Opium tincture

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Opii tinctura normata according to Ph. Eur. On a watch glass dish

Opium tincture (Latin tinctura opii ) is an alcoholic solution of opium . It was often prescribed until the early 20th century, but only rarely today. Until the 19th century it was also known as laudanum , poppy seed juice (Laudanum liquidum) or meconium .

It is used as the starting material for a drug ( magistral recipe ) manufactured in the pharmacy . Opium tincture is also available as a finished drug. Opium tincture is subject to the provisions of the Narcotics Act ( BtMG ). It can be prescribed as a second-line therapy to immobilize the bowel in severe diarrhea .

Extraction

Opium tincture is obtained from the dried milk juice of the unripe seed pods of the opium poppy ( Papaver somniferum ), after which the active ingredient content in the tincture is standardized. The active ingredients are in the tincture as well as in the milky sap of the plant. a. bound to meconic acid .

Composition and preparation

safety instructions
Surname

Tinctura Opii normata Ph.Eur.

CAS number

none, as a mixture

GHS labeling of hazardous substances
07 - Warning 02 - Highly / extremely flammable

Caution

H and P phrases H: 226-302
P: 102-211-233

The composition of the opium tincture has remained unchanged for over 100 years and is standardized in the European Pharmacopoeia (Ph. Eur 9.0). The opium is dissolved in a mixture of alcohol (31–34 vol%) and water, which contains all the alkaloids of the opium poppy. The content of the active ingredients contained, such as morphine (1%), codeine , thebaine , noscapine (= narcotine), papaverine , narceine and the like. a., is standardized in the tincture .

Since August 2018 opium tincture under the trade name Dropizol ( ATC Code A07DA02, Antimotility group) as a finished product (1 x 10 ml, 4 x 10 ml, 10 x 10 mL) in three package sizes available in Germany. It is approved for the treatment of severe diarrhea in adults (e.g. diarrhea caused by cytostatics, radiation or neuroendocrine tumors) if the use of other antidiarrheal drugs does not have an adequate effect (specialist information August 2019).

In Germany: According to § 2 of the Narcotics Prescription Ordinance (BtMVV ), the doctor may prescribe a maximum of 40,000 mg of opium tincture (40 g, corresponds to approx. 40 ml) for a patient within 30 days. Accordingly, according to the package size ordinance, the maximum amount that can be dispensed for opium tincture is also 40 ml (N3). If no finished medicinal product is used, the required amount is transferred from the delivered tincture (raw material) in the pharmacy under protective precautions after an incoming inspection from the shipping container into a suitable container with a child-resistant closure, labeled and given to the patient.

According to the German Medicines Codex - New Formulation Form (DAC / NRF), the use-by period after opening is four weeks after first use by the patient.

history

Laudanum, medicine bottle 100 ml (19th century, replica)

An opium tincture under the name "Laudanum" has been described in various compositions by, among others, the doctor, alchemist and naturalist Paracelsus . He believed that he had invented a panacea with laudanum , which is why he called his tincture the stone of immortality . Its main ingredients were around 90 percent wine and about 10 percent opium , but the composition is controversial. Further additives are henbane , the common mandrake and belladonna called.

The origin of the word is not clearly clarified. Many sources refer to the Latin ladanum - the name for the resin of the rock rose . Latin laudare means “to praise”. It is possible that these two meanings were merged into one term when the name was given.

Since its invention in the 16th century, the laudanum has been widely used in Europe. Over the next several centuries, it enjoyed great popularity as a universal tonic and wonder drug. Its outstanding property, however, was not a life-prolonging, but rather its pain-relieving and calming effect. The diluted tincture was even given to children to restrain them without hesitation.

Laudanum was freely available for sale and cheap, so it was very popular in all walks of life in Europe . Its distribution in the 18th and 19th centuries can roughly be compared with that of ASS today. For a while the term was also used as a synonym for painkillers in general.

