Opioid chronic effects

Efficacy and clinical use Naltrexone (Crabtree, 1984 Gonzalez and Brogden, 1988) is a pure opioid antagonist and has no analgesic activity. It is used for the treatment of opioid adverse effects, for opioid detoxification and as maintenance treatment for former addicts to avoid a relapse. In chronic opioid users, naltrexone may precipitate an acute withdrawal reaction. 

McNicol E, Horowicz-Mehler N, Fisk RA, et al. Management of opioid side effects in cancer-related and chronic noncancer pain a systematic review. J Pain. 2003 4 231-256. 

Even the most severe acute pain (that lasting hours to days) can usually be well controlled—with significant but tolerable adverse effects—with currently available analgesics, especially the opioids. Chronic pain (lasting weeks to months), however, is not very satisfactorily managed with opioids. It is now known that in chronic pain, presynaptic receptors on sensory nerve terminals in the periphery contribute to increased excitability of sensory nerve endings (peripheral sensitization). 

The chronic effects of abused drugs include tolerance and sensitization as well as the neurobiologic substrates for withdrawal symptoms. Much has been learned about these neurobiologic substrates for withdrawal in opioid dependence, including the activation of adrenergic brain systems such as the locus ceruleus during withdrawal. The latter findings have important treatment implications, such as the use of clonidine for opioid withdrawal. 

ROLE OF G PROTEINS IN CHRONIC EFFECTS OF DELTA OPIOIDS... 

The effects of buprenorphine (sublingually or by injection) in an opioid-dependent population have been studied (23,24). There was benefit in using buprenorphine to counteract opioid withdrawal effects in patients with chronic heroin use and subsequent dependence. However, the results are limited and the benefits shortterm if psychosocial support is not in place as part of an overall treatment package before buprenorphine is prescribed (25). 

The use of modified-release tramadol in chronic malignant pain has been examined in an open, prospective study in 146 patients with moderate to severe cancer pain 90 patients completed the 6-week trial (53). Dropouts were due to opioid adverse effects (20%), inadequate pain relief (9%), or both (2.5%). There was at least one adverse effect in 86%. Overall, 433 adverse effect events were reported but some reduced in frequency over the 6 weeks. Modified-release tramadol (400 mg/day) provided fast and efficient pain relief in almost 60% of patients both during initial dosing and long-term treatment. 

The acquired immunodeficiency S5mdrome (AIDS) epidemic has served to increase awareness that the adverse consequences of drug abuse extend beyond the acute and chronic effects produced by these drugs on the brain. The immune system has received considerable attention because both opioid and cannabinoid receptors have been identified in spleen cells. Additionally, specific effects of several drug classes on immune function are now well documented. These studies not only provide important insights into the potential harm that drugs of abuse inflict on a compromised immune system they provide opportunities to elucidate the mechanism of action these drugs. 

Methadone PO 2.5-10 mg q 3-4 h (acute)"" IM 2.5-10 mg q 3-4 h (acute)"" PO 5-20 mg q 6-8 h (chronic)"" Effective in severe chronic pain Sedation can be major problem Some chronic pain patients can be dosed every 12 hours The equianalgesic dose of methadone when compared with other opioids will decrease progressively the higher the previous opioid dose has been... 

Breivogel, C. S Selley, D. E., and Childers, S. R. (1997) Acute and chronic effects of opioids on delta and mu receptor activation of G-proteins in NG108-15 and SK-N-SH cell membranes. J. Neurochem. 68,1462-1472. 

As an NSAID, diclofenac is easy to use, and has been shown to be efficacious in arthritic syndromes, as well as for acute treatment of migraines, and small procedures. A major advantage of diclofenac, as with other NSAIDs, is its use in multimodal analgesia. In patients who are post-operative or with certain chronic pain syndromes, diclofenac can be used to provide additive analgesia and an opioid-sparing effect. Diclofenac has decreased side effects when compared to opioids in terms of nausea, respiratory depression, sedation, and constipation. 

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). 

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... 

Carroll KM, Ball SA, Nich C, et al Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence. Arch Gen Psychiatry 38 755-761, 2001 Centers for Disease Control and Prevention Recommendation for prevention and control of hepatitis (virus (HCV) infection and HCV-related chronic disease. MMWR Recommendations and Reports 47(RR19) l-39, 1998 Charney DS, Steinberg DE, Kleber HD, et al The clinical use of clonidine in abrupt withdrawal from methadone. Arch Gen Psychiatry 38 1273-1277, 1981 Charney D S, Heninger OR, Kleber H D The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 143 831-837, 1986... 

Make a plan for analgesia, in conjunction with a pain management service if possible, to control and prevent pain. Recommend an analgesic with ease of dosing and minimal side effects, realizing that patients with chronic pancreatitis may require large doses of opioids. 

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