, ene.-mar. 2022. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1375619

ABSTRACT

RESUMEN El lactato es un metabolito altamente dinámico que, en condiciones anaerobias, es producido por hipoxia o isquemia; y en condiciones aerobias, es sintetizado por un mecanismo impulsado por la estimulación adrenérgica, a través del receptor β2, que potencia la acción de la bomba sodio-potasio, y por un estado de glicólisis aerobia acelerada. Este metabolito es capaz de intercambiarse entre diferentes células productoras y consumidoras, con lo que asegura la materia prima para obtener energía. El sistema nervioso simpático responde a los estímulos de estrés con la liberación de catecolaminas, que actúan como hormonas y como neurotransmisores en varios tejidos del cuerpo y permiten un aumento del metabolismo que eleva los valores de glucosa y el oxígeno disponible. Existe una relación fisiológica de dependencia entre las catecolaminas y la producción de lactato que predispone al organismo para responder de forma efectiva ante una situación de estrés. Sin embargo, en tejidos sensibles, la respuesta adrenérgica exacerbada puede ocasionar efectos exagerados que pueden incrementar la probabilidad de fallo. En base al conocimiento de estos mecanismos, se plantean estrategias terapéuticas enfocadas en regular la actividad simpática.


ABSTRACT Lactate is a highly dynamic metabolite that is produced, under anaerobic conditions, due to hypoxia or ischemia. Under aerobic conditions, it is synthesized by a mechanism driven by the stimulation of the β2 adrenergic receptor, which increases the activity of the sodium-potassium pump, and by a state of accelerated aerobic glycolysis. This metabolite is capable of being exchanged between different producing and consuming cells, ensuring the raw material for energy production. The sympathetic nervous system responds to stress stimuli through the release of catecholamines, which act as hormones and neurotransmitters in various tissues of the body, allowing an increase in metabolism that raises glucose and available oxygen levels. There is a physiological dependence between catecholamine levels and lactate production, predisposing the body to respond effectively to a stressful situation. However, an exacerbated adrenergic response may cause exaggerated effects on sensitive tissues that increase the probability of failure. Based on the knowledge of these mechanisms, therapeutic strategies focused on regulating the sympathetic activity are proposed.

4.
Article in Chinese | WPRIM | ID: wpr-934313

ABSTRACT

Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion and age-related macular degeneration, which seriously affects patient's vision. β receptors are expressed in conjunctiva, corneal epithelial cells, corneal endothelial cells, extraocular muscles, trabecular meshwork, ciliary muscle, lens and retina. β adrenergic receptor antagonists bind to β receptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1, interleukin-6 and other angiogenic cytokines; reducing macrophage-related inflammatory response; increasing the expression of anti-angiogenic factors. In the treatment of corneal neovascularization, choroidal neovascularization, and retinopathy of prematurity, it can significantly reduce the area of neovascularization and delay disease progression. Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs. At effective therapeutic concentrations, β-adrenergic receptor antagonists are well tolerated; they have broader targets than anti-VEGF drugs, which offers new treatment strategies for ocular neovascularization such as corneal, choroidal and retinal neovascularization.

