Gene/Protein Disease Symptom Drug Enzyme Compound
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Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater. In placebo-controlled comparative studies, sumatriptan reduced migraine headache from 'moderate or severe' to 'mild or none' within 2 hours in 50 to 73% of patients following oral administration of 100 or 200 mg, and within 1 hour in 70 to 80% of patients following subcutaneous doses of 6 to 8 mg or intranasal doses 20 mg into each nostril. In addition, sumatriptan alleviated the accompanying symptoms of nausea, vomiting, and photophobia/phonophobia more effectively than placebo, and permitted higher percentages of patients to resume normal daily activities. Sumatriptan 100 mg orally was more effective in the acute treatment of migraine than oral combination therapy consisting of ergotamine 2 mg plus caffeine 200 mg or aspirin 900 mg plus metoclopramide 10 mg. Pooled data from nearly 5000 patients treated with either oral or subcutaneous sumatriptan in clinical trials indicate that it is well tolerated. However, migraine recurrence within 24 or 48 hours of initial symptom resolution developed in approximately 40% of patients treated with sumatriptan, irrespective of route of administration. It is likely that migraine recurrence is related to the short half-life of the drug (approximately 2 hours). Future studies should attempt to ascertain whether additional doses of sumatriptan will help prevent migraine recurrence in patients with attacks of long duration and if so, should determine the optimum interval between dosages. In conclusion, sumatriptan is an important addition to the range of drugs currently available for acute treatment of migraine. It provides rapid relief from debilitating symptoms in a high percentage of patients, particularly after subcutaneous administration. At this stage in its development a number of questions remain to be answered - most notably whether repeat doses will help prevent recurrent attacks and which patients are most likely to respond to therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and tolerability that is unique in this particular clinical setting.
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PMID:Sumatriptan. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache. 137 52

The purpose of prescribing combined oral contraceptives (OCs) is achievement of good cycle control and effective contraception with the least side effects, using an OC with the lowest possible dose of estrogen. Triphasil, Triquilar, Nordette, Microgynon 30, and Brevinor are good 1st choices because of the low estrogen dose (30-35 mcg). Women who probably cannot tolerate breakthrough bleeding and who need simple packaging should use a monophasic, more progestogenic OC, e.g., Nordette or Microgynon 30. Physicians should suggest a low dose estrogen and low dose antiandrogenic progestogen (OC) (e.g., Diane-35 ED) for women who have acne. They should advise patients that when they take OCs, their menstrual periods usually become shorter, regular, and lighter. Women need not take a break from OC usage. Vitamin C, antibiotics, griseofulvin, rifampicin, and anticonvulsants (except sodium valproate) interact with OCs. Women using warfarin and oral hypoglycemics and wanting to start using OCs need to consult their physician about changing requirements for warfarin and oral hypoglycemics. The effectiveness of OCs can be diminished by diarrhea and vomiting. Absolute contraindications to OCs include pregnancy, use during the first 2 weeks postpartum, history of thromboembolism, undiagnosed abnormal vaginal bleeding, focal migraine, coronary heart disease, steroid-dependent tumors, recent impaired liver function, and cardiovascular accidents. Some relative contraindications are older than 35 years old and smoking, breast feeding, and hypertension. This article provides a section on how to manage common side effects. For example, if the side effect is acne, the physician should prescribe an OC with increased estrogen and reduced progestogen (e.g., Triphasil/Triquilar to Biphasil/Sequilar). This article lists trade names of various OCs and their estrogen and progestogen doses, e.g., Nordette has 30 mcg ethinyl estradiol and 150 mcg levonorgestrel.
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PMID:Combined oral contraception. 147 9

