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      Tramadol: a valuable treatment for pain in Southeast Asian countries

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          Abstract

          Background

          The supply of controlled drugs is limited in the Far East, despite the prevalence of health disorders that warrant their prescription. Reasons for this include strict regulatory frameworks, limited financial resources, lack of appropriate training amongst the medical profession and fear of addiction in both general practitioners and the wider population. Consequently, the weak opioid tramadol has become the analgesic most frequently used in the region to treat moderate to severe pain.

          Methods

          To obtain a clearer picture of the current role and clinical use of tramadol in Southeast Asia, pain specialists from 7 countries in the region were invited to participate in a survey, using a questionnaire to gather information about their individual use and experience of this analgesic.

          Results

          Fifteen completed questionnaires were returned and the responses analyzed. Tramadol is used to manage acute and chronic pain caused by a wide range of conditions. Almost all the specialists treat moderate cancer pain with tramadol, and every one considers it to be significant or highly significant in the treatment of moderate to severe non-cancer pain. The reasons for choosing tramadol include efficacy, safety and tolerability, ready availability, reasonable cost, multiple formulations and patient compliance. Its safety profile makes tramadol particularly appropriate for use in elderly patients, outpatients, and for long-term treatment. The respondents strongly agreed that tighter regulation of tramadol would reduce its medical availability and adversely affect the quality of pain management. In some countries, there would no longer be any appropriate medication for cancer pain or the long-term treatment of chronic pain.

          Conclusions

          In Southeast Asia, tramadol plays an important part in the pharmacological management of moderate to severe pain, and may be the only available treatment option. If it were to become a controlled substance, the standard of pain management in the region would decline.

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          Most cited references 38

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          Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study.

          Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines.
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            Management of cancer pain: ESMO Clinical Practice Guidelines.

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              Clinical pharmacology of tramadol.

              Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87-95% compared with capsules. Tramadol is rapidly distributed in the body; plasma protein binding is about 20%. Tramadol is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol and its metabolites are mainly excreted via the kidneys. The mean elimination half-life is about 6 hours. The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O- and N-demethylation of tramadol as well as renal elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation of tramadol is difficult because of differences between tramadol concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of tramadol and its active metabolites. The analgesic potency of tramadol is about 10% of that of morphine following parenteral administration. Tramadol provides postoperative pain relief comparable with that of pethidine, and the analgesic efficacy of tramadol can further be improved by combination with a non-opioid analgesic. Tramadol may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol appears to produce less constipation and dependence than equianalgesic doses of strong opioids.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2018
                24 October 2018
                : 11
                : 2567-2575
                Affiliations
                [1 ]Department of Anaesthesiology, University Malaya Medical Centre, Kuala Lumpur, Malaysia, ramani.vijayan@ 123456gmail.com
                [2 ]Department of Anaesthesiology, The Aga Khan University, Karachi, Pakistan
                [3 ]Department of Anaesthesia, Hameed Latif Hospital, Lahore, Pakistan
                [4 ]Department of Anaesthesiology, Hospital Selayang, Selangor, Malaysia
                [5 ]Department of Pain Medicine, Primus Hospital and Fortis Group of Hospitals, New Delhi, India
                [6 ]Pain Management Clinic, Department of Anesthesiology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
                [7 ]Department of Physical Medicine & Rehabilitation, Yangon General Hospital, University of Medicine-1, Yangon, Myanmar
                [8 ]Department of Anaesthesia & Pain Medicine, Virinchi Hospitals, Hyderabad, India
                [9 ]Pain Management Center, St Luke’s Medical Center, Metro Manila, Philippines
                [10 ]Department of Anesthesiology, Kulsum International Hospital, Islamabad, Pakistan
                [11 ]Department of Anesthesiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [12 ]Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Hatyai, Songkhla, Thailand
                [13 ]Department of Anesthesiology, Intensive Therapy, and Hospital Pain Management, Premier Bintaro Hospital, South Tangerang, Indonesia
                [14 ]Center for Pain Medicine, Department of Anesthesiology, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines
                [15 ]Pain Management Department, Sri Ramakrishna Hospital, Coimbatore, Tamil Nadu, India
                Author notes
                Correspondence: Ramani Vijayan, Department of Anaesthesiology, University Malaya Medical Centre, Lembah Pantai, 50603 Kuala Lumpur, Malaysia, Tel +60 37 949 2052, Fax +60 34 042 9987, Email ramani.vijayan@ 123456gmail.com
                Article
                jpr-11-2567
                10.2147/JPR.S162296
                6205131
                © 2018 Vijayan et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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