Opioids Withdrawal syndrome

The abrupt cessation of a repeatedly or continuously administered opioid agonist, or the administration of an antagonist typically results in the withdrawal syndrome. Signs and symptoms include sweating, tachycardia, hypertension, diarrhea, hyperventilation, and hyperre-flexia. 

A protracted abstinence syndrome may follow the acute opioid withdrawal syndrome and last for many weeks (Martin et al. 1973). In one study ofher-oin addicts detoxified with methadone, withdrawal distress peaked at day 20,... 

Personality variables, state of mind at time of withdrawal, and expectations of severity of symptoms all may affect withdrawal severity (Kleber 1981). One study found that merely providing addicts information about the withdrawal syndrome resulted in lower levels of withdrawal symptoms (Green and Gos-sop 1988). Naloxone rapidly induces a severe withdrawal syndrome, which peaks within 30 minutes and then declines rapidly. Until the antagonist is eliminated, only partial suppression of the withdrawal syndrome is possible, and then only by using very high opioid doses, which may cause respiratory depression when naloxone is metabolized. 

The answer is c. (Hardman, p 546.) Pentazocine is a mixed agonist-antagonist of opioid receptors. When a partial agonist, such as pentazocine, displaces a full agonist, such as methadone, the receptor is less activated this leads to withdrawal syndrome in an opioid-dependent person. 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Cessation of chronic cannabis use is known to produce a withdrawal syndrome consisting of restlessness, irritability, insomnia, nausea, and muscle cramping (table 10.9) (O Brien 1996). However, this syndrome is only seen in people who use high daily amounts and then suddenly stop (O Brien 1996). These symptoms are not usually seen in clinical populations, and frequent users of cannabis are not driven by a fear to avoid a withdrawal syndrome as seen in opioid addiction. 

Nicotine injection immediately reverses somatically expressed nicotine withdrawal syndrome (Malin et al. 1992), but it fails to do so after pretreatment with naloxone to block opiate receptors (Malin et al. 1996a). This suggests that nicotine relieves this aspect of nicotine withdrawal syndrome through inducing renewed release of endogenous opioid peptides. 

Severe opioid withdrawal syndromes Severe opioid withdrawal syndromes precipitated by accidental naltrexone ingestion have occurred in opioid-dependent individuals. Withdrawal symptoms usually appear within 5 minutes or less of ingestion and may last up to 48 hours. 

Symptoms of withdrawal -The opioid agonist abstinence syndrome is characterized by some or all of the following restlessness, lacrimation. 

It is inactive orally because of high first pass metabolism in liver. Metabolised by glucuronidation in liver. The main use of naloxone is in the treatment of acute opioid overdose (acute morphine poisoning). It also precipitates withdrawal syndrome when administered to morphine addicts. The constricted pupils of addicts dilate after administration of naloxone. This has been used as a diagnostic tool for opioid addiction. 

In defence of methadone, the main difficulties some individuals have are of adjusting first to its (relatively) noneuphoriant effect, and then to the prospect of being without drugs altogether (Milby et al. 1986). Methadone is used for more difficult candidates than non-opioid detoxification, and courses may become protracted partly due to actual reluctance to reduce, which compounds any difficulties relating to the drug. If detoxification has been imposed on an individual who is not ready to do it, the particular withdrawal syndrome of methadone is unlikely to be the critical factor, although it may not help. 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

Other indications for the use of antipsychotics include Tourette s syndrome, disturbed behavior in patients with Alzheimer s disease, and, with antidepressants, psychotic depression. Antipsychotics are not indicated for the treatment of various withdrawal syndromes, eg, opioid withdrawal. In small doses, antipsychotic drugs have been promoted (wrongly) for the relief of anxiety associated with minor emotional disorders. The antianxiety sedatives (see Chapter 22) are preferred in terms of both safety and acceptability to patients. 

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