B1tta/Drug-ACE huggingface dataset:
[Title]: Individualizing high-dose oral busulfan: prospective dose adjustment in a pediatric population undergoing allogeneic stem cell transplantation for advanced hematologic malignancies.
[Abstract]: We investigated whether adjusting the oral busulfan (BU) dosage on the basis of early pharmacokinetic data to achieve a targeted drug exposure could reduce transplant-related complications in children with advanced hematologic malignancies. Twenty-five children received a preparative regimen consisting of thiotepa (250 mg/m2 i.v. daily for 3 days), BU (40 mg/m2 per dose p.o. every 6 h for 12 doses), and cyclophosphamide (60 mg/kg i.v. daily for 2 days) and then underwent allogeneic stem cell transplantation. Busulfan clearance and area under concentration time-curve (AUC) were determined after the first dose using a one-compartment pharmacokinetic (PK) model with first-order absorption. The initial PK analysis was successfully completed after the first BU dose in 21 patients (84%). A final AUC of 1000-1500 microM x min/dose was targeted and subsequent doses were modified as necessary to achieve this value. Fourteen of the 25 patients (56%) required dose adjustment. Follow-up PK analysis was completed in 21 patients and 16 of these achieved the targeted BU exposure for the course of therapy. Interpatient variability in BU clearance was high (up to five-fold). The most frequent regimen-related toxicities were cutaneous and gastrointestinal (stomatitis and diarrhea). Only one patient developed hepatic veno-occlusive disease. Our study demonstrates the feasibility of adjusting the oral BU dose in individual pediatric patients. Although toxicity associated with BU seemed to be reduced, this conclusion is tempered by the fact that the overall regimen-related toxicity (RRT) remains substantial and reflected the effects of all agents used in the preparative regimen.
[Drug-Disease]: thiotepa - hematologic malignancies
[Title]: Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).
[Abstract]: BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.
[Drug-Disease]: enalapril - coronary atherosclerosis
[Title]: Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).
[Abstract]: BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.
[Drug-Disease]: Simvastatin - coronary atherosclerosis
[Title]: Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.
[Abstract]: Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.
[Drug-Disease]: diazepam - Hallucinations
[Title]: Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.
[Abstract]: Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.
[Drug-Disease]: ketamine - pain
[Title]: An assessment of the safety, efficacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study.
[Abstract]: The effects of intranasal fentanyl citrate (INFC) were assessed in 12 hospice inpatients with cancer-related breakthrough pain. Patients received 20 microg of fentanyl citrate and were asked to rate their pain using a visual analogue scale (VAS) before INFC, then after 3, 5, 10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in pain scores, four within 5 minutes and seven within 10 minutes of taking INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%), moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine, INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine patients (75%) said they would continue to use INFC. Of the three patients who did not experience a positive result, two were taking relatively higher baseline opioid doses and one was found to have a fracture. No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use. Intranasal fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose-ranging studies are required to confirm these findings.
[Drug-Disease]: fentanyl citrate - pain
[Title]: Gabapentin vs. amitriptyline in painful diabetic neuropa+B42thy: an open-label pilot study.
[Abstract]: The objective of this study was to compare the efficacy and tolerability of gabapentin and amitriptyline monotherapy in painful diabetic neuropathy. This was a 12-week, open-label, prospective, randomized trial. Twenty-five type-II diabetic patients with pain attributed to diabetic neuropathy and a minimum score of 2 on a pain intensity scale ranging from 0 (no pain) to 4 (excruciating pain) were randomized to receive either gabapentin, titrated from 1,200 mg/day to a maximum of 2,400 mg/day, or amitriptyline, titrated from 30 mg/day to a maximum of 90 mg/day. Both drugs were titrated over a 4-week period and maintained at the maximum tolerated dose for 8 weeks. The main outcome measures were weekly pain intensity and paresthesia intensity, measured on two categorical scales. Thirteen patients received gabapentin and 12 received amitriptyline. All 25 patients completed the trial. Gabapentin produced greater pain reductions than amitriptyline (mean final scores were 1.9 vs. 1.3 points below baseline scores; P = 0.026). Decreases in paresthesia scores also were in favor of gabapentin (1.8 vs. 0.9 points; P = 0. 004). Adverse events were more frequent in the amitriptyline group than in the gabapentin group: they were reported by 11/12 (92%) and 4/13 (31%) of patients, respectively (P = 0.003). Side effects were the main limiting factor preventing dose escalation. Gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy. Additionally, gabapentin was better tolerated than amitriptyline. Further controlled trials are needed to confirm these preliminary results.
[Drug-Disease]: gabapentin - pain
[Title]: A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.
[Abstract]: BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.
[Drug-Disease]: olanzapine - bipolar disorder
[Title]: A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.
[Abstract]: BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.
[Drug-Disease]: clozapine - bipolar disorder
[Title]: A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.
[Abstract]: BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.
[Drug-Disease]: risperidone - bipolar disorder
[Title]: A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics.
[Abstract]: In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics--haloperidol and chlorpromazine--and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between "sedative" and "activating" neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anti-cholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency difference among neuroleptics may be the degree of built-in anticholinergic activity.
[Drug-Disease]: chlorpromazine - schizophrenia
[Title]: A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics.
[Abstract]: In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics--haloperidol and chlorpromazine--and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between "sedative" and "activating" neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anti-cholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency difference among neuroleptics may be the degree of built-in anticholinergic activity.
[Drug-Disease]: haloperidol - schizophrenia
[Title]: Apomorphine: an update of clinical trial results.
[Abstract]: Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.
[Drug-Disease]: Apomorphine - erectile dysfunction