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Wikipedia

Laudanum

Laudanum is a tincture of opium containing approximately 10% powdered opium by weight (the equivalent of 1% morphine).[1] Laudanum is prepared by dissolving extracts from the opium poppy (Papaver somniferum) in alcohol (ethanol).

Laudanum
Combination of
OpiumAnalgesic
EthanolTincture
Clinical data
Pronunciation/ˈlɔːdənəm/ LAW-dən-əm
Trade namesDropizol
Routes of
administration
Oral, buccal, sublingual
ATC code
Legal status
Legal status
  (verify)

Reddish-brown in color and extremely bitter, laudanum contains several opium alkaloids, including morphine and codeine. Laudanum was historically used to treat a variety of conditions, but its principal use was as a pain medication and cough suppressant. Until the early 20th century, laudanum was sold without a prescription and was a constituent of many patent medicines. Laudanum has since been recognized as addictive and is strictly regulated and controlled as such throughout most of the world. The United States Controlled Substances Act, for example, lists it on Schedule II, the second strictest category.

Laudanum is known as a "whole opium" preparation since it historically contained all the alkaloids found in the opium poppy, which are extracted from the dried latex of ripe seed pods (Papaver somniferum L., succus siccus). However, the modern drug is often processed to remove all or most of the noscapine (also called narcotine) present as this is a strong emetic and does not add appreciably to the analgesic or antipropulsive properties of opium; the resulting solution is called Denarcotized Tincture of Opium or Deodorized Tincture of Opium (DTO).

Laudanum remains available by prescription in the United States (under the generic name "opium tincture") and in the European Union and United Kingdom (under the trade name Dropizol), although the drug's therapeutic indication is generally limited to controlling diarrhea when other medications have failed.

The terms laudanum and tincture of opium are generally interchangeable, but in contemporary medical practice, the latter is used almost exclusively.

History edit

Paracelsus's laudanum edit

Paracelsus, a 16th-century Swiss alchemist, experimented with various opium concoctions, and recommended opium for reducing pain. One of his preparations, a pill which he extolled as his "archanum" or "laudanum", may have contained opium.[2] Paracelsus' laudanum was strikingly different from the standard laudanum of the 17th century and beyond, containing crushed pearls, musk, amber, and other substances.[3]

British laudanum edit

One researcher has documented that "Laudanum, as listed in the London Pharmacopoeia (1618), was a pill made from opium, saffron, castor, ambergris, musk and nutmeg".[4]: 45 

Sydenham's laudanum edit

In the 1660s English physician Thomas Sydenham (1624–1689) popularized a proprietary opium tincture that he also named laudanum, although it differed substantially from the laudanum of Paracelsus. In 1676 Sydenham published a seminal work, Medical Observations Concerning the History and Cure of Acute Diseases, in which he promoted his brand of opium tincture, and advocated its use for a range of medical conditions.[3]

18th-century edit

By the 18th century, the medicinal properties of opium and laudanum were well known, and the term "laudanum" came to refer to any combination of opium and alcohol.

In the 18th century several physicians published work about it, including John Jones, who wrote The Mysteries of Opium Revealed (1700), which was described by one commentator as "extraordinary and perfectly unintelligible."[5][6] The Scottish physician John Brown, creator of the Brunonian system of medicine, recommended opium for what he termed asthenic conditions, but his system was discredited by the time of his death.[7][8] The most influential work was by George Young, who published a comprehensive medical text entitled Treatise on Opium (1753).[9] Young, an Edinburgh surgeon and physician, wrote this to counter an essay on opium by his contemporary Charles Alston, professor of botany and materia medica at Edinburgh who had recommended the use of opium for a wide variety of conditions. Young countered this by emphasising the risks '...that I may prevent such mischief as I can, I here give it as my sincere opinion... that opium is a poison by which great numbers are daily destroyed.' Young gives a comprehensive account of the indications for the drug including its complications. He is critical about writers whose knowledge of the drug is based on chemical or animal experiments rather than clinical practice. The treatise is a detailed, balanced and valuable guide to prevailing knowledge and practice.[3][10] As it gained popularity, opium, and after 1820, morphine, was mixed with a wide variety of agents, drugs and chemicals including mercury, hashish, cayenne pepper, ether, chloroform, belladonna, whiskey, wine and brandy."[4]: 104 

 
Confessions of a laudanum drinker, The Lancet, 1866

During the late 18th and early 19th centuries, patients undergoing surgery were often administered laudanum and alcohol, and had their hands restrained and bodies held down while the operation was performed.[11]

19th-century edit

By the 19th century, laudanum was used in many patent medicines to "relieve pain ... to produce sleep ... to allay irritation ... to check excessive secretions ... to support the system ... [and] as a soporific".[12][13] The limited pharmacopoeia of the day meant that opium derivatives were among the most effective of available treatments, so laudanum was widely prescribed for ailments from colds to meningitis to cardiac diseases, in both adults and children. Laudanum was used during the yellow fever epidemic.

Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches. Nurses also spoon-fed laudanum to infants. The Romantic and Victorian eras were marked by the widespread use of laudanum in Europe and the United States. Mary Todd Lincoln, for example, the wife of the US president Abraham Lincoln, was a laudanum addict, as was the English poet Samuel Taylor Coleridge, who was famously interrupted in the middle of an opium-induced writing session of Kubla Khan by "a person on business from Porlock".[14] Initially a working class drug, laudanum was cheaper than a bottle of gin or wine, because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage.

As one researcher has noted: "To understand the popularity of a medicine that eased—even if only temporarily—coughing, diarrhoea and pain, one only has to consider the living conditions at the time". In the 1850s, "cholera and dysentery regularly ripped through communities, its victims often dying from debilitating diarrhoea", and dropsy, consumption, ague and rheumatism were all too common.[4]: 44–49 

An 1869 article in Scientific American describes a farmer growing and harvesting poppy in Indian Springs, Georgia, and subsequently selling the raw material to a local pharmacist who prepared laudanum.[15]

20th-century edit

Laudanum was used in home remedies and prescriptions, as well as a single medication. For example, a 1901 medical book published for home health use gave the following two "Simple Remedy Formulas" for "dysenterry" [sic]: (1) Thin boiled starch, 2 ounces; Laudanum, 20 drops; "Use as an injection [meaning as an enema] every six to twelve hours"; (2) Tincture rhubarb, 1 ounce; Laudanum 4 drachms; "Dose: One teaspoonful every three hours." In a section entitled "Professional Prescriptions" is a formula for "diarrhoea (acute)": Tincture opium, deodorized, 15 drops; Subnitrate of bismuth, 2 drachms; Simple syrup, 12 ounce; Chalk mixture, 112 ounces, "A teaspoonful every two or three hours to a child one year old." "Diarrhoea (chronic)": Aqueous extract of ergot, 20 grains; Extract of nux vomica, 5 grains; Extract of Opium, 10 grains, "Make 20 pills. Take one pill every three or four hours."[16]

The early 20th century brought increased regulation of all manner of narcotics, including laudanum, as the addictive properties of opium became more widely understood, and "patent medicines came under fire, largely because of their mysterious compositions".[4]: 126  In the US, the Food and Drug Act of 1906 required that certain specified drugs, including alcohol, cocaine, heroin, morphine, and cannabis, be accurately labeled with contents and dosage. Previously many drugs had been sold as patent medicines with secret ingredients or misleading labels. Cocaine, heroin, cannabis, and other such drugs continued to be legally available without prescription as long as they were labeled. It is estimated that sale of patent medicines containing opiates decreased by 33% after labeling was mandated.[17] In 1906 in Britain and in 1908 in Canada "laws requiring disclosure of ingredients and limitation of narcotic content were instituted".[4]: 126 

The Harrison Narcotics Tax Act of 1914 restricted the manufacture and distribution of opiates, including laudanum, and coca derivatives in the US. This was followed by France's Loi des stupéfiants in 1916, and Britain's Dangerous Drugs Act in 1920.[4]: 126 

