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)

A single familial hemiplegic migraine locus has been previously mapped to 19p13.1 and associated with mutations in a calcium channel gene (CACNL1A4). We describe a new 39-member four-generation family from Wyoming of German-Native American descent with autosomal dominant familial hemiplegic migraine that is not linked to the chromosome 19p locus. Affected individuals showed a stereotypic pattern of migrainous headache associated with hemisensory and hemiparetic attacks, without other headache types. Eighty-three percent reported minor head trauma as a trigger for individual attacks. Seventy-two percent reported other typical migraine triggers for the attacks. Attack frequency decreased with age and the overall course was benign. Genetic linkage studies of this family found strong evidence for the disease gene in this family being located at chromosome 1q31. Multipoint analysis showed lod scores > 3 in a 44-cm region flanked by D1S158 and D1S2781, using 80% penetrance and a phenocopy rate of 1/50. Haplotype and multipoint analysis, including flanking markers, suggested incomplete penetrance and variable expressivity of the disease. A single affected patient who reports atypical symptoms including daily headaches likely represents a phenocopy. This new locus for hemiplegic migraine suggests that mutations of additional calcium channels in the region may cause the disease.
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PMID:A new locus for hemiplegic migraine maps to chromosome 1q31. 937 90

In most cases, successful preventive therapy for migraines requires daily medication for months or years. Perimenstrual use of a preventive agent is a common exception. Preventive therapy is usually undertaken in patients who have more than two headache episodes per month or those very much disabled by headaches. Beta blockers are usually the first choice for preventive therapy, and amitriptyline is also commonly used. Despite widespread use of calcium channel blockers for prevention of migraine, their benefits are controversial. Although effective for prevention of migraine, methysergide and phenelzine are usually relegated to last-resort use because of potentially serious side effects. The migraine patient who is refractory to standard preventive therapy may have rebound headache related to overuse of abortive migraine medications, or concomitant psychopathology.
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PMID:Drug treatment of migraine: Part II. Preventive therapy. 940 13

A total of 34 Italian patients (15 males and 19 females) suffering from Moyamoya disease (MMD) and selected by a questionnaire survey in 12 neuropediatric and neuroradiologic departments were studied in a multicentric study. The onset of the disease appeared either in childhood (27 patients, aged 0-16 years, mean 5.4 years) or in adulthood (seven patients, aged 25-55 years, mean 35 years). The early clinical symptoms consisted of transient ischemic attacks and/or stroke (20 cases), recurrent migraine-like headaches (seven cases), seizures (six cases) and hemorrhage (one case). A total of four familial cases were found. The final diagnosis was based in all cases on the conventional angiographic findings and more recently also on the magnetic resonance angiography (ten patients). The mean lag time between the first clinical manifestation and the angiographic diagnosis was about 2 years. A medical treatment (vasodilators, antiplatelet agents, calcium channel blockers) was followed by 21 patients, while five cases underwent a surgical revascularization. The follow-up ranges from 1 to 15 years (mean 6 years): A motor (16 cases) and/or mental impairment (14 cases) was detected especially in the childhood onset MMD; only one patient died. In nine cases the long-term outcome persisted without neurological deficit.
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PMID:Clinical and neuroradiological findings of moyamoya disease in Italy. 940 6

Neurotologic symptoms are common with migraine, yet relatively little is known about the pathophysiology of such symptoms. Motion sensitivity with bouts of motion sickness occurs in about two thirds of patients with migraine. Episodes of vertigo occur in about one fourth of patients and, in some, vertigo is the only symptom (so-called "migraine equivalent"). Phonophobia is the most common auditory symptom, but fluctuating hearing loss and acute permanent hearing loss occur in a small percentage. Migraine can mimic Meniere's disease and so-called "vestibular Meniere's disease" is usually associated with migraine. The recent discovery of a mutation in a brain calcium-channel gene in families with hemiplegic migraine and in families with episodic vertigo and ataxia suggests a possible mechanism for neurotologic symptoms in patients with more common varieties of migraine. A defective calcium channel, primarily expressed in the brain and inner ear, could lead to reversible hair cell depolarization and auditory and vestibular symptoms. This hypothesis is currently being investigated in other families with migraine headaches and neurotologic symptoms. Hopefully, such studies will lead to improved diagnosis and better treatments in the future.
Headache
PMID:Neurotology of migraine. 943 80

