Pharmacological effects opium

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Doctors tended to be enthusiastic about the powers of opium and to minimize its negative effects. In 1868, George Wood, a noted medical professor at the University of Pennsylvania and the president of the American Philosophical Society, described opium s pharmacological effects as follows ... 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

The pharmacological effects of this complex mixture of alkaloids in opium may, in some respects, be more beneficial than the effects of an individual alkaloid. The effect of opium in the treatment of diarrhoea is better than that of either morphine or codeine given individually. It is possible to calm the gastrointestinal tract with a dose which contains only half of the dose which would be necessary for morphine alone. The combination of the increase in stretch reflex caused by morphine and the inhibition of increased peristaltic action by papaverine leads to a better therapeutic effect. The increase in muscle tone due to morphine is reduced by papaverine, and other benzylisoquinolines also participate in this tranquillisation of the g.i. tract. In the normal 50 mg dosage of opium used for the treatment of diarrhoea there is about 5 mg of morphine, 0.5 mg of papaverine and 3 mg of nos-capine which contrasts markedly with a dose of 100—200 mg of papaverine if this were given alone. The analgaesic activity of opium is due mainly to the morphine present, as the levels of codeine, neopine and papaverine are relatively small. The respiratory depression effect of opium is also due to the morphine content and the antagonistic effects of noscapine and narcotoline are not so pronounced. Thus the main use of opium in medicine is for the treatment of diarrhoea. 

Enkephalins and Endorphins. Morphine (142), an alkaloid found in opium, was first isolated in the early nineteenth century and widely used in patent medicines of that eta. It is pharmacologically potent and includes analgesic and mood altering effects. Endogenous opiates, the enkephalins, endorphins, and dynotphins were identified in the mid-1970s (3,51) (see Opioids, endogenous). Enkephalins and endorphins ate Hsted in Table 9. 

Noscapine [128-62-1] (45) is the second most abundant alkaloid found in opium. Unlike most opium alkaloids, however, it has an isoquinoline rather than a phenanthrene ting system. Noscapine was first isolated in 1817 but its antitussive activity was not demonstrated pharmacologically until 1952 (63). Clinical studies have confirmed its effectiveness. It is not a narcotic and has a wide margin of safety when given orally. Death could be produced in rats only with doses > 800 mg/kg (64). Noscapine is isolated from the water-insoluble residue remaining after processing opium for the manufacture of morphine. 

Opioids. Activation of opioid receptors in the enteric nerve plexus results in inhibition of propulsive motor activity and enhancement of segmentation activity. This antidiarrheal effect was formerly induced by application of opium tincture (paregoric) containing morphine. Because of the CNS effects (sedation, respiratory depression, physical dependence), derivatives with peripheral actions have been developed. Whereas diphenoxylate can still produce clear CNS effects, loperamide does not Lullmann, Color Atlas of Pharmacology... 

Morphine was isolated from opium in 1806, which was a significant step in scientific pharmacology. For the first time, a powerful, pain-relieving medicine was available whose effects were predictable. However, it eventually became clear that the addictive potential of morphine is equal to that of opium, with many of the same side effects. Undaunted, scientists began the quest, which is ongoing, for the perfect opioid—a drug with the analgesic power of morphine, but with much milder side effects and little or no addictive potential. 

It was not until 1806 that a German chemist was able to isolate morphine from opium. This was a major breakthrough in pharmacology a pure, highly effective analgesic was finally available. Unlike opium, morphine s potency is always the same, which allows for accurate scientific study of its effects. Data from studies of morphine have provided specific information about the safest and most effective dosages to use. 

The prototypical opioid is morphine (A.137) (Figure A.39). Isolated in a crude form, called opium, morphine has been recognized as a potent pain killer for thousands of years. Although effective, morphine has a low oral availability (F = 25%). Two common derivatives of morphine include hydrocodone (Vicodin, A.138) and oxycodone (A.139), both of which have oral availabilities of greater than 75%. Oxycodone is often sold in an oral continuous-release form under the trade name of OxyContin. Not all opioids are semisynthetic derivatives of morphine. Dextropropoxyphene (Darvon, A.140) and tramadol (Tramal, A.141) are fully synthetic opioids. Both compounds preserve the pharmacophore of morphine as described in the morphine rule (see Chapter 11). Dextropropoxyphene and tramadol are depicted in Figure A.39 to highlight possible pharmacologically active conformations that resemble morphine. 

Laudanosine (6,7,3, 4 -tetramethoxy-1 -benzyltetrahydroisoquinoline) was isolated for the first time by Hesse (371) from opium. Intravenous administration of this substance to rabbits reduced the intraocular pressure (372). The whole effect manifested itself by motor restlessness, convulsions, disorders in coordination of movements, salivation, etc., which indicated an involvement of the extrapyramidal system and the mesencephalon. The effect produced by synthetic racemic laudanosine on rabbits was similar to that of the (+) form, but it was more toxic (373). The pharmacological properties of laudanosine have also been described (374). 

The term opiate describes the class of molecules structurally and pharmacologically related to morphine, the main alkaloid of opium, which is a product of Papaver somniferum, a plant illegally cultivated in Asia, whose effects have been recognized since 4000bc by the Sumers. 

Papaverine is an alkaloid present in opium, although it is not related chemically or pharmacologically to other opium alkaloids. It has a direct relaxant effect on smooth muscle, partly attributable to inhibition of phosphodiesterase. 

Papaverine Hydrochloride, USP. Papaverine hydrochloride. 6.7-dimelhoxy-l-veratryliso< uinoline hydrochloride. was isolated by Merck in 1848 from opium, in which it occurs to the extent of about Although its natural origin is closely related to morphine, the pharmacological actions of papaverine hydrochloride are unlike those of morphine. Its main effect is as a spasmolytic on smooth muscle, acting as a direct, nonspecific relaxant on vascular, cardiac, and other smooth muscle. Because of its broad antispas-modic action on ACh muscarinic receptors, it is often called a nonspecific antagonist. Papaverine hydrochloride has been used in the treatment of peripheral vascular disorders, but its u.se is limited by lack of potency. 

I. Pharmacology. Morphine is the principal alkaloid of opium and is a potent anal-gesio and sedative agent. In addition, it decreases venous tone and systemio vascular resistance, resulting in reduced preload and afterload. Morphine is variably absorbed from the gastrointestinal tract and is usually used parenterally. After intravenous injection, peak analgesia is attained within 20 minutes and usually lasts 3-5 hours. Morphine is eliminated by hepatic metabolism, with a serum half-life of about 3 hours however, the clearance of morphine is slowed, and duration of effect is prolonged in patients with renal failure. 

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