5.
Chinese Journal of Digestion ; (12): 336-339, 2022.
Article in Chinese | WPRIM | ID: wpr-934154

ABSTRACT

Objective:To observe whether α1 adrenergic receptor (α1AR) blocker can reduce and antagonize portal hypertension caused by α1AR activation in rats, and to provide a new approach for the clinical treatment of portal hypertension.Methods:Phenylephrine was chosen as α1AR agonist, and alfuzosin was used as α1AR blocker. The route of administration was portal vein injection, and the pressure was measured by trans-portal vein puncture. According to random number table, 32 male Sprague-Dawley rats were divided into 4 groups: control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group. The portal venous pressure (PVP) was measured in all rats before administration. The rats in the control group were injected with 0.9% sodium chloride solution (1 L/g), and the rats in portal hypertension model group were injected with phenylephrine(1.5 μg/g), and the PVP of the above two groups was measured again at 5 and 10 min after injection. The rats in alfuzosin treatment group were injected with phenylephrine(1.5 μg/g), PVP was measured again at 5 min after administration, and then the rats were given alfuzosin(0.9 μg/g), PVP was measured again at 5 min after administration. The rats in alfuzosin prevention group were injected with alfuzosin(0.9 μg/g), PVP was measured at 1 min after administration, and then the rats were given phenylephrine(1.5 μg/g), PVP was measured again at 1, 5 and 10 min after phenylephrine injection respectively. One way analysis of variance and Dunnett- t test were used for statistical analysis. Results:The portal vein puncture was successfully performed in 4, 6, 8 and 5 rats in the control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group, respectively. The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was (18.045±7.636) and (15.515±5.440) mmHg (1 mmHg = 0.133 kPa), respectively, which were both higher than that before administration ((8.452±2.830) mmHg), and the differences were statistically significant ( t=2.89 and 2.82, both P<0.05). At 5 min after alfuzosin injection, the PVP of rats in the alfuzosin treatment group was (10.088±3.743) mmHg, which was lower than that of rats at 5 min after phenylephrine injection ((16.146±4.324) mmHg) and that of portal hypertension model group at 10 min after phenylephrine injection, and the differences were statistically significant ( t=3.00 and 2.22, both P<0.05). There were no significant differences in PVP in the alfuzosin prevention group before administration, at 1 min after injection of alfuzosin, and at 1, 5 and 10 min after injection of phenylephrine (all P > 0.05). Conclusions:α1AR is an important factor involved in the regulation of PVP, and its blockers can reduce and antagonize the portal hypertension caused by α1AR activation, which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.

6.
Article in Chinese | WPRIM | ID: wpr-931611

ABSTRACT

Objective:To investigate the effects of finasteride combined with tamsulosin hydrochloride administered during the perioperative period on glandular microvessel density in patients with benign prostatic hyperplasia.Methods:Ninety patients with benign prostatic hyperplasia who received treatment in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from August 2017 to August 2019 were included in this study. They were randomly assigned to receive either oral tamsulosin hydrochloride alone (control group, n = 45) or oral finasteride combined with tamsulosin hydrochloride (observation group, n = 45) during the perioperative period of transurethral resection of the prostate. All patients received 6 weeks of medication. Clinical efficacy, adverse reactions, and urodynamic indexes, glandular microvessel density, International Prostatism Symptom Score, bother score, and urine color/degree of haematuria score pre- and post-treatment were compared between the two groups. Results:The maximum urinary flow rate in each group significantly increased 6 weeks after treatment compared with before treatment. The detrusor pressure and residual urine volume in each group decreased 6 weeks after treatment compared with before treatment. After 6 weeks of treatment, the maximum urinary flow rate was significantly higher in the observation group than in the control group [(15.63 ± 2.26) mL/s vs. (13.14 ± 2.23) mL/s], and residual urine volume was significantly lower in the observation group than in the control group [(29.19 ± 4.81) mL vs. (32.25 ± 5.52) mL, t = 5.26, 2.80, both P < 0.05). International Prostatism Symptom Score measured 6 weeks after treatment and urine color/degree of haematuria score measured 1 week after treatment were (12.09 ± 2.17) points and (1.51 ± 0.27) points, respectively in the observation group, which were significantly lower than those in the control group [(14.28 ± 2.22) points, (2.03 ± 0.38) points, t = 4.73, 7.48, both P < 0.05]. Factor VIII related antigen- and CD34-positive glandular microvessel density values in the observation group were (14.74 ± 3.05) counts/visual field and (19.41 ± 3.07) counts/visual field, respectively, which were significantly lower than those in the control group [(18.08 ± 3.16) counts/visual field, (22.27 ± 3.16) counts/visual field, t = 5.10, 4.35, both P < 0.05]. The incidence of postoperative hematuria was significantly lower in the observation group than in the control group [15.56% (7/45) vs. 35.56% (16/45), χ2 = 4.73, P < 0.05]. Conclusion:Compared with tamsulosin hydrochloride alone, finasteride combined with tamsulosin hydrochloride administered during the perioperative stage can greatly improve the urodynamic indexes of patients with benign prostatic hyperplasia, reduce microvessel density value, International Prostatism Symptom Score, bother score, and decrease the incidence of hematuria. The combined therapy provides a novel idea for preventing perioperative bleeding in patients with benign prostatic hyperplasia.