Laudanum was supplied to druggists and physicians in regular and concentrated versions. For example, in 1915, Frank S. Betz Co., a medical supply company in Hammond, Indiana, advertised Tincture of Opium, U.S.P., for $2.90 per lb., Tincture of Opium Camphorated, U.S.P, for 85 cents per lb., and Tincture of Opium Deodorized, for $2.85 per lb.[18] Four versions of opium as a fluid extract were also offered: (1) Opium, Concentrated (assayed) "For making Tincture Opii (Laudanum) U.S.P. Four times the strength of the regular U.S.P." tincture, for $9.35 per pint; (2) Opium, Camphorated Conc. "1 oz. making 8 ozs. Tr. Opii Camphorated U.S.P (Paregoric)" for $2.00 per pint; (3) Opium, Concentrated (Deodorized and Denarcotized) "Four times the strength of tincture, Used when Tinct. Opii U.S.P. is contraindicated" for $9.50 per pint, and (4) Opium (Aqueous), U.S.P., 1890, "Tr. (assayed) Papaver Somniferum" for $2.25 per pint.[19]

In 1929–30, Parke, Davis & Co., a major US drug manufacturer based in Detroit, Michigan, sold "Opium, U.S.P. (Laudanum)", as Tincture No. 23, for $10.80 per pint (16 fluid ounces), and "Opium Camphorated, U.S.P. (Paregoric)", as Tincture No. 20, for $2.20 per pint. Concentrated versions were available. "Opium Camphorated, for U.S.P. Tincture: Liquid No. 338" was "exactly 8 times the strength of Tincture Opium Camphorated (Paregoric) [italics in original], U.S.P., "designed for preparing the tincture by direct dilution," and cost $7 per pint. Similarly, at a cost of $36 per pint, "Opium Concentrated, for U.S.P. Tincture: Liquid No. 336", was "four times the strength of the official tincture", and "designed for the extemporaneous preparation of the tincture".[20] The catalog also noted: "For quarter-pint bottles add 80c. per pint to the price given for pints."

Toward the middle 20th century, the use of opiates was generally limited to the treatment of pain, and opium was no longer a medically accepted "cure-all". Further, the pharmaceutical industry began synthesizing various opioids, such as propoxyphene, oxymorphone and oxycodone. These synthetic opioids, along with codeine and morphine were preferable to laudanum since a single opioid could be prescribed for different types of pain rather than the "cocktail" of laudanum, which contains nearly all of the opium alkaloids. Consequently, laudanum became mostly obsolete as an analgesic, since its principal ingredient is morphine, which can be prescribed by itself to treat pain. Until now, there has been no medical consensus on which of the two (laudanum or morphine alone) is the better choice for treating pain.

In 1970, the US adopted the Uniform Controlled Substances Act, which regulated opium tincture (Laudanum) as a Schedule II substance (currently DEA #9630),[21] placing even tighter controls on the drug.

By the late 20th century, laudanum's use was almost exclusively confined to treating severe diarrhea.

21st-century edit

The current prescribing information for laudanum in the US states that opium tincture's sole indication is as an anti-diarrheal, although the drug is occasionally prescribed off-label for treating pain and neonatal withdrawal syndrome.[citation needed]

Historical varieties edit

 
Italian Sydenham laudanum tincture from the 1950s

Several historical varieties of laudanum exist, including Paracelsus' laudanum, Sydenham's Laudanum (also known as tinctura opii crocata), benzoic laudanum (tinctura opii benzoica),[22] and deodorized tincture of opium (the most common contemporary formulation), among others. Depending on the version, additional amounts of the substances and additional active ingredients (e.g. saffron, sugar, eugenol) are added, modifying its effects (e.g., amount of sedation, or antitussive properties).

There is probably no single reference that lists all the pharmaceutical variations of laudanum that were created and used in different countries during centuries since it was initially formulated. The reasons are that in addition to official variations described in pharmacopeias, pharmacists and drug manufacturers were free to alter such formulas. The alcohol content of Laudanum probably varied substantially; on the labels of turn-of-the-century bottles of Laudanum, alcoholic content is stated as 48%. In contrast, the current version of Laudanum contains about 18% alcohol.

The four variations of laudanum listed here were used in the United States during the late 19th century. The first, from an 1870 publication, is "Best Turkey opium 1 oz., slice, and pour upon it boiling water 1 gill, and work it in a bowl or mortar until it is dissolved; then pour it into the bottle, and with alcohol of 70 percent proof 12 pt., rinse the dish, adding the alcohol to the preparation, shaking well, and in 24 hours it will be ready for use. Dose—From 10 to 30 drops for adults, according to the strength of the patient, or severity of the pain. Thirty drops of this laudanum will be equal to one grain of opium. And this is a much better way to prepare it than putting the opium into alcohol, or any other spirits alone, for in that case much of the opium does not dissolve."[23] The remaining three formulas are copied from an 1890 publication of the day:

  1. Sydenham's Laudanum:[24] "According to the Paris Codex this is prepared as follows: opium, 2 ounces; saffron, 1 ounce; bruised cinnamon and bruised cloves, each 1 drachm; sherry wine, 1 pint. Mix and macerate for 15 days and filter. Twenty drops are equal to one grain of opium."
  2. Rousseau's Laudanum: "Dissolve 12 ounces white honey in 3 pounds warm water, and set it aside in a warm place. When fermentation begins add to it a solution of 4 ounces selected opium in 12 ounces water. Let the mixture stand for a month at a temperature of 86° Fahr.; then strain, filter, and evaporate to 10 ounces; finally strain and add 412 ounces proof alcohol. Seven drops of this preparation contain about 1 grain of opium."
  3. Tincture of Opium (Laudanum), U.S.P., attributed to the United States Pharmacoepia of 1863: "Macerate 212 ounces opium, in moderately fine powder in 1 pint water for 3 days, with frequent agitation. Add 1 pint alcohol, and macerate for 3 days longer. Percolate, and displace 2 pints tincture by adding dilute alcohol in the percolator."[25]

Modern status edit

United Kingdom edit

Opium tincture remains in the British Pharmacopoeia, where it is referred to as Tincture of Opium, B.P., Laudanum, Thebaic Tincture or Tinctura Thebaica, and "adjusted to contain 1% w/v of anhydrous morphine."[26] It is a Class A substance under the Misuse of Drugs Act of 1971. At least one manufacturer (Macfarlan Smith) still produces opium tincture in the UK as of 2011.[27] "Gee's Linctus" is also available from most UK pharmacies, especially independent stores. This contains "Opium Tincture", at 0.083 mL, per 5 mL.[citation needed]

United States edit

Tincture of Opium is available by prescription in the United States. It is regulated as a Schedule II drug (No. 9639) under the Controlled Substances Act.

In the United States, opium tincture is marketed and distributed by several pharmaceutical firms, each producing a single formulation of the drug, which is deodorized. Each mL contains 10 mg of anhydrous morphine (the equivalent of 100 mg of powdered opium), other opium alkaloids (except noscapine), and ethanol, 19%. It is available packaged in bottles of four US fluid ounces (118 mL) and 16 US fluid ounces (1 US pt; 473 mL).[citation needed]

Tincture of Opium is known as one of many "unapproved drugs" regulated by the U.S. Food and Drug Administration (FDA); the marketing and distribution of opium tincture prevails only because opium tincture was sold prior to the Federal Food, Drug & Cosmetic Act of 1938.[28] Its "grandfathered" status protects opium tincture from being required to undergo strict FDA drug reviews and subsequent approval processes. However, the FDA closely monitors the labeling of opium tincture. Bottles of opium tincture are required by the FDA to bear a bright red "POISON" label given the potency of the drug and the potential for overdose (see discussion about confusion with Paregoric below). Additionally, in a warning letter to a manufacturer of opium tincture in late 2009, the FDA noted that "we found that your firm is manufacturing and distributing the prescription drug Opium Tincture USP (Deodorized – 10 mg/mL). Based on our information, there are no FDA-approved applications on file for this drug product."[29]

Pharmacology edit

Opium tincture is useful as an analgesic and antidiarrheal. Opium enhances the tone in the long segments of the longitudinal muscle and inhibits propulsive contraction of circular and longitudinal muscles. The pharmacological effects of opium tincture are due principally to its morphine content. The quantity of the papaverine and codeine alkaloids in opium tincture is too small to have any demonstrable central nervous system effect.[30]

Most modern formulations of opium tincture do not contain the alkaloid narcotine (also known as noscapine), which has antitussive properties. Even modest doses of narcotine can induce profound nausea and vomiting.[31] Since opium tincture is usually prescribed for its antidiarrheal and analgesic properties (rather than as an antitussive), opium tincture without narcotine is generally preferred. This "de-narcotized" or "deodorized" opium tincture is formulated using a petroleum distillate to remove the narcotine.[30]

