immunological and histopathological changes of Tramadol, Tramadol/Acetaminophen and Acetaminophen in male Albino rats "Comparative study"

Tramadol is a synthetic opioid analgesic. It is commonly prescribed for moderate to severe pain, becoming abused more popular among teens in most countries. Paracetamol as anti-inflammatory drugs [acetaminophen] [APAP] is widely used as an analgesic and antipyretic agent. Meanwhile, tramadol/acetaminophen [tramacet] is effective in acute or chronic moderate-to-moderately severe pain. In comparative study, the current investigation threw the light on the effect of over doses of tramadol and/or APAP on the immune function and hepatocytes in adult male Sprague-Dawley rats. Treated rats received oral doses of each drug for 15 consecutive days and after last treatment, they kept three days later for withdrawal studies. The rats were divided into four treatment groups, in the first group, rats received saline and used as control. The second, third and fourth groups treated with tramadol [45 mg/kg], tramadol/APAP [45/450 mg/kg], APAP [450 mg/kg] respectively, once a-day at the first week and ending with 90, 90/900, 900 mg/kg at the second week. Rats were sacrificed at the end of the first, second weeks and three days of last treatment. Daily doses of tramadol and /or APAP exposure in rats decreased the cellularity of spleen. Moreover, phagocytic and killing of S. aureus by PMN and macrophage cells caused a highly significant decrease in treated groups. IFN-gamma was reduced in a statistically different treated group of rats. Serum IL-10 was unaffected by any of the treatment regimens but increased only in tramadol/APAP treated rats. Spleen histology exhibited mild pathological alteration with different injures between treated groups. Splenic white pulp accompanied by ill deformed which reflected the reduction of white pulp zones, thickened vasculature in the splenic net work, fibrous trabeculae become prominent feature, where splenic red pulp occupied large areas of the splenic network with predominant edema and megakaryocytes. On the other hand, the effect of tramadol and/or APAP induced DNA alterations of hepatocytes in dose dependent pattern as elucidated by dendrogramatic analysis. Liver histopathological changes of treated groups included vacuolated hepatocytes, dilated sinusoid with proliferated Kupffer cells; atrophied hepatocytes with nuclei reduced in size and darkly stained. Many areas of hepatocytes showed loss of architecture, congested central vein, expanded portal area with edema and inflammatory reaction. It could be concluded that the effect of tramadol/APAP induced anti-inflammatory cytokines than tramadol and APAP alone. Tramadol and/or APAP may display severe pathological consequences of hepatocytes. These hepatic lesions may be caused impairment of the liver function

Adverse drug reactions to antiretroviral therapy in AIDS patients at a tertiary care hospital in India: A prospective observational study.

Objectives: To identify the adverse drug reactions (ADRs) to antiretroviral therapy (ART) and to assess their impact on treatment compliance in patients with HIV/AIDS. Materials and Methods: Two hundred and thirty-five (235) AIDS patients who received ART were monitored for ADRs over a period of 6 months. The incidence and nature of ADRs occurring with different ART regimens were recorded. We also assessed the severity, causality as well as the impact of ADRs on the patients' compliance. Results: Of 235 patients receiving ART, 90.6% patients experienced ADRs. A total of 618 ADRs involving various systems were observed. A majority were related to gastrointestinal (42.39%) and central nervous (25.57%) system. 23.1% ADRs were severe in intensity. Severe ADRs occurred in 41 out of 235 (17.4%) patients necessitating drug withdrawal. A majority of the patients (87.8%) who complained of severe ADRs received combination of stavudine, lamivudine and nevirapine. Causality assessment revealed 6.63% ADRs were probable and 93.3% ADRs were possible. Non-compliance due to ADRs was observed in 28.9% patients. Conclusions: Myriad ADRs are associated with ART which leads to poor patient compliance. With the increasing access to ART in India, it is prudent that antiretroviral drugs are used judicially with regular monitoring of ADRs.

