opiate

narcotic

[nahr-kot-ik]

Drug that produces analgesia (see analgesic), narcosis (stupor or sleep), and drug addiction. In most people narcotics also produce euphoria. Those that occur naturally in the opium poppy, notably morphine, have been used since ancient Greek times. The main therapeutic use of narcotics is for pain relief. Most countries limit the production, sale, and use of narcotics because of their addictive properties and detrimental effects and the incidence of drug abuse. With the development in the 19th century of the hypodermic needle and of heroin, five to 10 times as potent as morphine, the use and abuse of narcotics increased dramatically. A narcotic overdose can cause central nervous system depression, respiratory failure, and death.

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For other uses see Opiate (disambiguation), or for the class of drugs see Opioid.

In medicine, the term opiate describes any of the narcotic alkaloids found in opium, as well as any derivatives of such alkaloids.

Overview

Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy, Papaver somniferum. The major biologically active opiates found in opium are morphine, codeine, thebaine and papaverine. Synthetic opioids such as heroin and hydrocodone are derived from these substances, especially morphine and codeine. Noscapine, narceine and approximately 25 other alkaloids are also present in opium, but have little to no effect on the human central nervous system, and are not usually considered to be opiates. Opium is mostly produced in Asia.

The alkaloids

Morphine

Morphine is by far the most prevalent alkaloid in opium, making up anywhere from 10% to 16% of the total mass, and is responsible for many of its potentially harmful effects, such as pulmonary edema, respiratory depression, coma, cardiac and/or respiratory failure, with a normal lethal dose of 120 to 250 mg which corresponds to approximately two grams of opium.) However, the occurrence of pulmonary edema is uncommon. The most frequently-reported occurrences of opiate-induced pulmonary edema are among recreational heroin users. Although uncommon, reports of morphine-induced pulmonary edema are not unheard of. The primary difference is the more careful supervision of morphine administration compared to the lack of supervision and medical expertise among illicit heroin users. On the other hand, morphine may also be used in the treatment of pulmonary edema. Despite morphine's being the most medically-significant alkaloid, larger quantities of the milder codeine — most of it manufactured from morphine — are consumed medically.

The expression of the morphine content of opium as a percentage depends in part on the moisture content. When the government purchases the opium, as soon as practicable after it is collected, the moisture content is then usually about 30%. Commercial opium usually has around 10% to 15% moisture. Opium dried at ordinary temperatures still retains considerable moisture — usually about six percent — which can be driven off at about 103 degrees Celsius.

The quantity of morphine produced by poppy plants in the form of opium depends on two factors: the percentage of morphine in the opium, and the quantity of opium produced. The latter factor, in turn, depends in part on whether each capsule is bled several times, or just once. In Turkey, Bulgaria, Greece, and the Balkans, each capsule is bled only once, but, in most other opium-producing countries, like Iran, India, and Afghanistan, the capsules are incised repeatedly, often four or five times on different days, until they will yield no more latex. The quantity of latex falls off rapidly with later incisions, and so does the morphine content. Usually, all the opium obtained is mixed together. This is probably the chief reason for the often lower morphine content of Iranian and Indian opiums as compared with Turkish and Balkan opiums, although it must also be recognized that there are low-yielding and high-yielding strains of the poppy, one or the other of which may predominate in a given region.

Samples of opium assaying some 15% morphine from Japan, Indochina, and Afghanistan, as well as from Turkey, Greece, and the Balkans have been examined by the United Nations Secretariat. Afghanistan at one time exported two grades of opium, one of about 15% morphine and the other about 10%. The morphine content of dry capsule-chaff is about 0.25% to 0.5%, when not washed out by rain. Here again there are low-yielding and high-yielding varieties, but proper agricultural selection of poppies for morphine production means taking into account not only the percentage yield of morphine, but also the total weight of capsule-chaff produced per hectare, the poppy seed production per hectare, and other factors.

Most of the licit morphine is used to manufacture codeine through O-methylation. Morphine is also used to manufacture other drugs, such as heroin, dihydromorphine, hydromorphone, and many others. Of these, the conversion of morphine to heroin is particularly noteworthy due to heroin's unusual pharmacological properties. The acetylation of morphine's two hydroxyl groups results in a different drug in chemical structure, but nearly identical with regard to pharmacological properties, the principal difference being lipid solubility. This increase in lipid solubility allows heroin to enter the brain more rapidly than morphine. As heroin is not pharmacologically active it must first be metabolized. The active metabolites of heroin are morphine, 6-monoacetylmorphine and 3-monoacetylmorphine.

Codeine

The codeine content of opium is related inversely to the morphine content, but only in a general way. Codeine yield is closely related to the type of opium produced in a given district or even in some cases in an entire country. The opiums of the principal exporting countries have approximately the following percentages of codeine: Balkans 1.25%; Turkey 1.25%; Iran 3.4%; India 3.0%.

The highest percentages of codeine obtained by the United Nations Secretariat (averaging about 4.3%) were found in opium samples that came from north-eastern Asia (Korea, northern China).

The manufacturers’ statistics do not ordinarily show all the codeine obtained from opium. Some of it co-precipitates with the morphine, and there is no necessity of purifying the morphine completely of its codeine content, especially if it is to be used to manufacture more codeine.

Codeine is used to manufacture dihydrocodeine, hydrocodone, and others. It may also be used to manufacture the drugs ordinarily made by conversion of thebaine.

Thebaine and papaverine

The United Nations Secretariat is currently engaged in a survey, the most extensive ever attempted in this field, of opium samples from different regions for their thebaine and papaverine percentages. As yet, it is premature for general conclusions. However, the highest thebaine percentages found (nearly 5%) were in some samples from Indochina, which at the same time had virtually no papaverine. Both thebaine and papaverine have been high in most Iranian samples run. Papaverine is low in some Afghan and Indian opiums

Thebaine is the most poisonous opium alkaloid and is scarcely used for medical purposes. It is even omitted from some of the preparations of mixed opium alkaloids that are used as soluble substitutes for opium. However, it is converted into several other narcotics that have medical use: hydrocodone, acetyldihydrocodeine, oxycodone, and the highly-potent and powerful narcotic oxymorphone. Also Buprenorphine is made of it.

Papaverine has a considerable medical use, so much so that supplies available from opium have sometimes run short. It is then manufactured synthetically.

Terminology

In the traditional sense, opiate has referred to not only the alkaloids in opium but also the natural and semi-synthetic derivatives of morphine (itself an opiate). The term is often incorrectly used to refer to all drugs with opium- or morphine-like pharmacological action, which are more properly classified under the broader term opioid.

References

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