Oral doses of opium tincture are rapidly absorbed in the gastrointestinal tract and metabolized in the liver. Peak plasma concentrations of the morphine content are reached in about one hour, and nearly 75% of the morphine content of the opium tincture is excreted in the urine within 48 hours after oral administration.[citation needed]

Medical uses edit

Diarrhea edit

Opium tincture is indicated for the treatment of severe fulminant (intense, prolific) diarrhea that does not respond to standard therapy (e.g., Imodium or Lomotil).[30] The usual starting dose is 0.3 mL to 0.6 mL (about six to 12 drops) in a glass of water or juice four times a day.[30] Refractory cases (such as diarrhea resulting from the complications of HIV/AIDS) may require higher than normal dosing, for example, 1 to 2 mL every 3 hours, for a total daily dose of up to 16 mL a day. In terminal diseases, there is no ceiling dose for opium tincture; the dose is increased slowly until diarrhea is controlled.[32]

Neonatal abstinence syndrome edit

Opium tincture is used to treat neonatal opioid withdrawal syndrome (NOWS) when diluted 1:25 (one part opium tincture to 25 parts water).[33] The recommended dose is 0.2 mL of the diluted solution under the tongue every three hours, which may be increased by 0.05 mL every three hours until no objective signs of withdrawal are observed.[33] In no event, however, should the dose exceed 0.7 mL every three hours.[33] The opium tincture is gradually tapered over a 3- to 5-week period, at which point the newborn should be completely free of withdrawal symptoms.[33]

Hazards edit

Potency of laudanum edit

Opium tincture is one of the most potent oral formulations of morphine available by prescription. Accidental or deliberate overdose is common with opium tincture given the highly concentrated nature of the solution. Overdose and death may occur with a single oral dose of between 100 and 150 mg of morphine in a healthy adult who has no tolerance to opiates.[34][35] This represents the equivalent of between two and three teaspoons (10–15 mL) of opium tincture. Suicide by laudanum was common in the mid-19th century.[36] Prudent medical judgment necessitates toward dispensing very small quantities of opium tincture in small dropper bottles or in pre-filled syringes to reduce the risk of intentional or accidental overdose.

Danger of confusion with paregoric edit

In the United States, opium tincture contains 10 mg per mL of anhydrous morphine. By contrast, opium tincture's weaker cousin, paregoric, also confusingly known as "camphorated tincture of opium", is 1/25th the strength of opium tincture, containing only 0.4 mg of morphine per mL. A 25-fold morphine overdose may occur if opium tincture is used where paregoric is indicated. Opium tincture is almost always dosed in drops, or fractions of a mL, or less commonly, in minims, while paregoric is dosed in teaspoons or tablespoons. Thus, an order for opium tincture containing directions in teaspoons is almost certainly in error. To avoid this potentially fatal outcome, the term "camphorated tincture of opium" is avoided in place of paregoric since the former can easily be mistaken for opium tincture.[37]

In 2004, the FDA issued a "Patient Safety" news bulletin stating that "To help resolve the confusion [between opium tincture and paregoric], FDA will be working with the manufacturers of these two drugs to clarify the labeling on the containers and in the package inserts."[38] Indeed, in 2005, labels for opium tincture began to include the concentration of morphine (10 mg/mL) in large text beneath the words "Opium Tincture". The FDA has also alerted pharmacists and other medical practitioners about the dangers of confusing these drugs, and has recommended that opium tincture not be stocked as a standard item (i.e., that it should not be "on the shelf"), that opium tincture be dispensed in oral syringes, and that pharmacy software alert the dispenser if unusually large doses of opium tincture appear to be indicated.[39]

Despite the FDA's efforts over the past few years, the confusion persists, sometimes with deadly results.[40] The Institute for Safe Medication Practices recommends that opium tincture not be stocked at all in a pharmacy's inventory, and that "It may be time to relegate opium tincture and paregoric to the museum of outmoded opioid therapy."[37] Despite the risk of confusion, opium tincture, like many end-stage medications, is indispensable for intractable diarrhea for terminally ill patients, such as those with AIDS and cancer.[32]

Misinterpretation of "DTO" edit

The abbreviation "DTO," traditionally used to refer to Deodorized Tincture of Opium, is sometimes also erroneously employed to abbreviate "diluted tincture of opium." Diluted tincture of opium, also known as Camphorated Tincture of Opium (Paregoric) is a 1:25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opioids while pregnant. The United States Pharmacopeia and FDA recommend that practitioners refrain from using DTO in prescriptions, given this potential for confusion. In cases where pharmacists have misinterpreted DTO, and given "deodorized tincture of opium" when "diluted tincture of opium" was meant, infants have received a massive 25-fold overdose of morphine, sometimes resulting in fatalities.[37]

Side effects edit

Side effects of laudanum are generally the same as with morphine, and include euphoria, dysphoria, pruritus, sedation, constipation, reduced tidal volume, respiratory depression, as well as psychological dependence, physical dependence, miosis, and xerostomia. Overdose can result in severe respiratory depression or collapse and death. The ethanol component can also induce adverse effects at higher doses; the side effects are the same as with alcohol. Long-term use of laudanum in nonterminal diseases is discouraged due to the possibility of drug tolerance and addiction. Long-term use can also lead to abnormal liver function tests; specifically, prolonged morphine use can increase ALT and AST blood serum levels.[citation needed]

Treatment for overdose edit

Life-threatening overdose of opium tincture owes to the preparation's morphine content. Morphine produces a dose-dependent depressive effect on the respiratory system, which can lead to profound respiratory depression, hypoxia, coma and finally respiratory arrest and death. If overdose of opium tincture is suspected, rapid professional intervention is required. The primary concern is re-establishing a viable airway and institution of assisted or controlled ventilation if the patient is unable to breathe on their own. Other supportive measures such as the use of vasopressors and oxygen may be indicated to treat cardiac and/or pulmonary failure. Cardiac arrhythmias or arrest will require advanced life-saving measures.[citation needed]

Intravenous naloxone or nalmefene, quick-acting opioid antagonists, are the first-line treatment to reverse respiratory depression caused by an overdose of opium tincture. Gastric lavage may be of some use in certain cases.

Fiction edit

Literature edit

  • In Mary Shelley's novel Frankenstein (1818), Victor Frankenstein takes laudanum as his only means of sleeping and thus preserving his life while in recovery from months of fever and a series of horrible events.[41]
  • In Charles Dickens's novel Oliver Twist (1837), Nancy gave William "Bill" Sikes laudanum to keep him asleep while she ran away to meet Rose Maylie.[42]
  • In Uncle Tom's Cabin (1852), an anti-slavery novel by Harriet Beecher Stowe, an enslaved woman named Cassy talks about how she killed her newborn by laudanum overdose to spare him from experiencing the horrors of slavery.[43]
  • In the novel Silas Marner: The Weaver of Raveloe by George Eliot (Mary Ann Evans) (1861), Silas finds and adopts a two-year old girl who had wandered into his house. The girl had been abandoned while walking with her opium-addicted mother, Molly Farren, who had fallen asleep in the snow and died. Earlier in the novel, in Chapter 3, it is specified that she uses laudanum.... if Molly should take a drop too much laudanum some day, and make a widower of you.[44]
  • A laudanum-addicted character also appeared in Wilkie Collins' novel Armadale (1864–1866).[45]
  • Wilkie Collins' novel The Moonstone (1868) features laudanum "as an essential ingredient of the plot." Collins based his description of the drug's effects on his own experiences with it.[46]
  • Laudanum appears in Charles Baudelaire's prose poem The Double Room, published in his collection Le Spleen de Paris in 1869.[47]
  • In the novel Anna Karenina (1878) by Leo Tolstoy, the eponymous character becomes addicted to laudanum.
  • In the novel Red Harvest (1929) by Dashiel Hammett, The Continental Op drinks gin doped with laudanum and has a series of strange dreams before awakening to find himself framed for murder.
  • Laudanum is portrayed as the surgical drug of choice for fifteenth-century physicians in Lawrence Schoonover's novel The Burnished Blade (1948), the plot of which deals in part with the smuggling of expensive raw opium into France from the Empire of Trebizond.[48]
  • In William Faulkner's novel Requiem for a Nun (1951), Compson, Doctor Peabody, and Ratcliffe give whiskey tainted with laudanum to a group of rowdy lynchers and a militia band that had joined together. Upon their falling asleep, they were gathered up and locked in jail while still unconscious.[49]
  • Stephen Maturin, one of the main characters in Patrick O'Brian's Aubrey–Maturin series of novels (1969–2004) about the Napoleonic wars, is a sometime laudanum addict.[50]
  • Laudanum is prescribed in Glendon Swarthout's novel The Shootist (1975) to the character J.B. Books, played by John Wayne in Don Siegel's movie adaptation (1976).[51]
  • In the book series All the Wrong Questions (2012–2015) by Daniel Handler, Who Could That Be at This Hour? (2012) Lemony Snicket's tea had laudanum. Laudanum is mentioned and used throughout the series, mostly by The Inhuman society.
  • In Eleanor Catton's novel The Luminaries (2013), and the subsequent TV adaptation (2020), many characters are addicted to laudanum and it is used to murder Crosbie Wells.
  • In Sara Collins' novel The Confessions of Frannie Langton (2019), and the subsequent TV adaptation (2022), the titular character becomes addicted to laudanum.

