Posts Tagged ‘analgesia’

Tramadol…safe and Effective

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In the wake of growing concerns over the fatal effects of some pain relievers in the market, pain specialists continue developed recommendations for alternatives – as effective yet not as dangerous.

News on the rising deaths of patients using COX-2 inhibitors and traditional NSAIDS (Nonsteroidal Antiinflammatory Drugs) has prompted medical experts to recommend the ban or withdrawal of drugs with these ingredients from the market.

After discussing the safety data for both NSAIDs and the COX-2 inhibitors, the group endorsed an expanded role for weak opioids, which are more effective in moderate-to-severe pain than NSAIDs. At the same time these possess other significant advantages included titratability, reversibility and lack of prostaglandin-associated side effects.

The role of combinations of weak opioids and other analgesic agents – in particular, tramadol plus paracetamol – merits particular attention.

A group of international pain specialists considered that tramadol and tramadol combinations offered a useful advantage in that they were ‘NSAID-sparing’. The drug could be used in combination with lower-than-usual doses of NSAIDs. Use of tramadol is recommended by medical societies.

The panel also recommended the proper utilization of weak opioids. Side-effects, they stressed, are a common reason given for non-compliance.

The panel agreed that a policy of ‘go low, go slow’ – starting with a low dose and increasing it gradually – should be used to achieve good analgesia without intolerable side-effects.

After thorough deliberations, the group concluded that it is very important to communicate clear guidance to physicians on appropriate prescribing of analgesics in this new climate of uncertainty regarding the continuing use of COX-2 inhibitors.

Way back in 2004, there was a move for the global withdrawal of rofecoxib (Vioxx), which and concerns regarding use of other COX-2 inhibitors. Rofecoxib is used to relieve pain, tenderness and stiffness caused by arthritis. It is in a class of COX-2 exhibitors.

This then raised concerns for the need of prompt and clear guidance to physicians regarding prescription of drugs with these compositions.

NSAIDS and Cox-2

There actually are two Cox enzymes, Cox 1 and Cox-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only Cox-1 produces prostaglandins that support platelets and protect the stomach.

NSAIDs block the Cox enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced.

Since the prostaglandins that protect the stomach and support the platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding.

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Assessment of Tramadol in the Management of Pain

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Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used as an analgesic for postoperative or chronic pain since the late 1970s, and became one of the most popular analgesics of its class in Germany. International interest has been renewed during the past few years, when it was discovered that tramadol not only acts on opioid receptors, but also inhibits serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake. This review aims to provide a risk-benefit assessment of tramadol in the management of acute and chronic pain syndromes.

Tramadol has been used intraoperatively as part of balanced anaesthesia. Such use is under discussion, however, as it was associated with a high incidence of intraoperative recall and dreaming, and postoperative respiratory depression has been described after intraoperative administration of high doses. Postoperatively, intravenous and intramuscular tramadol has been used with good efficacy. Analgesic doses were comparable with pethidine (meperidine) and 10 times higher than morphine. Nausea and vomiting were the most frequently reported adverse effects.

In controlled studies, haemodynamic and respiratory parameters were only minimally impaired. The risk of severe respiratory depression in typical dosages is negligible in comparison with other opioids used for postoperative pain management. Tramadol has been used with good results for the management of labour pain without respiratory depression of the neonate. It was also effective for the treatment of pain from myocardial ischaemia, ureteric colic and acute trauma. Good results have been published for cancer pain management with tramadol in several studies.

The potential for abuse or addiction seems to be minimal, and serious complications have not been reported. For patients with severe pain, the efficacy of morphine is superior, and most patients with adequate analgesia from tramadol had to be changed to a more potent opioid after a few weeks due to increased nociceptive input during tumour progression.

Tramadol can be recommended as a safe and efficient drug for step II according to the World Health Organization guidelines for cancer pain management.

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Tramadol CLINICAL PHARMACOLOGY – Pharmacodynamics

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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.

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.

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).

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.

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.

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.

This page is provided for educational and informational purposes only and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.