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1.
Pharmacogenomics J ; 24(4): 19, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890281

RESUMEN

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.


Asunto(s)
Bloqueadores de los Canales de Calcio , Nimodipina , Farmacogenética , Hemorragia Subaracnoidea , Humanos , Nimodipina/administración & dosificación , Nimodipina/efectos adversos , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/complicaciones , Persona de Mediana Edad , Femenino , Masculino , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Anciano , Farmacogenética/métodos , Resultado del Tratamiento , Relación Dosis-Respuesta a Droga , Adulto , Medicina de Precisión/métodos , Vasoespasmo Intracraneal/tratamiento farmacológico
2.
J Drugs Dermatol ; 23(6): 446-449, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38834225

RESUMEN

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.


Asunto(s)
Acné Vulgar , Vasodilatadores , Humanos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/epidemiología , Estudios Retrospectivos , Masculino , Adulto , Femenino , Vasodilatadores/administración & dosificación , Persona de Mediana Edad , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Adulto Joven , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/efectos adversos
3.
HPB (Oxford) ; 26(3): 418-425, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38135550

RESUMEN

BACKGROUND: Repurposing existing drugs for use in oncology is more efficient, cost-effective and safe than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance. This study assessed the impact of calcium channel blockers (CCB) in pancreatic cancer. METHODS: Retrospective population study of patients undergoing resection (curative intent) of pancreatic ductal adenocarcinoma (SEER-Medicare, 2007-2017). Cox models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, the impact of CCB was assessed separately in patients receiving neoadjuvant chemotherapy. RESULTS: 6,223 patients were included, of whom 660 were prescribed CCB. In total, 591 received neoadjuvant chemotherapy; in this cohort CCB prescription was associated with improved overall survival when adjusting for multiple prognostic factors (aHR = 0.715, 0.514-0.996, P = 0.047). This effect was not observed in patients not receiving neoadjuvant chemotherapy (aHR = 1.082, 0.982-1.191, P = 0.112). CONCLUSION: CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy, mirroring the chemosensitising effect in laboratory studies. This defines patients receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Anciano , Estados Unidos , Terapia Neoadyuvante/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Medicare , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
4.
Rev Med Liege ; 79(2): 104-109, 2024 Feb.
Artículo en Francés | MEDLINE | ID: mdl-38356427

RESUMEN

Vasoreactive pulmonary arterial hypertension (PAH) in children is a form of idiopathic PAH that responds to vasoreactive testing with nitric oxide (NO) by a significant decrease of pulmonary vascular resistances and pressure. Oral calcium channel antagonists (CCA) that allow pulmonary arterial vasodilation are the treatment of choice. The therapeutic effect is strongly depending on adequate drug intake. In growing children, drug dose must be adapted to weight. In case of unavailability of low-dose pharmaceutical preparations, officinal formulations become mandatory. Officinal formulations may be related to a multitude of errors at different steps including prescription, transcription, preparation and administration. This may have life-threatening consequences for the child.To illustrate this, we report a case of a compounding error with underdosage of CCA, leading to acute cardiovascular failure in an adolescent with vasoreactive PAH.


L'hypertension artérielle pulmonaire (HTAP) vasoréactive chez l'enfant est une forme d'HTAP idiopathique qui répond au test de vasoréactivité au monoxyde d'azote (NO) par une diminution significative des pressions et résistances vasculaires pulmonaires. Le traitement de choix de cette forme d'HTAP est l'administration d'antagonistes des canaux calciques (ACC) par voie orale. Ce traitement entraîne une vasodilatation artérielle pulmonaire, elle-même étroitement dépendante de la prise adéquate du médicament. Chez les enfants en croissance, la dose du médicament doit être adaptée au poids. De façon générale, en l'absence de préparation à faible dose disponible dans les laboratoires pharmaceutiques, l'utilisation de formulations officinales devient obligatoire. De la prescription à l'administration, en passant par la transcription et la préparation, de nombreuses erreurs humaines et techniques peuvent survenir qui peuvent impacter la morbi-mortalité de l'enfant. Nous rapportons le cas d'une adolescente avec HTAP vasoréactive chez qui une erreur de préparation magistrale avec sous-dosage de l'ACC a conduit à une décompensation cardio-vasculaire aiguë et discutons de mesures préventives potentielles.


