Gene/Protein Disease Symptom Drug Enzyme Compound
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Five autopsy cases of sudden death caused by intestinal obstruction are reported. The causes of death of the cases were duodenal obstruction of impacted food stuff, ileocaecal obstruction caused by Crohn's disease, incarceration of inguinal hernia, intestinal obstruction caused by heterotopic pancreas and paralytic ileus. In three cases, the patient was in cardiopulmonary arrest on arrival at hospital, and in the remaining cases the patient died within 12 hours from the beginning of treatment; therefore, a correct clinical diagnosis was not made before the death in all cases. All the patients had from one to three days history of nausea and abdominal pain, major complications of intestinal obstruction. Among all cases, the duration from the onset to death was the shortest in the case of a patient complicated with schizophrenia. It is characteristic that the patients of all cases died suddenly and resuscitation was not successful. Regarding the laboratory data of a hospitalized patient, marked hemoconcentration and an increased level of BUN/Cr ratio and blood sugar were shown. The patient who died from duodenal obstruction caused by impacted food-stuff had suffered from depression for six years, and the patient who died from paralytic ileus had suffered from schizophrenia for about 23 years. In both cases, it is characteristic that the complaints of the patient were poorer than what would be expected. Furthermore, these patients had been taking medication of psychotic, anti-depressant and anti-parkinsonism drugs; therefore the combination of these drugs was thought to be reflected in the bowel movement.
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PMID:[Analysis of sudden death caused by intestinal obstruction]. 954 55

This double-blind, controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features. After a 1-week placebo run-in period, 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day. At study completion, 28 (80%) of 35 patients treated with fluvoxamine plus placebo and 29 (80.5%) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders (reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0). In the third and fourth weeks, the response rates were significantly superior in the fluvoxamine plus pindolol group (p = 0.0001, p = 0.023, respectively). Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded. No significant difference was found comparing plasma levels of fluvoxamine between groups, thus excluding a pharmacokinetic interaction. Other than mild nausea and sedation in a few patients, treatments were well tolerated. No medically significant adverse events occurred. Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment. Thus, the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder. A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields, given the direct and indirect costs of depression.
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PMID:Faster onset of action of fluvoxamine in combination with pindolol in the treatment of delusional depression: a controlled study. 986 75

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.
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PMID:Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease. 1034 74

The most effective method to maintain clinical improvement in the course of schizophrenia is the continuation of neuroleptic therapy. Sometimes we face the dilemma whether neuroleptic administration could be discontinued. There are some unconditional indications for treatment cessation (signs of intolerance, complications, general medical conditions); all other situations can be considered as relative indications. The risk and benefit of treatment discontinuation should be carefully evaluated. Neuroleptic withdrawal seems to be safer among older patients, with single episode of the psychosis of mild severity, with no family history of schizophrenia. It is necessary to achieve a stable clinical improvement before neuroleptic withdrawal. Worsening of the clinical status creates the most important risk of treatment discontinuation. Other risk factors include unacceptable threatening behavior, increase of family burden. The appearance of withdrawal symptoms such as nausea, vomiting, dyskinesia, insomnia, anxiety, etc. are to be considered. These symptoms are rare, and the risk of relapse is smaller when patients were treated with depot neuroleptics before treatment discontinuation than in the case of treatment with oral neuroleptics. Neuroleptic discontinuation and introduction of placebo cause more risk of relapse than continuation of active treatment.
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PMID:[The risk of neuroleptic discontinuation in schizophrenia]. 1078 16

Risperidone is a potent antagonist of both dopamine (D2) and serotonin (5-HT2) receptors, demonstrating improvement of both positive and negative symptoms and a lower propensity for inducing extrapyramidal symptoms (EPS) than typical neuroleptics. Its most common side-effects, found in the Canadian multi-centre trial (Chouinard et al., 1993), were agitation, anxiety, insomnia, EPS, headache and nausea, in order of frequency. With regard to endocrine effects, risperidone causes an increase in prolactin levels similar to that of other neuroleptics (Claus et al., 1992). In open clinical trials (De Cuyper, 1991), the overall incidence of risperidone-induced endocrine side-effects was quite low: 2.9 % for amenorrhoea and 1-2% for galactorrhoea. However, it is assumed that the incidence can vary depending upon the characteristics of patients and the drug regimen, i.e. dosage and titration schedule. In our experience, hyperolactinaemia is likely to occur when prescribing risperidone to female or first-onset psychotic patients: we are reporting 5 cases of risperidone-induced hyperprolactinaemia with these characteristics.
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PMID:Hyperprolactinaemia induced by risperidone. 1128 51

