Pharmacology
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Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. ⋯ These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.
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We investigated whether capsaicin induces itching in skin with existing inflammation. We induced skin inflammation by intradermal injection of complete Freund's adjuvant (CFA) in the neck of mice. Four days later, we injected capsaicin in the same area and counted the number of scratching bouts for 30 min. ⋯ In animals injected with capsaicin into the hind paws, licking behavior was significantly inhibited via a μ-receptor-dependent mechanism. Our results show that TRPV1 activation, which normally induces pain, evokes an itch-related response in the presence of inflammation. This model may be interesting for future studies to explore the mechanism of a painful stimuli-induced itch observed under pathological conditions.
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Randomized Controlled Trial
Co-administration of ondansetron decreases the analgesic efficacy of tramadol in humans.
Tramadol, a central analgesic acting on serotonin neurotransmission, is often co-used with ondansetron, a 5-HT(3) antagonist, for the management of postoperative pain to decrease nausea and vomiting. The aim of the study is to test the hypothesis that this drug combination raises tramadol requirement by patient-controlled analgesia (PCA). ⋯ Tramadol consumption (mg × kg(-1) × h(-1)) was higher in the ondansetron group at the 2-hour time point compared to the control group (0.24 ± 0.1 vs. 0.17 ± 0.16; p = 0.01). Our study suggests that ondansetron acutely reduces the analgesic efficacy of tramadol.
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In most cancer patients, pain is successfully treated with pharmacological measures using opioid analgesics for moderate to severe pain (strong opioids) alone or in combination with adjuvant analgesics (coanalgesics). Opioids for mild to moderate pain (weak opioids) are usually recommended in the treatment of cancer pain of mild to moderate intensity. ⋯ All these drugs are metabolized through CYP2D6, an important enzyme for approximately 25% of all drugs administered in clinical practice. The aim of this review is to summarize data on the impact of CYP2D6 polymorphism on pharmacokinetics, pharmacodynamics and adverse effects of weak opioids.
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Metformin is a widely used antidiabetic agent that is generally considered safe. However, metformin-associated lactic acidosis (MALA), though not common, occurs from time to time and results in significantly high mortality. A series of 23 MALA cases in a local major hospital in Hong Kong is reported in this article to demonstrate the epidemiological data, risk factors, clinical features as well as the clinical outcomes for better understanding of this disease entity. ⋯ The majority of patients were found to have significantly raised creatinine versus a normal baseline value before the acute illness. Concomitant illnesses taking place alongside MALA were common. With a high utility rate of renal replacement therapy (82.6%) in the study group, the mortality rate was 30.4%.