Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol granulomas of the head are relatively rare. Isolated lesions of the cerebellopontine angle are even more uncommon. In this report, 17 cases of petrous apex cholesterol granulomas are presented and management is discussed. Symptoms at presentation included dizziness (14 patients), pressure (nine patients), tinnitus (eight patients), hearing loss (eight patients), otalgia (six patients), headache (six patients), nausea (three patients), drainage from ear (two patients), facial pain (two patients), seizure (two patients), lightheadedness (one patient), hemifacial spasm (one patient), and facial numbness (one patient). Six cases were managed without surgery and 11 patients underwent operative procedures. The approaches used included the infralabyrinthine (eight patients), transcanal-infracochlear (two patients), and translabyrinthine (one patient). The mean follow-up period for all cases was 29.5 months. Of those patients managed without surgery, symptoms improved in all except one, whose tinnitus was slightly worse. Of surgically treated patients, symptoms improved or remained the same except in one with worsened dizziness. There were nine patients with hearing present presurgery and seven whose hearing was preserved postsurgery. The authors present a case that was managed at another center where an attempt at surgical resection through a subtemporal middle fossa approach was unsuccessful. This lesion was successfully treated using an infralabyrinthine approach with drainage into the mastoid cavity. Cholesterol granulomas of the petrous apex can be managed without surgery when symptoms are stable or improve. Otherwise, a transmastoid extradural approach with simple drainage into the mastoid sinus or middle ear produces symptomatic improvement with low morbidity. Resection of petrous apex cholesterol granulomas is not necessary.
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PMID:Cholesterol granulomas of the petrous apex: combined neurosurgical and otological management. 881 66

Lesopitron, a 5-hydroxytryptamine 1A agonist, is a new potential anxiolytic of the azapirone class. It has greater potency in animal models of anxiety than buspirone, gepirone, or ipsapirone, and it lacks the antidopaminergic effects associated with buspirone. Lesopitron has been tolerated at single doses up to 50 mg and repeated dosages of 45 mg/day in healthy volunteers. Forty-two patients with generalized anxiety disorder (GAD) were enrolled in this double-blind bridging study to determine the safety and tolerability of fixed doses of lesopitron (20, 25, 30, 40, 45, 50, and 60 mg two times a day) over a 6 1/2-day inpatient administration period. Each of the seven panels included six patients (four drug/two placebo). One patient in the 25-mg, two-times-a-day panel voluntarily withdrew because of increased anxiety symptoms. One patient experienced severe orthostatic hypotension at 60 mg two times a day, and moderate to severe adverse events (dizziness, lightheadedness, nausea, headache) occurred in two other patients at this dosage. The most commonly reported adverse events in all the panels were headache, dizziness, and nausea. Lesopitron is rapidly absorbed in patients, having a time to maximum concentration (Tmax) ranging from 0.5 to 1 hour, and its elimination half-life ranged from 1.1 to 5.6 hours. Peak plasma concentrations showed high interindividual variability for lesopitron, but increased linearly with dose for the main metabolite, 5-hydroxylesopitron. We defined the maximum tolerated dose in GAD patients as 50 mg two times a day, twice as high as the highest dose tested in healthy volunteers.
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PMID:Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder: a bridging study. 895 72

Dysregulation in blood pressure control can occur as a result of psychological stress in either the hypertensive or hypotensive direction. Applied psychophysiological techniques incorporating biofeedback and relaxation have been shown to be efficacious in controlled studies of hypertensive patients. Electromyograph, thermal, skin conductance and direct blood pressure feedback have been utilized alone or in combination with relaxation, blood pressure monitoring, and medication. Prediction models are proposed to define what type of hypertensive is most likely to respond with significant blood pressure decrease. Neurocardiogenic syncope is a cardiovascular disorder which manifests itself as lightheadedness, dizziness, syncope, and often migraine-type headache. Preliminary indications suggest that biofeedback-assisted relaxation may also prove beneficial to patients with this syndrome.
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PMID:Good news--bad press: applied psychophysiology in cardiovascular disorders. 903 12

L-365,260 is a CCKB antagonist which has been shown to completely prevent CCK-4-induced symptoms of panic attack in single-dose (50 mg) placebo-controlled studies in patients with panic disorder. The present report is data from one site (n = 38) in a multicenter study (n = 88) designed to assess the preliminary efficacy and safety of L-365,260 in patients meeting DSM-III-R criteria for panic disorder, with or without agoraphobia. In order to participate, male and female patients were between 18-55 years of age and in good physical health. Following a one-week single-blind placebo lead-in, patients were randomized to 30 mg four times daily of L-365,260 (n = 18; 7 M, 11 F) or placebo (n = 20; 9 M, 11 F) for six weeks. At end of study, none of the efficacy measures, including the frequency of panic attacks, the Physician's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety, were significantly improved over baseline values. L-365,260 was well-tolerated; the most common drug-related adverse events were headache and lightheadedness. Further testing of L-365,260 at higher dosages, or testing of other CCKB antagonists, is required to rule out the usefulness of this novel treatment approach.
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PMID:Pilot study of a CCKB antagonist in patients with panic disorder: preliminary findings. 916 May 64

The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way, crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC infinity) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5-20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days. The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p < or = 0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show that the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.
Cephalalgia 1997 Jun
PMID:Safety, tolerability, and pharmacokinetics of sumatriptan in healthy subjects following ascending single intranasal doses and multiple intranasal doses. 920 76