With 5388 patients in the marketing application dossiers and post-marketing experience of more than 130 million prescriptions of levofloxacin worldwide, the tolerability profile of this anti-infective is now well defined. During clinical trials, 12 per cent of patients treated with levofloxacin experienced an adverse event considered to be related to the study drug compared with 13 per cent of the patients with a comparator. Nausea and diarrhoea were the most frequent adverse effects. During clinical trials, the frequency of tendinitis, psychotic episodes and seizures was less than 0.1 per cent. Following recent concerns with some fluoroquinolones, specific attention was paid in post-marketing surveillance worldwide. The notification rate of significant severe liver injuries (hepatitis, necrosis, hepatic failure) has been less than 1 for 5 million prescriptions. Cardiac tolerability is satisfactory and the phototoxic potential of levofloxacin is one of the lowest amongst fluoroquinolones.
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PMID:[Levofloxacin adverse effects, data from clinical trials and pharmacovigilance]. 1132 15

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). In contrast, 140 trovafloxacin-treated patients developed hepatic problems, 14 of which were severe, and 8 required transplantation. The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1-3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions (ADRs) associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2-10% for other fluoroquinolones). Ofloxacin and levofloxacin have a very low phototoxic potential, whereas this is a problem for sparfloxacin, enoxacin, and pefloxacin. The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.
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PMID:Comparison of side effects of levofloxacin versus other fluoroquinolones. 1154 84

Well-known adverse effects of amisulpride include nausea, insomnia or tiredness, gastrointestinal, extrapyramidal and endocrine symptoms. Cardiac disorders, however, appear to be an extremely rare complication of the drug. Only a few case reports on this complication have been published so far, which deal with QT prolongation, hypotension, hypertension and palpitations. Bradycardia has not yet been mentioned. Here, we will report on a case of asymptomatic bradycardia that developed subsequent to therapeutic doses of amisulpride in a 25-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient had been rehospitalized for an acute exacerbation of the psychosis. When the patient failed to respond at the beginning of hospitalization, the treatment was changed from clozapine to amisulpride. After a complete switchover to amisulpride, the patient's ECG showed sinus bradycardia and QT prolongation. When the daily dose of amisulpride was reduced from 800 mg/d to 600 mg/d, the patient's ECG quickly normalized (including blood pressure and pulse rate) within a few days. The patient did not report any cardiovascular-related complaints. Since the cardiovascular-specific diagnostics did not yield any indicative results, bradycardia may be a rare complication of amisulpride treatment.
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PMID:Asymptomatic bradycardia associated with amisulpride. 1177 48

30 patients suffered from psychogeneous depressions with anxiety have been treated with the fluvoxamine (100-300 mg/day) by 8 weeks. The disorder have been developed after the severe psychogenic trauma--the death of one of the close relatives. Assessment of the fluvoxamine efficacy and safety have been carried out by means of both the data of the psychopathological investigation and of some rating scales: Clinical Global Impression Scale--CGI, the Hamilton Depression Scale--HAM-D, the Scale of Side Effects, etc.). The pronounced clinical improvement have been achieved in 63.3% of cases beginning from the 2nd week of treatment. HAM-D scores decreased from 27 to 9 (p < 0.01). The reduction of the anxious and depressive symptoms occurred synchronously but reduction of somatic anxiety preceded the psychotic one. The side effects (sleepiness, nausea, etc.) have been noted only in 7 cases (23.3%) during the 1st week of treatment, and then disappeared.
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PMID:[Fluvoxamine (fevarin) in psychogenic depression]. 1181 Nov 27

In the course of treatment of psychiatric patients, it is often necessary to switch antipsychotic medications. In recent years, atypical antipsychotic agents have become the first-line therapeutic interventions for treating psychotic symptoms. Reasons for switching patients from the typical antipsychotics to the atypical agents can include enhanced efficacy against negative symptoms, improvement in cognitive capacity, and reduction of risk of extrapyramidal side effects. The presumed long-term benefits of switching to the new antipsychotic drug should be assessed. Pharmacokinetic and pharmacodynamic properties of antipsychotic agents and drug-drug interactions should be considered during the switch process. Two methods are employed for the switch process: crossover ("crosstitration") and an abrupt switch. With the crossover method, the patient's current medication is tapered over a period of several days to several months to prevent potential withdrawal symptoms, such as nausea, vomiting, insomnia, muscle aches, and diaphoresis. Due to withdrawal symptoms, clozapine is the only atypical agent recommended to proceed with a slow dose taper when switching to another atypical drug. Sudden cessation could also precipitate the emergence of motor symptoms, which can include pseudoparkinsonism, dystonia, akathisia, and dyskinesia. The initiation of the new antipychotic occurs concurrently with the tapering of the previous drug. In an abrupt switch, the previous antipsychotic is discontinued suddenly, independent of its dose, and the new antipsychotic is started on the next day. Both methods have been used in clinical practice and double-blind studies. To date, only two medications have been studied in large multicenter clinical trials. These are olanzapine and ziprasidone. The olanzapine study revealed optimal benefits when the previous agents were gradually withdrawn and olanzapine was initiated at 10 mg/day. The ziprasidone switch study demonstrated both reduced adverse side effects from the previous agents and improvements in clinical efficacy. Additional studies are needed to examine the optimal methods for switching patients from one atypical agent to another atypical antipsychotic.
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PMID:Clinical significance of drug binding, protein binding, and binding displacement drug interactions. 1247 62


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