7.
Article in Chinese | WPRIM | ID: wpr-931143

ABSTRACT

Objective:To investigate the effect of gene polymorphism of β1 adrenergic receptor (β1-AR) G1165C and A145G locus on myocardial hypertrophy and the efficacy in patients with hypertension.Methods:Two hundred and twenty-seven cases of patients with hypertension admitted to Binhai County People′s Hospital from January to December 2019 were enrolled. Among them, there were 113 cases of hypertension with myocardial hypertrophy and 114 cases of hypertension without myocardial hypertrophy. In addition, 115 patients with normal physical examination during the same period were selected as the control group. DNA in the peripheral blood leukocytes was extracted, polymerase chain reaction-restriction fragment length polymorphism method was used to detect β1-AR G1165C and A145G locus gene polymorphism, and the differences in the efficacy of β blockers in hypertensive patients with different genotypes were compared.Results:There was no statistically significant differences in the distribution of β1-AR A145G genotypes among the three groups ( P>0.05). Compared with the healthy control group, the frequency of Gly/Gly genotype carrying β1-AR G1165C locus was higher in hypertension with myocardial hypertrophy group, and the frequency of Gly/Arg and Arg/Arg gene were lower; compared with hypertension without myocardial hypertrophy group, the frequency of Gly/Arg+Gly/Gly gene in hypertension with myocardial hypertrophy group was higher; taking Arg/Arg genotype as the control group, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive patients by 3.159 times ( OR = 3.159, 95% CI 1.240 - 7.412, P<0.05).The frequency of G1165C allele Arg in the hypertension with myocardial hypertrophy group was significantly lower than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); the frequency of G1165C allele Gly was significantly higher than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); taking Arg/Arg genotype as the control, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive ( OR = 3.417, 95% CI 1.357 - 7.965, P<0.05). The left ventricular mass index of Gly/Gly genotype patients was (120.38 ± 28.41) g/m 2, which was significantly higher than (99.76 ± 25.16) g/m 2 and (90.30 ± 19.54) g/m 2 of Gly/Arg and Arg/Arg, with statistically significant differences ( F = 10.89, P<0.01). After the treatment, the resting heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure of patients with G1165C allele Arg hypertension with myocardial hypertrophy were lower than those with G1165C allele Gly, with statistically significant differences ( P<0.05). Conclusions:β1-AR G1165C gene polymorphism is related to the risk of myocardial hypertrophy in hypertensive patients. Carrying the G1165C allele Gly may increase the risk of susceptibility to cardiac hypertrophy, and β-blockers are more effective in hypertensive patients with myocardial hypertrophy who carry the G1165C allele Arg.

8.
Acta Pharmaceutica Sinica B ; (6): 2374-2390, 2022.
Article in English | WPRIM | ID: wpr-929392

ABSTRACT

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

9.
Acta Pharmaceutica Sinica B ; (6): 637-650, 2022.
Article in English | WPRIM | ID: wpr-929316

ABSTRACT

Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gα q activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.

10.
Acta Pharmaceutica Sinica B ; (6): 3063-3072, 2022.
Article in English | WPRIM | ID: wpr-939951

ABSTRACT

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β 3-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