The safety and tolerability of mibefradil, a selective T-type calcium channel antagonist, were evaluated in 3,430 patients with essential hypertension and chronic stable angina pectoris treated in 15 double-blind placebo and active-controlled clinical trials and 2 open-label, long-term safety studies. Of these patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100 mg) and form the basis of this report. With the 50-mg dose of mibefradil, the incidence of each adverse event was similar to, or lower than, that observed in the placebo-treated patients. Treatment with the 100-mg dose was associated with a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lightheadedness (2.1% vs 0.4%). The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in patients treated with placebo. In active-controlled trials, a lower incidence of pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%), diltiazem SR/CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was better tolerated than amlodipine and nifedipine SR/GITS and was as well tolerated as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse experiences with the 50- and 100-mg doses were 2.5% and 3.5%, respectively, compared with placebo (3.5%). No consistent pattern of laboratory adverse experiences were observed for mibefradil. Sinus bradycardia (heart rate <45 beats/minute) and first-degree atrioventricular block were the only relevant treatment-emergent electrocardiographic changes that occurred more frequently with mibefradil than with placebo. No evidence of first-dose effects was observed in mibefradil-treated patients, and withdrawal effects were not observed in clinical trials. There were no clinically important differences in safety profiles in the demographic subgroups for age, gender, or race. The results of this comprehensive safety analysis indicate that treatment with the recommended doses of mibefradil is well tolerated and safe.
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PMID:Safety of mibefradil, a new once-a-day, selective T-type calcium channel antagonist. 928 53

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

Mibefradil is the prototype of a new class of calcium antagonists that selectively block T-type voltage-gated plasma membrane calcium channels in vascular smooth muscle. The drug is structurally and pharmacologically different from traditional calcium antagonists. It does not have negative inotropism at therapeutic concentrations, and is not associated with reflex activation of neurohormonal and sympathetic systems. In clinical studies of hypertension, mibefradil 50 and 100 mg/day reduced trough sitting diastolic and systolic blood pressures in a dose-related manner. Dosages exceeding 100 mg/day generally did not result in significantly greater efficacy, but were associated with a higher frequency of adverse events. No first-dose hypotensive phenomenon was observed. Mibefradil has antiischemic properties resulting from dilation of coronary and peripheral vascular smooth muscle, and a slight reduction in heart rate. In clinical studies of chronic stable angina pectoris, dose-related increases in exercise duration, time to onset of angina, and time to 1-mm ST-segment depression during exercise tolerance tests occurred. Mibefradil reduced the number and duration of ischemic events recorded by 48-hour ambulatory electrocardiograph (ECG) monitoring, as well as number of anginal episodes and nitroglycerin consumption. Favorable hemodynamic and clinical profiles are reported, including high trough:peak ratios (> 80%), high oral bioavailability, and long elimination half-life (17-25 hrs) permitting once/day dosing. Dizziness, headache, leg edema, and lightheadedness are frequently reported, but overall the agent is well tolerated. First-degree atrioventricular block and sinus bradycardia are the most frequent ECG changes caused by the drug. In vitro studies indicate mibefradil inhibits cytochrome P450 1A2, 2D6, and 3A4, resulting in elevated plasma concentrations of drugs metabolized by those isoenzymes. Therefore, it is contraindicated in patients receiving terfenadine, astemizole, cisapride, lovastatin, or simvastatin.
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PMID:Mibefradil, a pharmacologically distinct calcium antagonist. 962 98

Preclinical studies indicate that dihydropyridine-type calcium channel antagonists modulate dopamine neurotransmitter function and can reduce cocaine-reinforced behaviors. Amlodipine, a long-acting dihydropyridine-type calcium channel antagonist related to isradipine and nifedipine, was administered in open label fashion for 12 weeks to 26 cocaine-dependent patients. In subjects expressing cocaine craving, craving significantly declined during the course of the 12 weeks. Five individuals reported flushing, headache, fatigue, nocturia, nausea, and lightheadedness. No conclusions regarding efficacy can be made due to the small number of subjects and the open-label design.
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PMID:Amlodipine treatment of cocaine dependence. 1043 93

The new generation fluoroquinolones -- sparfloxacin, levofloxacin, grepafloxacin and trovafloxacin -- have been designed to respond to the clinical need for extended antimicrobial cover in the face of increasing global microbial resistance. Their main focus is in the treatment of respiratory infections, particularly those acquired in the community. CNS adverse effects, such as dizziness and headache, are known to occur relatively commonly with some fluoroquinolones and are not, in general, well tolerated by patients. The structural component of the fluoroquinolone molecule believed to be responsible for improved gram-positive activity is also believed to be implicated in the production of CNS adverse effects, including those arising from drug interactions with theophylline and NSAIDs. Inhibition of brain gamma-aminobutyric acid (GABA) receptor binding appears to be a strong indicator of CNS activity, though N-methyl-D-aspartate receptor binding has also been implicated. In accordance with the results of these predictive studies, clinical trials have found sparfloxacin, levofloxacin and grepafloxacin to be associated with a low incidence of CNS events. Trovafloxacin has been found to be associated with a higher incidence of CNS events (particularly lightheadedness and dizziness) than the other 3 agents. Ongoing and future clinical studies will help to define the usefulness of the predictive models, as well as reveal the full CNS adverse event profile of these and other investigational fluoroquinolones.
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PMID:Potential interactions of the extended-spectrum fluoroquinolones with the CNS. 1045 80


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