Impacto del síndrome de iris flácido intraoperatorio (IFIS) en cirugía de cataratas mediante facoemulsificación: análisis de 622 casos / Impact of intraoperative floppy IRIS syndrome in cataract surger by phacoemulsification: Analysis of 622 cases

Introducción Los síndromes de pupila estrecha, incluido el síndrome de iris flácido intraoperatorio (IFIS), aumentan el riesgo de complicaciones durante la cirugía de cataratas si no se realiza una correcta planificación quirúrgica. La tamsulosina se asocia a un incremento muy significativo del riesgo de IFIS, debido a la inactivación prolongada de los receptores alfa-1 adrenérgicos en la fibra muscular lisa del iris. Material y métodos Estudio prospectivo observacional unicéntrico, llevado a cabo en el Hospital de l’Esperança - Parc de Salut Mar.ResultadosSe incluyeron 622 ojos de 502 pacientes, de los cuales 337 (62%) eran mujeres. La media de edad de la muestra era de 74,8 años. Se observaron 61 casos de IFIS (11%), de los cuales 13 recibían tratamiento con tamsulosina y uno con doxazosina. Se observaron 23 casos de IFIS en pacientes mujeres. La ratio mujer:hombre fue de aproximadamente 1:3. Se observaron 19 casos (3%) de IFIS severo, de los cuales 6 recibían tratamiento con alfa-antagonistas, sin correlación estadísticamente significativa.La media del tiempo quirúrgico fue de 13,80min (desviación estándar [DE]: 4,01min) en pacientes sin IFIS y de 16,93min (DE: 4,32min) en pacientes con IFIS. La relación entre la duración del procedimiento quirúrgico en minutos y la presencia de IFIS fue estadísticamente significativa, aplicando un test t-Student «a dos colas» o bilateral con un p valor de 0,01. Conclusión Independientemente del grado de severidad, el diagnóstico de IFIS alarga el tiempo quirúrgico en cirugía de cataratas. Esto supone otra evidencia más que apoya la utilización de tratamientos antagonistas adrenérgicos menos alfa-1 selectivos que la tamsulosina o la realización de la cirugía de cataratas antes de iniciar dichos tratamientos. (AU)

Background Small pupil syndromes, including intraoperative-floppy iris syndrome (IFIS), increase the risk of complications during cataract surgery if proper surgical planning is not performed. Tamsulosin is associated with a very significant increase in the risk of IFIS, due to the prolonged inactivation of alpha-1 adrenergic receptors in the smooth muscle fiber of the iris. Material and methods Single-center prospective observational study, carried out at the Hospital de l’Esperança – Parc de Salut Mar.ResultsSix hundred and twenty-two eyes of 502 patients were included, of which 337 (62%) were women. The mean age of the sample is 74.8 years. Sixty-one cases of IFIS (11%) were observed, of which 13 received treatment with Tamsulosin and 1 with Doxazosin. Twenty-three cases of IFIS were observed in female patients. The female:male ratio was approximately 1:3. Nineteen cases (3%) of severe IFIS were observed, of which 6 received treatment with alpha-antagonists, with no statistically significant correlation.The mean surgical time was 13.80min (standard deviation – SD: 4.01min) in patients without IFIS and 16.93min (SD: 4.32min) in patients with IFIS. The relationship between the duration of the surgical procedure in minutes and the presence of IFIS was statistically significant, applying a ‘two-tailed’ or bilateral t-Student test with a p value of 0.01. Conclusion Regardless of the degree of severity, the diagnosis of IFIS lengthens the surgical time in cataract surgery. This represents yet another piece of evidence that supports the use of less selective alpha-1 adrenergic antagonist treatments than tamsulosin or the performance of cataract surgery before starting these treatments. (AU)

A metabolomics study: Could plasma metabolites be a guide for the prevention of tamsulosin side effects?

BACKGROUND: The understanding of precision medicine, which aims for high efficacy and low toxicity in treatments, has gained more importance with omics technologies. In this study, it was aimed to reach new suggestions for low-toxicity treatment by clarifying the relationship between tamsulosin side effects and metabolome profiles. MATERIALS AND METHODS: Plasma samples of control and tamsulosin-treated rats were analyzed by LC-Q-TOF/MS/MS. MS/MS data was processed in XCMS software for the identification of metabolite and metabolic pathway analysis. Data were classified with MATLAB 2019b for multivariate data analysis. 34m/z values were found to be significantly different between the drug and control groups (P≤0.01 and fold analysis≥1.5) and identified by comparing METLIN and HMDB databases. RESULTS: According to multivariate data analysis, α-Linolenic Acid, Thiamine, Retinoic acid, 1.25-Dihydroxyvitamin D3-26.23-Lactone, L-Glutamine, L-Serine, Retinaldehyde, Sphingosine 1-phosphate, L-Lysine, 23S.25-Dihydroxyvitamin D3, Sphinganine, L-Cysteine, Uridine 5'-diphosphate, Calcidiol, L-Tryptophan, L-Alanine levels changed significantly compared to the control group. Differences in the metabolisms of Retinol, Sphingolipid, Alanine-Aspartate-Glutamate, Glutathione, Fatty Acid, Tryptophan, and biosynthesis of Aminoacyl-tRNA, and Unsaturated Fatty Acid have been successfully demonstrated by metabolic pathway analysis. According to our study, vitamin A and D supplements can be recommended to prevent side effects such as asthenia, rhinitis, nasal congestion, dizziness and IFIS in the treatment of tamsulosin. Alteration of aminoacyl-tRNA biosynthesis and sphingolipid metabolism pathways during tamsulosin treatment is effective in the occurrence of nasal congestion. CONCLUSIONS: Our study provides important information for tamsulosin therapy with high efficacy and low side effects in precision medicine.

