Morphine effects

Opium Street Names Auntie Emma, big O. black stuff, block, gum, hop, ope, tar (brand generic called tincture of opium, laudanum, paregoric (CIII), B O suppositories [CIII]) Use Some medical uses (antidiarrheal, antitussive, antispas-modic) illegally used to produce morphine and h oin can be swallowed or smoked Actions Narcotic contains morphine Effects Pain relief, euphoria, drowsiness/N, constipation, confusion, sedation, resp dqjression and arrest, tol -ance, addiction, unconsciousness, coma, death... 

It is a potent and long acting opioid with partial mu receptor agonist property. 25 times more potent than morphine. Effects are similar to morphine but constipation is less marked. It undergoes extensive presystemic elimination and therefore is... 

Hasegawa, A.E. and Zacny, J.P. The influence of three L-type calcium channel blockers on morphine effects in healthy volunteers, Anesth. Analg. 1997, 85, 633-638. 

Buprenorphine is derived from thebaine. It is a partial mu agonist with kappa antagonist activity. Buprenorphine has 25 to 50 times the potency of morphine. It is used to produce a longer-lasting analgesia than morphine. Effects of buprenorphine last longer because it is released more slowly from mu receptors than morphine. It is available as an injectable for intramuscular (IM) or intravenous administration in a 1-ml solution containing 0.3 mg buprenorphine (as buprenorphine HC1) for the relief of moderate to severe pain. It is also available to treat opioid dependence in the formulation of a tablet,51 alone or in combination with naloxone, in 2- or 8-mg... 

Abboud TK, Afrasiabi A, Davidson J, Zhu J, Reyes A, Khoo N, Steffens Z. Prophylactic oral naltrexone with epidural morphine effect on adverse reactions and ventilatory responses to carbon dioxide. Anesthesiology 1990 72(2) 233-7. 

Ultra-rapid alleles lxN, 2xN Codeine Increased morphine production Increased morphine effects and risk... 

It was not mentioned in these reports if ATP was included in the media. An absence of ATP may account for the failure to see effects at low K concentrations. In other experiments End et al. (67) have demonstrated morphine effects on Ca efflux from mouse neuroblastoma cells. 

In this most interesting series of papers a great number of oripavine derivatives have been prepared and screened and it has been demonstrated that the analgetic potency of morphine can be increased by an unprecedented degree. Also, dissociation of the morphine effects has been obtained, which may go beyond that which has been reached with other morphine derivatives. The question of addiction, which is of paramount importance with such highly active compounds, still seems to be unsolved. Little has been published on this aspect yet and, in general, clinical reports are still scarce. 

Importance of in vitro measurements of adrenocortical steroid synthesis in assessing locus of morphine effects Essman, Walter B. Rosenthal, Richard... 

Morphine effects on RNA synthesis in purified oligodendroglial nuclei... 

Hurwitz, A., M. Garty, and Z. Ben-Zvi. 1988. Morphine effects on gentamicin disposition and toxicity in mice. Toxicol. Appl. Pharmacol. 93(3) 413-20. 

Clinical pharmacology of synthetic opioid analgesics (fentanyl, sufentanil, remifentanil) is not substantially altered by renal failure. In contrast, morphine is a poor choice in patients with severe renal impairment, particularly when given repetitively. Morphine effects maybe prolonged due to very slow elimination of active metabolites. Postoperative analgesic regimens should also avoid nonsteroidal anti-inflammatory drugs. 

Morphine and its salts are very valuable analgesic drugs but are highly addictive. In addition to suppression of pain, morphine causes constipation, decreases pupillary size and depresses respiration. Only the (-l-)-stereoisoraer is biologically active. They appear to produce their effects on the brain by activating neuronal mechanisms normally activated by... 

Codeiae (2, R = CH3) occurs ia the opium poppy along with morphine (2, R = H) but usually ia much lower concentration. Because it is less toxic than morphine and because its side effects (including depression, etc) are less marked, it has found widespread use ia the treatment of minor pain and much of the morphine found ia cmde opium is converted to codeiae. The commercial coaversioa of morphine to codeiae makes use of a variety of methylating ageats, amoag which the most common are trimethylphenylammonium salts. Ia excess of two huadred toas of codeiae are coasumed anauaHy from productioa faciUties scattered arouad the world. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

The CCK system shares one property with the opioid system, ie, the existence of selective nonpeptide antagonists. These include aspedicine, a natural benzodiazepine (136), and Devazepide (L-364,718 MK-329) (137). Selective, potent peptide antagonists for CCK, eg, Cl-988 and PD 134308, have been developed that maybe useful as anxiolytics and as dmgs which increase the analgesic effect of morphine but at the same time prevent morphine tolerance (138) (see Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

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. 

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Codeine, mol wt 299.3, is a significantly less potent analgesic than morphine, requiring 60 mg (0.20 mmol) to equal the effectiveness of 10 mg (0.04 mmol) of morphine. However, codeine is orally effective, and it is less addictive and associated with less nausea than morphine. Codeine is used as an antitussive agent, although newer, nonaddictive agents are preferred (see Expectorants, antitussives, and related agents). 

The quest for compounds that combined the analgesic properties of morphine, were nonaddictive, and lacked the side effects of nalorphine, led to the development of the dmgs shown in Table 3. These compounds have both agonist and antagonist activities. Nalbuphine (14) (23) and buprenorphine... 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

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. 

Codeine, like morphine, is isolated from the opium poppy. However, the low yield of 0.7—2.5% does not provide sufficient material to meet commercial demands. The majority of marketed codeine is prepared by methylating the phenolic hydroxyl group of morphine. Morphine yields from opium poppy are 4—21%. When prescribed for cough, the usual oral dose is 10—20 mg, three to four times daily. At these doses, adverse side effects are very few. Although the abuse potential for codeine is relatively low, the compound can substitute for morphine in addicts (47). 

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. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

---