Asunto(s)
Hipertensión Pulmonar , Adolescente , Humanos , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Óxido Nítrico/uso terapéutico
6.
Clin Pharmacol Drug Dev ; 13(4): 367-379, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38315144

RESUMEN

Etripamil, a fast-acting nondihydropyridine L-type calcium channel blocker, is under investigation for potential self-administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double-blind studies: Study MSP-2017-1096 (sequential dose-escalation, crossover study design, n = 64) and NODE-102 (single dose, 4-way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5-8.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4-7 minutes of doses of 60 mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60 mg or greater. The mean terminal half-life ranged from about 1.5 hours with 60 mg to about 2.5-3 hours for the 70- and 105-mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60 mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.


Asunto(s)
Benzoatos , Bloqueadores de los Canales de Calcio , Adulto , Humanos , Bloqueadores de los Canales de Calcio/efectos adversos , Estudios Cruzados , Administración Intranasal
7.
BMJ Open ; 14(3): e080982, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38458796

RESUMEN

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.


Asunto(s)
Neoplasias de la Mama , Hipertensión , Femenino , Humanos , Bloqueadores de los Canales de Calcio/efectos adversos , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Estudios Longitudinales , Mastectomía , Australia/epidemiología , Hipertensión/tratamiento farmacológico , Estudios Observacionales como Asunto , Metaanálisis como Asunto
8.
Clin Pharmacol Drug Dev ; 13(5): 499-505, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38478175

RESUMEN

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.


Asunto(s)
Área Bajo la Curva , Bloqueadores de los Canales de Calcio , Estudios Cruzados , Preparaciones de Acción Retardada , Ayuno , Interacciones Alimento-Droga , Nifedipino , Comprimidos , Equivalencia Terapéutica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración Oral , Pueblo Asiatico , Bloqueadores de los Canales de Calcio/farmacocinética , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , China , Pueblos del Este de Asia , Voluntarios Sanos , Nifedipino/farmacocinética , Nifedipino/administración & dosificación , Nifedipino/efectos adversos
9.
Obstet Gynecol ; 143(6): 819-823, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626448

RESUMEN

There are limited data on the causative agents and characteristics of drug-induced liver injury in pregnant individuals. Data from patients with drug-induced liver injury enrolled in the ongoing multicenter Drug-Induced Liver Injury Network between 2004 and 2022 and occurring during pregnancy or 6 months postpartum were reviewed and compared with cases of drug-induced liver injury in nonpregnant women of childbearing age. Among 325 individuals of childbearing age in the Drug-Induced Liver Injury Network, 16 cases of drug-induced liver injury (5%) occurred during pregnancy or postpartum. Compared with drug-induced liver injury in nonpregnant women, pregnancy-related drug-induced liver injury was more severe ( P <.05). One elective termination and three miscarriages were documented; there were no maternal deaths. We recommend that isoniazid for latent tuberculosis be deferred to the postpartum period whenever feasible and that ß-blockers or calcium channel blockers rather than methyldopa be used for hypertension management during pregnancy.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Adulto , Complicaciones del Embarazo/tratamiento farmacológico , Estados Unidos/epidemiología , Adulto Joven , Isoniazida/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Periodo Posparto , Metildopa/efectos adversos , Antagonistas Adrenérgicos beta/efectos adversos , Antituberculosos/efectos adversos
10.
JAMA Neurol ; 81(8): 866-874, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38884986

RESUMEN

Importance: Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking. Objective: To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension. Design, Setting, and Participants: This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), ß-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024. Exposures: Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, ß-blockers, CCBs, or a combination of these antihypertensive medications. Main Outcomes and Measures: Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups. Results: Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received ß-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and ß-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs ß-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), ß-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease. Conclusions and Relevance: This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Epilepsia , Hipertensión , Humanos , Femenino , Hipertensión/epidemiología , Hipertensión/tratamiento farmacológico , Masculino , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Persona de Mediana Edad , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Estudios Retrospectivos , Anciano , Adulto , Antihipertensivos/uso terapéutico , Incidencia , Estudios de Cohortes , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Puntaje de Propensión , Bloqueadores de los Canales de Calcio/uso terapéutico , Bloqueadores de los Canales de Calcio/efectos adversos , Estados Unidos/epidemiología
11.
High Blood Press Cardiovasc Prev ; 31(3): 261-269, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38658522