Impact of intraoperative floppy IRIS syndrome in cataract surgery by phacoemulsification: Analysis of 622 cases.

BACKGROUND: Small pupil syndromes, including IFIS, increase the risk of complications during cataract surgery if proper surgical planning is not performed. Tamsulosin is associated with a very significant increase in the risk of IFIS, due to the prolonged inactivation of alpha-1 adrenergic receptors in the smooth muscle fiber of the iris. MATERIAL AND METHODS: Single-center prospective observational study, carried out at the Hospital de l'Esperança - Parc de Salut Mar. RESULTS: 622 eyes of 502 patients were included, of which 337 (62%) were women. The mean age of the sample is 74.8 years. 61 cases of IFIS (11%) were observed, of which 13 received treatment with Tamsulosin and 1 with Doxazosin. 23 cases of IFIS were observed in female patients. The female:male ratio was approximately 1:3. 19 cases (3%) of severe IFIS were observed, of which 6 received treatment with alpha-antagonists, with no statistically significant correlation. The mean surgical time was 13.80 min (Standard Deviation - SD: 4.01 min) in patients without IFIS and 16.93 min (SD: 4.32 min) in patients with IFIS. The relationship between the duration of the surgical procedure in minutes and the presence of IFIS was statistically significant, applying a 'two-tailed' or bilateral t-Student test with a p value of 0.01. CONCLUSION: Regardless of the degree of severity, the diagnosis of IFIS lengthens the surgical time in cataract surgery. This represents yet another piece of evidence that supports the use of less selective alpha-1 adrenergic antagonist treatments than Tamsulosin or the performance of cataract surgery before starting these treatments.

[Role of alphablockers in women: Systematic review]. / Place des alphabloquants chez la femme : revue de la littérature.

INTRODUCTION: Marketing authorization of alphablockers is limited principally to men with benign hypertrophy of prostate. The objective of this review is to evaluate clinical and urodynamic improvement of alphablockers in women. METHOD: A review of the literature was carried out on all prospective studies about the use of alphablockers in women with urination disorders. RESULTS: Seventeen articles have been included. The selected articles were classified according to the studied population: lower urinary tract disorders, bladder emptying disorders without details on mechanism, bladder outlet obstruction, detrusor hypoactivity overactive bladder. Four studies were randomized against placebo. There was an improvement in the IPSS in 8 studies going as far as a decrease of 11,7 points (4.6 vs. 16.3 P<0.05). The voiding IPSS subscore was improved overall in 8 studies with a decrease of up to 6,2 points (9.6±5.5 vs. 14.8±4 P<0.01). Two trials showed an improvement of clinical scores versus placebo with an improvement of IPSS from -11.7 vs -9.5 (P<0.05) and -5.6 vs -2.6 (P<0.05). Urodynamic parameters were also often improved with a decrase of Qmax going to+5.8mL/s (P<0.05). Alphablocker also appear to improve non obstructive voiding disorders. The benefit in overactive bladder seems limited. CONCLUSION: Alphablockers may be indicated in voiding disorders of women. Their exact role must be established.

Fourier convolution versus derivative spectrophotometry: Application to the analysis of two binary mixtures containing tamsulosin hydrochloride as a minor component.

Simple and rapid spectrophotometric methods are described for determination of two mixtures of tamsulosin (TM), as minor component, with either solifenacin (SL) or tolterodine (TL). The proposed methods involve treatment of the absorbance ratio spectra or zero order spectra by derivative or discrete Fourier function. TM and TL mixture could not be resolved by manipulation of their zero order spectra due to the strong overlap between both spectra and only derivative or Fourier function coefficients of ratio spectra could resolve their spectra. TM and SL mixture was fully resolved by the manipulation of both ratio and zero order spectra. The values of the derivative or the Fourier function coefficients of ratio spectra and/or zero order spectra, at either peak or trough points, were correlated to the concentration of each drug in each mixture. Calibration graphs were linear in ranges 2.5-40 and 30-500µg.mL-1 using derivative ratio and Fourier function ratio, 5-40 and 80-600µg.mL-1 using direct derivative and 2.5-40 and 30-300µg.mL-1 using direct Fourier function for TM and SL, respectively. The plots of derivative ratio amplitude and the Fourier function ratio coefficient versus concentration were linear over ranges 2.5-20 and 25-250µg.mL-1 for TM and TL, respectively. Higher sensitivity as indicated by lower values of detection and quantitation limits were obtained using Fourier convoluted spectra (ratio or zero order) compared to derivative methods. All validation aspects per ICH guidelines are included. The proposed methods were also applied for the studied drugs assay in their tablets and capsules.