11.
Einstein (Säo Paulo) ; 20: eAO6412, 2022. tab
Article in English | LILACS | ID: biblio-1364799

ABSTRACT

ABSTRACT Objective To investigate whether different genotypes of p.Arg16Gly, p.Gln27Glu, p.Arg19Cys and p.Thr164Ile variants interfere in response to treatment in children and adolescents with moderate to severe acute asthma. Methods This sample comprised patients aged 2 to 17 years with a history of at least two wheezing episodes and current moderate to severe asthma exacerbation. All patients received multiple doses of albuterol and ipratropium bromide delivered via pressurized metered-dose inhaler with holding chamber and systemic corticosteroids. Hospital admission was defined as the primary outcome. Secondary outcomes were changes in forced expiratory volume in the first second after 1 hour of treatment, and for outpatients, length of stay in the emergency room. Variants were genotyped by sequencing. Results A total of 60 patients were evaluated. Hospital admission rates were significantly higher in carriers of the genotype AA relative to those with genotype AG or GG, within the p.Arg16Gly variant (p=0.03, test χ2, alpha=0.05). Secondary outcomes did not differ between genotypes. Conclusion Hospital admission rates were significantly higher among carriers of the genotype AA within the p.Arg16Gly variant. Trial registration: ClinicalTrials.gov: NCT01323010


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Asthma/genetics , Asthma/drug therapy , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/therapeutic use , Nebulizers and Vaporizers , Metered Dose Inhalers , Albuterol/therapeutic use
12.
CES med ; 35(3): 213-229, sep.-dic. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374764

ABSTRACT

Abstract Objective: To determine the prescription patterns of antiarrhythmic drugs and variables associated with their use in a population of patients affiliated with the Colombian Health System. Methods: A cross-sectional study was performed on a population database with patients who received antiarrhythmics from March to May 2016. Sociodemographic, pharmacological and comedication variables were included. SPSS-24 was used for data analysis using X2 tests and multivariate analyses. Results: In total, 2772 patients were treated with antiarrhythmics in the evaluated period. The mean age was 70.1 ± 13.1 years, and 51.2% were women. In total, 79.4% used a β-blocker, 58.5% amiodarone and 2.9% a calcium channel blocker. Moreover, 1192 (43.0%) patients were prescribed a single antiarrhythmic, and 1580 (57.0%) received two or more. There were 2603 patients (93.9%) with comedication, including lipid-lowering drugs (62.6%), inhibitors of the renin angiotensin aldosterone system (62.6%) and antiplatelet drugs (42.0%). Age older than 65 years increased the probability of comedication (odds ratio [OR]: 2.48; 95% confidence interval [95% CI]: 1.59-3.85), and the risk was proportional to age. We identified 1364 patients treated with conditional risk medications for QT prolongation (49.2%), 68 with a possible risk (2.5%) and 171 (6.2%) with a known risk. Conclusion: Antiarrhythmic drugs recommended by clinical practice guidelines are mainly used; however, risk interactions interactions of QT prolongation were identified and should be taken into account by physicians to avoid adverse events or complications.


Resumen Objetivo: determinar los patrones de prescripción de fármacos antiarrítmicos y variables asociadas a su utilización en una población de pacientes afiliados al sistema de salud de Colombia. Métodos: estudio de corte transversal sobre una base de datos poblacional con pacientes que recibieron antiarrítmicos entre marzo y mayo de 2016. Se incluyeron variables sociodemográficas, farmacológicas y de comedicación. Para el análisis de datos se utilizó SPSS-24, realizando pruebas X2 y análisis multivariado. Resultados: se encontraron 2 772 pacientes en tratamiento con antiarrítmicos en el periodo evaluado, la edad promedio fue 70,1 ± 13,1 años, 51,2 % eran mujeres. El 79,4% utilizó algún β-bloqueador, 58,5% amiodarona y 2,9 % algún bloqueante de canales de calcio. Al 43 % se les prescribió un solo antiarrítmico y 57 % recibieron dos o más. El 93,9 % tenía con alguna comedicación, especialmente hipolipemiantes (62,6 %), inhibidores del sistema renina angiotensina aldosterona (62,6 %) y antiagregantes (42 %). Ser mayor de 65 años aumentó la probabilidad de comedicación (OR:2,48; IC95 %:1,59-3,85) y el riesgo fue proporcional al incremento de la edad. El 49,2 % (n=1364) estaban tratados con medicamentos de riesgo condicional de prolongación del QT, 2,5 % (n=68) con riesgo posible y 6,2% (n=171) de riesgo conocido. Conclusión: se están utilizando los mismos fármacos recomendados por las guías de práctica clínica; sin embargo, se encontraron interacciones de riesgo de prolongación del intervalo QT que deben ser tenidas en cuenta para evitar eventos o complicaciones en los pacientes.