Film and television edit

  • In the movie The Shootist (1976) John Wayne’s gunslinger character, John Books, is prescribed laudanum by the doctor (James Stewart) for his terminal cancer.
  • In the original version of the miniseries Roots (1977), upon Toby's arrival to Virginia and ready for sale, the slave doctor says he'll give laudanum to the wild ones, brandy to the dull ones and "let the buyer beware".
  • In Philippa Gregory's novel Wideacre (1987), the main character Beatrice Lacey nearly becomes addicted to laudanum when her eventual husband Dr. John MacAndrew prescribes it to her after her mother's death.
  • It plays a major role in the plot of James Clavell's historical novel Gai-Jin (1993).
  • In the film Tombstone (1993), Mattie Earp, Wyatt Earp's wife is addicted to laudanum.
  • In the adaptation Interview with the Vampire (1994), which was based on the 1976 novel with the same name, Claudia uses laudanum to try to kill Lestat: Under the pretext of making peace, she offers him some drunk noble-blood twins to feed on, when she actually had them overdose on the drug.[52]
  • In the film From Hell (2001), Inspector Abberline is a user of laudanum, and Jack the Ripper also uses laudanum for making his victims sleepy.
  • In the TV series Deadwood, (2004–2006) the town doctor recommends laudanum several times, bringing a bottle of it to a patient. Initially in the series, Alma Garrett is an addict to laudanum. Trixie is a former addict.
  • In the TV show American Horror Story: Murder House (2011), laudanum is repeatedly used to drug a main character, leaving him waking up unable to remember what had occurred.
  • In the TV series Outlander (2014), Claire uses laudanum in several episodes throughout the 18th century.
  • In the film Winchester (2018), Doctor Eric Price is addicted to laudanum due to his wife's suicide.[53]
  • In the film The Highwaymen (2019), Bonnie Parker (Emily Brobst) of Bonnie and Clyde fame is addicted to laudanum.
  • In the miniseries The North Water (2021), the main character, a surgeon who takes a job on a whaling ship in the Arctic, is addicted to laudanum.

See also edit

References edit

  1. ^ The Pharmacopoeia of the United States of America (10th Decennial Revision ed.). Philadelphia, USA: J. B. Lippincott Company. 1925. p. 400. Also labeled Tr. Opii, Tinctura Opii Deodorati, Tincture of Deodorized Opium, Opii tinctura. Tincture of Opium, U.S.P, "yields, from each 100 cc, not less than 0.95 gm and not more than 1.05 gm of anhydrous morphine". Source:
  2. ^ Sigerist HE (1941). "Laudanum in the Works of Paracelsus" (PDF). Bull. Hist. Med. 9: 530–544. Archived (PDF) from the original on 2022-10-09. Retrieved 5 September 2018.
  3. ^ a b c Davenport-Hines R (2004). "Early History". The Pursuit of Oblivion. Norton. ISBN 9780393325454. Retrieved 2009-01-16.
  4. ^ a b c d e f Hodgson, Barbara (2001). In the Arms of Morpheus: The Tragic History of Laudanum, Morphine, and Patent Medicines. Buffalo, New York, USA: Firefly Books.
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  9. ^ Young G. A treatise on opium, founded upon practical observations. London: printed for A.Millar; 1753
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  14. ^ "Camel Press". lincoln.coffeetownpress.com.
  15. ^ Scientific American. Munn & Company. 1869-05-29. p. 342.
  16. ^ Richardson JG (1901). Medicology or Home Encyclopedia of Health. New York, Philadelphia and London: University Medical Society. pp. 1276 and 1282.
  17. ^ Musto DF (1999). The American Disease: Origins of Narcotic Control (3rd ed.). Oxford University Press. ISBN 9780198028925.
  18. ^ Catalog No. N-15 (Report) (Second ed.). Hammond, Indiana, USA: Frank S. Betz Co. 1915. p. 320.
  19. ^ Catalog No. N-15 (Report) (Second ed.). Hammond, Indiana, USA: Frank S. Betz Co. 1915. p. 318.
  20. ^ Physicians' Catalog of the Pharmaceutical and Biological Products of Parke, Davis & Company (Report). 1929–1930. pp. 87–88.
  21. ^ . Office of Diversion Control. Drug Enforcement Administration, United States Department of Justice. Archived from the original on June 29, 2013. Retrieved August 1, 2010. Also under Schedule II are opium extracts, opium fluidextract, opium poppy (Papaver somniferum), granulated opium, powdered opium, and raw or gum opium, each with an individual DEA number.
  22. ^ Belgische Farmacopee, 5de uitgave, 1966; part 3.
  23. ^ Chase AW (1870). Dr. Chase's Recipes. Ann Arbor, Michigan: R. A. Beal. p. 133.
  24. ^ Thomas Sydenham, an English physician, formulated this version of Laudanum in the 1660s.
  25. ^ Dick WB (1890). Encyclopedia of Practical Receipts and Processes (Fifth ed.). New York: Dick & Fitzgerald, Publishers. pp. 416, 447 and 472.
  26. ^ The Extra Pharmacopeia Martindale. Vol. 1, 24th edition. London: The Pharmaceutical Press, 1958, page 924.
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  41. ^ Shelley M. Frankenstein. pp. 197–198. Ever since my recovery from the fever I had been in the custom of taking every night a small quantity of laudanum; for it was by means of this drug only that I was enabled to gain the rest necessary for the preservation of life. Oppressed by the recollection of my various misfortunes, I now swallowed double my usual quantity and soon slept profoundly. But sleep did not afford me respite from thought and misery; my dreams presented a thousand objects that scared me.
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External links edit

  Media related to Laudanum at Wikimedia Commons

  • Merck Prescribing Information for Laudanum/Opium Tincture. Includes detailed dosage information.

