Anticholinergic

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An anticholinergic ( plural : anticholinergics , synonym: Parasympath (ic) olytikum or parasympatholytic , muscarinic receptor antagonist , Antiparasympathomimetikum , Vagolytikum or antimuscarinic ) is an active ingredient of the effect of acetylcholine suppressed (ACh) in the parasympathetic nervous system by the muscarinic Competitively inhibits acetylcholine receptor (muscarinic receptor for short). This blocks the nerve stimuli that lead to a contraction of the smooth muscles and an increase in the secretion of the glands.

effect

The parasympathetic and sympathetic nervous systems act as opposites to each other. Therefore the effect of the anticholinergics is similar to that of the sympathomimetics . The exception to this is the effect on sweat glands, which are regulated by the sympathetic nervous system via ACh. In detail, anticholinergics have the following (vagolytic) effects:

  • Decrease in the tone of the smooth muscles of the gastrointestinal tract, the urinary tract and the bronchial muscles,
  • Increase in heart rate,
  • Increase in peripheral vascular resistance,
  • Suppression of saliva, gastric juice, bronchial and sweat secretions,
  • in the eye the dilatation of the pupil and
  • Accommodation of the eye at a distance.

In general, substances with an atropine-like effect are referred to as anticholinergics or parasympatholytics.

Active ingredients and use

Anticholinergics are most commonly used in the treatment of chronic obstructive pulmonary disease (COPD) and as standard therapy for overactive bladder (OAB) and are used to treat urinary incontinence because of their relaxing effect on the smooth muscles (M3 cholino receptor) and urge incontinence as well as an increased frequency of urination. In the guidelines of national and international specialist societies, all substances are assessed as effective and tolerable. A reduction in the contractility of the bladder muscle (lat. Detrusor) leads to an improvement in the symptoms, which consist of frequent urination during the day and at night ( pollakiuria and nocturia ), agonizing urination and urine loss with urination. Another field of application is the adjuvant treatment of Parkinson's disease . The anticholinergics are divided into two groups based on their effects, the neurotrophic and those that have both neurotropic and musculotropic effects. The only neurotropically acting anticholinergics can be further subdivided from a chemical point of view into belladonna alkaloids and relatives and others that are not related.

Anticholinergics were popular drugs in psychiatry until the beginning of the 20th century.

Belladonna Alkaloids and Relatives

The best-known anticholinergic of this group is atropine , an alkaloid found in deadly nightshade (Atropa belladonna). It is used in ophthalmology as a mydriatic and for colic of the biliary and urinary tract and in gastroenterology for gastrointestinal cramps. In the meantime, butylscopolamine has largely replaced atropine in this field of application. Ipratropium bromide and tiotropium bromide are used in medicine as bronchodilator agents in chronic obstructive pulmonary diseases ( COPD ). Trospium chloride is used for overactive bladder. Since it is hardly broken down, but is excreted largely unchanged in the urine, this means that the target organ is not only accessed via the bloodstream, but also directly via the bladder mucosa, which contains acetylcholine receptors in the tissue. Scopolamine is used in the form of patches (TTS) that are tied behind the ear to prevent nausea.

Other anticholinergics

Tolterodin , darifenacin and solifenacin are among the anticholinergics that are used to treat urinary incontinence , urge incontinence and increased micturition frequency because of their relaxing effect on the smooth muscles . The last two active ingredients, which only recently came on the market, are said to have a particularly high selectivity for the M3-choline receptors, which, however, did not result in improved tolerability. Glycopyrronium bromide is used to induce anesthesia to reduce the flow of saliva and the secretion of the bronchial system and to block bradycardia . The tropicamide has largely replaced atropine as a mydrate in ophthalmology, as it has a shorter duration of action. Biperiden , Metixen and Trihexyphenidyl are used in Parkinson's disease . Prifinium bromide is used in veterinary medicine. Aclidinium bromide is used as a bronchodilator agent in chronic obstructive pulmonary diseases ( COPD ).

Neurotropic-musculotropic anticholinergics

These anticholinergics have both an anticholinergic and a papaverine-like direct spasmolytic effect on the smooth muscles. These include oxybutynin and propiverine , which are approved for the treatment of overactive bladder or urinary urgency incontinence . Denaverine is used for spasms of the gastrointestinal and urogenital tracts and mebeverine for irritable colon. Pipenzolate is also used for spasms in the gastrointestinal tract, and orphenadrine for skeletal muscle spasms .

unwanted effects

The most common side effect of all substances is dry mouth, the frequency of which has reached 30% in studies. All substances belong either to the group of so-called tertiary amines or to the quaternary ammonium compounds . Quaternary ammonium ions have a positive charge and, in contrast to the tertiary amines, which can be described as lipophilic , are hydrophilic . Since lipophilic substances can pass through the blood-brain barrier into the liquor space , central nervous side effects such as sleep disorders, memory disorders, hallucinations or states of confusion are possible. Quaternary ammonium compounds as hydrophilic substances with a positive charge cannot cross the blood-brain barrier to any significant extent; Their absorption from the gastrointestinal tract is also significantly lower than that of the tertiary amines.

The liver enzymes (cytochromes) responsible for breaking down the active ingredients can be accelerated or inhibited in their activity by a large number of substances. When taken at the same time in combination with other drugs, an increase in effectiveness or a loss of effectiveness is possible.

In a long-term study of 3434 participants in an American study, a highly significant association (<0.001) between anticholinergics and Alzheimer's disease and dementia could be demonstrated. A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer's disease (trend test, P <0.001).

See also

literature

  • Anne Paschen: Heart. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 185–283, here: pp. 270 f. ( Vagolytics ), and Jörg Braun: Lunge. ibid pp. 285-310, here: p. 310 ( Parasympatholytics ).

Web links

Individual evidence

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  2. ^ Bangen, Hans: History of the drug therapy of schizophrenia. Pages 13–21 Pharmacotherapy at the dawn of modern psychiatry. Berlin 1992, ISBN 3-927408-82-4
  3. KJ Mansfield, K. Vaux, RJ Millard, E. Burcher: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. ICS, Montreal 2005.
  4. ME Valsecia, LA Malgor, JH Espindola, DH Carauni: New adverse effect of oxybutynin "night terror". In: Ann Pharmacother . 32, 1998, p. 506.
  5. ^ KB Womack, KM Heilman: Tolterodine and memory: dry but forgetful. In: Arch Neurol . 60; (203): 771-773
  6. ^ JW Tsao, KM Heilman: Transient memory impairment and hallucinations associated with tolterodine use. In: N Engl J Med . 349, 2003, pp. 2274-2275.
  7. Mutschler: drug effects. 9th edition. Scientific publishing company, Stuttgart 2008.
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  9. N. Brynne, C. Forslund, B. Hallen, LL Gustafsson, L. Bertilsson: Ketocanazole inhibits the metabolism of tolterodine in subjects sith deficient CYP2D6 activity. In: J Clin Pharmacol. , 48, 1999, pp. 564-572.
  10. VJ Colucci, MP Rivey: Tolterodine-warfarin drug interaction. In: Ann Pharmacoth. 33, 1999, pp. 1173-1176.
  11. Shelly L. Gray, Melissa L. Anderson, Sascha Dublin et al .: Cumulative Use of Strong Anticholinergics and Incident Dementia - A Prospective Cohort Study . In: JAMA Intern Med. Band 175 (3) , 2015, pp. 401-407 .