Tramadol as an analgesic for mild to moderate cancer pain

Abstract

In most cancer patients, pain is successfully treated with pharmacological measures such as opioid analgesics alone or opioid analgesics combined with adjuvant analgesics (co-analgesics). Opioids for mild-to-moderate pain (formerly called weak opioids) are usually recommended in the treatment of cancer pain of moderate intensity. There is a debate whether the second step of the WHO analgesic ladder, which, in Poland, is composed of opioids such as tramadol, codeine, dihydrocodeine (DHC), is still needed for cancer pain treatment. One of the most interesting and useful drugs in this group is tramadol. Its unique mechanism of action, analgesic efficacy and profile of adverse effects are responsible for its successful use in patients with different types of acute and chronic pain, including neuropathic pain. The aim of this article is to summarize the data regarding pharmacodynamics, pharmacokinetics, possible drug interactions, adverse effects, dosing guidelines, equipotency with other opioid analgesics and clinical studies comparing efficacy, adverse reactions and safety of tramadol to other opioids in cancer pain treatment.

Introduction

Tramadol ((1RS, 2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclo-hexanol) is a synthetic opioid from the aminocyclohexanol group, an analgesic with opioid agonist properties that acts on the neurotransmission of noradrenalin and serotonin [13, 31, 83]. The drug was developed in Germany by Grünenthal in 1962, entering West Germany in 1977, Poland in 1992, the US in 1995 and the UK in 1997. In comparison with typical opioid agonists such as morphine, pethidine and the partial agonist buprenorphine, tramadol rarely causes respiratory depression [33, 107] or physical dependence [81].

Tramadol possesses opioid agonist activity and activates the spinal pain inhibitory system. Tramadol can be administered orally, subcutaneously (sc), intravenously (iv), intramuscularly (im), rectally and spinally. In patients with postoperative pain of moderate or severe intensity, tramadol administered iv or im is equivalent to the analgesic potency of pethidine [35] and pentazocine (oral route) [41]. In patients with postoperative pain of moderate intensity, tramadol analgesia (when administered iv in doses of 50–150 mg) is equivalent to the analgesic efficacy of morphine in doses of 5–15 mg [33], although during epidural administration, tramadol possesses 1/30 of the analgesic efficacy of morphine [2, 16]. Tramadol’s main adverse reactions are nausea, dizziness, sedation, dry mouth and sweating. Respiratory depression has been observed in a small percentage of patients after iv tramadol administration [33, 107]. Intravenous tramadol administration during childbirth does not cause respiratory depression in neonates [35]. Tolerance and physical dependence during tramadol treatment of up to 6 months are not significant, but the possibility of physical dependence during long-term treatment cannot be completely excluded [81]. Experimental and clinical trials indicate that tramadol is an effective analgesic, with little influence on the respiratory center, suggesting that it may be successfully used in the acute and chronic pain treatment of moderate and, in some cases, severe intensity. In experimental studies, tramadol has little immunosuppressive effect [59], possesses antidepressant activity [37] and is as effective as pethidine in the prophylaxis of post-anesthetic shivering [67].