RESUMEN

INTRODUCTION: Despite high prevalence of hypertension, few studies have analysed the adverse effects (AEs) of antihypertensive medications, especially in older patients. AIM: To investigate the prevalence and associated factors of antihypertensive-related AEs, focusing on the influence of age on treatment tolerability. METHODS: We retrospectively investigated antihypertensive-related AEs in patients evaluated at the Hypertension Clinic of Careggi Hospital, Florence, Italy, between January 2017 and July 2020. Multivariable regression models were generated to analyse variables associated with AEs in the overall sample and in participants ≥75 years. RESULTS: Among 622 subjects (mean age 64.8 years, 51.4% female), the most frequently reported AEs were calcium-channel blockers (CCB)-related ankle swelling (26.8%) and ACEi-induced cough (15.1%). Ankle swelling was more common in older patients (35.7% vs 22.3%, p = 0.001; odds ratio [OR] 1.94, 95%CI 1.289-2.912) and was independently associated with Body Mass Index (BMI, adjOR 1.073) and angiotensin-receptor antagonists (adjOR 1.864). The association with BMI was confirmed in older patients (adjOR 1.134). ACEi-induced cough showed similar prevalence in younger and older patients (13.9% vs 15.6%, p = 0.634), being independently associated with female sex (adjOR 2.118), gastroesophageal reflux disease (GERD, adjOR 2.488) and SNRI therapy (adjOR 8.114). The association with GERD was confirmed in older patients (adjOR 3.238). CONCLUSIONS: CCB-related ankle swelling and ACEi-induced cough represent the most common antihypertensive-related AEs, also at old age. Older patients showed a two-fold increased risk of ankle swelling, that was also independently associated with BMI. ACEi-induced cough had similar prevalence at younger and old ages, being independently associated with GERD.


Asunto(s)
Antihipertensivos , Hipertensión , Humanos , Femenino , Masculino , Persona de Mediana Edad , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Anciano , Factores de Edad , Hipertensión/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Prevalencia , Italia/epidemiología , Medición de Riesgo , Presión Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Tos/inducido químicamente , Tos/epidemiología , Anciano de 80 o más Años , Edema/inducido químicamente , Edema/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico
12.
J Am Heart Assoc ; 13(9): e033780, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38686894

RESUMEN

BACKGROUND: Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. METHODS AND RESULTS: Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). CONCLUSIONS: Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.


Asunto(s)
Amlodipino , Atorvastatina , Combinación de Medicamentos , Ácidos Heptanoicos , Hipercolesterolemia , Hipertensión , Pirroles , Humanos , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Masculino , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/complicaciones , Hipercolesterolemia/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/epidemiología , Femenino , Persona de Mediana Edad , Atorvastatina/administración & dosificación , Anciano , Taiwán/epidemiología , Resultado del Tratamiento , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Estudios Retrospectivos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Anticolesterolemiantes/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Presión Sanguínea/efectos de los fármacos
13.
J Am Heart Assoc ; 13(15): e035177, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39056339

RESUMEN

BACKGROUND: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. METHODS AND RESULTS: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm. CONCLUSION: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.


Asunto(s)
Amlodipino , Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Benzazepinas , Quimioterapia Combinada , Tasa de Filtración Glomerular , Hidroclorotiazida , Hipertensión , Humanos , Amlodipino/uso terapéutico , Amlodipino/efectos adversos , Hidroclorotiazida/uso terapéutico , Hidroclorotiazida/efectos adversos , Masculino , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Anciano , Persona de Mediana Edad , Benzazepinas/uso terapéutico , Benzazepinas/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Resultado del Tratamiento , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Riñón/fisiopatología , Riñón/efectos de los fármacos , Factores de Tiempo , Factores de Riesgo , Medición de Riesgo , Bloqueadores de los Canales de Calcio/uso terapéutico , Bloqueadores de los Canales de Calcio/efectos adversos
14.
Pharm. care Esp ; 20(1): 72-77, 2018. tab
Artículo en Español | IBECS (España) | ID: ibc-172117

RESUMEN

Existen varias alternativas para el manejo de las taquicardias supraventriculares, algunas de ellas farmacológicas y otras no farmacológicas. Dentro de las farmacológicas, los antiarrítmicos bloqueantes de los canales del sodio, clase IC como la propafenona, han demostrado ser de alto riesgo en pacientes ancianos, por la posibilidad de precipitar el fallo cardiaco. Este caso ilustra un error de medicación consistente en un problema relacionado con la selección del medicamento antiarrítmico, en el cual el haber ignorado la alerta generada por el servicio farmacéutico, provocó una reacción adversa seria (fallo cardiaco), lo cual corresponde a un problema de seguridad completamente prevenible


There are several alternatives for the treatment of supraventricular tachycardias, some of them are pharmacological and others non-pharmacological. Among pharmacological agents, class IC antiarrhythmics such as propafenone have been shown to be highly dangerous in elderly patients because the potential of cardiac failure. This case shows a medication error, a problem related to the selection of the antiarrhythmic drug, ignoring the warning of the pharmaceutical service and causing a serious adverse reaction (heart failure) which was completely preventable


