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1.
Rev Med Chil ; 147(7): 932-934, 2019 Jul.
Artículo en Español | MEDLINE | ID: mdl-31859993

RESUMEN

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.


Asunto(s)
Acenocumarol/efectos adversos , Amlodipino/efectos adversos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Metformina/efectos adversos , Protrombina/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Acenocumarol/administración & dosificación , Administración Intravenosa , Anciano de 80 o más Años , Amlodipino/administración & dosificación , Humanos , Infarto de la Arteria Cerebral Media/etiología , Masculino , Metformina/administración & dosificación , Accidente Cerebrovascular/etiología , Tomografía Computarizada por Rayos X
3.
BMC Infect Dis ; 19(1): 715, 2019 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-31409277

RESUMEN

BACKGROUND: Gynecomastia is known to occur in some men taking an efavirenz-based antiretroviral therapy (ART) regimen. However, the incidence and outcomes of gynecomastia are not known in Zimbabwe. We described the characteristics and outcomes of gynecomastia among male patients on an efavirenz-based ART regimen. METHODS: We conducted a retrospective cohort review of data of all male patients aged ≥18 years taking an efavirenz-based regimen at Newlands Clinic, Harare, Zimbabwe before 31 March 2017. The primary outcome was gynecomastia as defined by breast/nipple enlargement reported by patient and confirmed by clinical palpation. Routinely collected data on demographics, baseline CD4, body mass index, duration on efavirenz, clinical presentation and outcomes were extracted from the clinic database and analysed using STATA 12.1. We investigated for any associations with concomitant medicines using cox regression. RESULTS: We analysed data for 1432 men with a median age of 40 years (IQR: 33-48). Half of the patients were in WHO stage 1 at ART commencement. Median body mass index and CD4 count at efavirenz commencement was 21 (IQR: 19-23) and 260 cells/mm3 (IQR: 126-412) respectively. The incidence of gynecomastia was 22/1000 person-years (IQR: 17.3-27.8). Over half of the cases (58%) were bilateral and 75% of all cases developed within two years of starting efavirenz. There were no significant associations with concomitant use of isoniazid (HR: 0.95, p = 0.87) or amlodipine (HR: 0.43, p = 0.24). Gynecomastia resolved in 83.5% of cases following withdrawal of efavirenz with a median time to resolution of 3 months (IQR: 2-9). CONCLUSION: The incidence of gynecomastia among patients taking efavirenz-based ART was low with most cases developing early on during treatment. Most cases resolved completely after withdrawing efavirenz.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Ginecomastia/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Adulto , Amlodipino/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Ginecomastia/epidemiología , Humanos , Incidencia , Isoniazida/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Zimbabwe/epidemiología
4.
Expert Opin Drug Metab Toxicol ; 15(9): 687-695, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31359804

RESUMEN

Introduction: S-amlodipine is main anti-hypertensive active enantiomer of amlodipine. Bisoprolol is a ß-blocker particularly suitable for hypertensive patients with sinus tachycardia. We evaluated the pharmacokinetic interaction between S-amlodipine and bisoprolol in healthy Chinese subjects. Areas covered: Thirty-two subjects were randomly divided into two equal groups. Subjects in group A were administered S-amlodipine 5 mg for 10 days followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 7 days. Subjects in group B were administered bisoprolol 5 mg for 7 days, followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 10 days. Blood samples were collected for evaluation of pharmacokinetic interaction. Tolerability was evaluated by interview, vital signs, 12-lead ECGs, physical examination, and clinical laboratory tests. Expert opinion: The geometric mean ratio (90% CI) for amlodipine AUCτ,ss and Css-max during the monotherapy and combination therapy periods were 1.0389 (0.9879, 1.0926) and 1.0213 (0.9556, 1.0915). For bisoprolol, it was 1.0193 (0.9834, 1.0566) and 0.9989 (0.9133, 1.0925). Most adverse events were mild-moderate. There was high incidence of elevated alanine aminotransferase, aspartate aminotransferase, and triglyceride.This study found no pharmacokinetic interaction between S-amlodipine and bisoprolol. Alanine aminotransferase, aspartate aminotransferase, and triglycerides should be closely monitored.


Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Bisoprolol/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Adulto , Amlodipino/efectos adversos , Amlodipino/farmacocinética , Antihipertensivos/efectos adversos , Antihipertensivos/farmacocinética , Área Bajo la Curva , Grupo de Ascendencia Continental Asiática , Bisoprolol/efectos adversos , Bisoprolol/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Persona de Mediana Edad , Estereoisomerismo , Transaminasas/sangre , Triglicéridos/sangre , Adulto Joven
5.
Rev Cardiovasc Med ; 20(2): 91-98, 2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-31345001

RESUMEN

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Cronoterapia de Medicamentos , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
6.
Basic Clin Pharmacol Toxicol ; 125(4): 345-352, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31058419

RESUMEN

The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUCτ , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUCτ , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUCτ , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.


Asunto(s)
Amlodipino/farmacocinética , Antihipertensivos/farmacocinética , Hemodinámica/efectos de los fármacos , Losartán/farmacocinética , Administración Oral , Adulto , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Voluntarios Sanos , Humanos , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
7.
BMJ Case Rep ; 12(5)2019 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-31142490

RESUMEN

Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.


Asunto(s)
Amlodipino/efectos adversos , Ciclosporina/efectos adversos , Sobrecrecimiento Gingival/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Adulto , Amlodipino/administración & dosificación , Quimioterapia Combinada , Humanos , Masculino , Ácido Micofenólico/efectos adversos
8.
Int J Mol Sci ; 20(8)2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-31027273

RESUMEN

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast's function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. MATERIALS AND METHODS: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. RESULTS: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. CONCLUSION: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.


Asunto(s)
Amlodipino/efectos adversos , Fibroblastos/metabolismo , Encía/patología , Sobrecrecimiento Gingival/inducido químicamente , Sobrecrecimiento Gingival/genética , Línea Celular , Fibroblastos/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Sobrecrecimiento Gingival/patología , Humanos
9.
Am J Cardiovasc Drugs ; 19(3): 313-323, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30919249

RESUMEN

BACKGROUND: Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension. OBJECTIVE: This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension. METHODS: Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg. RESULTS: Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison. CONCLUSIONS: Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension. TRIAL REGISTRATION: EudraCT (No. 2006-005799-42).


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Perindopril/administración & dosificación , Anciano , Amlodipino/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Perindopril/efectos adversos , Índice de Severidad de la Enfermedad
10.
N Engl J Med ; 380(25): 2429-2439, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-30883050

RESUMEN

BACKGROUND: The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS: In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS: The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, -3.14 mm Hg; 95% confidence interval [CI], -5.90 to -0.38; P = 0.03; and -3.00 mm Hg; 95% CI, -5.8 to -0.20; P = 0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was -0.14 mm Hg (95% CI, -2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS: These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467.).


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Perindopril/administración & dosificación , Adulto , África del Sur del Sahara , Grupo de Ascendencia Continental Africana , Anciano , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/efectos adversos , Hipertensión/etnología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Perindopril/efectos adversos , Método Simple Ciego
11.
Clin Ther ; 41(2): 233-248.e9, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30665829