Nitrates, which have been used for more than a century, are the second oldest drug (after digitalis alkaloids) in the cardiological pharmacological arsenal. However, several facets of their mode of use still remain controversial. Their vasodilator and arteriolodilator action (especially in coronary vessels) and their platelet aggregation inhibitory effect make them useful drugs, particularly in all clinical forms of ischaemic heart disease (unstable or stable angina and acute myocardial infarction), for the prevention or treatment of ischaemic episodes (silent or not) and also in heart failure where nitrates are useful not only as symptomatic treatment (alone or associated with diuretics), but also in view of their positive effect on survival (associated with hydralazine: V-Heft I trial). At the present time, nitrates can be administered via the sublingual, oral, intravenous of transdermal routes in the form of nitroglycerin and isosorbide dinitrate or mononitrate (short-acting and sustained-effect forms). Their rare contraindications concern patients suffering from severe hypotension (< 70 mmHg), severe anaemia, glaucoma or intracranial hypertension. The most serious adverse effects are pulsatile headache (which usually disappear after several days), postural hypotension (possibly causing fainting), facial erythema, vertigo, palpitations or nausea and vomiting. Most of these adverse effects can be controlled by dosage adaptation and it is rarely necessary to stop treatment. However, the major problem raised by the use of nitrates concerns the development of a tolerance. The pathophysiology of this multifactorial phenomenon is still unclear. The protagonist role played by loss of SH groups or activation of humoral feedback mechanisms, with an increase of circulating catecholamine levels, activation of the R-A-A system and increased plasma volume, has been postulated. This complication can be avoided by prescribing intermittent treatment, with a drug-free interval of 10-12 hours per day. A single dose of a sustained-release preparation (60 mg of isosorbide dinitrate or 40 to 60 mg of isosorbide mononitrate), or 2 or 3 doses of a short-acting preparation (20-40 mg of isosorbide mononitrate) can be prescribed via the oral route. When the transdermal route is used, the patch should be left in place for 12 hours. Treatment should be started at low doses, which are then gradually increased. The free period is usually at night, which can be covered, when necessary, by other antiischaemic drugs (for example, beta-blockers and/or calcium channel blockers), already usually used in combination with nitrates. This interruption is not accompanied by a rebound phenomenon. It must be remembered that nitrates potentiate the action of other vasodilators and calcium channel blockers and that, in some patients, intravenous nitroglycerin reduces the anticoagulant effect of heparin, while indomethacin can inhibit their vasodilator effect. Nitrates are therefore in very good health despite their advanced age and, when used correctly, they continue to be very useful in the pharmacological treatment of cardiovascular diseases.
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PMID:[Principles and rules of the use of nitrates]. 945 73

Migraine is a primary headache disorder characterized by recurring attacks of pain and associated symptoms. Migraine sufferers require a continuum of clinical care that depends on their disability and response to treatment. Treatment consists of: (1) prevention of attacks by avoidance of triggers; (2) the use of nonpharmacologic treatments; (3) treatment of the acute attack; and (4) long-term prophylactic therapy. Migraine is comorbid for affective disorders, epilepsy, stroke, and mitral valve prolapse. The therapy selected depends on the headache severity and frequency, the pattern of associated symptoms, comorbid illnesses, and the patient's treatment response profile. Acute treatment can be symptomatic or specific, using drugs such as dihydroergotamine (DHE) or sumatriptan. Preventive treatment can be episodic, subacute, or chronic. The major drug groups include beta-adrenergic blockers, anti-depressants, calcium channel blockers, serotonin antagonists, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs). These can be divided into two major categories and second-line choices.
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PMID:Migraine treatment. 947 12

