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 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.
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PMID:Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. 921 Oct 88

To minimize the symptoms of antidepressant discontinuation, gradual tapering is necessary for all serotonin reuptake inhibitors (SRIs) except fluoxetine, which has an extended half-life. Agents with shorter half-lives such as venlafaxine, fluvoxamine, and paroxetine should be tapered gradually. Discontinuation symptoms, which frequently emerge after abrupt discontinuation or intermittent non-compliance and, less frequently, during dose reduction, are generally mild, short-lived, and self-limiting but can be distressing and may lead to missed work days and decreased productivity. The symptoms may be somatic (e.g., dizziness and light-headedness; nausea and vomiting; fatigue, lethargy, myalgia, chills, and other flu-like symptoms; sensory and sleep disturbances) or psychological (anxiety and/or agitation, crying spells, irritability). Mild symptoms can often be treated by simply reassuring the patient that they are usually transient, but for more severe symptoms, it may be necessary to reinstitute the dosage of the original antidepressant and slow the rate of taper. Symptoms of discontinuation may be mistaken for physical illness or relapse into depression; misdiagnosing the symptoms may lead to unnecessary, costly tests and treatment. Thus, health care professionals need to be educated about the potential adverse effects of SRI discontinuation.
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PMID:Clinical management of antidepressant discontinuation. 981 35

In the paper we have described a case of acute, unintentional intoxication with clenbuterol, a selective beta 2-agonist. A 21-year-old bodybuilder to improve his physical fitness and to increase his muscle bulk was using clenbuterol in a dose of two tablets (20 mg) daily for a week before poisoning. On a day of acute intoxication he drank orange juice containing 48 tablets (4.8 g) of clenbuterol, which had been placed there by his friends. The patient was admitted to our clinic with tachycardia at rate 160 bpm, headache, dizziness, tremor, sweats, muscle weakness, agitation. Serum potassium concentration was 2.6 mmol/L, blood glucose level 18.7 mmol/L. All the symptoms and biochemical abnormalities disappeared after intravenous treatment with propranolol (1.0 mg) and potassium chloride (60 mmol) within five hour period. This case indicates that more attention should be paid to clenbuterol widely used as a stimulant by athletes, especially by bodybuilders.
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PMID:Acute poisoning with clenbuterol--a case report. 947 4

Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often be confronted with the treatment of risk patients; thus, the incidence of side effects can be expected to rise. In this study, 2731 patients receiving dental anesthesia were evaluated by questionnaire for risk factors, type and dosage of local anesthetic applied, type and duration of treatment, and complications associated with the administration of the local anesthetic. Of all patients, 45.9% had at least one risk factor in their medical histories, with cardiovascular diseases and allergies being the most frequent. The overall incidence of complications was 4.5%. It was significantly higher in risk patients (5.7%) than in nonrisk patients (3.5%). The most frequently observed complications (dizziness, tachycardia, agitation, nausea, tremor) were transient in nature and did not require treatment. Severe complications (seizure, bronchospasm) occurred in only two cases (0.07%). Articaine was found to be administered in over 90% of all dental anesthesias in Germany despite the great variety of local anesthetics available. Articaine 1:100,000 caused more sympathomimetic side effects than did articaine 1:200,000. Additionally, doses of local anesthetics proved not to be strictly determined according to body weight, especially for patients weighing less than 50 kg. In summary, it can be stated that dental local anesthesia can be considered safe. Nevertheless, the incidence of complications due to dental anesthesia can be expected to be further reduced if (a) patients are routinely evaluated for risk factors with an adequate medical history prior to dental treatment, (b) doses of local anesthetics are strictly determined according to body weight, (c) anesthetics with low concentrations of epinephrine are used, and (d) the concept of a differentiated dental anesthesia is applied.
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PMID:The incidence of complications associated with local anesthesia in dentistry. 948 57

