Opiates/opioids effects withdrawal

Amphetamine effects on aggression are markedly modulated by opiates and opioid peptides. Withdrawal from prolonged exposure to opiates may lead to increased defensive and aggressive responses in mice and rats and increased hostility in humans (Lai et al. 1971 Gossop and Roy 1976 ... 

An acute dose of 100-200 mg morphine, or its equivalent, in the non-tolerant adult can lead to respiratory depression, coma and death. In the tolerant individual, single doses or more than 10 times this amount are tolerated and have little visible effect. The development of tolerance to the opiates does not appear to be due to enhanced metabolism (metabolic tolerance) but is probably due to opioid receptor insensitivity (tissue tolerance). The dependent person therefore ultimately requires high doses of the opiate to prevent withdrawal effects. 

A study involving 16 opioid-dependent subjects found that amprenavir 1.2 g twice daily for 10 days decreased the AUCs for both f -methadone (active enantiomer) and 5-methadone (inactive enantiomer) by 13% and 40%, respectively. No clinically significant changes were noted in opioid effects and there was no evidence of opioid withdrawal. However, in another study methadone levels were reduced by 35% (range 28% to 87%) in 5 patients within 17 days of starting to take amprenavir 1.2 g twice daily and abacavir 600 mg twice daily. Two patients reported nausea before their daily methadone dose, which can be a sign of opiate withdrawal. Note that abacavir , (p.l75), may modestly reduce methadone levels, and could therefore have contributed to this effect. 

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... 

Suppression of heroin self-administration in opioid-dependent volunteers has been found to be greater at doses over lOOmg (Donny et al. 2005), and this relates to the three-level effects of methadone, the implications of which we often have to contend with in our discussions with patients. Basically low doses of methadone will suppress opiate withdrawal symptoms in dependent individuals, and this is what a lot of patients mean when they say that their dose (which may be considered too low by us) holds them. In medium to high levels of methadone there is less craving for opiates, and then at the highest doses there will be full narcotic blockade (Donny et al. 2002), but as already indicated the users themselves may not wish to take such dosages. 

This book is mainly concerned with the treatment of opiate misuse, for the simple reason that that is the form of drug misuse for which there are the most effective clinical approaches. As we have discussed, the treatment scene for opiate misusers, in contrast to other groups, is fundamentally altered by the widespread availability of the substitution option, in the form of methadone or alternative opioids. Physical dependence is part of the rationale for that approach, and the occurrence of clear-cut withdrawal symptoms also indicates the use of drugs such as lofexidine or clonidine, followed where possible by naltrexone. For reasons of severity of dependence and treatment options, it is therefore understandable that services are inclined to have caseloads dominated by opiate users. 

Narcotics (opiates and opioids) are natural, semisynthetic, and synthetic derivatives of the opium poppy. Drugs such as morphine, codeine, heroin, methadone, Darvon, and Percodan fall into this category. They are all depressants, but they are also potent painkillers, and except for heroin (which is illegal) they are prescribed to relieve pain and to control coughing and diarrhea. But because of their pleasurable effects and addictive properties, they can cause problems when taken for nonmedical reasons. Most nonmedical users take these drugs to experience euphoria, to avoid pain, and to relieve withdrawal symptoms. —... 

Methadone is used for the treatment of narcotic withdrawal and dependence. It occupies the opioid receptor in the brain and is the stabilizing factor that permits addicts to change their behavior and to discontinue heroin use. Methadone suppresses narcotic withdrawal for between 24 and 36 hours, and because it is effective in eliminating withdrawal symptoms, it is used in detoxifying opiate addicts. Ultimately, the patient remains physically dependent on the opioid, but is freed from the uncontrolled, compulsive, and disruptive behavior seen in heroin addicts.42... 

Opioids are known to alter mood states. For example, opiates such as morphine produce euphoria and pain relief. Prolonged use of and withdrawal from opiates produce depressive-like symptoms as well. Based on the mood-altering effects of opiates, the role of endogenous opiates in psychiatric symptoms of various diseases has been studied. In addition, endogenous opioids are believed to play a role in neuronal circuitry responsible for reward and pleasure. Therefore, it is thought that perhaps the anhedonia observed in depressed patients is due to dysregulation of endogenous opioids in neuronal reward circuitry. 

The opioid antagonists bind with high affinity to opioid receptors but fail to activate the receptor-mediated response. Administration of opioid antagonists produces no profound effects in normal individuals. However, in patients addicted to opioids, antagonists rapidly reverse the effect of agonists, such as heroin, and precipitate the symptoms of opiate withdrawal. 

Buprenorphine is a semi-synthetic, partial mu-agonist, highly lipophilic, opioid drug. Because it is a partial agonist, when buprenorphine competes with morphine or heroin for mu-receptors it can reduce their maximum effect. Buprenorphine binds strongly to mu and kappa opiate receptors it associates with the mu-receptor slowly (30 minutes), but with high affinity, low intrinsic activity and slow and incomplete dissociation. The slow dissociation from the receptor probably limits the intensity of withdrawal by preventing the rapid... 

Sublingual buprenorphine is an alternative to methadone in treating opiate dependence, but its opioid agonist effects pose the risk of intravenous abuse and subsequent dependence. This abuse potential may be hmited by using a combination of buprenorphine with naloxone, which will precipitate opiate withdrawal when given... 

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