Calcium antagonists are potent vasodilators and are widely used in the treatment of hypertension and angina pectoris. The currently available compounds belong to three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine and felodipine), (2) phenylalkylamines (e.g. verapamil) and (3) benzothiazepines (e.g. diltiazem). The three classes differ in their pharmacological profile and safety. For example, verapamil and diltiazem lower heart rate, while dihydropyridines increase it or leave it unchanged. With most of the latter compounds, a marked activation of the sympathetic nervous system has been noted. Most compounds exhibit negative inotropic effects, particularly the first-generation molecules, which is disadvantageous in patients with impaired left-ventricular function. The most common side effects of these drugs are flushing, headache and edema. With verapamil, constipation may represent a problem in certain patients. Hence, in spite of a large number of calcium antagonists available, there remains a need for new compounds with enhanced efficacy and improved tolerability. A new compound should lack any negative inotropism, avoid any increase in sympathetic outflow or heart rate and exhibit a high degree of vascular selectivity. Furthermore, a low incidence of side effects, particularly ankle edema and optimal pharmacokinetics allowing once-daily dosing would be desirable. Mibefradil is a new calcium antagonist with promising pharmacological and clinical properties. The compound has a high bioavailability, lacks negative inotropic effects at therapeutic concentrations, does not exhibit reflex tachycardia during vasodilation and actually slightly decreases heart rate. It is a potent direct vasodilator efficacious in hypertension and chronic angina pectoris, elicits endothelium-dependent relaxations and facilitates the effects of nitric oxide in vascular smooth muscle. The drug is a particularly efficacious vasodilator in intramyocardial coronary arteries which may be important for its anti-ischemic effects and the lack of steal in the coronary circulation. Furthermore, mibefradil has antiproliferative properties in human vascular smooth muscle cells in culture. As a unique property, mibefradil blocks T-type calcium channels and hence represents a new class of calcium channel blockers. In patients with hypertension, mibefradil has a high efficacy in controlling blood pressure. The drug does not cause constipation and has a low incidence of ankle edema. A large trial is under way to further delineate the properties of this new calcium antagonist in patients with heart failure.
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PMID:Comparative pharmacological properties among calcium channel blockers: T-channel versus L-channel blockade. 957 Apr 24

The TEAM trial investigated the effectiveness and tolerance of a fixed combination of the ACE inhibitor and calcium channel blocker (2 mg trandolapril and 180 mg verapamil retard) (preparation Tarka) in an open multicentre prospective study of treatment of moderately severe hypertension (diastolic pressure at the end of the two-week wash-out period 100-115 mm Hg). The trial comprised 163 patients who were treated first for four weeks by a monotherapy with 2 mg trandolapril. After these four weeks patients who attained normal blood pressure proceeded with trandolapril treatment. Hypertensive patients who did not attain normal diastolic pressure levels were treated for another four weeks by a fixed combination of trandolapril and verapamil SR. After four weeks of treatment with trandolapril 62 patients of 163 (37%) had a diastolic blood pressure of less than 90 mm Hg. The fixed combination of trandolapril and verapamil SR reduced the diastolic blood pressure to less than 90 mm Hg in 71.6% of the patients resistant to treatment with 2 mg trandolapril and in another 15.6% of patients it reduced the diastolic blood pressure by 10 mm Hg or more. After two months of treatment 60 patients had a normal blood pressure due to trandolapril (37%) and another 73 patients (45%) treated by a combination of trandolapril and verapamil SR, i.e. a total of 133 patients (82%) who originally suffered from moderately severe hypertension, attained a normal diastolic blood pressure. The mean decrease of diastolic pressure after two months of treatment was 19.5 mm Hg in "non-respondents" to trandolapril monotherapy and 23.6 mm Hg in "respondents". The mean decrease of systolic pressure in "non-respondents" and "respondents" after trandolapril treatment was 19.5 mm Hg and 35.0 mm Hg resp. The fixed combination of trandolapril and verapamil was not only effective but was associated with a minimum of undesirable effects. The incidence of headaches declined significantly. The combination of the above preparations is useful also because both preparations have a cardio- and nephroprotective effect and do not affect the lipid and carbohydrate metabolism. Treatment with a fixed combination of trandolapril and verapamil SR is indicated in moderately severe hypertension not responding to monotherapy, in particular when associated with diabetes, hyperlipoproteinaemia, ischaemic heart disease or left ventricular hypertrophy.
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PMID:[The TEAM study--a study of the effectiveness and tolerance of treatment of essential hypertension with a fixed combination of trandolapril and verapamil]. 982 54

