Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man.
Paracetamol has replaced aspirin as the analgesic of choice in many situations. The major reason is the damaging effect of aspirin on gastric mucosa. Alterations in gastric ionic fluxes and potential difference provide measures of aspirin-induced structural damage. We studied the effect of large doses of paracetamol (acetaminophen 2-0 g) on gastric ionic fluxes in man. In addition, the effect of 2-0 g paracetamol on gastric potential difference was compared with that of 600 mg aspirin. In contrast with salicylates, paracetamol caused no significant alteration in movement of H+ and Na+ ions over control periods. Aspirin causes a significant fall in transmucosal potential difference (PD) across gastric mucosa of 15 mv, while paracetamol cuased no significant change. Paracetamol in a dose four times that recommended does not alter gastric ionic fluxes or potential difference. These studies support choice of paracetamol as analgesic over aspirin where damage to gastric mucosa may be critical. (+info)
Incidence of analgesic nephropathy in Berlin since 1983.
BACKGROUND: Phenacetin was removed from the German market in 1986 and was replaced mainly in analgesic compounds by acetaminophen. Our objective was to examine the effect of this measure on the incidence of analgesic nephropathy in light of the changes in other end-stage renal diseases. METHODS: We therefore compared the proportion of renal diseases in all patients starting dialysis treatment during three 18-month periods: 4/1982-9/1983 (n=57); 1/1991-6/1992 (n=81); and 10/1995-3/1997 (n=76). RESULTS: On the one hand, the proportion of end-stage analgesic nephropathy decreased significantly from 30% in 1981-1982 to 21% in 1991-1992 and 12% in 1995-1997 (P=0.01). On the other hand, type II diabetes increased significantly from 7% to 22% (P=0.01) and 29%, (P=0.001). Using the chi2 distribution test to analyze the frequencies of seven diseases at three different time intervals, however, showed that the changes in renal-disease proportions between 1982-1983, 1991-1992 and 1995-1997 were not significantly independent. There was a significant median age increase from 52 years (CI0.95 44-58) in 1982-1983 to 63 (CI0.95 55-67) in 1991-1992 and 63 (CI0.95 60-66) in 1995-1997 (P=0.003) for all patients starting dialysis but not for those with analgesic nephropathy [59 (55-71) vs 64 (53-67) and 61 (50-72); n.s.]. CONCLUSION: The decrease of end-stage analgesic nephropathy since 1983 may be partially due to the removal of phenacetin from the German market in 1986. However, considering the general increase in numbers of dialysis patients, their higher age and the increased incidence of type II diabetes, the decrease in analgesic nephropathy is not a statistically significant independent variable. Altered admittance policies for dialysis treatment have yielded a new pattern of renal-disease proportion which interferes with changes in the incidence of analgesic nephropathy. (+info)
Comparison of effects of acetaminophen on liver microsomal drug metabolism and lipid peroxidation in rats and mice.
Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 observed among the components of the liver microsomal electron transfer system of rats and mice. (+info)
Postoperative behavioral outcomes in children: effects of sedative premedication.
BACKGROUND: Although multiple studies document the effect of sedative premedication on preoperative anxiety in children, there is a paucity of data regarding its effect on postoperative behavioral outcomes. METHODS: After screening for recent stressful life events, children undergoing anesthesia and surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using validated measures of anxiety, children were evaluated before and after administration of the intervention and during induction of anesthesia. On postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children was assessed using the Post Hospitalization Behavior Questionnaire. RESULTS: The intervention group demonstrated significantly lower anxiety levels compared with the placebo group on separation to the operating room and during induction of anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression model, the authors found that the presence or absence of postoperative behavioral changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that during postoperative days 1-7, a significantly smaller number of children in the midazolam group manifested negative behavioral changes. At week 2 postoperatively, however, there were no significant differences between the midazolam and placebo groups. CONCLUSIONS: Children who are premedicated with midazolam before surgery have fewer negative behavioral changes during the first postoperative week. (+info)
Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity.