RESUMEN

PURPOSE: Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free-equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia. METHODS: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial (J-TAROS-RCT) was an 8-week, multicenter, randomized, double-blind, parallel, Phase III clinical trial conducted at 9 hospitals in Korea. After a run-in period of >4 weeks, patients who fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for randomization to receive 1 of 3 treatments for 8 weeks: (1) telmisartan/amlodipine 80 mg/10 mg plus rosuvastatin 20 mg, (2) telmisartan/amlodipine 80 mg/10 mg, or (3) telmisartan 80 mg plus rosuvastatin 20 mg. The primary end point was efficacy evaluation of combination therapy with telmisartan/amlodipine/rosuvastatin by comparing the change in mean sitting systolic blood pressure (msSBP) and mean percentage change in LDL-C from baseline after 8 weeks of treatment. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: Among 148 patients, the changes in msSBP from baseline after 8 weeks of treatment were a mean (SD) of -24.41 (2.38) versus -9.31 (2.36) mm Hg in the telmisartan/amlodipine/rosuvastatin and telmisartan/rosuvastatin groups, respectively. Significantly more participants achieved the target BP at week 8 in the telmisartan/amlodipine/rosuvastatin group (41 patients [87.2%]) than in the telmisartan/rosuvastatin group (24 [50.0%], P < 0.001). The changes in mean (SD) LDL-C at 8 weeks compared with baseline values were -57.59% (11.59%) versus 6.08% (20.98%) in the telmisartan/amlodipine/rosuvastatin and telmisartan/amlodipine groups, respectively. The percentages of patients who achieved the target LDL-C according to their risk factors after 8 weeks of treatment were 97.87% vs 6.12% in the telmisartan/amlodipine/rosuvastatin and the telmisartan/amlodipine groups (P < 0.0001), respectively. No significant differences were found in the incidence of overall AEs and adverse drug reactions, and serious AEs were comparable among 3 groups. IMPLICATIONS: Fixed-dose combinations of telmisartan, amlodipine, and rosuvastatin decreased BP and LDL-C in patients with hypertension and dyslipidemia. The safety and tolerability profiles of fixed-dose telmisartan, amlodipine, and rosuvastatin combination therapy were comparable with those of telmisartan plus amlodipine or telmisartan plus rosuvastatin. ClinicalTrials.gov identifier: NCT03088254.


Asunto(s)
Amlodipino/administración & dosificación , Anticolesterolemiantes/administración & dosificación , Antihipertensivos/administración & dosificación , Dislipidemias/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Rosuvastatina Cálcica/administración & dosificación , Telmisartán/administración & dosificación , Anciano , Amlodipino/efectos adversos , Anticolesterolemiantes/efectos adversos , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Rosuvastatina Cálcica/efectos adversos , Telmisartán/efectos adversos
13.
Sleep Breath ; 23(1): 227-233, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29951886

RESUMEN

PURPOSE: ß-Blocker use has been controversial for a long time in the management of hypertensive patients with obstructive sleep apnea (OSA). The aim of present study was to compare the effects of metoprolol on BP lowering with amlodipine in hypertensive OSA patients. METHODS: Hypertensive subjects with OSA were randomly assigned to metoprolol and amlodipine groups, receiving 12 weeks of oral either metoprolol (47.5 mg once daily) or amlodipine (5 mg once daily) treatment. At baseline and after the 12-week treatment period, 24-h ambulatory blood pressure monitoring was performed in both groups. RESULTS: Both of metoprolol and amlodipine treatments significantly lowered 24-h blood pressure (BP) (from 143/88 to 132.3/81.6 mmHg; from 141.3/84.5 to 133.7/80.8 mmHg), daytime BP (from 146/90.2 to 136.4/84.6 mmHg; from 145.1/87.6 to 138.2/84.1 mmHg), and nighttime BP (from 139.1/83.9 to 125.7/76.2 mmHg; from 134.5/78.5 to 125.8/74.1 mmHg) (all P < 0.05). But there were no significant differences between the groups in BP variability (P > 0.05). Besides, metoprolol significantly reduced daytime heart rate (HR) (P < 0.05), while 24-h and nighttime HR values had no remarkable changes compared with baseline (P > 0.05). CONCLUSIONS: Metoprolol had similar therapeutic effects on BP lowering as amlodipine and could not decrease HR during the nighttime in hypertensive patients with OSA.


Asunto(s)
Amlodipino/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Metoprolol/uso terapéutico , Apnea Obstructiva del Sueño/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Amlodipino/efectos adversos , Monitoreo Ambulatorio de la Presión Arterial , Estudios de Cohortes , Comorbilidad , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Masculino , Metoprolol/efectos adversos , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/complicaciones
14.
Vasc Health Risk Manag ; 14: 265-278, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30349279

