Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry, pharmacology, pharmacokinetics, assay methodologies, adverse effects, and dosage of levamisole are described, and the clinical studies of levamisole therapy in patients with colorectal carcinoma are reviewed. Levamisole is a synthetic, orally active agent that has antihelmintic and immunomodulatory properties. It is capable of inducing T-cell differentiation and restoring depressed effector functions of peripheral lymphocytes and phagocytes to normal. The drug is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized by the liver. Gas chromatography and high-performance liquid chromatography are the most common methods used to measure concentrations of levamisole in biologic fluids. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with surgically resected Dukes stage C colon cancer; this combination is now recommended as standard therapy in these patients. Uses in patients with rectal carcinoma, Dukes stage B colon cancer, metastatic colon cancer, other malignancies, or nonmalignant disorders remain investigational. Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste, flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most serious adverse effect associated with levamisole is granulocytopenia. The FDA-approved dosage of levamisole is 50 mg orally every eight hours for three days every two weeks. Levamisole therapy is to be initiated no earlier than 7 and no later than 30 days after surgery and is to be continued for one year. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with resected stage C colon cancer. Further research is needed to more clearly define the mechanism of action, optimum dose and scheduling, and clinical efficacy of levamisole in treating other malignancies.
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PMID:Levamisole in the adjuvant treatment of colon cancer. 200 37

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.
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PMID:The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. 218 2

A survey of occupational physicians of the Food Industry Medical Officers Group was undertaken to establish details of medical kits supplied by their organizations to business travellers. The most common approach was an in-house medical kit with instructions emphasizing self treatment of the common ailments of travellers such as motion sickness, sleeplessness, diarrhoea, indigestion and headaches. The majority of kits included a small supply of needles, syringes, IV cannulae etc either in a commercial 'Aids Kit' or as inhouse supplies. Antimalarials were provided either as a standard kit item or as required. About half provided antibiotics for the self treatment of infections. Very few provided a telephone number for use in the event of medical emergencies. A standard medical kit specification is proposed.
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PMID:Medical kits for business travellers. 221 91

Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. 225 79

A yin-yang hypothesis is presented linking noradrenergic activity, thromboxane, melatonin, left hemisphere functioning, and cyclic AMP on the one hand, and dopamine, beta-endorphin, calcium, right hemisphere functioning, and cyclic GMP on the other. It is further suggested that there is a yoking of NA, TXA2, serotonin and melatonin in the left hemisphere, and a similar yoking of DA, BE, calcium and cGMP in the right. Evidence is presented to support the hypothesis that each element (NA, TXA2, etc.) on one side can modulate or balance a corresponding element (DA, BE, etc.) on the other. It is suggested that thromboxane is the key element in noradrenergic overactivity and that not taking this into consideration has confounded much prior research. This theory takes into account information processing models as well as pharmacological data and neurochemical theory on coupling of adenylate cyclase to its hormone receptors. Inhibiting noradrenergic overactivity can be obtained by inhibiting thromboxane and concomitantly activating opiate receptors. This protocol may have clinical utility in treating a wide range of disorders such as: anxiety, depression, schizophrenia, sleeplessness, withdrawal states, enuresis, Gilles de la Tourette syndrome, Parkinsonism, Alzheimers, dementia, anorexia, infant ruminations, essential tremor, spasticity of spinal cord injury, diarrhoea, ulcerative colitis, extrapyramidal symptoms, akathisia, neuroleptic malignant syndrome, attention deficit disorder, hyperhidrosis, and possibly AIDS.
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PMID:Inhibiting noradrenergic overactivity by inhibition of thromboxane and concomitant activation of opiate receptors via dietary means. 254 22

Hexamethylene bisacetamide (HMBA), a potent differentiating agent, was administered to patients with refractory malignant tumors. Thirteen patients received 30 evaluable courses. HMBA was given by continuous i.v. infusion for 5 days. Therapy was repeated every 28 days, if patients had recovered from toxicity. The starting dose was 24 g/m2/day. Because our previous trial had shown wide interpatient variability in HMBA pharmacokinetics and excess toxicity at HMBA plasma concentrations greater than 2 mM (HMBA doses between 24 and 33.6 g/m2/day), we attempted to individualize each patient's dose based on a dosing scheme using an adaptive (feedback) control algorithm, which assumed linear clearance for HMBA. In all courses, a plasma sample was assayed daily and infusion rates were adjusted to achieve an HMBA plasma concentration of 1.5-2.0 mM (300-400 mg/liter). The patients included 12 men and 1 woman with a median age of 56 years (range, 34-76) and median Karnofsky performance status of 90% (range, 60-100). All patients had received prior chemotherapy and 9 patients had also received radiation therapy. The linear adaptive control algorithm was reasonably precise, with a mean absolute error of 0.28 (SE 0.04) mM. However, adjustments in infusion rate systematically overshot the desired change in steady state concentration, probably due to nonlinear clearance of HMBA. For levels within 24 h of a change in infusion rate, this resulted in significant bias, with a mean error of 0.24 (SE 0.09) mM. The mean absolute error was 0.40 (SE 0.06) mM. A second adaptive control algorithm, using a pharmacokinetic model with parallel first-order (renal) clearance and Michaelis-Menten (nonrenal) clearance and using Bayesian parameter estimation with a priori estimates based on our previous phase I trial, proved to be much more precise than the linear method and was unbiased when applied retrospectively to the same observations, with a mean error (within 24 h of a change in infusion rate) of 0.02 (SE 0.06) mM and a mean absolute error of 0.22 (SE 0.03) mM. Toxicity was reversible in all cases. Neurotoxicity, consisting of hallucinations, agitation, somnolence, or confusion, was seen in 2 patients. Four patients complained of insomnia or anxiety. Mild asymptomatic acidosis was seen in 3 patients. Other toxicity included grade 1-2 nausea and vomiting (10 patients), grade 2 diarrhea (2 patients), grade 3 thrombocytopenia (3 patients), grade 1-3 leukopenia (3 patients), and oral herpes simplex infection (4 patients). Mild reversible renal insufficiency (measured by creatinine clearance) was seen in 8 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I trial using adaptive control dosing of hexamethylene bisacetamide (NSC 95580). 272 Jun 96

