Laudanum is an opium tincture containing about 10% heavy opium powder (equivalent to 1% morphine).
Reddish chocolate and very bitter, laudanum contains almost all opium alkaloids, including morphine and codeine. Laudanum has historically been used to treat various conditions, but its primary use is 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. Today, laudanum is recognized as an addiction and is strictly regulated and controlled as such in most parts of the world. United Uniform United Uniform Law, for example, lists it on Schedule II.
Laudanum is known as a "whole opium" preparation because it historically contains all opium alkaloids. Today, however, this drug is often processed to remove all or most of the noskapine (also called narcotine) because it is a strong emetic and does not add to the analgesic or anti-propulsion 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 and theoretically in the UK, although today indications of drug therapy are generally limited to controlling diarrhea, reducing pain, and reducing withdrawal symptoms in infants born to mothers who are addicted to heroin or other opioids. Recent enforcement actions by the US Food and Drug Administration (FDA) against paregoric and opium tincture manufacturers indicate that the availability of opium tincture in the US may be in jeopardy.
The terms laudanum and opium tincture are generally interchangeable, but in contemporary medical practice the latter is used almost exclusively.
Video Laudanum
Histori
Paracelsus, a 16th-century Swiss-German alchemist, found that alkaloids in opium are much more soluble in alcohol than water. After experimenting with various opium herbs, Paracelsus found a special opium tincture that is very useful in reducing pain. He calls this preparation laudanum, derived from the Latin verb laudare, to praise. Initially, the term "laudanum" refers to a combination of opium and alcohol. Indeed, the Paracelsus laudanum is very different from the standard laudanum of the seventeenth century and beyond. The preparations contain opium, crushed pearls, musk, amber, and other substances. A researcher has documented that "Laudanum, as listed in London Pharmacopoeia (1618), is a pill made of opium, saffron, caster, ambergris, musk and nutmeg."
Laudanum remained largely unknown until the 1660s when British physician Thomas Sydenham (1624-1689) complicated the proprietary opium tinctures which he also called laudanum, though substantially different from the Paracelsus laudanum. In 1676 Sydenham published a seminal work, the Medical Observations on the History and Acute Disease Healing , in which he promoted the brand of opium tincture, and advocated its use for various medical conditions. In the 18th century, the efficacy of opium and laudanum drugs are well known. Some doctors, including John Jones, John Brown, and George Young, the latter publish a comprehensive medical text entitled The Treatise on Opium praised the good of laudanum and recommended a cure for almost every disease. "Opium, and after 1820, morphine, mixed with everything imaginable: mercury, marijuana, cayenne, ether, chloroform, belladonna, whiskey, wine, and brandy."
As one researcher has noted: "To understand the popularity of the drug subsided - even if only temporarily - cough, diarrhea and pain, one should only consider the living conditions of the moment". In the 1850s, "cholera and dysentery regularly grabbed the community, victims often died from weakened diarrhea," and heredity, consumption, disease, and rheumatism were common.
In the 19th century, laudanum was used in many patent medicines to "reduce pain... to produce sleep... to eliminate irritation... to check excessive secretion... to support the system... [and] as sleeping pills". The limited pharmacopoeia at the time meant that opium derivatives were among the most effective in available treatments, so laudanum was widely prescribed for diseases from colds to meningitis to heart disease, both in adults and children. Laudanum is used during the epidemic of yellow fever.
Countless Victorian women are prescribed medications to relieve menstrual cramps and vague pain. The nurse also bribes a laudanum for the baby. The Romantic and Victorian Era is characterized by the widespread use of laudanum in Europe and the United States. Mary Todd Lincoln, for example, the wife of US president Abraham Lincoln, is a laudanum addict, like the famous English poet Samuel Taylor Coleridge, cut off in the midst of an opium-induced writing session of Kubla Khan. by "people from Porlock". Initially the working class drug, laudanum is cheaper than a bottle of gin or wine, because it is treated as a drug for legal purposes and is not taxed as an alcoholic beverage.
Laudanum is used in home remedies and prescriptions, as well as single medications. For example, a medical book of 1901 published for home health use provides the following two "Simple Remedy Formulas" for "dysentery" [ sic ]: (1) thin boiled flour, 2 ounces; Laudanum, 20 drops; "Use as an injection [meaning as an enema] every six to twelve hours"; (2) rhubarb Tincture, 1 oz; Laudanum 4 drachms; "Dosage: One teaspoon every three hours." In the section entitled "Professional Recipes" is the formula for "diarrhea (acute)": opium tincture, deodorized, 15 drops; Subnitrate bismuth, 2 drachms; Simple syrup, 1 / 2 ounce; Mixed lime, 1 1 / 2 ounce, "A teaspoon every two or three hours for a one-year-old child." "Diarrhea (chronic)": aqueous ergot extract, 20 grains; Extract nux vomica, 5 grains; Opium extract, 10 grains, "Make 20 pills Take one pill every three or four hours."