13.
Rev. bras. ter. intensiva ; 33(4): 600-615, out.-dez. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1357197

ABSTRACT

RESUMO O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.


ABSTRACT Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.


Subject(s)
Humans , Clonidine , Dexmedetomidine , Critical Care , Adrenergic alpha-2 Receptor Agonists , Hypnotics and Sedatives
14.
Int. braz. j. urol ; 47(4): 747-752, Jul.-Aug. 2021. tab
Article in English | LILACS | ID: biblio-1286764

ABSTRACT

ABSTRACT Purpose: To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. Materials and Methods: A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors. Results: The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes. Conclusions: Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.


Subject(s)
Humans , Male , Prostatic Hyperplasia , Pharmaceutical Preparations , Prazosin , Doxazosin , Adrenergic alpha-Agonists , Tadalafil , Tamsulosin
15.
Arq. bras. med. vet. zootec. (Online) ; 73(1): 62-72, Jan.-Feb. 2021. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1153037

ABSTRACT

Objetivou-se com este estudo comparar a associação de detomidina e cetamina ou dextrocetamina, por via intravenosa contínua, em oito cadelas submetidas a dois protocolos: GCD - indução anestésica com 5mg/kg e infusão intravenosa contínua de 20mg/kg/h de cetamina; e GDD - indução com 3,5mg/kg e infusão de 14mg/kg/h de dextrocetamina. Associou-se detomidina, 30µg/kg/h, em ambos os grupos. Registraram-se frequência cardíaca (FC), pressão arterial (PA), frequência respiratória (f), temperatura (TC), miorrelaxamento, analgesia, hemogasometria e eletrocardiograma, antes e 15 minutos após a MPA (Mbasal e Mmpa); após o início da infusão (Mic); a cada 10 minutos até 90 minutos (M10, M20, M30, M40, M50, M60, M70, M80 e M90); e 30 minutos após o fim da infusão (M120). Foi observada bradicardia em Mmpa no GCD e de Mmpa a M10 no GDD. Ocorreu hipotensão em Mmpa e hipertensão a partir de Mic. A f diminuiu de M10 a M30. Foram observados: onda T de alta amplitude, bloqueios atrioventriculares e parada sinusal. Ocorreu acidose respiratória. O período de recuperação foi de 219,6±72,3 minutos no GCD e de 234,1±96,8 minutos no GDD. A cetamina e a dextrocetamina, associadas à detomidina por infusão contínua, causam efeitos cardiorrespiratórios e anestésicos similares.(AU)


The combination of detomidine and ketamine or dextrocetamine for continuous intravenous infusion was compared in eight female dogs submitted to two protocols: GCD - 5mg/kg of anesthetic induction and continuous intravenous infusion of ketamine 20mg/kg/h; and GDD - induction with 3.5mg/kg and infusion of 14mg/kg/h of dextrocetamine. Detomidine, 30µg/kg/h was associated in both groups. Heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature (CT), myorelaxation, analgesia, blood gas analysis and electrocardiogram were recorded before and 15 minutes after MPA (Mbasal and Mmpa); after the start of infusion (Mic); every 10 minutes to 90 minutes (M10, M20, M30, M40, M50, M60, M70, M80 and M90); and 30 minutes after the end of infusion (M120). Bradycardia was observed in Mmpa in GCD and from Mmpa to M10 in GDD. There was hypotension in Mmpa and hypertension from Mic. The RR decreased from M10 to M30. High amplitude T wave, atrioventricular blocks and sinus arrest were observed. Respiratory acidosis occurred. The recovery period was 219.6±72.3 minutes in GCD and 234.1±96.8 minutes in GDD. Ketamine and S+ ketamine associated with detomidine for continuous infusion cause cardiorespiratory and similar anesthetic effects.(AU)


