Гипотензивное средство (диуретик, вазодилататор). По фармакологическим свойствам близок к тиазидным диуретикам (нарушение рсабсорбиии натрия в кортикальном сегменте петли Генле). Увеличивает выделение с мочой ионов натрия, хлора и, в меньшей степени, ионов калия и магния. Обладая способностью селективно блокировать "медленные" кальциевые каналы, повышает эластичность стенок артерий и снижает общее периферическое сосудистое сопротивление. Способствует уменьшению гипертрофии левого желудочка сердца. Не влияет на содержание липидов в плазме крови (триглицеридов, липопротеннов низкой плотности, липопротеинов высокой плотности); значительно не влияет на углеводный обмен, но при наличии гипокалиемии может увеличиваться уровень глюкозы в крови. Снижает чувствительность сосудистой стенки к норадреналину и ангиотензину II, стимулирует синтез простагландина PgE2α и простациклина PgI2, снижает продукцию свободных и стабильных кислородных радикалов. При назначении в высоких дозах не влияет на степень снижения артериального давления, несмотря на увеличение диуреза. При систематическом приеме терапевтический эффект отмечается через 1-2 недели, достигает максимума к 8-12 неделе и сохраняется до 8 недель; после приема однократной дозы максимальный эффект отмечается через 24 часа. .
Лекарственное взаимодействие
Салуретики (петлевые, тиазидные), сердечные гликозиды, глюко- и минералокортикоиды, тетракозактид, амфотерицин В (в/в), слабительные средства повышают риск развития гипокалиемии. При одновременном приеме с сердечными гликозидами повышается вероятность развития дигиталисной интоксикации; с препаратами кальция - гиперкальциемии; с метформином - возможно усугубление молочнокислого ацидоза. Повышает концентрацию ионов лития в плазме крови (снижает выведение с мочой), литий оказывает нефротоксическое действие. Астемизол, эритромицин (внутривенно), пентамидин, сультоприд, терфенадин, винкамин, антиаритмические препараты 1а класса (хинидин, днзопирамид) и III класса (амиодарон, бретилия тозилат, соталол) могут привести к развитию аритмии по типу "пируэт" за счет удлинения интервала QT. НПВП, ГКС, тетракозактид, симпатомиметики снижают гипотензивный эффект, баклофен - усиливает. Комбинация с калийсберегающими диуретиками может быть эффективна у некоторой категории больных, однако, при этом полностью не исключается возможность развития гипо- или гиперкалиемии, особенно у больных сахарным диабетом и почечной недостаточностью. Ингибиторы АПФ увеличивают риск развития артериальной гипотензии и/или острой почечной недостаточности (особенно при имеющемся стенозе почечной артерии). Увеличивает риск развития нарушений функции почек при использовании йодсодержащих контрастных средств в высоких дозах (обезвоживание организма). Перед применением йодсодержащих контрастных веществ больным необходимо восстановить потерю жидкости. Имипраминовые (трициклические) антидепрессанты и антипсихотические препараты усиливают гипотензивное действие и увеличивают риск развития ортостатической гипотензии. Циклоспорин повышает риск развития гиперкреатининемии. Снижает эффект непрямых антикоагуляитов (производных кумарина или индандиона) вследствие повышения концентрации факторов свертывания в результате уменьшения объема циркулирующей крови и повышения их продукции печенью (может потребоваться коррекция дозы). Усиливает блокаду нервно-мышечной передачи, развивающуюся под действием недеполяризующих миорелаксактов.
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