laudanum, confused, with, labdanum, cistus, ladanifer, this, article, multiple, issues, please, help, improve, discuss, these, issues, talk, page, learn, when, remove, these, template, messages, this, article, needs, additional, citations, verification, please. Not to be confused with labdanum or Cistus ladanifer This article has multiple issues Please help improve it or discuss these issues on the talk page Learn how and when to remove these template messages This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Laudanum news newspapers books scholar JSTOR February 2023 Learn how and when to remove this template message This page s infobox may require expansion verification or otherwise need cleanup Please make sure that the infobox meets Wikipedia s guidelines for infoboxes There might be relevant comments on the talk page You may also want to view the infobox template page to view the full parameter list and read guidance on usage of that infobox August 2023 Learn how and when to remove this template message Laudanum is a tincture of opium containing approximately 10 powdered opium by weight the equivalent of 1 morphine 1 Laudanum is prepared by dissolving extracts from the opium poppy Papaver somniferum in alcohol ethanol LaudanumCombination ofOpiumAnalgesicEthanolTinctureClinical dataPronunciation ˈ l ɔː d en e m LAW den emTrade namesDropizolRoutes ofadministrationOral buccal sublingualATC codeA07DA02 WHO Legal statusLegal statusUK Class A US Schedule II UN Narcotic Schedule I verify Reddish brown in color and extremely bitter laudanum contains several opium alkaloids including morphine and codeine Laudanum was historically used to treat a variety of conditions but its principal use was as a pain medication and cough suppressant Until the early 20th century laudanum was sold without a prescription and was a constituent of many patent medicines Laudanum has since been recognized as addictive and is strictly regulated and controlled as such throughout most of the world The United States Controlled Substances Act for example lists it on Schedule II the second strictest category Laudanum is known as a whole opium preparation since it historically contained all the alkaloids found in the opium poppy which are extracted from the dried latex of ripe seed pods Papaver somniferum L succus siccus However the modern drug is often processed to remove all or most of the noscapine also called narcotine present as this is a strong emetic and does not add appreciably to the analgesic or antipropulsive properties of opium the resulting solution is called Denarcotized Tincture of Opium or Deodorized Tincture of Opium DTO Laudanum remains available by prescription in the United States under the generic name opium tincture and in the European Union and United Kingdom under the trade name Dropizol although the drug s therapeutic indication is generally limited to controlling diarrhea when other medications have failed The terms laudanum and tincture of opium are generally interchangeable but in contemporary medical practice the latter is used almost exclusively Contents 1 History 1 1 Paracelsus s laudanum 1 2 British laudanum 1 3 Sydenham s laudanum 1 4 18th century 1 5 19th century 1 6 20th century 1 7 21st century 2 Historical varieties 3 Modern status 3 1 United Kingdom 3 2 United States 4 Pharmacology 5 Medical uses 5 1 Diarrhea 5 2 Neonatal abstinence syndrome 6 Hazards 6 1 Potency of laudanum 6 2 Danger of confusion with paregoric 6 3 Misinterpretation of DTO 6 4 Side effects 6 5 Treatment for overdose 7 Fiction 7 1 Literature 7 2 Film and television 8 See also 9 References 10 External linksHistory editParacelsus s laudanum edit Paracelsus a 16th century Swiss alchemist experimented with various opium concoctions and recommended opium for reducing pain One of his preparations a pill which he extolled as his archanum or laudanum may have contained opium 2 Paracelsus laudanum was strikingly different from the standard laudanum of the 17th century and beyond containing crushed pearls musk amber and other substances 3 British laudanum edit One researcher has documented that Laudanum as listed in the London Pharmacopoeia 1618 was a pill made from opium saffron castor ambergris musk and nutmeg 4 45 Sydenham s laudanum edit In the 1660s English physician Thomas Sydenham 1624 1689 popularized a proprietary opium tincture that he also named laudanum although it differed substantially from the laudanum of Paracelsus In 1676 Sydenham published a seminal work Medical Observations Concerning the History and Cure of Acute Diseases in which he promoted his brand of opium tincture and advocated its use for a range of medical conditions 3 18th century edit By the 18th century the medicinal properties of opium and laudanum were well known and the term laudanum came to refer to any combination of opium and alcohol In the 18th century several physicians published work about it including John Jones who wrote The Mysteries of Opium Revealed 1700 which was described by one commentator as extraordinary and perfectly unintelligible 5 6 The Scottish physician John Brown creator of the Brunonian system of medicine recommended opium for what he termed asthenic conditions but his system was discredited by the time of his death 7 8 The most influential work was by George Young who published a comprehensive medical text entitled Treatise on Opium 1753 9 Young an Edinburgh surgeon and physician wrote this to counter an essay on opium by his contemporary Charles Alston professor of botany and materia medica at Edinburgh who had recommended the use of opium for a wide variety of conditions Young countered this by emphasising the risks that I may prevent such mischief as I can I here give it as my sincere opinion that opium is a poison by which great numbers are daily destroyed Young gives a comprehensive account of the indications for the drug including its complications He is critical about writers whose knowledge of the drug is based on chemical or animal experiments rather than clinical practice The treatise is a detailed balanced and valuable guide to prevailing knowledge and practice 3 10 As it gained popularity opium and after 1820 morphine was mixed with a wide variety of agents drugs and chemicals including mercury hashish cayenne pepper ether chloroform belladonna whiskey wine and brandy 4 104 nbsp Confessions of a laudanum drinker The Lancet 1866During the late 18th and early 19th centuries patients undergoing surgery were often administered laudanum and alcohol and had their hands restrained and bodies held down while the operation was performed 11 19th century edit By the 19th century laudanum was used in many patent medicines to relieve pain to produce sleep to allay irritation to check excessive secretions to support the system and as a soporific 12 13 The limited pharmacopoeia of the day meant that opium derivatives were among the most effective of available treatments so laudanum was widely prescribed for ailments from colds to meningitis to cardiac diseases in both adults and children Laudanum was used during the yellow fever epidemic Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches Nurses also spoon fed laudanum to infants The Romantic and Victorian eras were marked by the widespread use of laudanum in Europe and the United States Mary Todd Lincoln for example the wife of the US president Abraham Lincoln was a laudanum addict as was the English poet Samuel Taylor Coleridge who was famously interrupted in the middle of an opium induced writing session of Kubla Khan by a person on business from Porlock 14 Initially a working class drug laudanum was cheaper than a bottle of gin or wine because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage As one researcher has noted To understand the popularity of a medicine that eased even if only temporarily coughing diarrhoea and pain one only has to consider the living conditions at the time In the 1850s cholera and dysentery regularly ripped through communities its victims often dying from debilitating diarrhoea and dropsy consumption ague and rheumatism were all too common 4 44 49 An 1869 article in Scientific American describes a farmer growing and harvesting poppy in Indian Springs Georgia and subsequently selling the raw material to a local pharmacist who prepared laudanum 15 20th century edit Laudanum was used in home remedies and prescriptions as well as a single medication For example a 1901 medical book published for home health use gave the following two Simple Remedy Formulas for dysenterry sic 1 Thin boiled starch 2 ounces Laudanum 20 drops Use as an injection meaning as an enema every six to twelve hours 2 Tincture rhubarb 1 ounce Laudanum 4 drachms Dose One teaspoonful every three hours In a section entitled Professional Prescriptions is a formula for diarrhoea acute Tincture opium deodorized 15 drops Subnitrate of bismuth 2 drachms Simple syrup 1 2 ounce Chalk mixture 11 2 ounces A teaspoonful every two or three hours to a child one year old Diarrhoea chronic Aqueous extract of ergot 20 grains Extract of nux vomica 5 grains Extract of Opium 10 grains Make 20 pills Take one pill every three or four hours 16 The early 20th century brought increased regulation of all manner of narcotics including laudanum as the addictive properties of opium became more widely understood and patent medicines came under fire largely because of their mysterious compositions 4 126 In the US the Food and Drug Act of 1906 required that certain specified drugs including alcohol cocaine heroin morphine and cannabis be accurately labeled with contents and dosage Previously many drugs had been sold as patent medicines with secret ingredients or misleading labels Cocaine heroin cannabis and other such drugs continued to be legally available