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		<title>Tramadol Drug Abuse and Dependence</title>
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		<pubDate>Thu, 23 Oct 2008 03:36:08 +0000</pubDate>
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<p>Tramadol Hydrochloride may induce psychic and physical dependence of the morphine-type (µ-opioid). (See <strong><strong>WARNINGS</strong></strong> .) Dependence and abuse, including drug-seeking behavior and taking illicit actions to obtain the drug are not limited to those patients with prior history of opioid dependence.</p>
<p>The risk in patients with substance abuse has been observed to be higher. Tramadol is associated with craving and tolerance development. Withdrawal symptoms may occur if Tramadol Hydrochloride is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations.</p>
<p>Other symptoms that have been seen less frequently with reference listed drug discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be relieved by reinstitution of opioid therapy followed by a gradual, tapered dose reduction of the medication combined with symptomatic support.</p>
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		<pubDate>Thu, 23 Oct 2008 02:36:55 +0000</pubDate>
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<p>ULTRAM is a centrally acting synthetic analgesic compound. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to m-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.</p>
<p>Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to m-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producinganalgesia and 200 times more potent in m-opioid binding.</p>
<p>Tramadol induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound (see CLINICAL PHARMACOLOGY, Pharmacokinetics).</p>
<p>Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of ULTRAM. Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours.</p>
<p>Apart from analgesia, ULTRAM administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of an opioid.</p>
<p>However, tramadol causes less respiratory depression than morphine at recommended doses (see OVERDOSAGE). In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, ULTRAM has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic hypotension has been observed.</p>
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