Tolerance doesn’t develop to which of the following symptoms/signs in opiate dependence?
C. Recent research has shed new light on the mechanisms involved in the development of opioid tolerance and dependence. Stimulation of opioid receptors located on critical cells such as those located in the locus coeruleus produces a decrease in cell fi ring. This effect reflects cellular hyperpolarization that results from both the activation of potassium channels and the inhibition of slowly depolarizing sodium channels. These actions occur in conjunction with a decrease in intracellular cyclic adenosine monophosphate (cAMP) levels. Among the given choices, both constipation and miosis have been traditionally thought to be resistant to tolerance. Kollars and Larson reviewed the two studies conducted in the late 60s which are often quoted to show that miosis does not develop tolerance. They quote a number of other studies which have shown that miosis is susceptible to tolerance. There are comparatively few data refuting the lack of tolerance response for constipation. Clinical experience hints that constipation is a major problem that persists without development of tolerance, especially in elderly people who are prescribed opiates as analgesics. This can be very difficult to treat, at times requiring enemas and in severe cases requiring manual evacuation.
References:
Donna is an active opiate user, who recently found out that she is pregnant. She approaches her GP saying she wants to stop her substance use and is not considering maintenance therapy with methadone. She is worried about withdrawal symptoms. Her GP calls you about the best time for Donna to undergo opiate withdrawal during pregnancy.
Which of the following is the most appropriate answer?
B. The view of treatment of opiate dependence has changed over the past 25 years. Previously it was thought that all patients should undergo withdrawal prior to delivery. Current practice acknowledges the fact that an abstinence state is almost impossible to achieve in this population. Hence most experts now advocate methadone maintenance as a way to reduce illegal drug use and remove the woman from a hazardous drug-seeking environment. Current consensus is that undertaking a medical withdrawal regimen could be accomplished most safely during the second trimester, with careful monitoring of foetal welfare by perinatal experts. The consensus is that opiate withdrawal could be best accomplished through stabilization with methadone followed by gradual reduction of the methadone dosage by 2–2.5 mg every 7–10 days. This should ideally be done only in a secondary care setting with the involvement of obstetricians and neonatologists.
Reference:
Which of the following symptoms is NOT found in opiate withdrawal?
B. Lacrimation – not dry eyes – is a symptom seen in opiate withdrawal. DSM-IV states that opiate withdrawal can be precipitated by cessation of (or reduction in) opioid use that has been heavy and prolonged (several weeks or longer) or administration of an opioid antagonist after a period of opioid use. Other symptoms typically associated with withdrawal are dysphoric mood, nausea or vomiting, muscle aches, rhinorrhoea, pupillary dilation, piloerection, sweating, diarrhoea, yawning, fever, and insomnia. Piloerection along with general ‘secretion’ from most of the glands is called the ‘cold turkey’, when people tend to detox without medical help.
Which of the following treatments for opioid dependence has been shown to reduce risk-taking behaviours associated with HIV transmission?
B. Systematic reviews of methadone maintenance vs. non-opioid therapy conducted by the Cochrane collaboration shows that methadone has a superior retention rate than control conditions. Methadone maintenance treatment has also been shown to reduce risk behaviours (specifically reduction in needle sharing) and thereby has achieved a reduction in the transmission of HIV. Intake of illicit opioids decreased in the methadone maintenance group, as shown by fewer positive urine tests for ‘morphine’ in these groups. Although criminal activity was found to be less in the group that was on methadone maintenance, the statistics did not show a significant difference. Nevertheless, individual randomized controlled trials have shown that methadone maintenance decreases criminal activity. In addition, methadone maintenance has shown to decrease rates of suicide and overdose in this population.
The half life of methadone in a patient with opioid dependence is:
C. Elimination of most synthetic opioids is complex. The peak plasma concentrations of oral methadone are reached within 2–6 hours, and initially plasma half-life is 4–6 hours in opioid-naive people and 24–36 hours after steady dosing of any type of opioid. It generally requires once daily dosing. Methadone is highly protein bound and equilibrates widely throughout the body, which ensures little post-dosage variation in steady-state plasma concentrations. Methadone can be used for short-term detoxification (7–30 days), long-term detoxification (up to 180 days), and maintenance (treatment beyond 180 days) of opioid-dependent individuals. In contrast, the elimination of a sublingual dosage of buprenorphine occurs in two phases: an initial phase with a half-life of 3–5 hours and a terminal phase with a half-life of more than 24 hours. Buprenorphine dissociates from its receptor binding site slowly, which permits an every-other-day dosing schedule.
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