The early 20th century brought an increase in the regulation of all kinds of narcotics, including laudanum, because the addictive addictive nature became more widely understood, and "patent medicines were attacked, largely because of their mysterious compositions". In the US, the Food and Drug Act of 1906 requires certain drugs, including alcohol, cocaine, heroin, morphine, and marijuana, to be accurately labeled with content and dosage. Previously many drugs were sold as patent drugs with secret ingredients or misleading labels. Cocaine, heroin, marijuana, and such drugs continue to be legally available without a prescription as long as they are labeled. It is estimated that sales of patented drugs containing opiates decreased by 33% after labeling was mandated. In 1906 in Britain and in 1908 in Canada "the law that requires disclosure of substances and restrictions on narcotic content is institutionalized".
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 the French Loi des stupÃÆ' Â © fiants in 1916, and the UK Dangerous Drug Act of 1920.
Laudanum is supplied to druggists and doctors in regular and concentrated versions. For example, in 1915, Frank S. Betz Co., a medical supply company in Hammond, Indiana, advertises Tincture of Opium, USP, for $ 2.90 per lb., Tincture of Opium Camphorated, USP, at 85 cents a lb., and Opium Deodorized Tingtur, for $ 2.85 per lb. Four versions of opium as a liquid extract are also offered: (1) Opium, Concentrated (tested) "To create Tincture Opii (Laudanum) USP Four times the usual USP strength" tincture, for $ 9.35 per liter; (2) Opium, Camphorated Conc. "1 oz Creating 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 the tincture, Used when the USP Titus is contraindicated" to $ 9.50 per pint, and (4) Opium (Aqueous), USP, 1890, "Tr. (assayed) Papayer Somniferum "for $ 2.25 per pint.
In 1929-30, Parke, Davis & amp; Co., a major US drug manufacturer based in Detroit, Michigan, sells "Opium, USP (Laudanum)", as Tincture No. 23, for $ 10.80 per pint (16 ounces of liquid), and "Kamphorated Opium, USP (Paregoric)", such as Tincture No. 20, for $ 2.20 per pint. The concentrated version is available. "Camphorated Opium, for USP Tinctures: Liquid No. 338" is "exactly 8 times the strength of the (legally) original," USP "Oppos Camphorated (Paregoric) Tinctures," designed to prepare the tincture directly. dilution, "and a cost of $ 7 per pint.Likewise, at a cost of $ 36 per pint," Opium Concentrated, for USP Tincture: Liquid No. 336 ", is" four times the power of the official tincture ", and" designed for preparation without tincture preparation. "The catalog also notes:" For a quarter pint bottle, add 80c. per pint to the price given for the pint. "
By the middle of the 20th century, opiate use was generally limited to pain medication, and opium was no longer medically accepted as an "all-drug". Furthermore, the pharmaceutical industry began to synthesize various opioids, such as propoxyphene, oxymorphone and oxycodone. This synthetic opioid, together with codeine and morphine is preferred over laudanum because a single opioid can be prescribed for various types of pain rather than laudanum cocktails, which contain almost all opium alkaloids. As a result, laudanum becomes very obsolete as an analgesic, since the main ingredient is morphine, which can be prescribed by itself to treat pain. Until now, no medical consensus from either (laudanum or morphine alone) is a better option for treating pain.
In 1970, the United States adopted the Uniform Controlled Uniform Act, which regulates opium tincture (Laudanum) as Schedule II substance (currently DEA # 9630), placing tighter controls on the drug.
At the end of the 20th century, the use of laudanum was almost exclusively limited to treat severe diarrhea. Current prescription information for laudanum in the US states that the only indication of opium tincture is as anti-diarrhea, although it is sometimes prescribed off-label for treating pain and neonatal withdrawal syndrome.
Maps Laudanum
Historical varieties
Several historical varieties of laudanum exist, including laudanum Paracelsus, Laudanum Sydenham (also known as tinctura opii crocata benzoic laudanum ( tinctura opii benzoica ), and opium deodorizer from opium (the most common contemporary formulation), among others. Depending on the version, additional amounts of additional active ingredients and ingredients (eg saffron, sugar, eugenol) are added, modifying the effect (eg, amount of sedation, or anti-tusive properties).