The purpose of this study was to examine whether intracellular metallothionein (MT) protects against acetaminophen hepatotoxicity. MT-I/II knockout (MT-null) and control mice were given acetaminophen (150-500 mg/kg i.p.), and liver injury was assessed 24 h later. MT-null mice were more susceptible than controls to acetaminophen-induced lethality and hepatotoxicity, as evidenced by elevated serum enzyme activities and histopathology. Zinc pretreatment, a method of MT induction, protected against acetaminophen hepatotoxicity in control mice, but not in MT-null mice. The susceptibility of MT-null mice to acetaminophen hepatotoxicity was not due to the increased acetaminophen bioactivation, as cytochrome P-450 enzymes, and acetaminophen-reactive metabolites in bile and urine were not increased in MT-null mice. Western blots of liver cytosol indicated that acetaminophen covalent binding at 4 h increased with acetaminophen dose, but there was no consistent difference between control and MT-null mice. Acetaminophen injection depleted cellular glutathione similarly in both control and MT-null mice, but produced more lipid peroxidation in MT-null mice, as evidenced by the abundance of thiobarbiturate-reactive substances, and by immunohistochemical localization of 4-hydroxynonenal and malondialdehyde protein adducts. MT-null hepatocytes were more susceptible than control cells to oxidative stress and cytotoxicity produced by N-acetylbenzoquinoneimine, a reactive metabolite of acetaminophen, as determined by oxidation of 2', 7'-dichlorofluorescin diacetate and lactate dehydrogenase leakage. In summary, this study demonstrated that MT deficiency renders animals more vulnerable to acetaminophen-induced hepatotoxicity. The increased sensitivity does not appear to be due to increased acetaminophen activation, glutathione depletion, or covalent binding, but appears to be associated with the antioxidant role of MT. (+info)
Frequency of arrhythmias and other cardiac abnormalities in fulminant hepatic failure.
In a series of 106 patients with fulminant hepatic failure and grade 4 encephalopathy, cardiac arrhythmias and other abnormalities occurred in 92 per cent. The most common was sinus tachycardia (75%) and this was the only abnormality in 22 per cent of the patients. Sudden cardiac arrest occurred in 25 per cent, various ectopic beats in 20 per cent, and heart block or bradycardia in 18 per cent. Other electrocardiographic abnormalities, mostly of the T wave and ST segment, were found in 31 per cent. Cardiac and respiratory arrests were usually unrelated to each other and both frequently occurred without warning. Only 7 out of 71 patients with arrhythmias other than sinus tachycardia survived, compared with 15 out of 31 patients without them (P less than 0-005). During the latter part of the series when an arrhythmia computer was used to monitor 38 patients, it was shown that significantly lower arterial oxygen levels occurred in those with arrhythmias, other than sinus tachycardia, than in those without. They were also found to be more acidotic and hyperkalaemic, and a higher number required dialysis and ventilation. Macroscopical cardiac abnormalities including scattered petechial haemorrhages, small pericardial effusions, and fatty, pale, and flabby ventricles, were found at necropsy in 64 per cent of the patients examined. Combinations of these macroscopical abnormalities occurred, particularly in the paracetamol overdose group. Another necropsy finding of possible significance in the pathogenesis of arrhythmias was cerebral oedema, present in 48 per cent of the patients examined, and often associated with coning of the brain stem. However, 7 of the 16 patients who suffered asystolic cardiac arrests had no macroscopical abnormality of either heart or brain. In the management of patients with fulminant hepatic failure continuous cardiac monitoring is essential. Correction of the biochemical and coagulation defects may decrease the frequency of arrhythmias but studies of the mechanism and control of cerebral oedema and its relation to cardiovascular function are urgently needed. (+info)
Gastric emptying after elective abdominal aortic aneurysm surgery: the case for early postoperative enteral feeding.
