Opioids effects

Administration of naloxone prevents or reverses the effects of the opiates. The exact mechanism of action is not fully understood, but it is believed that naloxone reverses opioid effects by competing for opiate receptor sites (see Chap. 19). If the individual has taken or received an opiate, the effects of the opiate are reversed. 

Opioidergic agents. Naltrexone and nalmefene, opioid antagonists with no intrinsic agonist properties, have been studied for the treatment of alcohol dependence. Naltrexone has been studied much more extensively than nalmefene for this indication. In 1984 naltrexone was approved by the FDA for the treatment of opioid dependence, and in 1994 it was approved for the treatment of alcohol dependence. Nalmefene is approved in the United States as a parenteral formulation for the acute reversal of opioid effects (e.g., after opioid overdose or analgesia). 

Opioid A recent study has shown activity of hypericum extracts at opioid receptors (Simmen et al. 1998). Extracts displace naloxone from p and x opioid receptors in the micromolar range (IC50 25 and 90 pg/ml, respectively). In contrast, extracts of the sedative herb Valeriana officinalis do not have this effect. This effect is due to unidentified constituents and not by the flavonoids quercetin or kaemferol. Opioids are known to have effects on emotion, so it is conceivable that activity of hypericum at p and k receptors contributes to its therapeutic effects (Gerra et al. 1998 Tejedor-Real et al. 1995 Walker and Zacny 1998). Although they are not conventional treatment for depression, opioids such as buprenorphine have been effective in treatment of refractory depression (Bodkin et a. 1995). However, for any further conclusions to be drawn, it would be necessary to further e uddate the opioid effects of hypericum to determine what functional effect, if any, hypericum has on the receptors. 

Neuroimaging of people with opioid dependence shows differences in this population compared to controls (Gerra et al. 1998). However, these differences may be more related to concurrent psychiatric disturbances than the opioid effects (Gerra et al. 1998). Chronic opioid dependence with comorbid depression is associated with decreased perfusion in the right frontal and left temporal lobes. A negative correlation... 

Opioid effects on memory are consistent in humans and animal models (Braida et al. 1994 Saha et al. 1991). Verbal and visual memory are impaired by morphine one hour after oral administration (Hanks et al. 1995 Kerr et al. 1991). These could be due to direct neuronal effects of opioids, or perhaps through indirect effects on cholinergic transmission. However, in some animal paradigms morphine can enhance memory consolidation through indirect dopaminergic mechanisms (Castellano et al. 1994). 

Tramadol is an opioid analgesic, which acts by exerting an opioid effect and through the stimulation of adrenergic and serotonin pathways. Compared with the other opioids, tramadol is less likely to cause the typical opioid side-effects, such as respiratory depression, and constipation. It is also less likely to cause addiction. 

Reversal of opioid effects Complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Opioid overdose Management of known or suspected opioid overdose. 

Patients tolerant to or physically dependent on op/o/c/s. Nalmefene may cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids. Closely observe these patients for symptoms of withdrawal. Administer subsequent doses with intervals of at least 2 to 5 minutes between doses to allow the full effect of each incremental dose of nalmefene to be reached. Reversal of postoperative opioid depression Use 100 mcg/mL dosage strength (blue label) refer to the following table for initial doses. The goal of treatment with nalmefene in the postoperative setting is to achieve reversal of excessive opioid effects without inducing a complete reversal and acute pain. This is best accomplished with an initial dose of 0.25 mcg/kg followed by 0.25 mcg/kg... 

Pharmacology The mechanism of action is not fully understood evidence suggests that it antagonizes the opioid effects by competing for the same receptor sites. Pharmacokinetics ... 

Instruct the patient to consume the lozenge over a 15-minute period. Longer or shorter consumption times may produce less efficacy than reported in clinical trials. If signs of excessive opioid effects appear before the unit is consumed, remove the drug matrix from the patient s mouth immediately and decrease future doses. 

CR/ER/SR If signs of excessive opioid effects are observed early in a dosing interval, the next dose should be reduced. If this adjustment... 

Dosage individualization Once therapy is initiated, pain relief and other opioid effects should be frequently assessed. Titrate patients to adequate effect (generally mild or no pain with the regular use of no more than 2 doses of supplemental analgesia per 24 hours). Patients who experience breakthrough pain may require dosage adjustment or rescue medication. Because steady-state plasma concentrations are approximated within 24 to 36 hours, dosage... 