The authors review the literature discribing non-dyskinetic antipsychotic withdrawal phenomena. Withdrawal of these agents can cause nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgia, paresthesia, anxiety, agitation, restlessness, and insomnia. Psychotic relapse is often presaged by increased anxiety, agitation, restlessness and insomnia, but the temporal relationship of these prodromal symptoms to reduction in the dosage or discontinuation of neuroleptics distinguishes them from the effects of abrupt withdrawal.
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PMID:Antipsychotic withdrawal symptoms: phenomenology and pathophysiology. 289 77

The literature describing nondyskinetic antipsychotic withdrawal symptoms is reviewed. The withdrawal of antipsychotic agents can result in nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. Psychotic relapse is often presaged by increased anxiety, agitation, restlessness, and insomnia. However, the temporal relationship of these prodromal symptoms to reduction in the dosage or discontinuation of neuroleptics distinguishes them from the effects of abrupt withdrawal.
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PMID:Antipsychotic withdrawal phenomena in the medical-surgical setting. 290 18

Data on adverse reactions due to the quinolone antibacterial agents--ciprofloxacin, ofloxacin, pefloxacin, norfloxacin, and enoxacin--observed in a patient sample of approximately 30,000 are reviewed. Overall rates of adverse reactions were 4.0%-8.0%, and adverse reactions necessitated discontinuation of therapy in 1.0%-2.6% of patients. Patterns of organ-system involvement and of signs and symptoms were quite similar, with gastrointestinal effects predominating (nausea, vomiting, diarrhea, or abdominal pain in 1.0%-5.0% of the patients), followed by effects on the central nervous system (dizziness, headache, and/or insomnia in 0.1%-0.3% of the patients) and skin (0.5%-2.2% of the patients). Elevation in levels of hepatic enzymes occurred in 1.8%-2.5% of the patients, azotemia in 0.2%-1.3%, and eosinophilia in 0.2%-2.0%. These adverse effects were reversible after drug withdrawal and were generally not dose-dependent. Within the constraints of the relatively small number of well-documented patients and the unique mechanism of action of these antimicrobial agents, the safety profile of these drugs seems to make them acceptable for use when their administration is well directed and specific. In addition, close surveillance for new phenomena should be maintained.
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PMID:Adverse effects of the fluoroquinolones. 327 99

A double-blind, randomized, crossover study was conducted to compare the efficacy and safety of high-dose dexamethasone (Protocol D) with a combination of dexamethasone, metoclopramide and diphenhydramine (Protocol DMD) in the management of chemotherapy-induced nausea and vomiting in cancer patients. All entered patients had received no prior chemotherapy. During the study chemotherapy was administered on an inpatient basis. The majority of patients (94%) were treated with cytotoxic drugs of significant emetogenic activity and 40% of the study group received cis-platin-containing combinations. Of the 60 evaluable patients, complete antinausea and antivomiting effects of D were observed in 30 (50%) and 34 (57%), respectively and of DMD in 17 (28%) and 26 patients (43%) respectively. The difference was not statistically significant (P = 0.09 and 0.24, respectively). Lack of significant difference between the two regimens was demonstrated irrespective of the administered cytotoxic drugs. The DMD protocol caused more adverse reactions than D. While 27 patients (45%) experienced no side effects from D, only 14 (24%) remained free of complications due to DMD (P = 0.001). Furthermore, DMD produced more sedation, insomnia, headache, diaphoresis, dizziness and diarrhoea than the D regimen. In addition it gave rise to more adverse effects on appetite and activity. Upon direct questioning, 37 patients (62%) expressed a preference for D, 14 (23%) preferred DMD and 9 (15%) found no difference between the two regimens. We conclude that, while the short DMD protocol has an antiemetic activity equivalent in its effectiveness to D, its associated adverse reactions would minimize its usefulness. Therefore, further investigations should be conducted to find a safer and more potent combination of antiemetics suitable for therapy in an outpatient setting.
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PMID:Antiemetic efficacy of high-dose dexamethasone: randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine. 328 2


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