Simultaneous HPLC determination of alfuzosin, tamsulosin and vardenafil in human plasma and pharmaceutical formulations using time programmed fluorescence detection.

Alfuzosin and tamsulosin are recently co-administrated with vardenafil to treat symptoms of benign prostatic hyperplasia and erectile dysfunction. A highly sensitive and simple liquid chromatographic method was developed and validated for the simultaneous determination of the three drugs using moxifloxacin as an internal standard. Isocratic separation was achieved within 7.0 min using phenyl-hexyl column (250 × 4.6 mm i.d.) and a mobile phase composed of acetonitrile/0.25% phosphoric acid (30:70, v/v) at pH 3.0. The analysis was performed at a flow rate of 1.2 mL/min with fluorescence detection at 246/450 nm for Alfuzosin and vardenafil, and 226/322nm for tamsulosin using time programming technique. The proposed method was linear over the concentration ranges of 5.0-50.0ng/mL, 10.0-200.0ng/mL and 20.0-400.0ng/mL for alfuzosin, vardenafil and tamsulosin, with limits of detection of 0.56ng/mL, 0.98ng/mL and 2.81 ng/mL in a respective order. The developed method was successfully applied to determine the studied drugs in dosage forms and human plasma samples and the results were satisfactory as revealed by statistical analysis of the data.

[How to act when an alpha-blocker is associated with a potent inhibitor of CYP3A4]. / Conduite à tenir en cas d'association d'un alpha-bloquant et d'un inhibiteur puissant du cytochrome 3A4.

OBJECTIVE: Combination of alpha-blockers with potent CYP3A4 inhibitors is either contra-indicated or not recommended. We searched data supporting this classification and guiding prescribers when such an interaction occurs. METHODS: We analyzed reports published by the French agency for drug safety, reference books and performed search in databases of pharmacokinetics studies and case or case series related with these interactions. RESULTS: The classification of the potential severity of these interactions defined by the French agency for drug safety evolved over time. Our literature search did not identify any cases or case series reporting serious clinical consequences of such interactions and no pharmacoepidemiological studies on the association between alpha-blockers and inhibitors of CYP3A4. The content of the summaries of product characteristics indicate that the combination of ketoconazole with alfuzosin, silodosin and tamsulosin increases the area under the curve of the alpha-blocker 3 fold. CONCLUSION: Data demonstrating the clinical consequences of an association between alpha-blocker and a potent CYP3A4 inhibitor are lacking. The 3 fold increase of the area under the curve for alfuzosin, silodosin and tamsulosin associated with ketoconazole while the association with the two first is contra-indicated and is not recommended with the third raises questions. This lack of data leaves doctors and pharmacists in a situation of uncertainty on how to proceed when such an interaction occurs.

[Role of tamsulosin in improving double-J ureteric stent-related symptoms. A prospective multi-center, randomized study]. / Évaluation de l'efficacité de la tamsulosine pour améliorer la tolérance des sondes urétérales JJ. Étude prospective multicentrique randomisée.

PURPOSE: We evaluated the use of tamsulosine versus placebo for management of ureteral stent discomfort. PATIENTS AND METHODS: This prospective and randomized study was realized in the Department of Urology of three university hospital. The participation was proposed at all patient having indication to receive an ureteral stent except for cancer. The evaluation of the tolerance used two validate questionnaires: Ureteral Stent Symptom Questionnaire (USSQ) and IPSS completed by each patient the day of the insertion, next day, one week later and the day before and after the removal. The main assessment criterion was the question "global quality of life" one week after the stent insertion. RESULTS: Seventy-nine patients were randomized between June, 2010 and October, 2012. Despite phone reminders only 38 (48.1%) were complete questionnaires. Out of 39, 18 patients in the tamsulosine group and out of 40, 20 in the phloroglucinol group. The majority of the patients (92%) were included for stone disease. There is not significant difference between the 2 groups using the USSQ and IPSS at day+1, day+7, pre-ablation and day+1 ablation. A significant improvement of the scores was noted to day+1 by the ablation of the JJ in 2 groups. CONCLUSION: Our study did not show superiority of tamsulosine versus placebo in the improvement of the tolerance of ureteral stent. LEVEL OF EVIDENCE: 2.