without prescription as long as they were labeled It is estimated that sale of patent medicines containing opiates decreased by 33 after labeling was mandated 17 In 1906 in Britain and in 1908 in Canada laws requiring disclosure of ingredients and limitation of narcotic content were instituted 4 126 The Harrison Narcotics Tax Act of 1914 restricted the manufacture and distribution of opiates including laudanum and coca derivatives in the US This was followed by France s Loi des stupefiants in 1916 and Britain s Dangerous Drugs Act in 1920 4 126 Laudanum was supplied to druggists and physicians in regular and concentrated versions For example in 1915 Frank S Betz Co a medical supply company in Hammond Indiana advertised Tincture of Opium U S P for 2 90 per lb Tincture of Opium Camphorated U S P for 85 cents per lb and Tincture of Opium Deodorized for 2 85 per lb 18 Four versions of opium as a fluid extract were also offered 1 Opium Concentrated assayed For making Tincture Opii Laudanum U S P Four times the strength of the regular U S P tincture for 9 35 per pint 2 Opium Camphorated Conc 1 oz making 8 ozs Tr Opii Camphorated U S P Paregoric for 2 00 per pint 3 Opium Concentrated Deodorized and Denarcotized Four times the strength of tincture Used when Tinct Opii U S P is contraindicated for 9 50 per pint and 4 Opium Aqueous U S P 1890 Tr assayed Papaver Somniferum for 2 25 per pint 19 In 1929 30 Parke Davis amp Co a major US drug manufacturer based in Detroit Michigan sold Opium U S P Laudanum as Tincture No 23 for 10 80 per pint 16 fluid ounces and Opium Camphorated U S P Paregoric as Tincture No 20 for 2 20 per pint Concentrated versions were available Opium Camphorated for U S P Tincture Liquid No 338 was exactly 8 times the strength of Tincture Opium Camphorated Paregoric italics in original U S P designed for preparing the tincture by direct dilution and cost 7 per pint Similarly at a cost of 36 per pint Opium Concentrated for U S P Tincture Liquid No 336 was four times the strength of the official tincture and designed for the extemporaneous preparation of the tincture 20 The catalog also noted For quarter pint bottles add 80c per pint to the price given for pints Toward the middle 20th century the use of opiates was generally limited to the treatment of pain and opium was no longer a medically accepted cure all Further the pharmaceutical industry began synthesizing various opioids such as propoxyphene oxymorphone and oxycodone These synthetic opioids along with codeine and morphine were preferable to laudanum since a single opioid could be prescribed for different types of pain rather than the cocktail of laudanum which contains nearly all of the opium alkaloids Consequently laudanum became mostly obsolete as an analgesic since its principal ingredient is morphine which can be prescribed by itself to treat pain Until now there has been no medical consensus on which of the two laudanum or morphine alone is the better choice for treating pain In 1970 the US adopted the Uniform Controlled Substances Act which regulated opium tincture Laudanum as a Schedule II substance currently DEA 9630 21 placing even tighter controls on the drug By the late 20th century laudanum s use was almost exclusively confined to treating severe diarrhea 21st century edit The current prescribing information for laudanum in the US states that opium tincture s sole indication is as an anti diarrheal although the drug is occasionally prescribed off label for treating pain and neonatal withdrawal syndrome citation needed Historical varieties edit nbsp Italian Sydenham laudanum tincture from the 1950sSeveral historical varieties of laudanum exist including Paracelsus laudanum Sydenham s Laudanum also known as tinctura opii crocata benzoic laudanum tinctura opii benzoica 22 and deodorized tincture of opium the most common contemporary formulation among others Depending on the version additional amounts of the substances and additional active ingredients e g saffron sugar eugenol are added modifying its effects e g amount of sedation or antitussive properties There is probably no single reference that lists all the pharmaceutical variations of laudanum that were created and used in different countries during centuries since it was initially formulated The reasons are that in addition to official variations described in pharmacopeias pharmacists and drug manufacturers were free to alter such formulas The alcohol content of Laudanum probably varied substantially on the labels of turn of the century bottles of Laudanum alcoholic content is stated as 48 In contrast the current version of Laudanum contains about 18 alcohol The four variations of laudanum listed here were used in the United States during the late 19th century The first from an 1870 publication is Best Turkey opium 1 oz slice and pour upon it boiling water 1 gill and work it in a bowl or mortar until it is dissolved then pour it into the bottle and with alcohol of 70 percent proof 1 2 pt rinse the dish adding the alcohol to the preparation shaking well and in 24 hours it will be ready for use Dose From 10 to 30 drops for adults according to the strength of the patient or severity of the pain Thirty drops of this laudanum will be equal to one grain of opium And this is a much better way to prepare it than putting the opium into alcohol or any other spirits alone for in that case much of the opium does not dissolve 23 The remaining three formulas are copied from an 1890 publication of the day Sydenham s Laudanum 24 According to the Paris Codex this is prepared as follows opium 2 ounces saffron 1 ounce bruised cinnamon and bruised cloves each 1 drachm sherry wine 1 pint Mix and macerate for 15 days and filter Twenty drops are equal to one grain of opium Rousseau s Laudanum Dissolve 12 ounces white honey in 3 pounds warm water and set it aside in a warm place When fermentation begins add to it a solution of 4 ounces selected opium in 12 ounces water Let the mixture stand for a month at a temperature of 86 Fahr then strain filter and evaporate to 10 ounces finally strain and add 41 2 ounces proof alcohol Seven drops of this preparation contain about 1 grain of opium Tincture of Opium Laudanum U S P attributed to the United States Pharmacoepia of 1863 Macerate 21 2 ounces opium in moderately fine powder in 1 pint water for 3 days with frequent agitation Add 1 pint alcohol and macerate for 3 days longer Percolate and displace 2 pints tincture by adding dilute alcohol in the percolator 25 Modern status editUnited Kingdom edit Opium tincture remains in the British Pharmacopoeia where it is referred to as Tincture of Opium B P Laudanum Thebaic Tincture or Tinctura Thebaica and adjusted to contain 1 w v of anhydrous morphine 26 It is a Class A substance under the Misuse of Drugs Act of 1971 At least one manufacturer Macfarlan Smith still produces opium tincture in the UK as of 2011 update 27 Gee s Linctus is also available from most UK pharmacies especially independent stores This contains Opium Tincture at 0 083 mL per 5 mL citation needed United States edit Tincture of Opium is available by prescription in the United States It is regulated as a Schedule II drug No 9639 under the Controlled Substances Act In the United States opium tincture is marketed and distributed by several pharmaceutical firms each producing a single formulation of the drug which is deodorized Each mL contains 10 mg of anhydrous morphine the equivalent of 100 mg of powdered opium other opium alkaloids except noscapine and ethanol 19 It is available packaged in bottles of four US fluid ounces 118 mL and 16 US fluid ounces 1 US pt 473 mL citation needed Tincture of Opium is known as one of many unapproved drugs regulated by the U S Food and Drug Administration FDA the marketing and distribution of opium tincture prevails only because opium tincture was sold prior to the Federal Food Drug amp Cosmetic Act of 1938 28 Its grandfathered status protects opium tincture from being required to undergo strict FDA drug reviews and subsequent approval processes However the FDA closely monitors the labeling of opium tincture Bottles of opium tincture are required by the FDA to bear a bright red POISON label given the potency of the drug and the potential for overdose see discussion about confusion with Paregoric below Additionally in a warning letter to a manufacturer of opium tincture in late 2009 the FDA noted that we found that your firm is manufacturing and distributing the prescription drug Opium Tincture USP Deodorized 10 mg mL Based on our information there are no FDA approved applications on file for this drug product 29 Pharmacology editOpium tincture is useful as an analgesic and antidiarrheal Opium enhances the tone in the long segments of the longitudinal muscle and inhibits propulsive contraction of circular and longitudinal muscles The pharmacological effects of opium tincture are due principally to its morphine content The quantity of the papaverine and codeine alkaloids in opium tincture is too small to have any demonstrable central nervous system effect 30 Most modern formulations of opium tincture do not contain the alkaloid narcotine also known as noscapine which has antitussive properties Even modest doses of narcotine can induce profound nausea and vomiting 31 Since opium tincture is usually prescribed for its antidiarrheal and analgesic properties rather than as an antitussive opium tincture without narcotine is generally preferred This de narcotized or deodorized opium tincture is formulated using a petroleum distillate to remove the narcotine 30 Oral doses of opium tincture are rapidly absorbed in the gastrointestinal tract and metabolized in the liver Peak plasma concentrations of the morphine content are reached in about one hour and nearly 75 of the morphine