Использование в клинике и фармацевтические препараты. Боль-

ным с выраженной седацией и угнетением дыхания(менее 8 вдохов в 1 мин) налоксон назначают внутривенно в начальной дозе 10 мкг. Эта доза удваивается каждые 23 мин (20, 40, 80, 160 мкг) вплоть до пробуждения пациента и нормализации дыхания. В последующем необходимо продолжать инфузии налоксона или вводить повторно те же дозы. Пациентам в состоянии апноэ и не пробуждающимся налоксон вводят в дозе0,4 мг. Налоксона гидрохлорид выпускают в растворе концентрацией 0,02, 0,4 и 1 мг/мл. Для взрослых чаще всего используют ампулы с содержанием налоксона 0,4 мг/мл.

Пероральные антагонисты

Налтрексон

Налтрексон в отличие от налоксона весьма эффективен при назначении внутрь и оказывает выраженное антагонистическое в отношении опиоидов действие на протяжении 24 ч. Препарат выпускают в таблетках по50 мг и применяют при лечении морфинистов [308].

ЗАКЛЮЧЕНИЕ

Опиоиды, помимо их местного обезболивающего и нестероидного противовоспалительного действия, служат фармацевтической основой эффективного преодоления послеоперационной боли. Читатель, особенно анестезиолог, может удивиться, что при обсуждении опиоидов минимальное внимание было уделено их парентеральному или спинальному (эпидуральному и субарахноидальному) путям введения. Однако философские принципы авторов этой книги заключаются в том, что практический врач, устраняющий послеоперационные боли (можно сказать, анестезиолог), должен быть полноценным специалистом. Преодоление послеоперационной боли продолжается после прекращения сложных инвазивных вмешательств. Это требует совершенных, а не поверхностных знаний по фармакологии опиоидов. Цель данной главы – обеспечить врачей подобными знаниями.

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9

Локальные анестетики

Бенджамин Г. Ковино (Benjamin G. Covino)

Локальными анестетиками называют фармакологические препараты, вызывающие потерю чувствительности на ограниченном участке тела. Подобные локальные формы анестезии обусловлены либо угнетением процессов возбуждения нервных окончаний, либо блокадой процессов проведения по периферическим нервам. Региональная анестезия берет свое начало с 1884 г., когда Koller описал местные обезболивающие свойства кокаина, алкалоида, выделенного из листьев Erytroxylin coca. В последующем было синтезировано большое число средств со свойствами локальных анестетиков. Эти средства в настоящее время используются для региональной анестезии. Особенности их применения в клинике отражены в табл. 9-1.

ФАРМАКОДИНАМИКА

Механизм действия

В состоянии покоя трансмембранный потенциал нервный клетки отрицателен и равен 60-90 мВ (так называемый мембранный потенциал покоя). При стимуляции нерва вначале наблюдается фаза относительно медленной деполяризации. Отрицательный электрический потенциал клетки в это время прогрессивно снижается (рис. 9-1). Когда электрический потенциал между внутренней и наружной поверхностями мембраны достигает критического уровня (так называемый пороговый потенциал), наступает фаза быстрой деполяризации. Это приводит к реверсии электрических потенциалов: внутренняя поверхность клеточной мембраны приобретает положительный заряд, а наружная - отрицательный. На пике потенциала действия положительный заряд на внутренней поверхности мембраны достигает примерно40 мВ по отношению к наружной поверхности. Общая амплитуда потенциала действия равна примерно 100 мВ. После завершения фазы деполяризации начинается фаза реполяризации нерва. На внутренней поверхности клетки прогрессивно растет отрицательный заряд до восстановления потенциала покоя на уровне 60-90 мВ. Весь процесс деполяризации и реполяризации длится 1 мс, и около 30% этого времени занимает деполяризация. Фаза реполяризации протекает медленнее (70% периода потенциала действия).

Течение указанных электрофизиологических процессов зависит от следующих факторов:

1)соотношение концентрации электролитов в цитоплазме нервной клетки и в экстрацеллюлярной жидкости;

2)проницаемость клеточной мембраны для различных ионов, особенно ионов натрия и калия.