Selfotel (CGS 19755), a competitive N-methyl-D-aspartate antagonist, is neuroprotective in experimental models of ischemic cerebral injury. We studied the safety and tolerability of a single intravenous dose (0.5 to 2.0 mg/kg) of selfotel in neurosurgery patients. Thirty-two neurosurgical patients undergoing intracranial surgery were given ascending doses of selfotel 2 to 14 h before surgery. Serum selfotel levels were measured over a period of 24 h. Cerebrospinal fluid (CSF) levels were measured 1.5 to 18 h after dosing. Frequent side effects included psychomimetic symptoms such as hallucinations, abnormal dreaming, agitation, and paranoia among 20 (66%) patients. Ataxia was seen among five (16%) and dizziness among eight (25%). Symptoms occurred 38 min to 40 h from administration and persisted 5 min to 4 days. Symptom severity worsened with increasing area under the curve measurements and doses above 1.0 mg/kg. All symptoms were reversible and easily treated with intravenous haloperidol. Modest elevations of hepatic enzymes were observed among four patients. No patient had severe adverse reactions. Maximum selfotel levels attained were 143 mumol (serum) and 4.76 mumol (CSF). Peak serum levels among six patients were within potentially neuroprotective ranges. CSF levels remained detectable up to 18 h after dosing. No obvious relationship was seen between CSF drug levels and symptoms. Selfotel in doses of 0.5 to 2.0 mg/kg can be administered safely to neurosurgical patients. Maximum serum levels attained were within the range shown to be neuroprotective in experimental studies. Side effects even at the highest levels are tolerable and reversible. Selfotel use in patients at risk for cerebral injury should be further explored.
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PMID:Dose escalation safety and tolerance study of the competitive NMDA antagonist selfotel (CGS 19755) in neurosurgery patients. 957 82

The Waterhouse-Friderichsen (WFS) syndrome, also known as purpura fulminans, is described as acute hemorrhagic necrosis of the adrenal glands and is most often caused by meningococcal infection. This clinical entity is more frequently seen in the pediatric than the adult population and is associated with a high morbidity and mortality. The initial presenting complaints for patients with the WFS usually include a diversity of nonspecific, vague symptoms such as cough, dizziness, headache, sore throat, chills, rigors, weakness, malaise, restlessness, apprehension, myalgias, arthralgias, and fever. These symptoms are usually abrupt in their onset. Petechiae are present in approximately 50-60% of patients. The clinical diagnosis of WFS may be relatively straightforward or extremely challenging. Patients who appear in the initial and nontoxic-appearing stage without any skin lesions may be difficult to distinguish from a benign viral illness. When a patient presents with fever and petechiae, WFS must be considered, even when the patient has a non-toxic appearance. Due to the rapid progression and often devastating consequences, therapy should be instituted as soon as the diagnosis is suspected.
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PMID:Rupert Waterhouse and Carl Friderichsen: adrenal apoplexy. 969 86

The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability, headache. Patients also presented a decrease of nausea, and of anorexia.
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PMID:[Prospective evaluation of antidepressant discontinuation]. 969 14

