Physical dependence begins to occur within 24 h if morphine is given 4-hourly, and after surgery some patients may be unwittingly subjected to a withdrawal syndrome that passes for general postoperative discomfort.
Acquired tolerance may rapidly reach a high degree, and an addict may take morphine 600 mg (heroin equivalent 400 mg) or even more several times a day. An average addict is more likely to take about 300 mg. Duration of tolerance after cessation of administration is variable for different actions, from a few days to weeks. Thus, addicts who have undergone withdrawal and lost tolerance, and who later resume their opioid careers may overdose themselves inadvertently.
Morphine or heroin dependence is more disabling physically and socially than is opium dependence (treatment of pain in opioid dependent subjects, see p. 343). Chronic exposure to opioids leads to adaptive changes in the endogenous opioid system and no doubt in receptor numbers, sensitivity and cellular response. The abrupt withdrawal of administered opioid usually provokes rebound or a withdrawal syndrome. This consists largely of the opposite of the normal actions of opioids. Also, noradrenergic mechanisms are modulated by endogenous opioids and these mechanisms are depressed by continuous opioid administration. Abrupt withdrawal rebound can be described as 'noradrenergic storm'.
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