Opiates withdrawal

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. 

Use antihypertensive, tt2-agonist, relief of symptoms of opiate withdrawal... 

The initial dose of buprenorphine should be given at least 12-24 hours after the last heroin dose, 24 hours after the last methadone dose, or 48 hours after the last LAAM dose (see Table 2-3). The methadone dosage of methadone maintenance patients should be reduced to 30 mg/day before the transfer to buprenorphine is attempted. Ideally patients should show clear evidence of opiate withdrawal before receiving the first dose of buprenorphine, to avoid the risk that buprenorphine will precipitate more severe withdrawal. For the first day, sublingual buprenorphine/naloxone doses of 2/0.5-4/1 mg can be given every 2-4 hours, up to a maximum total dose of 8/2 mg/day. On the... 

Delfs JM, Zhu Y, Druhan JP, et al Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403 430 34, 2000... 

Gold MS, Redmond DE, Kleber HD Clonidine in opiate withdrawal. Lancet 1 929-930, 1978... 

Gossop M, Bradley B, Phillips GT An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21 -day in-patient methadone detoxification procedure. Addict Behav 12 1-6, 1987 GreenJ, Jaffe JH Alcohol and opiate dependence. J Stud Alcohol 38 1274-1293,1977 Green L, Gossop M Effects of information on the opiate withdrawal syndrome. Br J Addict 83 305-309, 1988... 

Maany I, Dhopesh V, Arndt lO, et al Increase in desipramine serum levels associated with methadone treatment. Am J Psychiatry 146 1611—1613, 1989 Maas U, Kattner E, Weingart-Jesse B, et al Infrequent neonatal opiate withdrawal following maternal methadone detoxification during pregnancy. J Perinat Med 18 111-118, 1990... 

Wesson DR, Ling W The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs 35 253-259, 2003... 

TABLE 33-5. Clinical Opiate Withdrawal Scale (COWS)... 

Bone or joint aches if patient was having pain. Previously, only the additional component attributed to opiates withdrawal is scored... 

Legradi GA, Rand WM, Hitz S, Nillni EA, Jackson IMD and Lechan RM (1996). Opiate withdrawal increases ProTRH gene expression in the ventrolateral column of the midbrain periaqueductal gray. Brain Research, 729, 10-19. 

Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray. J Neurosci 1997 17 8520-8527. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Conventional drug therapy for opiate withdrawal has been methadone, a synthetic opiate. Usual starting doses have been 20 to 40 mg/day. The dosage can be tapered in decrements of 5 to 10 mg/day until discontinued. Some clinicians use discontinuation schedules over 30 days or over 180 days. 

Clonidine can attenuate the noradrenergic hyperactivity of opiate withdrawal without interfering significantly with activity at the opiate receptors. Monitoring should include blood pressure checks, supine and standing, at least daily. 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

Rose JS, Branchey M, Buydens-Branchey L, Stapleton JM, Chasten K, Werrell A, Maayan ML. (1996). Cerebral perfusion in early and late opiate withdrawal a technetium-99m-HMPAO SPECT study. Psychiatry Res. 67(1) 39 7. 

The abstinence syndrome, evoked in animals by the withdrawal of nicotine, appears to be similar to that seen following opiate withdrawal (Malin et al. 1992). Furthermore, Malin and co-workers have reported that the abstinence syndrome can be provoked by the administration of the opiate antagonist, naxolone, to nicotine-treated rats (Malin et al. 1993). These results suggest that the abstinence syndrome... 

Gossop M (1988) Clonidine and the treatment of the opiate withdrawal syndrome. Drug Alcohol Depend 21 253-259... 

The cocaine addict most often presents during withdrawal after a binge of cocaine use. Cocaine withdrawal is not life threatening and does not require medical intervention in the same sense as alcohol or opiate withdrawal. It is, however, associated with a profound depression that can render the addict suicidal for 24-48 hours. The crashing cocaine addict should be assessed for suicide risk and, if indicated, the patient should be monitored in an emergency psychiatric setting or may require a brief 1-2 day inpatient psychiatric admission until the withdrawal resolves and the suicide risk is relieved. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

Paregoric [Camphorated Tincture of Opium] [C lll] [Narcotic Antidiarrheal] Uses D, Pain neonatal opiate withdrawal synd Action Narcotic Dose Adults. 5—10 mL PO daUy-qid PRN Peds. 0.25-0.5 mL/kg daily-qid Neonatal withdrawal 3-6 gtt PO q3-6 h PRN to relieve Sxs x 3-5 d, then taper ovo 2-4 wk Caution [B (D w/ prolonged use/high dose near term, +]... 

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