The subjective response to treatment with zolpidem, an imidazopyridine hypnotic, was assessed in patients with insomnia under normal treatment conditions in an outpatients' practice in Germany. The uncontrolled clinical surveillance study included 16944 outpatients with subjective difficulties in initiating and/or maintaining sleep. Office-based neurologists, psychiatrists, internists and general practitioners were asked individually to adjust the dosage of zolpidem (age < or = 65 years, 10-20 mg; age > 65 years, 5-10 mg) over a recommended period of 3-4 weeks. In total, 82.8% of patients completed the survey (36% men, 64% women, mean age 58.8 +/- 14.9 years; 58.6% without previous hypnotic medication; duration of sleep complaints > 6 months in 40.6%, 1-6 months in 27.8%). Most patients (63.9%) took zolpidem on a daily basis. The average dose was 10 mg zolpidem per night in 74.8%, 5 mg in 19.8%, 20 mg in 2.4% and > 20 mg in 10 cases. Most physicians (87.6%) rated the efficacy of zolpidem as 'very good' or 'good'. One hundred and eighty-two (1.1%) of the 16 944 patients reported 268 adverse events (one adverse event in 113 cases, two adverse events in 53 cases and more than two adverse events in 16 cases). One hundred and eighteen (64.8%) of these patients (0.006% of all participating patients) discontinued treatment because of adverse events. Nausea (n = 36), dizziness (n = 35), malaise (n = 23), nightmares (n = 20), agitation (n = 19), and headache (n = 18) were the most common adverse events. There was one serious adverse reaction in a 48-year-old women who developed paranoid symptoms during the documentation phase. No life-threatening adverse event occurred. The adverse event profile reflected the pharmacological properties of zolpidem and underlined the cumulative good experience with the drug internationally.
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PMID:Safety and tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16944 cases. 972 26

The pyrazoloacridine (PZA) analogue NSC366140 (PD115934) entered clinical trial based on unique preclinical characteristics including solid tumor selectivity in vitro, marked antitumor activity in vivo against murine solid tumors, selectivity against noncycling cells, and activity against multidrug-resistant tumor cells. After identification of the pre-clinical efficacy and an acceptable toxicity profile, a Phase I study of PZA was carried out. A total of 28 patients was entered and received a total of 67 treatment courses. The drug was administered via a 1-h infusion every 21 days. The starting dose was 30 mg/m2 with 2-fold dose escalations through 480 mg/m2. The next dose escalation was 50%, to 720 mg/m2. Grade I through grade IV toxicities were observed. Since no dose-limiting toxicities were observed at 480 mg/m2, and up to grade IV toxicities were observed at 720 mg/m2, an intermediate dose, 600 mg/m2, was evaluated. Dose-limiting toxicities at 720 mg/m2 were hematological (grade III and IV neutropenia) in four of six patients and neurological (up to grade III cerebral toxicities, including restlessness, dizziness, agitation/anxiety, personality changes, and nightmares, as well as myoclonus) in three of six patients treated. The pharmacokinetic parameters which helped predict these toxicities included area under the curve and peak plasma level. Pharmacokinetic studies showed interpatient variations in all parameters studied. The mean area under the curve levels of PZA at the highest two dose levels in patients were near the level detected in mice at their maximum tolerated total dose. The recommended starting dose for Phase II trials using this schedule is 600 mg/m2.
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PMID:Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934). 981 48

Eight patients with stage I-II hypertension received a continuous IV infusion of the selective dopamine-1 agonist, fenoldopam, for up to 48 hours at rates from 0.4 to 1.9 micrograms/kg/min. Hemodynamics and clinical symptoms during infusion were compared to the same parameters in the 24-hour periods before and after infusion. Fenoldopam lowered blood pressure and increased heart rate. Greatest changes occurred during the first 12 hours of infusion and gradually returned toward preinfusion values throughout the remaining 36 hours in the six patients who completed 48 hours of infusion. Fenoldopam was discontinued within 2 hours of starting the infusion in two patients who received drug rates of 0.9 microgram/kg/min and 1.9 micrograms/kg/min because of precipitous bradycardia. Clinical symptoms noted at fenoldopam doses higher than 0.8 microgram/kg/min were headache, dizziness, diaphoresis, nausea and vomiting, and restlessness. In this pilot study, fenoldopam effectively reduced blood pressure in patients with stage I-II hypertension for up to 48 hours, but fixed-dose infusion rates above 0.8 microgram/kg/min were associated with a high frequency of clinically significant and often intolerable adverse effects.
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PMID:Sustained hemodynamic effects of the selective dopamine-1 agonist, fenoldopam, during 48-hour infusions in hypertensive patients: a dose-tolerability study. 1023 94


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