RESUMEN

Background: The EPHES trial (Evaluation of influence of fixed dose combination Perindo-pril/amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) compared the dynamics of target organ damage (TOD) in hypertensive patients with and without ischemic heart disease (IHD) treated with the fixed-dose combination (FDC) perindopril + amlodipine. Methods: The analysis included 60 hypertensive patients (aged >30 years): 30 without IHD and 30 with IHD. At randomization, FDC was administered at a daily baseline dose of 5/5 mg with uptitration to 10/10 mg every two weeks. If target blood pressure (BP<140/90 mmHg) was not achieved after six weeks, indapamide 1.5 mg was added to the regimen. All patients underwent body mass index measurements, office and ambulatory BP measurements, pulse wave velocity (PWVe) and central systolic BP evaluation, augmentation index adjusted to heart rate 75 (Aix@75) evaluation, biochemical analysis, ECG, echocardiography with Doppler, ankle-brachial index measurement, and intima-media thickness measurement. The follow-up period was 12 months. Results: Therapy based on FDC perindopril/amlodipine was effective in lowering BP (office, ambulatory, central) in both groups. We noted significant decrease in Aix@75 with the therapy in both groups, but ΔAix@75 was lesser in the group with IHD than the group without IHD. FDC provided significant improvement in PWVe and left ventricular diastolic function, and decrease in albuminuria, left ventricular hypertrophy (LVH), and left atrium size. ΔPWVe was significantly (P<0.005) less in patients without IHD than those with IHD (2.5±0.2 vs 4.4±0.5 m/s, respectively). In spite of almost equal LVH regression, the positive dynamics of ΔE/A and ΔE/E´ were more in patients with IHD than those without IHD (64.4% and 54.1% vs 39.8 and 23.2%, respectively; P<0.05 for both comparisons). Adverse reactions were in 2 (6.5%) patients without IHD and 3 (10%) with IHD (P=NS). In the group with IHD, we noted significant decrease in angina episode rate - from 2.5±0.4 to 1.2±0.2 (P<0.01) per week. Conclusion: Thus, treatment based on FDC was effective in decreasing BP and TOD regression in both patients with and without IHD. However, the dynamics of changes in TOD were different between the two groups, which should be taken into consideration during management of patients with and without IHD.


Asunto(s)
Amlodipino/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Arterial/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Isquemia Miocárdica/complicaciones , Perindopril/uso terapéutico , Adulto , Amlodipino/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Perindopril/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Ucrania
15.
Hypertension ; 72(4): 986-993, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30354704

RESUMEN

Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102-107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15-2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09-3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80-13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21-4.30), and any CVD event (HR, 2.12; 95% CI, 1.12-3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.


Asunto(s)
Amlodipino , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares , Hipertensión , Hipotensión Ortostática , Metoprolol , Ramipril , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Determinación de la Presión Sanguínea/métodos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Monitoreo de Drogas/métodos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/tratamiento farmacológico , Hipotensión Ortostática/fisiopatología , Masculino , Metoprolol/administración & dosificación , Metoprolol/efectos adversos , Persona de Mediana Edad , Ramipril/administración & dosificación , Ramipril/efectos adversos , Estados Unidos
16.
Expert Rev Clin Pharmacol ; 11(11): 1073-1084, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30362840

RESUMEN

INTRODUCTION: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.


Asunto(s)
Amlodipino/administración & dosificación , Celecoxib/administración & dosificación , Hipertensión/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Amlodipino/efectos adversos , Amlodipino/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacología , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Antihipertensivos/farmacología , Celecoxib/efectos adversos , Celecoxib/farmacología , Combinación de Medicamentos , Humanos , Hipertensión/etiología , Osteoartritis/complicaciones , Dolor/tratamiento farmacológico , Dolor/etiología
17.
Kardiologiia ; 58(9): 21-30, 2018 09.
Artículo en Ruso | MEDLINE | ID: mdl-30295196

RESUMEN

AIM: to assess antihypertensive efficacy of the fixed-dose amlodipine/indapamide/perindopril arginine combination in hypertensive patients in real clinical setting. METHODS: We included in the 3­month clinical program 1 599 patients with arterial hypertension (AH) (38.8 % men, mean age 61.6±10 years). Primary outcomes were change of office and ambulatory (home blood pressure monitoring) systolic and diastolic blood pressure (SBP and DBP) from baseline to 3 months and rate of achievement of target BP.