There may not be a single reference that lists all variations of laudanum pharmaceuticals that have been made and used in different countries for centuries since they were first formulated. The reason is that in addition to the official variations described in the pharmacopoeia, pharmacists and drug manufacturers are free to change the formula. Laudanum alcohol content may vary substantially; on the Laudanum bottle label that changed from the 20th century, the alcohol content was 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 at the end of the 19th century. The first, from an 1870 publication, is "Best Turkish 1 ounce of turkey, sliced ​​and poured on top of boiling water 1 gills, and work in a bowl or mixture until dissolved, then pour it into a bottle, and with 70 percent alcohol proof < span> 1 / 2 pt., rinse the dish, add the alcohol to the preparation, shake it well, and within 24 hours it will be ready for us Dose - From 10 to 30 drops for adults, according to the strength of the patient, or the severity of the pain.These thirty drops of laudanum will equal one opium pellet and this is much better to prepare than to put opium into alcohol, or other spirits alone, because in that case a lot of opium does not dissolve. "The remaining three formulas were copied from the publication of 1890:
- Laudanum Sydenham: "According to Paris Codex it is prepared as follows: opium, 2 ounces, saffron, 1 ounce, bruised cinnamon and bruised cloves, each 1 drachm; sherry wine, 1 pint, mix and maserate for 15 days and strain Twenty drops equal to one poppy. "
- Laudanum Rousseau: "Dissolve 12 ounces of white honey in 3 pounds of warm water, and set aside in warm place When fermentation begins to add to it a 4 ounce solution of opium is selected in 12 ounces of water Let the mixture stand for a month at a temperature of 86 Â ° Fahr, then strain, strain, and evaporate up to 10 ounces, finally strain and add 4 1 / 2 ounce alcohol proof. this preparation contains about 1 poppy grain. "
- Opium Tingtur (Laudanum), USP, associated with United States Pharmacoepia in 1863 : "Macerate 2 1 / 2 opium ounce, in a fine powder in 1 liter of water for 3 days, with frequent agitation Add 1 liter of alcohol, and maserate for 3 days longer Percolate, and replace 2 liter of tincture by adding dilute alcohol in percolator. "
Modern status
United States
Tincture of Opium is available by prescription in the United States. It is organized as a drug Schedule II (No. 9639) under the Controlled Substance Act.
In the United States, opium tincture is marketed and distributed by several pharmaceutical companies, each producing a drug formulation, which is odorless. Each mL contains 10 mg of anhydrous morphine (equivalent to 100 mg of opium powder), other opium alkaloids (except noskapin), and ethanol, 19%. It is available packaged in four-ounce bottles (118 mL) and 16 ounces (1 pint or 473 mL).
Tincture of Opium is known as one of many "unapproved drugs" administered by the US Food and Drug Administration (FDA); marketing and distribution of opium tincture apply today simply because opium tincture is sold before Federal Food, Drug & amp; Cosmetic Act of 1938. The "grandfathered" status protects the opium tincture from being required to undergo a rigorous FDA drug review and subsequent approval process. However, the FDA closely monitors opium tincture labeling. Opium tincture bottles are required by the FDA to provide a bright red "POISON" label considering potential drug and potential overdose (see discussion of confusion with Paregoric below). Although opium tincture becomes the "unapproved drug" as discussed above, the FDA website search does not reveal any current attempt to ban opium tincture or limit its use; In fact, until now the FDA has a web page devoted to the education of patients and practitioners about opium tincture. However, in a warning letter to the opium tincture manufacturer at the end of 2009, the FDA notes that "With regard to unapproved drugs, we found that your company produces and distributes the USP (Deodorized - 10 mg/mL) Opium Tincture prescription drug." Based on our information, there is no FDA-approved application on file for this drug product. "This warning may indicate an FDA policy change to ban the opium tincture or at least require the product to be brought within the FDA regulatory framework.
United Kingdom
Arium tincture remains in English 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 anhydrous morphine." This is a Class A substance under the Drug Abuse Act of 1971. At least one producer (Macfarlan Smith) is still producing opium tincture in the UK in 2011. "Gee's Linctus" is also available in most UK pharmacies, especially Independent stores. It contains "Opium Tinctures", at 0.083ml, per 5ml, and Squill Oxymel, a bitterly herbaceous plant extract, at 1,667 ml per 5ml.