Opium tincture bottle with a capacity of 5 liters

In writers' circles, the laudanum came into fashion partly to stimulate creative abilities; however, the constant use of the tincture seemed to wipe out one's own creativity . Among the best-known avowed laudanum consumers are u. a. English lyric poet Samuel Taylor Coleridge and writer Thomas de Quincey; and Welsh writer Edward Williams (known as Iolo Morganwg). All three appear to have been heavily dependent for a long time in their lives . The English author Wilkie Collins processed his own experiences with opium in his novel The Moonstone .

The French poet Charles Baudelaire (1821–1867) mentions his “old, terrible mistress”, the laudanum bottle in the prose poem The double room , one of the prose poems in Le Spleen de Paris (1857–1866).

In fact, it was not until the 19th century that European society began to seriously grapple with the addictive and harmful nature of long-term opium consumption and thus also of laudanum. Towards the end of the 19th century, medicine increasingly had new means available that could replace the questionable opiates . In 1920 England finally banned the free sale of opiates by law. In 1929 the so-called Opium Act came into force in Germany .

Use and Risks

Tincture of opium found widespread use in medicine as a pain reliever and sedative drug until the early 19th century. It was also widely used for depression . There were clinics that treated depression with opium until the 1970s. Opium tincture is dangerous if overdosed or accidentally swallowed by children: the symptoms of poisoning are very similar to those of poisoning with morphine and are also easily accessible to the measures and antidotes used there , such as the active ingredient naloxone , a so-called opiate antagonist .

There are older case reports and case series on the therapeutic attempt with highly diluted opium tincture for the treatment of neonatal abstinence syndrome (NAS; opiate withdrawal syndrome in newborns), although this procedure is now considered obsolete. The reason is that opium tincture contains a mixture of alkaloids and therefore more adverse effects must be expected than when using the pure substance morphine. The tincture also contains around 33% (V / V) ethanol, which is generally considered to be problematic in the treatment of newborns.

The doctor's prescription of an opium tint cure for severe diarrhea , e.g. B. in diarrhea caused by cytostatics, radiation or neuroendocrine tumors, if the use of other antidiarrheal drugs has not achieved sufficient effect. In the gastrointestinal tract , opium tincture primarily attacks μ- opioid receptors , reduces intestinal motility, reduces secretion, slows down intestinal peristalsis , and increases the tone of the anal sphincter. Studies of the human intestine indicate that-opioid and ?-opinoid receptors have a smaller, but potentially clinically meaningful, contribution to opioid-induced inhibition of muscle activity in the gastrointestinal tract. The antidiarrheal effect of Optium tincture in the large intestine is not subject to any development of tolerance (in contrast to the pain- relieving effect and the effect on motility in the upper gastro- intestinal tract). This is due to differences in signal transmission and the regulation of the u-opioid receptor.

Severe diarrhea, potentially treatable with tincture of opium, occurs in 50–80% of patients treated with chemotherapy, especially those treated with fluoropyrimidines and irinotecan for colorectal cancer and gastrointestinal malignancies . 20–70% of patients who have to undergo radiation therapy of the abdomen or pelvis are temporarily affected by severe diarrhea. In the current guidelines of the German Society for Hematology and Medical Oncology e. V. (DGHO) the recommendation is made: "In the case of loperamide -refractory diarrhea, opium drops, codeine, morphine or atropine can be used."

Patients with short bowel syndrome (after illness such as ulcerative colitis , Crohn's disease , trauma, or vascular events) often suffer from severe diarrhea. People with an ileostomy often have very thin excretions, which are thickened by tincture of opium if other measures do not work.

The doses of opiates (especially morphine ) in the so-called opium tincture are much lower in the treatment of diarrhea than in pain therapy (on average 5–15 mg / d versus 36 mg / d in adults).

The central effects are significantly less and less frequent after oral administration than after parenteral (sc or im) administration. Side effects are above all the unwanted effects that occur with morphine, such as constipation, effects on the psyche (mostly drowsiness, euphoria , occasionally also dysphoria ), tiredness, changed taste sensations, dizziness, physical and psychological dependence.