OBJECTIVE: To assess gastric emptying with a view to early postoperative enteral nutrition after elective abdominal aortic aneurysm (AAA) surgery. METHODS: The paracetamol absorption test was used to assess gastric emptying in 13 consecutive patients at 6, 18 and 32 h following elective AAA surgery. All patients received postoperative analgesia with marcaine given via an epidural catheter during the first 48 postoperative hours. Normal emptying was defined as an area under the plasma paracetamol concentration curve at 60 min (AUC-60) of > 600 mg/min/l. RESULTS: The median time to normal gastric emptying was 18 +/- 7.7 h. One patient (7.6%) had normal emptying at 6 h, nine (69%) at 18 h and 12 (92%) at 32 h. The nasogastric tubes were removed at a median of 3.2 days after surgery, and enteral feeding was commenced on day 4. CONCLUSIONS: Gastric emptying was normal 18 h post-AAA surgery as assessed by the paracetamol absorption test. In view of the importance of maintaining an intact gastrointestinal mucosa, enteral nutrition may be commenced on the second postoperative day. (+info)
Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review.
BACKGROUND: Day-case surgery is of great value to patients and the health service. It enables many more patients to be treated properly, and faster than before. Newer, less invasive, operative techniques will allow many more procedures to be carried out. There are many elements to successful day-case surgery. Two key components are the effectiveness of the control of pain after the operation, and the effectiveness of measures to minimise postoperative nausea and vomiting. OBJECTIVES: To enable those caring for patients undergoing day-case surgery to make the best choices for their patients and the health service, this review sought the highest quality evidence on: (1) the effectiveness of the control of pain after an operation; (2) the effectiveness of measures to minimise postoperative nausea and vomiting. METHODS: Full details of the search strategy are presented in the report. RESULTS - ANALGESIA: The systematic reviews of the literature explored whether different interventions work and, if they do work, how well they work. A number of conclusions can be drawn. RESULTS-ANALGESIA, INEFFECTIVE INTERVENTIONS: There is good evidence that some interventions are ineffective. They include: (1) transcutaneous electrical nerve stimulation in acute postoperative pain; (2) the use of local injections of opioids at sites other than the knee joint; (3) the use of dihydrocodeine, 30 mg, in acute postoperative pain (it is no better than placebo). RESULTS-ANALGESIA, INTERVENTIONS OF DOUBTFUL VALUE: Some interventions may be effective but the size of the effect or the complication of undertaking them confers no measurable benefit over conventional methods. Such interventions include: (1) injecting morphine into the knee joint after surgery: there is a small analgesic benefit which may last for up to 24 hours but there is no clear evidence that the size of the benefit is of any clinical value; (2) manoeuvres to try and anticipate pain by using pre-emptive analgesia; these are no more effective than standard methods; (3) administering non-steroidal anti-inflammatory drugs (NSAIDs) by injection or per rectum in patients who can swallow; this appears to be no more effective than giving NSAIDs by mouth and, indeed, may do more harm than good; (4) administering codeine in single doses; this has poor analgesic efficacy. RESULTS-ANALGESIA, INTERVENTIONS OF PROVEN VALUE: These include a number of oral analgesics including (at standard doses): (1) dextropropoxyphene; (2) tramadol; (3) paracetamol; (4) ibuprofen; (5) diclofenac. Diclofenac and ibuprofen at standard doses give analgesia equivalent to that obtained with 10 mg of intramuscular morphine. Each will provide at least 50% pain relief from a single oral dose in patients with moderate or severe postoperative pain. Paracetamol and codeine combinations also appear to be highly effective, although there is little information on the standard doses used in the UK. The relative effectiveness of these analgesics is compared in an effectiveness 'ladder' which can inform prescribers making choices for individual patients, or planning day-case surgery. Dose-response relationships show that higher doses of ibuprofen may be particularly effective. Topical NSAIDs (applied to the skin) are effective in minor injuries and chronic pain but there is no obvious role for them in day-case surgery. RESULTS-POSTOPERATIVE NAUSEA AND VOMITING: The proportion of patients who may feel nauseated or vomit after surgery is very variable, despite similar operations and anaesthetic techniques. Systematic review can still lead to clear estimations of effectiveness of interventions. Whichever anti-emetic is used, the choice is often between prophylactic use (trying to prevent anyone vomiting) and treating those people who do feel nauseated or who may vomit. Systematic reviews of a number of different anti-emetics show clearly that none of the anti-emetics is sufficiently effective to be used for prophylaxis. (ABSTRACT TRUNCATE (+info)