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Tramadol hydrochloride sr 150 mg every 12 hr or as prescribed Table 7 Nursing Mothers Precautions for Opioids during Pregnancy and Lactation Opioid analgesics have anticholinergic properties that are likely to exacerbate respiratory distress in neonates and may cause respiratory depression in lactating women. The addition of buprenorphine or naloxone may be considered to enhance postpartum analgesia when opioids are used regularly and should be withheld during lactation. Carcinogenic Properties Opiates may be carcinogenic. The International Agency for Research on Cancer (IARC) has established that no carcinogenic potential exists for either opium or morphine in humans (Group 2A). The World Health Organization (WHO) classified both morphine and opium as Group 1 (a "Group I" carcinogen). The World Health Organization also categorizes all analgesics as Group 3 (Group 2A) carcinogen-causing substances. The IARC and WHO cancer groups were established for purposes of hazard identification. Since the original designation, a wide variety of data has been accumulated and the carcinogenicity of both morphine and opium has been investigated by numerous studies. Opiates are genotoxic with the exception of morphine, which is not likely to cause DNA damage. Morphine causes damage at a dose of 200 mg/kg/day. Inactivation morphine by the indole deaminase method was carried out in rats given 500 mg/kg/day for 30 days (1). The indole deaminase method is most sensitive available for the detection of DNA-damaging agents. An important study conducted by the American Cancer Society in 1983 concluded that, "[l]ong-term chronic opioid use is considered to be a carcinogenic agent" (2). Epidemiologic studies have confirmed that opium use is associated with an increased risk of lung cancer, while the effects of morphine and diamorphine use are not well defined (3). A recent study of 3.2 million cancer cases reported that users of heroin and cocaine (but not opium) exhibited higher risks of lung cancer, while users crack cocaine had a greater risk of colorectal cancer (4). One cohort study found a 5-fold increase in lung cancer risk users of cannabis with opium versus without (5). Inhibition of P450 Both morphine and opium are inhibited by the action of p-glycoprotein 5 (P-gp) (6). P-gp is a glycoprotein in human immune cells called the immunoglobulin E (IgE) receptor superfamily. The IgE family is most important of the IgE receptor superfamily; it is also the most active isoform of receptor. The IgE receptors have four structural members, three of which have unique functions. The receptors that mediate pharmacologic action of opioids are members the IgE receptor superfamily. receptors are expressed on the surface of mast cells, basophils, basoreadiomas, lymphocytes, macrophages, neutrophils, dendritic cells, and other nonerythroid lymphocytes. In addition, the IEGR has been found in the blood and other body fluids of patients with various types cancer (4,7). Because of the potential for opioid analgesics to inhibit the activity of P-gp, presence immunoglobulin E ligands has Tramadol 50 mg tablet price been examined to ascertain their role in the induction of antitumor immunity. The p-glycoprotein 5 is an IgE-binding protein that contains two domains, one of which resembles a ligand-binding domain and the other a catalytic domain that interacts with the receptor. receptor-binding domain is a C-terminal region comprising seven globular domains and a transmembrane domain. One end of the ligand-binding domain contains six transmembrane domains that interact with the IgE ligand/receptor. transmembrane domain is critical for binding both the ligand and receptor (6). It was initially determined that morphine binds to the IgE receptor in only one position. However, several different in vitro studies, morphine binding to both the C-terminal and transmembrane domains of the receptors was found (8). These studies suggest that morphine and opium bind to the IgE receptor multiple times. However, the two receptor components are believed to be highly heterogeneous so that the binding domains of different receptor subtypes are likely to be equally effective at binding morphine and opium (12). Thus, the pharmacologic effects of morphine and opium are likely influenced by interactions of the different receptor subtypes. Dose-Response Studies Many studies indicate an opioid analgesic dose-response relationship, with acute opioid doses (with peak and duration of effect) generally being larger in comparison to repeated opioids or nonopioid analgesics ()

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