Optimal treatment of hypertension requires the use of effective antihypertensive drugs. Calcium channel blockers are widely used in the treatment of hypertension and appear to be particularly efficacious in ethnic Chinese patients. The aim of this open-label study was to prospectively investigate the efficacy and tolerability of three dihydropyridine calcium channel blockers in sequence, using the same protocol for each. After 2 weeks of placebo treatment, 73 males and 45 females (mean age, 45 +/- 10 years; mean weight, 67 +/- 10 kg) with essential hypertension (diastolic blood pressure, 95 to 115 mm Hg) were treated with amlodipine (n = 41), felodipine (n = 38), or isradipine (n = 39) for 8 weeks, with dose titration after 4 weeks. Mean seated systolic and diastolic blood pressure decreased by 23/17, 30/17, and 20/15 mm Hg after 8 weeks of treatment with amlodipine, felodipine, and isradipine, respectively. These reductions were all statistically significant. Blood pressure was controlled (defined as diastolic pressure < 90 mm Hg at the final visit or a decrease from baseline of > or = 10 mm Hg) in 85%, 74%, and 74% of patients receiving amlodipine, felodipine, and isradipine, respectively. There were no significant changes in heart rate, plasma lipid levels, or serum biochemistry markers with any of the three treatments. No serious adverse events occurred, but mild adverse effects, including headaches, flushing, tachycardia, dizziness, and edema, were reported; 1 (2%), 6 (16%), and 5 (13%) patients receiving amlodipine, felodipine, and isradipine, respectively, withdrew from the study (P < 0.05). The results of this study indicate that all three drugs are highly effective in lowering blood pressure and are well tolerated in Chinese patients with mild-to-moderate hypertension.
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PMID:Amlodipine, felodipine, and isradipine in the treatment of Chinese patients with mild-to-moderate hypertension. 991 9

This document presents the primary care diagnosis and management of headache in women. The varying patterns of chronic headache among females during their reproductive years are related to the changing hormonal levels. Migraine occurs in 25% and tension-type of headache occurs in 88% of women. These changes occur during menarche, menstrual cycling, oral contraceptive use, pregnancy and menopause as a result of the changes in sex steroid levels. The physiological relationship between estradiol and other neurotransmitters that causes headache is described. Diagnosis of headache includes physical and neurologic examinations. Treatment of headache depends on the woman's reproductive stage. Acute-care headache treatments include analgesics, opioids, ergotamines, and the triptans for 2-3 days a week. Chronic or tension-type headaches require preventive therapy, which includes the daily use of antidepressants, beta-blockers, calcium channel blockers, and antiepilepsy medications. Menstrual migraine medication includes serotonin and prostaglandin active agents during chronic headaches and beta-blockers, antidepressants, calcium channel blockers or valproic acid. Nonpharmacologic treatment of headache is preferred for pregnant women.
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PMID:Focus on primary care diagnosis and management of headache in women. 1035 52


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