Morphine narcotic effect

Morphine is self-administered by Friedrich Wilhelm Sertiirner and is named after Morpheus, the Greek god of dreams, after he experiences its narcotic effects. 

Tolerance develops to the narcotic and analgesic actions of morphine, so that increasingly larger doses are needed to render patients pain free. Tolerance develops to many effects of morphine such as analgesia, euphoria, narcosis, respiratory depression, hypotension, and antidiuresis. Morphine-induced bradycardia may be experienced. However, no tolerance develops to morphine-induced miosis or constipation. If the administration of morphine is discontinued, the tolerance is lost and the preaddiction analgesic doses of morphine become effective once more. 

Opium has been widely used as a recreational drug and pain-killing remedy for centuries. The analgesic and narcotic effects of opium are largely due to morphine. Poppy seed tea, which contains morphine, was used as a folk remedy in parts of England until World War II. 

Morphine Morph ine-6-glucu ron ide Possibly more active than parent compound may contribute to prolonged narcotic effect in renal failure patients... 

In a medical sense, a narcotic is a substance that causes narcosis nomen est omen). Narcosis primarily means a decrease in activity, maybe decrease of pain, hallucinations, a decrease of interest in the external world, a sort of introversion. Prohibited narcotics include heroin, morphine, marijuana, and LSD (lysergic acid diethylamide). Cocaine does not have any of these classic narcotic effects. Medically, it is a stimulant, a substance that increases activity. This has dangers of its own, so prohibiting the use of cocaine without doubt serves the interests of society in general. 

Narceine is an opium alkaloid produced by the Papaver somniferum (opium poppy) plant. It is a bitter, crystalline compound with narcotic effects and was formerly used as a substitute for morphine (Fig. 15.5). 

The role of biogenic amines as related to narcotic effects continues to be an active field. Further studies appeared concerning enhcuiced cerebral serotonin turnover,53 balance wi th the catecholamine system,5 dopamine turnover in toe striatum,35 and homovanillic acid content in the caudate nucleus.5° Additional details of the cyclic-AMP antagonism of morphine analgesia,57 and its effect on tolerance and physical depend-ence5 were also published. 

Narcotic Antitussives. Since its isolation in 1832, codeine [76-57-3] (27) has been one of the most widely used and effective compounds for the treatment of cough. Though less potent than morphine [57-27-2] (28), it has become the reference against which most antitussives are measured. 

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. 

A characteristic feature of the action of the opium alkaloids is their simultaneous depressing and exciting action on the central nervous system. In this respect there is no clear line of demarcation between the morphine group—morphine, codeine and thebaine—and the papaverine-narcotine group, and as the series is ascended in the order, morphine, papaverine, codeine, narcotine, thebaine, narcotic action diminishes and power of rellex stimulation increases until in thebaine a strychnine-like effect is exhibited. 

Thehaine stands at the other end of the series from morphine and is a convulsant poison rather than a narcotic (see table, p. 261). Hildebrandt states that it excites the reflexes of cold-blooded animals but in dogs it exerts a narcotic and anti-emetic effect resembling that of morphine rather than that of chloromorphide. The alkaloid is scarcely used in medicine as such, but is a primary material for the preparation of certain of the modern morphine derivatives, such as hydroxydihj dro-codeinone and methyldihydromorphinor.e. 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

The major use of the narcotic analgesic is to relieve or manage moderate to severe acute and chronic pain. The ability of a narcotic analgesic to relieve pain depends on several factors, such as the drug, the dose, the route of administration, the type of pain, the patient, and the length of time the drug has been administered. Morphine is the most widely used opioid and an effective drug for... 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Extensive molecular dissection of the morphine molecule over the past several decades led to a host of molecules which showed narcotic analgesic activity even though they possessed but faint suggestion of the structural features present in morphine itself. Thus, both cyclic molecules such as meperidine (70) and alphaprodine (71), and acyclic Compounds such as methadone (72) were found to be effective analgesics. Common features of these compounds were formalized by the Beckett-Casy rule, which states as minimal required structural features (a) an aromatic ring attached to... 

Russell J, Bass P, Goldberg LI, Schuster CR, Merz H. (1982) Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists. Eur J Pharmacol 78 255-261. 

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