Pharmacol Rep
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Randomized Controlled Trial
Preoperative tramadol combined with postoperative small-dose tramadol infusion after total abdominal hysterectomy: a double-blind, randomized, controlled trial.
This double blind, randomized, controlled trial investigated whether a single preoperative intravenous (iv) dose of tramadol (100 mg) given 30 min before abdominal hysterectomy resulted in improved analgesic efficacy, reduced postoperative morphine patient-controlled analgesia (PCA) use and reduced side effects when combined with a postoperative small-dose tramadol infusion. Two-hundred twenty-four patients undergoing elective abdominal hysterectomy were randomly allocated to one of two groups: the tramadol group (n = 113) received iv tramadol (100 mg) 30 min before surgery, and the control group (n = 111) received an equivalent volume of normal saline. Upon awakening from general anesthesia, all patients received a loading dose of 0.5 mg/kg of tramadol and a small-dose infusion of tramadol (0.1 mg/kg/h) for 48 h. ⋯ Preemptive tramadol was associated with superior analgesia at rest and with movement in the first 24 h after surgery (p < 0.01), a longer interval to first morphine PCA request (p = 0.019), and reduced morphine PCA use (p = 0.017). The tramadol group had reduced nausea (p = 0.015), dizziness (p = 0.001) and drowsiness (p = 0.0001), while other side-effects were similar. In conclusion, a single dose of iv tramadol (100 mg) 30 min prior to abdominal hysterectomy improves analgesia, and reduces morphine PCA requirements, nausea, dizziness and drowsiness when combined with a postoperative small-dose tramadol infusion and morphine PCA when compared to the same analgesic regimen that omitted the preemptive tramadol.
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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. ⋯ 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.
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Recent studies have suggested that melanocortins contribute to the generation and/or maintenance of pathological pain. Experimental evidence indicates a primary role for melanocortin 4 (MC4) receptors in pathological pain. In a previous study, we described the presence of MC4 receptor transcripts in the dorsal root ganglia (DRG). ⋯ Together, painful neuropathy resulted in the up-regulation of MC4 receptors in the spinal and peripheral nociceptive pathways. This up-regulation of MC4 receptors promotes the pronociceptive action of their endogenous ligands. Therefore, a block of the MC4 receptors results in the antagonism of neuropathic pain and such treatment could be beneficial therapeutically for individuals with chronic neuropathic pain.
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Mildronate (3-(2,2,2-trimethylhydrazinium) propionate), which is mostly used in cardiological practice and is considered an anti-ischemic drug, was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation. Recently it was shown that the mitochondrial respiratory chain may also be a target for mildronate action. In this study, we aimed to investigate whether mildronate can protect the liver against a 90-min normothermic ischemia/30-min reperfusion-induced mitochondrial dysfunction. ⋯ No steatotic livers were observed in any experimental groups after mildronate pre-treatment. In conclusion, 90 min of liver ischemia followed by a 30 min reperfusion has a deleterious effect on rat liver mitochondrial function. Mildronate pre-treatment of rats at doses of 100 or 200 mg/kg/day for one or two weeks did not prevent ischemia/reperfusion-induced mitochondrial dysfunction and liver injury.
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Comparative Study
Optimization of lidocaine application in tumescent local anesthesia.
Tumescent local anesthesia is based upon the infusion of large volumes of neutralized anesthetic solutions, mainly lidocaine, at very low concentrations. This results in the paralysis of sensory nerve endings and minute nerve twigs, leading to a reduction in pain. The aim of this study was to assess the safety of lidocaine application in tumescent local anesthesia on different regions of patient's bodies. ⋯ The study of lidocaine concentration and pharmacokinetic parameters also showed that there may potentially be a higher risk of a large anesthetic concentration developing within a short period of time during anesthesia of the upper parts of the body. During tumescent anesthesia, significantly higher plasma concentrations of lidocaine were observed in the face and neck than in the hypogastrium, buttocks and thighs, axillae, breast and trunk 0.5 to 4 h after its infusion. This indicates the need for carefully conducted patient observations immediately after infiltration into the aforementioned areas.