Maintenance of anesthesia - After endotracheal intubation, decrease the infusion rate of remifentanil in accordance with the dosing guidelines in the table above. Because of the rapid onset and short duration of action of remifentanil, the rate of administration during anesthesia can be titrated upward in 25% to 100% increments or downward in 25% to 50% decrements every 2 to 5 minutes to attain the desired level of p-opioid effect. In response to light anesthesia or transient episodes of intense surgical stress, supplemental bolus doses of 1 mcg/kg may be administered every 2 to 5 minutes. At infusion rates more than 1 mcg/kg/min, consider increases in the concomitant anesthetic agents to increase the depth of anesthesia. 

Diphenoxylate Lomotil) is a meperidine derivative used as an antidiarrheal. It exhibits no morphinelike effects at low doses, but it produces mUd opioid effects, such as sedation, euphoria, and dependence, at higher doses. Its salts are highly insoluble in water, which reduces recreational use. Preparations often include atropine. 

E. Fentanyl patches have the same effect as fentanyl, only in a time-release manner. Thus, the purpose of the question is delineation of opioid effects—respiratory depression and constipation. The respiratory depression is life-threatening when the patch is used in nonambulatory patients, and it is therefore contraindicated for that purpose. 

The role of endogenous opioid peptides in mood and anxiety is relatively unknown. However, their existence in large concentrations within relevant limbic structures supports the hypothesis (M. S. Gold et al. 1982a). Direct opioid effects reportedly include anxiolysis and mood enhancement. The selective involvement of the opioids alone is unlikely because their activity is interdigitated with several conventional monoamines such as dopamine, serotonin, and norepinephrine. 

Levopropoxyphene is the stereoisomer of the weak opioid agonist dextropropoxyphene. It is devoid of opioid effects, although sedation has been described as a side effect. The usual antitussive dose is 50-100 mg every 4 hours. 

When given in the absence of an agonist drug, these antagonists are almost inert at doses that produce marked antagonism of agonist opioid effects. 

When given intravenously to a morphine-treated subject, the antagonist completely and dramatically reverses the opioid effects within 1-3 minutes. In individuals who are acutely depressed by an overdose of an opioid, the antagonist effectively normalizes respiration, level of consciousness, pupil size, bowel activity, and awareness of pain. In dependent subjects who appear normal while taking opioids, naloxone or naltrexone almost instantaneously precipitates an abstinence syndrome. 

Naloxone Antagonist at P-, 5, and receptors Rapidly antagonizes all opioid effects Opioid overdose Duration 1-2 h (may have to be repeated when treating overdose) Toxicity Precipitates abstinence syndrome in dependent users... 

Diphenoxylate Similar to loperamide, but high doses can cause CNS opioid effects and toxicity... 

Respiratory depression becomes an important side-effect when opioids are used for postoperative pain treatment, since the anesthetic agent and most adjuncts of anesthesia induce a long-lasting depressant effect on respiration, which can increase the opioid effects up to respiratory arrest. Therefore careful supervision of respiration during the postoperative period is mandatory (Mulroy, 1996). Opioid-induced respiratory depression can be interrupted by the opioid antagonist naloxone. 

Opioid receptor binding Oxycodone (Chen et al., 1991) is a p-selective opioid with a 10-fold higher receptor affinity than codeine. Both the parent compound and the high affinity metabolite oxymorphone mediate the opioid effects of the compound (Cleary et al., 1994). 

Serotonin is also involved in opioid effects on the transmission and processing of nociceptive information at a level rostral to the PAG. Borszcz (1999) and Borszcz and Streltsov (2000) have demonstrated that the antinociceptive effect of morphine administered into the PAG can be attenuated be serotonin antagonism in the central nucleus of the amygdala and the parafascicular nucleus of the thalamus, suggesting that serotonin is also involved in pain processing in higher brain centers. 

This discussion shows that the well-documented enhancement of opioid effects by antidepressants ( opioidsparing effect ) is likely to be related to a synergistic effect on monoaminergic transmission, possibly both at the spinal and at the supraspinal level. This synergistic interaction is based on the blockade by antidepressants of the reuptake of serotonin and/or noradrenaline released by the action of an opioid. 

M6G, on the other hand, is pharmacologically active and exerts important clinical opioid effects, especially when it is allowed to accumulate in the plasma of patients who have renal failure. However, after short-term morphine administration, the contribution of M6G to both analgesia and... 

Conley, K.M. et al., Modulating effects of a cold water stimulus on opioid effects in volunteers, Psychopharmacology, 131, 313, 1997. 

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