Opiates withdrawal from

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

The locus cemleus is important for the regulation of attentional states and autonomic nervous system activity. It has also been implicated in the autonomic and stress-like effects of opiate withdrawal. A noradrenergic pathway originating from the locus cemleus which descends into the spinal cord is part of the descending inhibitory control system, which has an inhibitory effect on nociceptive transmission in the dorsal horn. 

Drug-Indueed Aggression in Rats (Withdrawal from Opiates) ... 

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 ... 

Kantak and Miczek 1986). Amphetamine and cocaine, as well as dopaminergic agonists, increase further the already high levels of defensive responses in aggregated rats undergoing withdrawal from opiates, leading in extreme cases to the death of the subjects (Lai et al. 1971 Puri and Lai 1973). 

The LC neurons express a variety of autoreceptors, which allow compounds such as clonidine to decrease, and others such as yohimbine to increase LC firing (Buccafusco, 1992). Clonidine is used in the treatment of opiate withdrawal, since it decreases LC firing during the withdrawal from morphine. 

As indicated, buprenorphine can offer a quicker option than methadone, with a three-day course reported to be effective for withdrawal from heroin (Cheskin et al. 1994). The side-effects of clonidine which render it unsuitable for community treatment can be manageable in the inpatient setting, although the drug is being superseded by lofexidine where that is available. Controlled studies have found clonidine and lofexidine to be equally effective in alleviating withdrawal symptoms in inpatient detoxification from heroin (Lin et al. 1997) and from methadone (Khan et al. 1997), with lofexidine resulting in less hypotension and fewer adverse effects. Another double-blind controlled study found lofexidine to be broadly as effective as a ten-day methadone detoxification in inpatient opiate withdrawal (Bearn et al. 1996). 

Petursson H Lader MH (1981). Withdrawal from long-term benzodiazepine treatment. British Medical Journal, 238, 643-5 Philips G, Gossop M Bradley M (1986). The influence of psychological factors on the opiate withdrawal syndrome. British Journal of Psychiatry, 149, 135-8 Philhps AN, Gazzard BG, Clumeck N, Losso MH Lundgren JD (2007). When should antiretroviral therapy for HIV be started British Medical Journal, 334, 76-8 Poikolainen K (2002). Antecedents of substance use in adolescence. Current Opinion in Psychiatry, 15, 241-5... 

Similar sensitization of DA overflow in forebrain reward loci has been reported for opiates (Schrater et al. 1993 Spanagel and Shippen-berg 1993). With chronic continuous administration (or chronic intermittent treatment involving high doses) of psychostimulants, there is decreased DA synthesis (Brock, Ng, and Justice 1990), and—in withdrawal from such dosing regimens—depletion of basal extracellular DA in such brain reward loci as Acb (Parsons et al. 1991 Robertson,... 

Clonidine (Catapres) is another drug used to treat opiate addiction. It can relieve the anxiety, runny nose, salivation, sweating, abdominal cramps, and muscle aches of opiate withdrawal. Side effects are dry mouth, dizziness, and drowsiness. Clonidine is initially taken at 0.8-1.2 mg a day, maintained for a few days, and then gradually decreased. Combined with the opiate blocker naltrexone, clonidine can allow a more rapid detoxification (the removal of morphine from the body). Detox in a single day can be accomplished by heavy sedation or anesthesia while giving naltrexone to an unconscious addict. This controversial method has not been studied in controlled trials. 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

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. 

Clonidine [KLOE ni deen] is an a2 agonist that is used in essential hypertension to lower blood pressure because of its action in the CNS (see p. 189). It can be used to minimize the symptoms that accompany withdrawal from opiates or benzodiazepines. Clonidine acts centrally to produce inhibition of sympathetic vasomotor centers. Recently, an endogenous substance, agmantine, which appears to be the natural ligand at clonidine binding sites, has been identified. 

Addiction Abrupt withdrawal from barbiturates may cause tremors, anxiety, weakness, restlessness, nausea and vomiting, seizures, delirium, and cardiac arrest. Withdrawal is much more severe than that associated with opiates and can result in death. 

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