content of the opium tincture is excreted in the urine within 48 hours after oral administration citation needed Medical uses editDiarrhea edit Opium tincture is indicated for the treatment of severe fulminant intense prolific diarrhea that does not respond to standard therapy e g Imodium or Lomotil 30 The usual starting dose is 0 3 mL to 0 6 mL about six to 12 drops in a glass of water or juice four times a day 30 Refractory cases such as diarrhea resulting from the complications of HIV AIDS may require higher than normal dosing for example 1 to 2 mL every 3 hours for a total daily dose of up to 16 mL a day In terminal diseases there is no ceiling dose for opium tincture the dose is increased slowly until diarrhea is controlled 32 Neonatal abstinence syndrome edit Opium tincture is used to treat neonatal opioid withdrawal syndrome NOWS when diluted 1 25 one part opium tincture to 25 parts water 33 The recommended dose is 0 2 mL of the diluted solution under the tongue every three hours which may be increased by 0 05 mL every three hours until no objective signs of withdrawal are observed 33 In no event however should the dose exceed 0 7 mL every three hours 33 The opium tincture is gradually tapered over a 3 to 5 week period at which point the newborn should be completely free of withdrawal symptoms 33 Hazards editPotency of laudanum edit Opium tincture is one of the most potent oral formulations of morphine available by prescription Accidental or deliberate overdose is common with opium tincture given the highly concentrated nature of the solution Overdose and death may occur with a single oral dose of between 100 and 150 mg of morphine in a healthy adult who has no tolerance to opiates 34 35 This represents the equivalent of between two and three teaspoons 10 15 mL of opium tincture Suicide by laudanum was common in the mid 19th century 36 Prudent medical judgment necessitates toward dispensing very small quantities of opium tincture in small dropper bottles or in pre filled syringes to reduce the risk of intentional or accidental overdose Danger of confusion with paregoric edit In the United States opium tincture contains 10 mg per mL of anhydrous morphine By contrast opium tincture s weaker cousin paregoric also confusingly known as camphorated tincture of opium is 1 25th the strength of opium tincture containing only 0 4 mg of morphine per mL A 25 fold morphine overdose may occur if opium tincture is used where paregoric is indicated Opium tincture is almost always dosed in drops or fractions of a mL or less commonly in minims while paregoric is dosed in teaspoons or tablespoons Thus an order for opium tincture containing directions in teaspoons is almost certainly in error To avoid this potentially fatal outcome the term camphorated tincture of opium is avoided in place of paregoric since the former can easily be mistaken for opium tincture 37 In 2004 the FDA issued a Patient Safety news bulletin stating that To help resolve the confusion between opium tincture and paregoric FDA will be working with the manufacturers of these two drugs to clarify the labeling on the containers and in the package inserts 38 Indeed in 2005 labels for opium tincture began to include the concentration of morphine 10 mg mL in large text beneath the words Opium Tincture The FDA has also alerted pharmacists and other medical practitioners about the dangers of confusing these drugs and has recommended that opium tincture not be stocked as a standard item i e that it should not be on the shelf that opium tincture be dispensed in oral syringes and that pharmacy software alert the dispenser if unusually large doses of opium tincture appear to be indicated 39 Despite the FDA s efforts over the past few years the confusion persists sometimes with deadly results 40 The Institute for Safe Medication Practices recommends that opium tincture not be stocked at all in a pharmacy s inventory and that It may be time to relegate opium tincture and paregoric to the museum of outmoded opioid therapy 37 Despite the risk of confusion opium tincture like many end stage medications is indispensable for intractable diarrhea for terminally ill patients such as those with AIDS and cancer 32 Misinterpretation of DTO edit The abbreviation DTO traditionally used to refer to Deodorized Tincture of Opium is sometimes also erroneously employed to abbreviate diluted tincture of opium Diluted tincture of opium also known as Camphorated Tincture of Opium Paregoric is a 1 25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opioids while pregnant The United States Pharmacopeia and FDA recommend that practitioners refrain from using DTO in prescriptions given this potential for confusion In cases where pharmacists have misinterpreted DTO and given deodorized tincture of opium when diluted tincture of opium was meant infants have received a massive 25 fold overdose of morphine sometimes resulting in fatalities 37 Side effects edit Side effects of laudanum are generally the same as with morphine and include euphoria dysphoria pruritus sedation constipation reduced tidal volume respiratory depression as well as psychological dependence physical dependence miosis and xerostomia Overdose can result in severe respiratory depression or collapse and death The ethanol component can also induce adverse effects at higher doses the side effects are the same as with alcohol Long term use of laudanum in nonterminal diseases is discouraged due to the possibility of drug tolerance and addiction Long term use can also lead to abnormal liver function tests specifically prolonged morphine use can increase ALT and AST blood serum levels citation needed Treatment for overdose edit Life threatening overdose of opium tincture owes to the preparation s morphine content Morphine produces a dose dependent depressive effect on the respiratory system which can lead to profound respiratory depression hypoxia coma and finally respiratory arrest and death If overdose of opium tincture is suspected rapid professional intervention is required The primary concern is re establishing a viable airway and institution of assisted or controlled ventilation if the patient is unable to breathe on their own Other supportive measures such as the use of vasopressors and oxygen may be indicated to treat cardiac and or pulmonary failure Cardiac arrhythmias or arrest will require advanced life saving measures citation needed Intravenous naloxone or nalmefene quick acting opioid antagonists are the first line treatment to reverse respiratory depression caused by an overdose of opium tincture Gastric lavage may be of some use in certain cases Fiction editThis article has multiple issues Please help improve it or discuss these issues on the talk page Learn how and when to remove these template messages This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Laudanum news newspapers books scholar JSTOR January 2021 Learn how and when to remove this template message This article may contain irrelevant references to popular culture Please remove the content or add citations to reliable and independent sources April 2023 Learn how and when to remove this template message Literature edit In Mary Shelley s novel Frankenstein 1818 Victor Frankenstein takes laudanum as his only means of sleeping and thus preserving his life while in recovery from months of fever and a series of horrible events 41 In Charles Dickens s novel Oliver Twist 1837 Nancy gave William Bill Sikes laudanum to keep him asleep while she ran away to meet Rose Maylie 42 In Uncle Tom s Cabin 1852 an anti slavery novel by Harriet Beecher Stowe an enslaved woman named Cassy talks about how she killed her newborn by laudanum overdose to spare him from experiencing the horrors of slavery 43 In the novel Silas Marner The Weaver of Raveloe by George Eliot Mary Ann Evans 1861 Silas finds and adopts a two year old girl who had wandered into his house The girl had been abandoned while walking with her opium addicted mother Molly Farren who had fallen asleep in the snow and died Earlier in the novel in Chapter 3 it is specified that she uses laudanum if Molly should take a drop too much laudanum some day and make a widower of you 44 A laudanum addicted character also appeared in Wilkie Collins novel Armadale 1864 1866 45 Wilkie Collins novel The Moonstone 1868 features laudanum as an essential ingredient of the plot Collins based his description of the drug s effects on his own experiences with it 46 Laudanum appears in Charles Baudelaire s prose poem The Double Room published in his collection Le Spleen de Paris in 1869 47 In the novel Anna Karenina 1878 by Leo Tolstoy the eponymous character becomes addicted to laudanum In the novel Red Harvest 1929 by Dashiel Hammett The Continental Op drinks gin doped with laudanum and has a series of strange dreams before awakening to find himself framed for murder Laudanum is portrayed as the surgical drug of choice for fifteenth century physicians in Lawrence Schoonover s novel The Burnished Blade 1948 the plot of which deals in part with the smuggling of expensive raw opium into France from the Empire of Trebizond 48 In William Faulkner s novel Requiem for a Nun 1951 Compson Doctor Peabody and Ratcliffe give whiskey tainted with laudanum to a group of rowdy lynchers and a militia band that had joined together Upon their falling asleep they were gathered up and locked in jail while still unconscious 49 Stephen Maturin one of the main characters in Patrick O Brian s Aubrey Maturin series of novels 1969 2004 about the Napoleonic wars is a sometime laudanum addict 50 Laudanum is prescribed in Glendon Swarthout s novel The Shootist 1975 to the character J B Books played by John Wayne in Don Siegel s movie adaptation 1976 51 In the book series All the Wrong Questions 