Subject(s)
Animals , Female , Dogs , N-Methylaspartate/agonists , Adrenergic alpha-Agonists/analysis , Anesthetics, Combined/analysis , Ketamine/therapeutic use , Acidosis, Respiratory/veterinary , Respiratory Rate , Heart Rate , Anesthesia, Intravenous/veterinary
17.
Arq. bras. cardiol ; 116(1): 100-105, Jan. 2021. tab
Article in English, Portuguese | LILACS | ID: biblio-1152972

ABSTRACT

Resumo Fundamento Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. Objetivo Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. Métodos Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). Resultados Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. Conclusão O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105)


Abstract Background Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. Objective Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. Methods We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). Results Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. Conclusion Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105)


Subject(s)
Humans , Male , Child , Adolescent , Coronary Artery Disease , Metoprolol/adverse effects , Outpatients , Radiation Dosage , Retrospective Studies , Coronary Angiography , Computed Tomography Angiography , Heart Rate
18.
Acta Pharmaceutica Sinica B ; (6): 2768-2782, 2021.
Article in English | WPRIM | ID: wpr-888886

ABSTRACT

Pyroptosis is the process of inflammatory cell death. The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection. Excessive pyroptosis, however, leads to several inflammatory diseases, including sepsis and autoimmune disorders. Pyroptosis can be canonical or noncanonical. Upon microbe infection, the canonical pathway responds to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), while the noncanonical pathway responds to intracellular lipopolysaccharides (LPS) of Gram-negative bacteria. The last step of pyroptosis requires the cleavage of gasdermin D (GsdmD) at D275 (numbering after human GSDMD) into N- and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11 (caspase 4/5 in humans, caspase 11 in mice) in the noncanonical pathway. Upon cleavage, the N-terminus of GsdmD (GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1

20.
Chinese Journal of Geriatrics ; (12): 1522-1525, 2021.
Article in Chinese | WPRIM | ID: wpr-933004

ABSTRACT

Objective:To analyze the effects of β-receptor blockers on all-cause mortality in elderly patients with mild-moderate chronic heart failure(CHF)and chronic obstructive pulmonary disease(COPD), and to analyze risk factors relevant to death.Methods:This was a multicenter retrospective cohort study from January 2013 to December 2017.The 400 elderly patients with CHF and COPD treated in Rizhao People's Hospital(187 cases), Shandong Provincial Hospital(122 cases)and Beijing Anzhen Hospital(91 cases)were enrolled.The patients receiving β-receptor blockers were included as β-receptor blockers group(n=200), and the patients matching for similar age and cardio-pulmonary function, not receiving β-receptor blockers were selected as the control group(n=200). All patients were followed up until December 31, 2019.The primary endpoints were all-cause mortality.The risk factors for all-cause death were compared and analyzed.Results:Among 400 patients, the average age was(72.2±11.7)years with 226 males(56.5%). There was no significant difference in baseline data such as age, gender ratio, body mass index, heart function, lung function, and treatment regimen after matching between the two groups(all P>0.05). At end of 3-years follow-up, risks of all-cause mortality( χ2=7.284, P<0.01), and re-hospitalization risk due to worsening heart failure( χ2=6.782, P<0.01), acute exacerbation of COPD( χ2=6.921, P<0.01)were significantly reduced in β-receptor blockers group versus control group.Multivariate Cox regression analysis showed that age ≥75 years( HR=2.142), diabetes( HR=1.929), ratio of baseline forced expiratory volume in the first second / forced vital capacity <66.8%( HR=1.114), baseline glomerular filtration rate <72.0 ml/min( HR=3.572)and left ventricular ejection fraction <46.4%( HR=2.294)at end of 3-year follow-up were risk factors for mortality, whileβ-receptor blockers( HR=0.745)was a protective factor(all P<0.05). Conclusions:β-receptor blockers can significantly reduce the mortality and re-hospitalization rate in elderly patients with CHF and COPD.

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