Low-dose bupivacaine-fentanyl spinal anaesthesia for transurethral prostatectomy

We evaluated the effect of low-dose bupivacaine plus fentanyl administered intrathecally in elderly patients undergoing transurethral prostatectomy. Patients were randomly assigned to one of two groups. Group F received plain bupivacaine 4 mg with 25 mg of fentanyl and sterile water to a total of l.5 ml, and Group B received only 0.5% plain bupivacaine 7.5 mg for spinal anaesthesia. Sensory block was adequate for surgery in all patients. The mean level of motor block was higher and the duration of motor block was longer in Group B [p < 0.0001]. Hypotension and shivering were significantly more common in Group B [p < 0.05]. The addition of fentanyl 25 mg to plain bupivacaine 4 mg provides adequate analgesia for transurethral prostatectomy with fever side-effects in elderly patients when compared with the conventional dose of bupivacaine

Postoperative control of pain after total knee replacement: epidural infusion of bupivacaine-sufentanil and levobupivacaine-sufentanil mixtures

Regional anasthesia [particulary epidural technique] leads to reduction in intraoperative and postoperative complications thus improving morbidity and mortality after major surgery [1-2], minimizing or preventing side effects and risk are economic benefits which can be balanced against, or purchased by costs, especially in terms of postoperative morbidity and hospital stay [3-4-5]. Racemic bupivacaine has been widely used as a local anesthetic beacuse of its long duration of action and beneficial ratio of sensory to motor block when used for epidural analgesia. However there have been reports of death attributable to bupivacaine-induced cardiotoxicity in patients after accidental intravascular injection [6] or during intravenous regional anaesthesia [7]. Levobupivacaine was developed because of concern regarding bupivacaine cardiotoxicity and preclinical evidence suggesting that there is stereospecificity with regard to blockade of impulse conduction in the cardiovascular system. Clinical studies have shown that levobupivacaine is equipotent to bupivacaine in vitro and in vivo in terms of anaesthesia efficacy. This study was conducted on fort patients classified into two groups, each of twenty, undergoing total knee replacement, comparing the analgesic efficacy, effects on hemodynamic parameters and the occurrence of side effects, between two groups receiving either bupivacaine sufentanil or levobupivacaine-sufentanil mixtures for post operative control of pain. This study revealed non-significant difference between the two groups as regard the effectiveness of pain control as determined by monitoring the 100 mm visual analogue scale, degree of sedation as detected by the four points sedation score also changes in the hemodynamic parameters were comparable between the two groups as well as the prevalence of side effects

Intrathecal neostigmine versus intrathecal morphine, their combination for postoperative analgesia in patients undergoing herniorrhaphy

We designed this study to evaluate the postoperative analgesic efficacy and safety of intrathecal [IT] neostigmine, intrathecal [IT] morphine, and their combination in patients undergoing herniorrhaphy under spinal anesthesia. Eighty adult patients were randomly divided into four groups to receive isotonic sodium chloride solution 0.5 ml, neostigmine 100ug, morphine 0.3 mg or the combination of IT neostigmine 50 ug and morphine 0.15 mg with IT 0.5 0/0 hyperbaric bupivacaine 15 mg. There were no significant differences among the four groups with regard to spinal anesthesia, age, heart rate, or mean arterial blood pressure. Postoperative analegisa was provided by IM diclofenac. Compared with the saline group, the time to first use of analgesic was significantly longer in neostigmine group [p= 0.02], with lower 24 h analgesic consumption [p=0.001]. Nausea and vomiting were the most common side effects of IT neostigmine 60 0/0. Analgesic effectiveness was similar between the neostigmine and morphine groups. Compared with the neostigmine group, the combination group had significantly longer analgesic effects [P=0.02] with less incidence of nausea and vomiting [p=0.04]. Compared with the morphine group, the combination group tended to have prolonged times to first use of analgesic [p=0.02] with lower incidence of pruritus [p=0.03]. the combination of IT neostigmine 50 ug and IT morphine 0.15 mg produce longer postoperative analgesia with fewer side effects than IT neostigmine 100ug or IT morphine 0.3 mg alone. Intrathecal [IT] neostigmine 100ug produced postoperative analgesia for herniorraphy similar to [IT] morphine 0.3mg, but with high incidence of nausea and vomiting, morphine group had high incidence of pruritus. Thus, combination of both has higher analgesic effects with lower side effects than single drug alone

Effect of intrathecal midazolam or midazolam-fentanyl with bupivacaine for cesarean section

Sixty healthy pregnant women at term scheduled for elective cesarean section under spinal anesthesia were randomly assigned to three equal groups, each of 20 women. The first group received 10 mg bupivacaine [B group], the second group received 2 mg midazolam added to 10 mg bupivacaine [BM group], while the third group received 2 mg midazolam, 10 mug fentanyl added to 10 mg bupivacaine [group BMF]. Midazolam significantly improved the quality of intraoperative anesthesia and analgesia, as none of the patients in BM group experienced pain which required analgesic supplement compared with eight patients in B group. Further more improved analgesia was achieved with the midazolam-fentanyl combination. The study concluded that adding a small dose of intrathecal midazolam to bupivacaine improved the quality of anesthesia reduction of the postoperative pain and reduction of analgesic consumption for cesarean section delivery. Combining midazolam with fentanyl much further improved analgesia without increasing the side effects