2012 2015 by Daniel Handler Who Could That Be at This Hour 2012 Lemony Snicket s tea had laudanum Laudanum is mentioned and used throughout the series mostly by The Inhuman society In Eleanor Catton s novel The Luminaries 2013 and the subsequent TV adaptation 2020 many characters are addicted to laudanum and it is used to murder Crosbie Wells In Sara Collins novel The Confessions of Frannie Langton 2019 and the subsequent TV adaptation 2022 the titular character becomes addicted to laudanum Film and television edit In the movie The Shootist 1976 John Wayne s gunslinger character John Books is prescribed laudanum by the doctor James Stewart for his terminal cancer In the original version of the miniseries Roots 1977 upon Toby s arrival to Virginia and ready for sale the slave doctor says he ll give laudanum to the wild ones brandy to the dull ones and let the buyer beware In Philippa Gregory s novel Wideacre 1987 the main character Beatrice Lacey nearly becomes addicted to laudanum when her eventual husband Dr John MacAndrew prescribes it to her after her mother s death It plays a major role in the plot of James Clavell s historical novel Gai Jin 1993 In the film Tombstone 1993 Mattie Earp Wyatt Earp s wife is addicted to laudanum In the adaptation Interview with the Vampire 1994 which was based on the 1976 novel with the same name Claudia uses laudanum to try to kill Lestat Under the pretext of making peace she offers him some drunk noble blood twins to feed on when she actually had them overdose on the drug 52 In the film From Hell 2001 Inspector Abberline is a user of laudanum and Jack the Ripper also uses laudanum for making his victims sleepy In the TV series Deadwood 2004 2006 the town doctor recommends laudanum several times bringing a bottle of it to a patient Initially in the series Alma Garrett is an addict to laudanum Trixie is a former addict In the TV show American Horror Story Murder House 2011 laudanum is repeatedly used to drug a main character leaving him waking up unable to remember what had occurred In the TV series Outlander 2014 Claire uses laudanum in several episodes throughout the 18th century In the film Winchester 2018 Doctor Eric Price is addicted to laudanum due to his wife s suicide 53 In the film The Highwaymen 2019 Bonnie Parker Emily Brobst of Bonnie and Clyde fame is addicted to laudanum In the miniseries The North Water 2021 the main character a surgeon who takes a job on a whaling ship in the Arctic is addicted to laudanum See also editConfessions of an English Opium Eater Kendal Black Drop Poppy teaReferences edit The Pharmacopoeia of the United States of America 10th Decennial Revision ed Philadelphia USA J B Lippincott Company 1925 p 400 Also labeled Tr Opii Tinctura Opii Deodorati Tincture of Deodorized Opium Opii tinctura Tincture of Opium U S P yields from each 100 cc not less than 0 95 gm and not more than 1 05 gm of anhydrous morphine Source Sigerist HE 1941 Laudanum in the Works of Paracelsus PDF Bull Hist Med 9 530 544 Archived PDF from the original on 2022 10 09 Retrieved 5 September 2018 a b c Davenport Hines R 2004 Early History The Pursuit of Oblivion Norton ISBN 9780393325454 Retrieved 2009 01 16 a b c d e f Hodgson Barbara 2001 In the Arms of Morpheus The Tragic History of Laudanum Morphine and Patent Medicines Buffalo New York USA Firefly Books JONES JOHN 1645 1709 cleric Dictionary of Welsh Biography National Library of Wales Retrieved 2021 07 10 Hardy EG 1899 Jesus college PIMS University of Toronto London F E Robinson and co Lawrence C 1988 Cullen Brown and the poverty of essentialism Medical History Supplement 8 1 21 ISSN 0950 5571 PMC 2557347 Risse GB January 2005 The Royal Medical Society versus Campbell Denovan Brunonianism the Press and the Medical Establishment New Medical Challenges during the Scottish Enlightenment Brill pp 105 132 doi 10 1163 9789004333000 007 ISBN 978 90 04 33300 0 Young G A treatise on opium founded upon practical observations London printed for A Millar 1753 Macintyre IM 2012 A sceptic and an empiric in medicine George Young 1692 1757 and the beginnings of the Scottish medical Enlightenment The Journal of the Royal College of Physicians of Edinburgh 42 4 352 360 doi 10 4997 JRCPE 2012 415 ISSN 2042 8189 PMID 23240124 Adkins L Adkins R 2013 Eavesdropping on Jane Austen s England How our ancestors lived two centuries ago London Little Brown Book Group p 312 ISBN 978 1 4055 1364 7 Potter SO 1902 Opium A Compend of materia medica therapeutics and prescription writing P Blakiston Son amp Company Retrieved 2007 10 13 Brecher EM Chapter 1 Nineteenth century America a dope fiend s paradise Licit amp Illicit Drugs Boston USA Little Brown and Company 1972 pp 3 7 Camel Press lincoln coffeetownpress com Scientific American Munn amp Company 1869 05 29 p 342 Richardson JG 1901 Medicology or Home Encyclopedia of Health New York Philadelphia and London University Medical Society pp 1276 and 1282 Musto DF 1999 The American Disease Origins of Narcotic Control 3rd ed Oxford University Press ISBN 9780198028925 Catalog No N 15 Report Second ed Hammond Indiana USA Frank S Betz Co 1915 p 320 Catalog No N 15 Report Second ed Hammond Indiana USA Frank S Betz Co 1915 p 318 Physicians Catalog of the Pharmaceutical and Biological Products of Parke Davis amp Company Report 1929 1930 pp 87 88 List of Controlled Substances Office of Diversion Control Drug Enforcement Administration United States Department of Justice Archived from the original on June 29 2013 Retrieved August 1 2010 Also under Schedule II are opium extracts opium fluidextract opium poppy Papaver somniferum granulated opium powdered opium and raw or gum opium each with an individual DEA number Belgische Farmacopee 5de uitgave 1966 part 3 Chase AW 1870 Dr Chase s Recipes Ann Arbor Michigan R A Beal p 133 Thomas Sydenham an English physician formulated this version of Laudanum in the 1660s Dick WB 1890 Encyclopedia of Practical Receipts and Processes Fifth ed New York Dick amp Fitzgerald Publishers pp 416 447 and 472 The Extra Pharmacopeia Martindale Vol 1 24th edition London The Pharmaceutical Press 1958 page 924 Macfarlan Smith Product List of Controlled Drugs Johnson Matthey Website Archived from the original on 2011 07 14 Retrieved 2011 02 14 Unapproved Drugs What s the Big Deal PDF International Journal of Pharmaceutical Compounding Winter 2006 Archived from the original PDF on 2010 07 05 Retrieved 2009 01 03 Warning Letter to Ohm Laboratories PDF Inspections Compliance Enforcement and Criminal Invesitations U S Food and Drug Administration December 21 2009 a b c d Opium Tincture Prescribing Information PDF Marathon Pharmaceuticals 2009 Archived from the original PDF on 2010 11 22 Retrieved 2009 01 03 Principles of Pharmacy entry on Tincture of Deodorized Opium W B Saunders Company 1917 1917 Retrieved 2008 01 27 a b End of Life Care for Patients with AIDS McGraw Hill 2006 2002 ISBN 9780070348837 Retrieved 2009 01 30 a b c d Neonatal Withdrawal Syndromes McGraw Hill 2006 2002 ISBN 9780071360012 Retrieved 2009 01 30 Material Safety Data Sheet for Morphine Sulfate Mallinckrodt Pharmaceuticals Archived from the original on 2008 10 15 Retrieved 2009 01 16 Medical Toxicology Toxic Dose of Morphine p 929 Wolter Kluwer Health 2004 ISBN 9780781728454 Retrieved 2009 03 06 The Brooklyn New York Daily Eagle January 10 1861 p 3 reported two unrelated instances in a single day a b c Hazard Alert Recurring Confusion Between Tincture of Opium and Paregoric Institute for Safe Medication Practices Archived from the original on 2007 10 15 Retrieved 2007 10 13 Dangerous Mixups Between Opium Tincture and Paregoric FDA Retrieved 2010 11 30 More Confusion Between Opium Tinctures Institute for Safe Medication Practices Retrieved 2009 01 17 permanent dead link Recurring Confusion Between Opium Tincture and Paregoric Pharmacy Times Retrieved 2009 01 30 permanent dead link Shelley M Frankenstein pp 197 198 Ever since my recovery from the fever I had been in the custom of taking every night a small quantity of laudanum for it was by means of this drug only that I was enabled to gain the rest necessary for the preservation of life Oppressed by the recollection of my various misfortunes I now swallowed double my usual quantity and soon slept profoundly But sleep did not afford me respite from thought and misery my dreams presented a thousand objects that scared me Chapter 47 Fatal Consequences Oliver Twist Charles Dickens Lit2Go ETC etc usf edu Stowe HB January 13 2006 Uncle Tom s Cabin via Project Gutenberg Eliot G 1861 3 Silas Marner The Weaver of Raveloe London William Blackwood and Sons p 19 Retrieved 2021 03 08 Collins W 1866 Armadale London Smith Elder amp Co p 122 Retrieved 2014 07 03 Clayton S November 21 1991 Heroine and after that the laudanum The Guardian Retrieved 2014 07 03 Four Page Translation of Charles Baudelaire s Prose Poem The Double Room The Met Museum Shellabarger S 1949 The Burnished Blade PDF London Macmillan amp Co pp 145 184 187 Archived from the original PDF on 2014 07 14 Retrieved 2014 07 03 Faulkner W Administrator ed Requiem for a Nun www potolkimaker com Archived from the original on 2016 09 18 Retrieved 2016 09 11 Surawicz B 2009 Doctors in Fiction Lessons from Literature Radcliffe Publishing p 19 ISBN 9781846193286 Retrieved 2014 07 03 Swarthout G 1975 The Shootist Doubleday p 68 Interview with the Vampire film Plot summary IMDb Winchester 2018 Rotten Tomatoes Fandango Media Retrieved Nov 5 2020 External links edit nbsp Media related to Laudanum at Wikimedia Commons Merck Prescribing Information for Laudanum Opium Tincture Includes detailed dosage information Retrieved from https en wikipedia org w index php title Laudanum amp oldid 1207192784, wikipedia, wiki, book, books, library,

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