Pharmacology
Arium tincture is useful as an analgesic and antidiarrheal. Opium increases the tone in the long segment of the longitudinal muscle and inhibits the propulsive contraction of the circular and elongated muscles. The pharmacological effects of opium tincture are mainly due to their morphine content. The quantity of papaverine and codeine alkaloid in opium tincture is too small to have a proven central nervous system effect.
Most modern formulations of opium tincture do not contain the narcotine alkaloids (also known as noscapine), which have antitussive properties. Even small doses of narcotics can cause profound nausea and vomiting. Since opium tincture is usually prescribed for its antidiarrheal and analgesic properties (not as antitussive), tincture of opium without narcotine is generally preferred. This "de-narcotics" or "deodorization" opium solution is formulated using an oil distillate to remove narcotics.
Oral doses of opium tincture are rapidly absorbed in the gastrointestinal tract and metabolized in the liver. Peak plasma concentration of morphine content is achieved in about an hour, and almost 75% of morphine content of opium tincture is excreted in urine within 48 hours after oral administration.
Medical use
Diarrhea
Arium tincture is indicated for the treatment of severe fulminant diarrhea (intense, fertile) that does not respond to standard therapy (eg, Imodium or Lomotil). 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. Refractory cases (such as diarrhea due to HIV/AIDS complications) may require a higher than normal dose, for example, 1-2 mL every 3 hours, for a daily total dose of up to 16mL daily. In terminal illness, there is no dose of ceiling for opium tincture; dose is increased slowly until diarrhea is controlled.
Neonatal abstinence syndrome
Arium tincture is used to treat neonatal abstinence syndrome (NAS) when diluted 1:25 (one part opium tincture to 25 parts water). The recommended dosage is 0.2 mL aqueous solution under the tongue every three hours, which can be increased by 0.05 mL every three hours until no objective withdrawal signs are observed. However, it should not, the dose exceeds 0.7 mL every three hours. Arium tincture gradually tapered for a period of 3-5 weeks, at which time the newborn should be completely free from withdrawal symptoms.
Pain
Given the high concentration of morphine, opium tincture is useful for treating moderate to severe pain. (The amount of codeine in the tincture is negligible and has no significant analgesic effect.) Tincture doses are generally the same as morphine in opioid-naÃÆ'¯ve patients, titrated upward as needed. The usual starting dose in adults is 1.5 mL per oral every 3 to 4 hours, representing the equivalent of 15 mg (about 1/4 grains) of morphine per dose. Patients who are opioid tolerant may require a higher than normal dose. For opioid-tolerant patients, doses in the 3-6 mL range every 3-4 hours will become commonplace. This will represent an equivalent daily dose of between 180 mg and 480 mg of morphine. There is a danger of overdose in treating pain with opium tincture; See below.
Today, morphine and codeine are available in various forms as single formulation products, which are easier to dose and much cheaper than opium tincture. Thus, opium is rarely prescribed to treat pain in contemporary medicine. Furthermore, opium tincture contains 17% to 19% alcohol, based on volume, which may complicate its use as an analgesic in patients for whom alcohol is contraindicated.
Dose
Extreme warning is recommended when giving a dose of Tincture of Opium. Dosage should be carefully measured by using a calibrated oral syringe or pipette. Pharmacist measurements should be avoided in contemporary medical prescriptions, and prescriber should dose opium tincture in mL or its fractions. If in the dosage prescriber dose assessment would be appropriate, it should be remembered that in contemporary medicine, there are 20 drops per mL.
The distinction between Tincture of Opium (Laudanum) and Camphorated Tincture of Opium (Paregoric) is important and should be remembered when managing any of these medicines. Care and precautions should always be done in dosing of Tincture of Opium, such as the use of dosage syringes or other appropriate measuring devices, and by pharmacists in preparing Paregoric from Laudanum, and to note that the doses in this article refer to Pharmacists of weight and size fluid. In particular, "the difference between the minimum and the fall must be kept in mind when calculating the dosage, at least always a sixty part of the liquid fluid regardless of the substantial character, while the decrease varies from one quarter to five two hundred and fifty parts, corresponding to the surface tension fluids. "Opium tungtur (Laudanum) and Camphorated Tinctures of Opium (Paregoric) each have 50.9 drops per gram; 50.0 drops per cc; 185.0 drops per liquid drachm; and 3.10 drops per minute. "The significance of this distinction is evident in the view of a false danger depending on the more general description of the Pharmacists' fluid steps, which usually lists 60 minutes per fluid dram, and 8 fluid drams per ounce of fluid (480 minims).
