Medicinal opium forms

Chinese immigrants were often blamed for bringing opium to America, but opium had been present in America for some time, both in its raw form and in countless medical concoctions created by patent medicine makers, the unlicensed pharmacists of the day. Nevertheless, the wave of Chinese immigrants, who had used opium in China or picked up the habit in America, enhanced the demand for opium and thus expanded the market. 

Archaeological evidence shows that early civilizations were keenly aware of the medicinal properties of certain plants. In a.d. 78, for example, the Greek physician Dioscorides wrote Materia Medica, a treatise in which he described about 600 plants known to have medicinal properties. Included in this list was the opium poppy, shown in this chapter s opening photograph. Incisions in the seed capsules of this plant yield a milky sap. When air-dried and kneaded, the sap forms a soft material known as opium, which contains opioids, a class of alkaloids known for their pain-killing and tranquilizing effects. The molecule shown is morphine, one of the more abundant and potent opioids. 

Codeine, also known as methylmorpliine, C H2 NOt H20, is a colorless white crystalline substance, mp 154.9 C, slightly soluble in water, soluble in alcohol and chloroform, effloresces slowly in dry air. Codeine is derived from opium by extraction or by the methylation of morphine. For medical use, codeine is usually offered as the dichlotide, phosphate, or sulfate. Codeine is habit forming. Codeine is known to exacerbate urticaria (familiarly known as hives). Since codeine is incorporated in numerous prescription medicines for headache, heartburn, fatigue, coughing, and relief of aches and pains, persons with a history of urticaria should make this fact known to their physician. Codeine is sometimes used ill cases of acute pericarditis to relieve severe chest pains in early phases of disease. Codeine is sometimes used in drug therapy of renal (kidney) diseases. 

Elixir is an example 23% alcohol with 40 mg of morphine in every bottle. Also, Mrs. Winslow s Soothing Syrup, with 0.05 g of morphine per bottle. Even patent medicines to cure morphine dependence were sold inevitably they contained alcohol or opium. Thomas Edison patented and marketed his own nostrum, Poly-Form. It contained morphine, chloroform, ether, chloral hydrate, alcohol, and spices. 

Lead was also used in medicines, and in pastes for the treatment of skin diseases 2,000 years ago. In the nineteenth century some doctors recommended lead acetate and opium mixtures for the treatment of diarrhoea. This was described in early versions of the British Pharmacopoeia (Pil. Plumbi cum Opio). Certain lead salts were believed to be powerful astringents which would help in the treatment of wounds and promote healing. Thus Goulard s extract (liquor plumbi subacetatis fortis, or lead acetate) was still recommended in textbooks in the early twentieth century in dilute form for the treatment of ulcers, acute inflammatory skin conditions, and eczema and as a gargle in tonsillitis. Lead compounds have also been used to treat inoperable cancer. 

Nevertheless, long before the structure of morphine was realized, its analgesic properties were recognized and applied to medicine. Since morphine was in the pure form, it was far more effective than crude opium as an analgesic. But there was also a price to be paid—the increased risks of addiction, tolerance, and respiratory depression. 

Pests, once estabUshed, are extremely difficult to eradicate and prevention is easier and less expensive than the total sacrifice of the contaminated product. Apart from the commonsense hygiene precautions, many commercial firms use a variety of techniques to eradicate insects in stored crude drugs. None of the methods presently available are ideal dry or moist heat may damage the constituents fumigation with hydrogen cyanide or methylbromide may cause toxicity, while the commonly used ethylene oxide has been banned by the EU because of the suspected carcinogenicity of the chlorohydrin formed from the gas. Some companies use irradiation. Many studies have been conducted on the effects of this controversial method on the constituents of medicinal plants. Most reported studies show no effect on chemical content, with the exception of opium where... 

Quinolines play a relatively minor role in fundamental metabolism, methoxatin, an enzyme cofactor of methylotrophic bacteria, being one of the small number of examples. There are also comparitively few quinoline-containing secondary metabolites, in contrast to isoquinoline, which occurs, mainly at the 1,2,3,4-tetrahydro-level, in a large number of alkaloids - the opium poppy alkaloids papaverine and, in more-elaborated form, morphine are examples. Emetine, with two tetrahydroisoquinoline units, is a medicinally important amoebicide. 

The isoquinoline ring system is observed in the alkaloid papaverine, which is found in the opium plant. It has been used in medicine for many years, and it is still employed as a muscle relaxant and vasodilator. It is a member of a subclass of isoquinoline alkaloids called the benzyhsoquinoline alkaloids because of the presence of a form of a benzyl substituent (C6H5CH2-) at the 1-position. 

Adrenaline is produced in the brain as a stress activator and it causes increased psychophysical activity. Compounds isolated from special sorts of poppy have frequently been used, in the form of impure substances, as tranquilizers and are known under the name opium. The name is drawn from the Greek word OJtiov which means poppy. The first pure substance isolated from opium is heroin, a compound that has also been synthesized for medicinal use. 

In modem medicine, mily the purified opium alkaloids and their derivatives are commonly employed. Although the ripe poppy capsule can contain up to 0.5 % total alkaloids, opium represents a much concentrated form and up to 25 % of its mass is composed of alkaloids. Of the many (>40) alkaloids identified, some six represent almost all of the total alkaloid content. Actual amounts vary widely, e.g., morphine (4-21 %), codeine (0.8-2.5 %), thebaine (0.5-2.0 %), papaverine (0.5-2.5 %), noscapine (narcotine) (4—8 %), and narceine (0.1-2 %). A t3q>ical commercial sample of opium would probably have a morphine content of about 12 %. Powdered opium is standardized to contain 10 % of anhydrous morphine, usually by dilution with an approved diluent, e.g., lactose or cocoa husk powder. The alkaloids are largely combined in salt form with meconic acid, opium containing some 3-5 % of this material. Meconic acid is invariably found in opium but, apart from its presence in other Papaver species, has not been detected elsewhere. It gives a deep red-colored complex with ferric chloride, and this has thus been used as a rapid and reasonably specific test for opium. Of the main opium alkaloids, only morphine and narceine display acidic properties, as well as the basic properties due to the tertiary amine. Narceine has a carboxylic acid function, while morphine is acidic due to its phenolic hydroxyl. This acidity can be exploited for the preferential extraction of these alkaloids (principally morphine) from an organic solvent by partitioning with aqueous base (Table 15.6). 

Meconic acid, also known as acidum mecrmicum and poppy acid, is a chemical substance found in certain plants of the Papaveraceae family (poppy) such as Papaver somniferum (opium poppy) and Papaver bracteatum. Meconic acid constitutes about 5 % of opium and can be used as an analytical marker for the presence of opium. Meconic acid has erroneously been described as a mild narcotic, but it has little or no physiological activity, and is not used medicinally. Meconic acid forms salts with alkaloids and metals. These salts as well as meconic acid esters are called meconates. Meconic acid was first isolated by Friedrich Sertiimer in 1805 (Fig. 15.5). 

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