Concomitant administration of the selective cox-2 inhibitor, nimesulide, and vitamin E, comared to indomethacin in experimental animals

This study was designed to assess the safety and efficacy of the selective COX-2 inhibitor, nimesulide, in comparison with the non-selective COX inhibitor, indomethacin. The potentiation of the anti-inflammatory activity of nimesulide by concomitant administration of the anti-oxidant. vitamin E, was also investi- gated. The anti-inflammatory effect was tested in 24 rats by the cot- ton pellet granulomatous test. Animals were arranged into four equal groups. The first group received no drugs and served as control. The other three groups were treated with indomethacin [2 nig/kg b.w.], nimesulide [4 nig/kg b.w.] and nimesulide in combination with vitamin E [each in a dose of 4 mg/kg b.w.], respectively. All drugs were given orally once daily for two weeks. The extent of inhibition of granulomatous formation by the test drugs was taken as a measure of antiinflamniatory activity. it was found that nimesulide alone possessed a significantly less anti-inflammatory activity compared to that of indometha cin. However, concomitant administration of vitamin E with nimesulide produced a significant increase in the anti-inflammatory activity of nimesulide so that it became more than that of indomethacin alone. The analgesic effect of the test drugs was evaluated in mice. Acetic acid was injected i.p. in a dose of 0.5 ml of 1% concentration to induce abdominal constrictions [Writhing test]. Forty mice were divided into four equal groups. The first [control] group was treated with 0.5 ml saline; the second with indomethacin [2 ing/kg b.w.]; the third with nimesulide [4 mg/ kg b.w.] and the fourth with nimesulide plus vitamin E [4 mg/ leg b.w. each]. Each drug was given as a single intramuscular injection half an hour before conducting the Writhing test The average number of abdominal constrictions per minute [Writhing Response: WR] was calculated between the 10th and 14th minutes after acetic acid injection. Reduction of this WR was taken as a measure of analgesic activity of the tested drugs. Indomethacin induced a significant analgesic effect while nimesulide induced a iess analgesic activity. Simultaneous vitamin E administration did not add to the analgesic activity of nimesulide. To study the potential gastric toxicity, tests were performed using ten times the therapeutic doses of indomethacin [20 mg/ kg b.w.] and nimesuiide [40 mg/kg b.w.] in normal fasting albino rats, each given as a single oral dose. Nimesulide administration was not associated wish gastric uiceration while indomethacin produced high incidence of gastric uiceration. In conclusion, from the present data, it couid be recommended that the selective COX-2 inhibitor, nimesulide, is a safer but less effective analgesic anti-inflammatory agent, compared with indomethacin. However, combined with vitamin E, the anti-inflammatory efficacy of nimesulide is increased. Thus, this combination could provide the double benefit of good anti-inflammatory activity beside inducing no appreciable gastric adverse effects, if any at all, when compared with the traditional NSAID, indomethacin

Comparison of tropisetron tropisterone plus dexamethasone granisetron and granisetron plus dexamethasone as anti-emetic propahylaxis after middle ear surgery

In a r and omized, placebo-controlled study the efficacy of a single intravenous [IV] bolus of tropisetron 5mg [Group T], granisetron 3mg [Group G]. tropisetron 5mg plus dexamethasone 8mg [Group T+D], granisetron 3mg plus dexamethasone 8mg [Group G+D], or saline [Group C] given at induction were compared in a group of 150 patients, [30, each group] undergoing middle ear surgery [MES]. The groups were similar with respect to demographic data and potential confounding variables. With regard to the incidence and score of postoperative nausea and vomiting [PONV] group [G+D] and group [T+D] were significantly superior to group T and G, [P<0.05]. Also tropisetron alone and in combination was significantly superior to granisetron, either alone or in combination [P<0.05]. It was reported that tropisetron was significantly superior to granisetron through 3 to 24 h than through 0 to 3 h. No statistical difference was reported between the four study groups with regard to rescue antiemetics or adverse events. In 5-hydroxy tryptamine type 3 [5-HT3] receptor antagonist tropisetron [5 mg] given as a single intravenous bolus at induction of anesthesia was excellent in preventing PONV and that combination of 5-HT3 antiemetic plus dexamethasone was more effective than each antiemetic alone for the prevention and treatment of PONV