Dangers
Potential laudanum
Arium tincture is one of the most powerful oral formulations available with prescription morphine. Accidental or intentional overdoses are common with opium tincture due to the highly concentrated nature of the solution. Overdose and death can occur with a single oral dose of between 100 and 150 mg of morphine in healthy adults unhabituated with opiates. It represents the equivalent of two to three teaspoons (10-15Ã, ml) of opium tincture. Suicide by laudanum is not uncommon in the mid-19th century. Careful medical judgment requires removing a very small amount of opium tincture in a small drop bottle or in a pre-filled syringe to reduce the risk of accidental or intentional overdose.
Dangers of confusion with paregoric
In the United States, opium tincture contains 10 mg per mL of anhydrous morphine. In contrast, a weaker, paregoric opium tincture cousin, also known as an opium "lime tonalure", is 1/25 of opium tincture strength, containing only 0.4 mg of morphine per mL, 25 times overdose of morphine can occur if opium tincture is used in which paregoric is indicated.Armum tincture is almost always covered with drops, or mL fractions, or less commonly, in minims, while paregoric is poured in a teaspoon or a tablespoon.Thus, an order for an opium tincture containing a hint in a teaspoon is almost certainly in error To avoid this potentially fatal result, the term "tonalure lime" is avoided at paregoric sites because the former can be easily mistaken for opium tincture.
In 2004, the FDA issued a "Patient Safety" bulletin stating that "To help resolve the confusion [between the opium and paregoric tincture], the FDA will work with these two drug manufacturers to clarify labeling on containers and packet inserts." Indeed, 2005, the label for opium tincture begins to incorporate the concentration of morphine (10 mg/mL) in large text under the words "Opium tincture". The FDA has also warned pharmacists and other medical practitioners about the dangers of confusing this drug, and has recommended that opium tincture is not stocked as standard items (ie, that it should not be "on the shelf"), that opium tincture becomes dispensed in oral syringes, and that pharmacy software warns dispensers if the overwhelming dose of opium tincture appears to be indicated.
Despite the FDA's efforts over the past few years, the confusion continues, sometimes with lethal results. The Institute for Safe Medication Practices recommends that opium tincture is not stockpiled at all in the pharmacy inventory, and that "It may be time to throw out opium and paregoric tinktures into an outdated opioid therapy museum." Despite the risk of confusion, opium tincture, like many end-stage drugs, is indispensable for diarrhea that is difficult to treat for severely ill patients, such as those suffering from AIDS and cancer.
Misinterpreted "DTO"
Deodorized Tincture of Opium (DTO) is sometimes also incorrectly used to abbrate " diluted opium tincture", a 1:25 mixture of opium tincture into water prescribed to treat withdrawal symptoms in newborns whose mothers use opioid. while pregnant. The United States Pharmacopeia and FDA recommends that practitioners refrain from using DTOs in prescriptions, given this potential for confusion. In cases where the pharmacist has misinterpreted the DTO meaning "deodorized tincture of opium" when "diluted tincture of opium" is intended, the infant has received a 25-fold large overdose of morphine, sometimes resulting in death. Side effects
Side effects of laudanum are generally similar to morphine, and include euphoria, dysphoria, pruritus, sedation, constipation, reduced tidal volume, respiratory depression, and psychological dependence, physical dependence, miosis, and xerostomia. Overdose can cause severe respiratory depression or collapse and death. The ethanol component may also cause adverse effects at higher doses; side effects similar to alcohol. Long-term use of laudanum in non-terminal diseases is not recommended because of the likelihood of drug tolerance and addiction. Long-term use may also lead to abnormal liver function tests; in particular, prolonged use of morphine may increase blood serum levels of ALT and AST.
Treatment for overdose
Overdose of life-threatening opium tincture owes to the preparation of morphine content. Morphine produces depressive effects depending on the dose on the respiratory system, which can lead to deep respiratory depression, hypoxia, coma and ultimately breathing and death. If an overdose of suspected opium is suspected, rapid professional intervention is required. The main concern is rebuilding the proper airway and the ventilation agency is assisted or controlled if the patient is unable to breathe on his own. Other supporting measures such as the use of vasopressor and oxygen may be indicated to treat heart and/or lung failure. Cardiac arrhythmias or arrests will require sophisticated life-saving measures.
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