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антихолинергический

Антихолинергические средства ( антихолинергические средства ) — вещества, блокирующие действие нейротрансмиттера ацетилхолина (АХ) в синапсах центральной и периферической нервной системы . [1] [2]

Эти агенты ингибируют парасимпатическую нервную систему , избирательно блокируя связывание АХ с его рецептором в нервных клетках . Нервные волокна парасимпатической системы отвечают за непроизвольные движения гладких мышц , присутствующих в желудочно-кишечном тракте , мочевыводящих путях , легких , потовых железах и многих других частях тела. [3]

В широком смысле антихолинергические средства делятся на две категории в соответствии с их конкретными целями в центральной и периферической нервной системе и нервно-мышечных соединениях: [3] антимускариновые средства и антиникотиновые средства ( ганглиоблокаторы , нервно-мышечные блокаторы ). [4]

Термин «антихолинергический» обычно используется для обозначения антимускариновых средств, которые конкурентно ингибируют связывание АХ с мускариновыми рецепторами ацетилхолина ; такие агенты не противодействуют связыванию никотиновых рецепторов ацетилхолина в нервно-мышечных соединениях , хотя этот термин иногда используется для обозначения агентов, которые действуют так. [3] [5]

Медицинское использование

Антихолинергические препараты используются для лечения различных состояний:

Антихолинергические средства обычно обладают антисиалагогическим эффектом (снижают выработку слюны), и большинство из них вызывают некоторый уровень седативного эффекта, что является преимуществом при хирургических процедурах. [8] [9]

До начала 20 века антихолинергические препараты широко использовались для лечения психических расстройств. [10]

Физиологические эффекты

Эффекты антихолинергических препаратов включают:

Клинически наиболее значимым признаком является делирий , особенно у пожилых людей, которые чаще всего страдают от токсидрома . [3]

Побочные эффекты

Длительное употребление может увеличить риск как когнитивного, так и физического ухудшения. [14] [15] Неясно, влияют ли они на риск смерти в целом. [14] Однако у пожилых людей они, по-видимому, увеличивают риск смерти. [16]

Возможные эффекты антихолинергических средств включают:

Possible effects in the central nervous system resemble those associated with delirium, and may include:

Older patients are at a higher risk of experiencing CNS side effects.[citation needed] The link possible between anticholinergic medication use and cognitive decline/dementia has been noted in weaker observational studies.[21] Although there is no strong evidence from randomized controlled trials to suggest that these medications should be avoided, clinical guidelines suggest that a consideration be made to decrease the use of these medications if safe to do so and the use of these medications be carefully considered to reduce any possible adverse effects including cognitive decline.[21]

Toxicity

An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine. Asystole has occurred after physostigmine administration for tricyclic antidepressant overdose, so a conduction delay (QRS > 0.10 second) or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.[22]

Pharmacology

Anticholinergics are classified according to the receptors that are affected:

Examples

Examples of common anticholinergics:

Antidotes

Physostigmine is one of only a few drugs that can be used as an antidote for anticholinergic poisoning. Nicotine also counteracts anticholinergics by activating nicotinic acetylcholine receptors. Caffeine (although an adenosine receptor antagonist) can counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.

Psychoactive uses

When a significant amount of an anticholinergic is taken into the body, a toxic reaction known as acute anticholinergic syndrome may result. This may happen accidentally or intentionally as a consequence of either recreational or entheogenic drug use, though many users find the side effects to be exceedingly unpleasant and not worth the recreational effects they experience. In the context of recreational use, anticholinergics are often called deliriants.[24]

Plant sources

The most common plants containing anticholinergic alkaloids (including atropine, scopolamine, and hyoscyamine among others) are:

Use as a deterrent

Several narcotic and opiate-containing drug preparations, such as those containing hydrocodone and codeine are combined with an anticholinergic agent to deter intentional misuse.[32] Examples include hydrocodone/homatropine (Tussigon, Hydromet, Hycodan), diphenoxylate/atropine (Lomotil), and hydrocodone polistirex/chlorpheniramine polistirex (Tussionex Pennkinetic, TussiCaps). However, it is noted that opioid/antihistamine combinations are used clinically for their synergistic effect in the management of pain and maintenance of dissociative anesthesia (sedation) in such preparations as meperidine/promethazine (Mepergan) and dipipanone/cyclizine (Diconal), which act as strong anticholinergic agents.[33]

References

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