Doxylamine
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-Doxylamine_Enantiomers_Structural_Formulae.png)
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| Non-proprietary name | Doxylamine | ||||||||||||
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| Molecular formula | C 17 H 22 N 2 O | ||||||||||||
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| Molar mass | 270.37 g · mol -1 | ||||||||||||
| Melting point |
<25 ° C (doxylamine) |
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| boiling point |
137–141 ° C (65 Pa ) (doxylamine) |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||
Doxylamine is a strongly sedating antihistamine from the group of ethanolamines . It is used as a sleep aid for short-term therapy and for nighttime relief from cold and allergy symptoms. In combination with pyridoxine (vitamin B 6 ) it is used against pregnancy sickness.
Clinical information
Application areas (indications)
Medicines containing doxylamine are approved for calming nervous patients, for the treatment of restlessness and agitation in children and for the medication required to treat problems falling asleep and staying asleep. It is also approved as an antiallergic agent for the treatment of allergic reactions of the upper and lower respiratory tract, including hay fever and allergic bronchial cramps, as well as allergic skin diseases and itching. Other areas of application in combination with vitamin B6 are the treatment of nausea and vomiting (no approval in Germany) and in combination with paracetamol , dextromethorphan and optionally ephedrine, the symptomatic treatment of colds.
Contraindications (contraindications)
Doxylamine must not be used in the case of known hypersensitivity to the active substance or in patients with an acute asthma attack, narrow-angle glaucoma , pheochromocytoma , prostatic hyperplasia with residual urine formation and epilepsy . In particular, doxylamine must not be used after acute poisoning with alcohol, sleeping pills, painkillers or psychotropic drugs. Simultaneous therapy with MAO inhibitors is contraindicated.
pregnancy and breast feeding period
For drugs containing doxylamine, no evidence of a teratogenic effect could be shown in epidemiological studies. No teratogenic or foetotoxic effects were observed in animal studies . After administration of high doses of doxylamine to rats, their offspring showed only a slightly reduced birth weight. Nevertheless, a risk-benefit assessment is recommended during pregnancy. Doxylamine-containing drugs are approved for the treatment of vomiting in the United States and Canada.
Doxylamine is excreted in breast milk. Therefore, breastfeeding should not be performed while using doxylamine.
Side effects
Depending on the dose, fatigue, drowsiness, drowsiness, dizziness, concentration disorders, headache, depression, muscle weakness and tinnitus can occur in particular. The responsiveness is reduced. These symptoms may persist the following day.
Paradoxical symptoms such as restlessness, excitement, tension, insomnia, confusion, hallucinations, tremors and, in rare cases, cerebral seizures are possible. These can also be observed after prolonged use of doxylamine has ended. Nausea, vomiting, diarrhea , loss of or increased appetite, and epigastric pain may occur during therapy . Very rarely, life-threatening paralytic ileus can occur.
Doxylamine has a pronounced anticholinergic active component. Anticholinergic side effects with doxylamine include accommodation disorders , dry mouth, nasal congestion, increased intraocular pressure, constipation, and urination disorders . Also tachycardic cardiac arrhythmias and changes in blood pressure can be attributed to it.
With doxylamine, respiratory function can be impaired by secretion thickening, bronchial obstruction and bronchospasm can occur.
Catecholamine release may occur in patients with pheochromocytoma after administration of doxylamine .
Interactions
Central depressant drugs, in particular other hypnotics , tranquilizers , antidepressants , neuroleptics , antiepileptics , anesthetics and analgesics of the opioid type lead with doxylamine to a mutual amplification of the effects and side effects. This also applies to the joint consumption of alcohol with doxylamine. Α 2 - sympathomimetics and other centrally acting antisympathotonics , such as clonidine , brimonidine , guanabenz and methyldopa , can also increase the sedative effects of doxylamine.
Anticholinergics such as atropine , butylscopolamine and biperiden , and other drugs with an anticholinergic active component, such as tricyclic antidepressants , can increase the side effects of doxylamine. MAOIs can increase the effects and side effects of the drug by slowing the breakdown of doxylamine.
In patients on doxylamine therapy, adrenaline must not be used to treat hypotension , as there is a risk of adrenaline reversal and thus an increase in hypotension.
pharmacology
Doxylamine is an H 1 antihistamine , i.e. an inhibitor of the action of histamine on the histamine H 1 receptor . By inhibiting the inflammatory mediator function of histamine, doxylamine acts as an antiallergic. In the central nervous system , doxylamine also inhibits some neurotransmitter functions of histamine and thus has a sedative and nausea- inhibiting effect . Doxylamine is also an anticholinergic at the M 1 receptor and has its usual side effects. The half-life in plasma is 10 hours.
Stereochemistry
Doxylamine has a stereogenic center and is therefore chiral . It is used as a racemate [1: 1 mixture of ( R ) -doxylamine and ( S ) -doxylamine], although the different physiological effects of enantiomers are known.
Trade names
Gittalun (D), Hoggar night (D), Schlafsterne (D), SchlafTabs (D), Sedaplus (D), Sanalepsi (CH), Valocordin-Doxylamine (D)
Vicks MediNait (CH), Wick cold syrup (A), Wick MediNait (D)
Individual evidence
- ↑ a b c Entry on doxylamine. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.
- ↑ a b Entry on doxylamine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
- ↑ a b Doxylamine succinate salt data sheet from Sigma-Aldrich , accessed on March 28, 2011 ( PDF ).
- ↑ a b c d e Specialist information Mereprine syrup. Casselia med. As of May 2001.
- ↑ Product information SchlafTabs-ratiopharm 25 mg tablets. Ratiopharm GmbH. Status: February 2008.
- ↑ P. Imming, C. Sinning, A. Meyer: Drugs, their targets and the nature and number of drug targets. In: Nature reviews. Drug discovery. Volume 5, Number 10, October 2006, pp. 821-834, doi : 10.1038 / nrd2132 , PMID 17016423 (review).
- ↑ Entry on Doxylamine in the DrugBank of the University of Alberta , accessed March 3, 2016.
- ^ Axel Kleemann, Jürgen Engel: Active pharmaceutical ingredients . 2nd Edition. Thieme-Verlag, Stuttgart 1982, ISBN 3-13-558402-X .
- ↑ EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology , European Journal of Clinical Pharmacology 26 (1984) 663-668, doi: 10.1007 / BF00541922 .
- ↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) , Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10 -9 , p. 738.