Asunto(s)
Humanos , Femenino , Anciano , Propafenona/efectos adversos , Bradicardia/inducido químicamente , Antiarrítmicos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Monitoreo de Drogas/métodos , Servicios Farmacéuticos/métodos , Farmacovigilancia , Insuficiencia Cardíaca/tratamiento farmacológico
16.
Rev. calid. asist ; 31(3): 134-140, mayo-jun. 2016. tab
Artículo en Español | IBECS (España) | ID: ibc-153365

RESUMEN

Objetivo. Determinar la frecuencia de prescripción simultánea entre bloqueadores beta y calcioantagonistas cardiodepresores, notificar a los responsables de la atención sanitaria el riesgo cardiovascular al que están expuestos esos pacientes y conseguir una reducción en el número de quienes los utilizan. Métodos. Estudio cuasi-experimental, prospectivo, desarrollando una intervención en médicos prescriptores de pacientes mayores de 65 años, tratados entre el 1 de enero y el 30 de julio de 2014, afiliados al Sistema de Salud en 101 ciudades de Colombia. Se identificaron 43.180 pacientes que mensualmente recibían algún bloqueador beta y 14.560 que recibían un calcioantagonista cardiodepresor. Se realizaron intervenciones educativas y se evaluó en los siguientes 3 meses la proporción de suspensión de alguno de los fármacos. Se evaluaron las variables sociodemográficas y farmacológicas. Resultados. Se identificaron 535 pacientes que recibían concomitantemente bloqueadores beta más calcioantagonista cardiodepresor, con edad media 75,8 ± 6,7 años. Tras 66 intervenciones educativas se logró modificación de la terapia en 235 pacientes (43,9% de usuarios). En 209 casos (88,9%) se suspendió uno de los 2 medicamentos, un 11,1% cambió por otros antihipertensivos. Las variables tener más de 85 años (OR: 1,93; IC 95%:1,07-3,50) y recibir comedicación con inhibidores del sistema renina-angiotensina (OR: 2,16; IC 95%: 1,28-3,65) se asociaron con un mayor riesgo de que el responsable de la atención en salud cambiara o suspendiera alguno de los fármacos. Conclusiones. Se logró una positiva adherencia por parte de los prestadores del servicio sanitario a recomendaciones sobre utilización adecuada de bloqueadores beta y calcioantagonistas cardiodepresores. Se deben reforzar programas de intervención de prescripciones inapropiadas que disminuyan potenciales riesgos para los pacientes en tratamiento para enfermedades cardiovasculares (AU)


Objective. To determine the frequency of simultaneous prescription of β-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. Methods. Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a β-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. Results. A total of 535 patients, with a mean age 75.8 ± 6.7 years received concomitant β-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. Conclusions. An improved adherence to recommendations for appropriate use of β-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently (AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Calidad de la Atención de Salud/normas , Evaluación de Resultados de Intervenciones Terapéuticas/métodos , Prescripción Inadecuada/efectos adversos , Prescripción Inadecuada/prevención & control , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Prescripciones de Medicamentos/normas , Evaluación de Procesos y Resultados en Atención de Salud/organización & administración , Evaluación de Procesos y Resultados en Atención de Salud/normas , Estudios Prospectivos , 50230 , Análisis de Datos/métodos , Modelos Logísticos , Análisis Multivariante , Farmacoepidemiología/métodos , Farmacoepidemiología/tendencias
18.
Int. braz. j. urol ; 40(1): 44-55, Jan-Feb/2014. tab
Artículo en Inglés | LILACS | ID: lil-704182

RESUMEN

Purpose: The proposal of this study was to determine the prevalence and the associated factors of erectile dysfunction (ED) among hemodialysis (HD) patients. Materials and Methods: This was a cross-sectional study based on data collected from HD male patients. Clinical, demographic and laboratory data of all patients were collected in three HD clinics from December 2010 to June 2011. Patients answered questions of erectile function domain from International Index of Erectile Function. Data were evaluated by descriptive analysis and by univariate (ULRA) and multivariate logistic regression analysis (MLRA). Results: Three hundred and five patients participated of the study. The prevalence of ED was 68.19%. ED was associated with diabetes (DM), benign prostatic hyperplasia, glomerulonephritis as cause of chronic renal failure (CRF), smoking habits, lower creatinine levels (ULRA), use of calcium channel blocker (MLRA), aging, lower education level, alcohol consumption, DM (as cause of CRF) and coronary insufficiency (ULRA and MLRA). Conclusions: ED was highly prevalent in the HD men. It was independently associated with aging, current use of alcohol, long alcohol use (even for those who do not drink more), lower education level, diabetes as cause of CRF, coronary insufficiency and use of channel blockers calcium. .