Legal situation

In Germany, opium tincture is classified as a narcotic due to its addictive effect and may only be prescribed on special narcotic prescriptions in accordance with the Narcotics Prescription Ordinance , whereby the maximum quantities mentioned above are set.

Trade names

  • Dropizol (D, A)

Others

In the Franco-Belgian comic series Asterix , one of the Roman camps bears the name Laudanum .

Web links

Wiktionary: Laudanum  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b Datasheet Tinctura Opii normata Ph.Eur. ( Memento of September 23, 2018 in the Internet Archive ) at Maros, accessed on September 23, 2018.
  2. ↑ Deutscher Apotheker Verlag (Ed.): European Pharmacopoeia 9th Edition, Basic Work 2017: Official German Edition (Ph. Eur. 9.0) . 2017, ISBN 3-7692-6641-2 .
  3. ↑ a b c Dropizol specialist information as of August 2019. Specialist information service, accessed on January 22, 2020 .
  4. ↑ a b Ordinance on prescribing, dispensing and providing evidence of the whereabouts of narcotics (Narcotics Prescription Ordinance - BtMVV). Federal Office of Justice, accessed on January 22, 2020 .
  5. ↑ Federal Office of Justice: Ordinance on the determination and labeling of pack sizes for pharmaceuticals in statutory health care (Packungs Sizverordnung - PackungsV). June 22, 2004, accessed January 27, 2020 .
  6. ↑ German Institute for Medical Documentation and Information: Change file for: Dosage forms that are not divided up for oral use. (PDF; 25.59 kB) January 2019, accessed on January 27, 2020 .
  7. ↑ DAC / NRF recipe information on opium (as of July 10, 2019). In: Recipe information database. ABDA - Federal Association of German Pharmacists' Associations e. V., Berlin, July 10, 2019, accessed on January 22, 2020 .
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  9. ↑ Guido Gallacchi: Pain Compendium: Understanding and Treating Pain. Georg Thieme Verlag, 2005, ISBN 978-3-13-128372-6 , p. 16.
  10. ^ Kathleen McCormack, Intoxication and the Victorian Novel. In: William Baker, Kenneth Womack (Eds.): A Companion to the Victorian Novel. Greenwood Press, Westport 2002, ISBN 0-313-31407-1 , p. 137 (English).
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  12. ^ Charles Baudelaire: Le Spleen de Paris. Poems in prose. In: ders .: Complete works / letters. In eight volumes. Edited by Friedhelm Kemp and Claude Pichois in collaboration with Wolfgang Drost. Volume 8. Munich: Hanser 1985, pp. 127-131.
  13. ↑ Detlev Ganten, Klaus Ruckpaul: diseases of the central nervous system. Springer Verlag, Berlin / Heidelberg / New York 1999, ISBN 3-540-64552-7 , p. 273 ( limited preview in the Google book search).
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  19. ↑ Al B. Benson, Jaffer A. Ajani, Robert B. Catalano, Constance Engelking, Steven M. Kornblau: Recommended guidelines for the treatment of cancer treatment-induced diarrhea . In: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology . tape 22 , no. 14 , July 15, 2004, p. 2918-2926 , doi : 10.1200 / JCO.2004.04.132 , PMID 15254061 .
  20. ^ Rachel J. Gibson, Dorothy MK Keefe: Cancer chemotherapy-induced diarrhea and constipation: mechanisms of damage and prevention strategies . In: Supportive Care in Cancer . tape 14 , no. 9 , April 8, 2006, p. 890-900 , doi : 10.1007 / s00520-006-0040-y ( springer.com [accessed September 10, 2018]).
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  23. ↑ Jervoise Andreyev: Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients . In: Lancet Oncology . tape 8 , no. November 11 , 2007, pp. 1007-1017 , doi : 10.1016 / S1470-2045 (07) 70341-8 , PMID 17976611 .
  24. ↑ Maria Vehreschild, Jörg Vehreschild J, Kai Hübel et al. for the Working Group on Infections (AGIHO) of the DGHO: Diarrhea and other gastrointestinal complications in patients with haematological and oncological diseases (as of August 2014). Internet: www.onkopedia.de.
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