Migraine is a common condition with, usually, stereotyped symptomatology, suggesting that it is a specific disease entity (a morbus sui generis). However, occasionally a migraine sufferer will exhibit atypical manifestations of the condition; also, some specific diseases such as systemic lupus erythematosus and arteriovenous malformations, may exactly mimic the symptoms of migraine. These latter considerations raise the possibility that migraine is a syndrome rather than a disease. The recent delineation of the trigeminovascular system allows a conception of migraine as being neither disease nor syndrome, but rather a constitutional predisposition of the neurovascular system to react excessively to internal or external stimuli by a pattern of hyperactivity of the brain and of the trigeminovascular apparatus. Activation of the trigeminovascular system, whether by neural impulses from the brain or humoral factors in the circulation, results in vascular headaches, while associated activity in the brain may produce such typically migrainous symptomatology as prodrome and aura, and nonspecific symptoms such as nausea, vomiting and dizziness. In this model specific diseases may gain access to the trigeminovascular apparatus, detonating it to produce vascular headaches and neurological symptomatology which may more or less exactly mimic migraine.
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PMID:Migraine--disease or syndrome? 149 11

The effect of the dopamine receptor blocking domperidone (Motilium) has been examined in 73 gynaecological patients in a wide indication field. The treatment was successful in controlling dyspeptic symptoms of different origins, nausea-vomiting of different etiologies, climacteric flushes, and in the prevention of migraines in 67.1% of the cases. Partial response was obtained in 19.2%, and no response in 13.7% of the cases. According to the opinion of the authors the gastrokinetic and antiemetic effect of domperidone is of high value, the use of the drug may be attempted as a monotherapy or an adjuvant therapy for the prevention of migraine and the treatment of climacteric flushes.
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PMID:Some possible gynaecological indications for peripheral antidopamine therapy. 158 81

The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine.
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PMID:Pharmacology of antimigraine drugs. 164 88

A double-blind, placebo-controlled multicentre study was carried out to evaluate the efficacy and tolerability of 100, 200 and 300 mg sumatriptan, a selective 5-hydroxytryptamine (5-HT)1-like receptor agonist, given in an oral dispersible form in the acute treatment of migraine attacks. A total of 1130 patients were recruited from 51 centres in eight countries and the efficacy results are presented from an interim analysis of 538 cases. Tolerability was evaluated in 227 patients. At 2 h, an improvement in headache severity from moderate or severe to mild or none was reported by 67% of patients who received 100 mg sumatriptan, 75% receiving 200 mg and 69% of patients receiving 300 mg sumatriptan, compared with 22% of patients who received placebo (P less than 0.001 all doses sumatriptan vs placebo). Adverse events were generally mild and transient, and appeared to be dose-related; the adverse event profile of 100 mg sumatriptan was similar to that of placebo. Overall, nausea/vomiting and "bitter taste" were the most common complaints. The proportion of patients withdrawn due to adverse events was similar in the placebo and 100 mg sumatriptan treatment groups (2% and 3%, respectively). It is concluded that 100 mg sumatriptan given orally is well tolerated with an anti-migraine efficacy comparable to that provided by the two higher doses.
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PMID:Clinical experience with oral sumatriptan: a placebo-controlled, dose-ranging study. Oral Sumatriptan Dose-defining Study Group. 164 90

The efficacy and safety of oral sumatriptan as a 100-mg dispersible tablet was compared with oral Cafergot (2 mg ergotamine tartrate, 200 mg caffeine) in a multicentre, randomized, double-blind, double-dummy, parallel-group trial. In the trial, 580 patients were treated from 47 investigating centres in nine European countries. Sumatriptan was significantly more effective than Cafergot at reducing the intensity of headache from severe or moderate to mild or none; 66% (145/220) of those treated with sumatriptan improved in this way by 2 h, compared with 48% (118/246) of those treated with Cafergot (p less than 0.001). The onset of headache resolution was more rapid with sumatriptan, whereas recurrence of migraine headache within 48 h was lower with Cafergot. Sumatriptan was also significantly more effective at reducing the incidence of nausea (p less than 0.001), vomiting (p less than 0.01) and photophobia/phonophobia (p less than 0.001) 2 h after treatment, and fewer patients on sumatriptan (24%) than on Cafergot (44%, p less than 0.001) required other medication after 2 h. The overall incidence of patients reporting adverse events was 45% after sumatriptan and 39% after Cafergot; the difference was not significant. The most commonly reported events in the sumatriptan-treated patients were malaise or fatigue and bad taste; these were generally mild and transient. Nausea and/or vomiting, abdominal discomfort, and dizziness or vertigo were reported by a greater proportion of Cafergot-treated patients. It is concluded that oral sumatriptan was well tolerated and is a more effective acute treatment for migraine than Cafergot.
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PMID:A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group. 165 39