Asunto(s)
Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Disfunción Eréctil/epidemiología , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos , Consumo de Bebidas Alcohólicas/efectos adversos , Brasil/epidemiología , Estudios Transversales , Bloqueadores de los Canales de Calcio/efectos adversos , Creatinina/sangre , Disfunción Eréctil/etiología , Análisis Multivariante , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Encuestas y Cuestionarios , Fumar/efectos adversos
19.
Nefrología (Madr.) ; 33(3): 377-380, abr.-jun. 2013. ilus, tab
Artículo en Español | IBECS (España) | ID: ibc-114523

RESUMEN

El líquido peritoneal turbio acelular de etiología no infecciosa es una entidad poco frecuente en diálisis peritoneal y se caracteriza por una concentración elevada de triglicéridos en el líquido peritoneal. Las causas más comunes son las neoplasias, las obstrucciones linfáticas, las pancreatitis, los traumatismos y se ha relacionado también con el uso de algunos fármacos, como los antagonistas del calcio. Las series con un mayor número de casos se han comunicado en población asiática. Recientemente hemos diagnosticado en nuestro centro 4 casos de líquido peritoneal turbio acelular relacionado con el uso de antagonistas del calcio. Nos planteamos revisar las características principales de los casos y estudiar la relación del antagonista del calcio con los niveles de triglicéridos en el líquido peritoneal de los pacientes estables en diálisis peritoneal durante el año 2010. De los cuatro enfermos con líquido peritoneal turbio acelular, el 75 % eran varones y el 75 % estaban en tratamiento con manidipino; en todos los casos se resolvió el problema con la retirada del fármaco. Los niveles de triglicéridos medios fueron de 314 mg/dl. Los niveles medios de triglicéridos de 36 pacientes estables de diálisis peritoneal fueron de 8,1 mg/dl, con un intervalo entre 1 y 35 mg/dl. La media de triglicéridos en los pacientes con o sin tratamiento con antagonistas del calcio fue muy similar: 7,81 y 8,6 mg/dl, respectivamente. No se observaron diferencias en relación con el tipo de antagonista del calcio prescrito. En nuestra experiencia, creemos que los antagonistas del calcio deben ser considerados como causa de líquido peritoneal turbio acelular en los enfermos en diálisis peritoneal, en especial el manidipino. No consideramos útil la determinación de triglicéridos en el líquido peritoneal de los enfermos asintomáticos en tratamiento con antagonistas del calcio (AU)


Turbid acellular peritoneal fluid of a non-infectious aetiology is an uncommon entity in peritoneal dialysis and is characterised by a high concentration of triglycerides in the peritoneal fluid. The most common causes include cancer, lymphatic obstructions, pancreatitis, trauma, and even the use of certain medications such as calcium antagonists. The largest studies concerning this entity have been carried out in patients of Asian descent. We recently diagnosed 4 cases of turbid acellular peritoneal fluid at our institution in relation to the use of calcium antagonists. We reviewed the primary characteristics of these cases and examined the relationship between the use of calcium antagonists and triglyceride levels in the peritoneal fluid of stable patients on peritoneal dialysis during 2010. Of the four patients with turbid acellular peritoneal fluid, 75% were male and 75% were on treatment with manidipine; in all cases, the issue was resolved by suspending medication. Mean triglyceride levels were 314mg/dl. Mean triglyceride levels in 36 stable patients on peritoneal dialysis were 8.1mg/dl, with a range of 1-35mg/dl. Mean triglyceride levels in patients with and without calcium antagonist treatment were very similar, at 7.81mg/dl and 8.6mg/dl, respectively. We did not observe significant differences in terms of the type of calcium antagonist prescribed. In our experience, we believe that calcium antagonists should be considered as a cause of turbid acellular peritoneal fluid in patients on peritoneal dialysis, in particular manidipine. We do not find it useful to determine triglyceride levels in the peritoneal fluid of asymptomatic patients on treatment with calcium antagonists (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Líquido Ascítico , Diálisis Peritoneal/métodos , Bloqueadores de los Canales de Calcio/efectos adversos , Insuficiencia Renal Crónica/fisiopatología , Verapamilo/efectos adversos , Factores de Riesgo
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