Asunto(s)
Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Arginina/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/uso terapéutico , Perindopril/uso terapéutico , Centros Médicos Académicos , Anciano , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Arginina/efectos adversos , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/fisiopatología , Indapamida/efectos adversos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Perindopril/efectos adversos , Federación de Rusia
19.
Dermatol Online J ; 24(5)2018 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-30142738

RESUMEN

Drug induced linear IgA bullous dermatosis (LABD) is a rare blistering disease that has been shown to be associated with the use of various medications. Although rarely seen together, some of the medications associated with LABD can lead to the syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which presents with fever, cutaneous eruption, and multi-organ involvement. We present a patient who developed fever and a generalized vesiculobullous eruption after recently starting amlodipine and meloxicam. Initial laboratory tests demonstrated elevated liver function tests, leukocystosis, and eosinophilia. Histopathologic examination of the punch biopsy revealed a bulla with sub-epidermal split and numerous neutrophils. Direct immunofluorescence demonstrated broad deposition of IgA along the dermal-epidermal junction. These findings were consistent with an overlap between LABD and DRESS. Drug induced LABD and DRESS are independently both rare diseases. It is even more uncommon to see the two concurrently in the same patient. In this patient, these two conditions were thought to be triggered by either amlodipine or meloxicam. Given the high mortality rate associated with DRESS, it is important to recognize the presentation and initiate the appropriate treatment plan as soon as possible.


Asunto(s)
Amlodipino/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Antihipertensivos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Dermatosis Bullosa IgA Lineal/inducido químicamente , Meloxicam/efectos adversos , Amlodipino/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antihipertensivos/uso terapéutico , Artralgia/tratamiento farmacológico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Meloxicam/uso terapéutico , Persona de Mediana Edad , Osteoartritis/complicaciones
20.
J Clin Psychopharmacol ; 38(5): 498-501, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30102628

RESUMEN

BACKGROUND: Amlodipine (AMLO) and ramipril (RAMI) belong to the most prescribed drugs in patients with hypertension, a condition also encountered in depression. Venlafaxine may worsen hypertension because of noradrenergic properties. Although of special clinical relevance, data on pharmacokinetic interactions between AMLO, RAMI, and venlafaxine (VEN) are lacking. METHODS: Two TDM databases consisting of plasma concentrations of VEN and its active metabolite O-desmethylvenlafaxine (ODVEN) were analyzed. We considered a group of patients comedicated with AMLO, VAMLO (n = 22); a group comedicated with RAMI, VRAMI (n = 20); and a 4:1 control group age matched to the VAMLO group receiving VEN without confounding medications, V0 (n = 88). Plasma concentrations of VEN, ODVEN, and active moiety, AM (VEN + ODVEN); metabolic ratio (ODVEN/VEN); and dose-adjusted plasma concentrations (C/D) were compared using nonparametric tests. RESULTS: Groups did not differ in daily VEN dose, age, or sex. The metabolic ratio (ODVEN/VEN) was lower in the AMLO group (P = 0.029), whereas the RAMI group showed lower values for ODVEN (P = 0.029). All other parameters showed no significant differences. CONCLUSIONS: Significantly lower values for the metabolic ratio in the AMLO group are unlikely to be explained by cytochrome P450 (CYP) 3A4 and weak CYP2D6 inhibition by AMLO. Other factors such as differences in CYP2D6 polymorphisms and metabolizer status may better explain the findings. Ramipril showed modest effects with changes in ODVEN concentrations that did not remain significant after dose-adjusted comparisons.


Asunto(s)
Amlodipino/farmacocinética , Antihipertensivos/farmacocinética , Hipertensión/tratamiento farmacológico , Ramipril/farmacocinética , Inhibidores de Captación de Serotonina y Norepinefrina/farmacocinética , Clorhidrato de Venlafaxina/farmacocinética , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Inhibidores del Citocromo P-450 CYP2D6/administración & dosificación , Inhibidores del Citocromo P-450 CYP2D6/efectos adversos , Inhibidores del Citocromo P-450 CYP2D6/farmacocinética , Bases de Datos Factuales , Interacciones Farmacológicas/fisiología , Prescripciones de Medicamentos/normas , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico , Masculino , Ramipril/administración & dosificación , Ramipril/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/administración & dosificación , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Clorhidrato de Venlafaxina/administración & dosificación , Clorhidrato de Venlafaxina/efectos adversos
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