A double-blind, randomized, multicentre, parallel-group study was carried out to compare intranasal sumatriptan with placebo in the treatment of migraine. Seventy-four patients (37 in each treatment group) were recruited into the study. Patients received two insufflations of the same treatment (sumatriptan or placebo) 15 min apart. Sumatriptan (20 mg plus 20 mg) was more effective than placebo at relieving headache, defined as a reduction in severity from moderate (grade 2) or severe (grade 3) to mild (grade 1) or none (grade 0), at 60 and 120 min. At 120 min, 75% of patients in the sumatriptan group reported headache relief, compared with 32% of patients in the placebo group (p less than 0.001); 53% of patients in the sumatriptan group were completely pain-free, compared with 11% in the placebo group. A clinically significant reduction in the incidence of nausea, vomiting and photophobia was observed in the sumatriptan group compared with the placebo group, and sumatriptan was also more effective at reducing the functional disability of the patients. A similar number of patients reported migraine recurrence, within 24 h in both treatment groups. The observed reduction in headache severity, functional disability and nausea following intranasal administration of sumatriptan would appear to obviate the need for a concomitant anti-emetic during a migraine attack. The results support the further development and testing of intranasal sumatriptan.
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PMID:A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group. 165 41

Headache in young children is frequently a cause of concern to parents and physicians. We have reviewed our experience with 104 children with onset of headaches prior to 7 years of age seen by age 9 years. Headaches could be classified in more than 90% of cases. The most common headache type in this population referred to a child neurologist was migraine that constituted 75% of the cases. Seventy-two of 78 cases were common migraine. Posttraumatic headaches accounted for an additional 12%. Associated symptoms such as autonomic signs, nausea, and vomiting were common, particularly in the migraine group. Neuroimaging studies when performed did not reveal any significant abnormalities. Other laboratory tests were also generally unhelpful. No child has gone on to develop new neurologic abnormalities or evidence of an intracranial tumor. We conclude that even in young children headaches are generally benign. Even in this population, neuroimaging studies have a very low yield in the absence of other symptoms and findings and are not always indicated.
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PMID:Headaches in children younger than 7 years of age. 849 99

There has been a great dealt of discussion as to the clinical significance of E.E.G. 14-6 per second positive spikes (14-6 PS), a short burst lasting one second or less which occurs during light sleep in monopolar recordings, mainly in the posterior temporal regions and usually involving the parietal and occipital regions as well, for the most part in unsymmetrical fashion. Early interpretations stress the epileptic nature of vegetative attacks in patients with an inter-critical E.E.G. reading characterized by 14-6 P.S. Subsequently, however, this hypothesis has been refuted, mainly because E.E.G. intra-critical recordings have never shown evidence of any sort of paroxysmal activity. At present time expert think that the presence of 14-6 PS may be merely an indication of an electrical alteration associated with disorders in the neurovegetative area. In order to evaluate the possibility of using them as a diagnostic marker of migraine equivalents and periodic syndromes, we reviewed wake and sleep E.E.G. recordings, carried out consecutively and hence not selectively, in 617 children aged 5-16 years. 14-6 PS were present in 109 children (17.6%), 63 of whom showed evident symptoms of periodic syndrome (headache, recurrent abdominal pain, cyclic vomiting, kinetosis, etc.); hence 46 E.E.G. recording were false positive. 510 children were lacking in 14-6 PS, 91 of these presented symptoms of periodic syndromes (false negative). 14-6 PS are hence a marker 40.9% sensitive, 90.1% specific, with a predictable value of 57.7%. The search for 14-6 PS in children with periodic syndrome is not particularly sensitive as a test, but it is fairly specific: it may well constitute an useful element in diagnosis.
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PMID:[A diagnostic controversy: the significance of 14-6/sec positive spikes in clinical electroencephalography]. 175 77


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