B1tta/Drug-ACE huggingface dataset:
[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
[Drug-Disease]: ketamine - hyperalgesic+B201:B204
[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
[Drug-Disease]: ketamine - pain
[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
[Drug-Disease]: alfentanil - hyperalgesic
[Title]: Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
[Abstract]: Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
[Drug-Disease]: alfentanil - pain
[Title]: Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.
[Abstract]: Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator's global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.
[Drug-Disease]: entacapone - Parkinson's Disease
[Title]: Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.
[Abstract]: Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator's global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.
[Drug-Disease]: levodopa - Parkinson's Disease
[Title]: Cholinergic stimulation of the lower esophageal sphincter in patients with vagotomy and antrectomy.
[Abstract]: Recently cholinergic stimulation of the lower esophageal sphincter (LES) with bethanechol has been shown to be effective in the treatment of chronic gastroesophageal reflux. Since chronic reflux and esophagitis also occur in patients with vagotomy and antrectomy, we studied the effect of bethanechol on sphincter pressure in 10 patients who had had vagotomy and antrectomy. Both subcutaneous (0.08 mg/kg) and oral (25 mg) administration of bethanechol caused significant increases in LES pressure in these patients. In addition, both subcutaneous and oral administration of bethanechol elevated hypotensive sphincter pressures to normal levels. Orally administered bethanechol produced a sustained increase in LES pressure throughout a 90-min study period. These studies suggest that cholinergic stimulation of the LES with bethanechol may be of therapeutic benefit in vagotomized and antrectomized patients with gastroesophageal reflux.
[Drug-Disease]: bethanechol - gastroesophageal reflux
[Title]: Serious adverse events experienced by patients with chronic heart failure taking spironolactone.
[Abstract]: In patients with chronic heart failure, spironolactone added to conventional treatment may lead to serious and, occasionally, fatal hyperkalaemia. In some cases this seems to happen because spironolactone causes diarrhoea. Four cases involving men with New York Heart Association functional class III heart failure are presented. As these cases revealed, close monitoring of blood chemistry is mandatory after starting spironolactone, and patients should be advised to stop spironolactone immediately if diarrhoea develops.
[Drug-Disease]: spironolactone - heart failure
[Title]: Preventing venous thromboembolism in general medical inpatients and after an ischaemic stroke.
[Abstract]: Clinical trials and meta-analyses have shown that low-molecular-weight heparin and unfractionated heparin are effective in preventing deep vein thrombosis (DVT) in acutely ill medical inpatients who are at risk as they are likely to be bedridden for 6 days or more. It is not known, however, if such prophylaxis can also reduce the likelihood of fatal pulmonary embolism or decrease all-causes mortality in this patient population. No recommendations can be made regarding thromboprophylaxis in those at a lower risk of venous thromboembolism or in short-stay inpatients, as these have not yet undergone clinical trial. Current evidence suggests that high doses of heparin should be avoided after an acute ischaemic stroke, as the results of recent large trials suggest any potential treatment benefit in preventing DVT is cancelled by the increased intracranial bleeding risk caused from the underlying disease.
[Drug-Disease]: heparin - deep vein thrombosis
[Title]: Induction with propofol target-concentration infusion vs. 8% sevoflurane inhalation and alfentanil in hypertensive patients.
[Abstract]: Haemodynamic parameters during an inhalation induction with 8% sevoflurane were compared with those obtained with a target-controlled infusion of propofol in 50 hypertensive patients in a prospective randomised study. Heart rate and arterial pressure were recorded continuously. End-tidal sevoflurane and nitrous oxide concentration, SpO2 and bispectral index (BIS) were also collected from the beginning of anaesthesia until 8 min after tracheal intubation. Patients either received 4 mg.l-1 target-concentration propofol or performed a vital capacity inhalation of 8% sevoflurane in a high flow of oxygen (8 l.min-1) supplemented with 50% nitrous oxide at loss of consciousness. As soon as BIS was < 60, 20 microg.kg-1 alfentanil and 0.6 mg.kg-1 rocuronium were injected and orotracheal intubation was then performed 1 min later. Thereafter, the end-tidal concentration of sevoflurane was reduced to 1.3 minimum alveolar concentration (MAC). Hypotension was defined as a 30% decrease in arterial pressure and was treated with repeated 3-mg boluses of ephedrine. When 12 mg ephedrine was unable to correct hypotension, the concentration of propofol was reduced by 1 mg.l-1 and that of sevoflurane by 0.5%. Hypotension occurred in 22 patients in the sevoflurane group and 21 in the propofol group, and hypertension occurred in two and three patients in each group, respectively. The maximal reduction in mean (SD) arterial pressure was similar in the sevoflurane (45 (4) mmHg) and propofol (41.3 (2.6) mmHg) groups, as were the ephedrine requirements (9.6 (1.1) vs. 9.1 (1.1) mg, sevoflurane vs. propofol, p > 0.05), the duration of hypotension (276 (37) vs. 292 (38) s, sevoflurane vs. propofol, p > 0.05), and the number of hypotensive episodes or anaesthetic changes and depth of anaesthesia. Nevertheless, heart rate was lower during the 8 min following tracheal intubation in the sevoflurane group. In both groups, the duration of hypotension was easily controlled either by ephedrine or by adjusting the anaesthetic concentrations. Overall, haemodynamic tolerance appears to be similar in the two techniques. Because hypotension occurred after alfentanil in most patients, this study questioned which is the best opioid dose, if any, to associate with propofol or sevoflurane for the induction in hypertensive patients.
[Drug-Disease]: ephedrine - hypotension