flunarizine and Chronic-Disease

In the anaesthetized, chronic atrioventricular block (CAVB) dog, ventricular ectopic beats and Torsade de pointes arrhythmias (TdP) are believed to ensue from an abrupt prolongation of ventricular repolarization and increased temporal dispersion of repolarization, quantified as short-term variability (STV). These TdP stop spontaneously or, when supported by substantial spatial dispersion of repolarization (SDR), degenerate into ventricular fibrillation. However, most studies involving ventricular arrhythmias do not quantify SDR by means of an electrophysiological parameter. Therefore, we reviewed the effects of 4 highly effective anti-arrhythmic drugs (flunarizine, verapamil, SEA-0400, and GS-458967) on the repolarization duration and associated STV. All drugs were tested as anti-arrhythmic strategies against TdP in CAVB dogs, their high anti-arrhythmic efficacy was defined as suppressing drug-induced TdP in 100% of the experiments. This comparison demonstrates that even though the anti-arrhythmic outcome was similar for all drugs, distinct responses of repolarization duration and associated STV were observed. Moreover, the aforementioned and commonly adopted electrophysiological parameters were not always sufficient in predicting TdP susceptibility, and additional quantification of the SDR proved to be of added value in these studies. The variability in electrophysiological responses to the different anti-arrhythmic drugs and their inconsistent adequacy in reflecting TdP susceptibility, can be explained by distinct modes of interference with TdP development. As such, this overview establishes the separate involvement of temporal and spatial dispersion in ventricular arrhythmogenesis in the CAVB dog model and proposes SDR as an additional parameter to be included in future fundamental and/or pharmaceutical studies regarding TdP arrhythmogenesis.

Topics: Action Potentials; Aniline Compounds; Animals; Anti-Arrhythmia Agents; Atrioventricular Block; Chronic Disease; Disease Models, Animal; Dogs; Electrophysiologic Techniques, Cardiac; Endpoint Determination; Flunarizine; Heart Rate; Phenyl Ethers; Pyridines; Time Factors; Torsades de Pointes; Triazoles; Verapamil

Tinnitus is the perception of sound or noise in the absence of an external or internal acoustic stimulation. It is a common and potentially distressing symptom for which no adequate therapy exists.. To assess the effectiveness of anticonvulsants in patients with chronic tinnitus.. We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, CENTRAL (2010, Issue 2), MEDLINE, EMBASE, bibliographies and additional sources for published and unpublished trials. The date of the most recent search was 26 May 2010.. We selected randomised controlled trials in patients with chronic tinnitus comparing orally administered anticonvulsants with placebo. The primary outcome was improvement in tinnitus measured with validated questionnaires. Secondary outcomes were improvement in tinnitus measured with self-assessment scores, improvement in global well-being or accompanying symptoms, and adverse drug effects.. Three authors assessed risk of bias and extracted data independently.. Seven trials (453 patients) were included in this review. These studies investigated four different anticonvulsants: gabapentin, carbamazepine, lamotrigine and flunarizine. The risk of bias of most studies was 'high' or 'unclear'. Three studies included a validated questionnaire (primary outcome). None of them showed a significant positive effect of anticonvulsants. One study showed a significant negative effect of gabapentin compared to placebo with an increase in Tinnitus Questionnaire (TQ) score of 18.4 points (standardised mean difference (SMD) 0.82, 95% confidence interval (CI) 0.07 to 1.58). A second study showed a positive, non-significant effect of gabapentin with a difference compared to placebo of 2.4 points on the Tinnitus Handicap Inventory (THI) (SMD -0.11, 95% CI -0.48 to 0.25). When the data from these two studies are pooled no effect of gabapentin is found (SMD 0.07, 95% CI -0.26 to 0.40). A third study reported no differences on the THI after treatment with gabapentin compared to placebo (exact numbers could not be extracted from the article).A meta-analysis of 'any positive effect' (yes versus no) based on a self-assessment score (secondary outcome) showed a small favourable effect of anticonvulsants (RD 14%, 95% CI 6% to 22%). A meta-analysis of 'near or total eradication of tinnitus annoyance' showed no effect of anticonvulsants (risk difference (RD) 4%, 95% CI -2% to 11%). Side effects of the anticonvulsants used were experienced by 18% of patients.. Current evidence regarding the effectiveness of anticonvulsants in patients with tinnitus has significant risk of bias. There is no evidence from studies performed so far to show that anticonvulsants have a large positive effect in the treatment of tinnitus but a small effect (of doubtful clinical significance) has been demonstrated.

Topics: Administration, Oral; Amines; Anticonvulsants; Carbamazepine; Chronic Disease; Cyclohexanecarboxylic Acids; Flunarizine; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Randomized Controlled Trials as Topic; Tinnitus; Triazines

Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification.. To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse.. We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine.. Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903).. Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.. Estudio comparativo de la efectividad del topiramato y la flunaricina en series independientes de pacientes con migraña cronica sin abuso de medicacion.. Introduccion. El topiramato y la onabotulinumtoxina A han mostrado ser eficaces en la migraña cronica con o sin abuso de farmacos segun los criterios recientes de la Clasificacion de Cefaleas de la Sociedad Internacional de Cefaleas. Objetivo. Demostrar que la flunaricina es tan efectiva como el topiramato en la migraña cronica sin abuso de farmacos. Pacientes y metodos. Estudio prospectivo, no aleatorizado, comparativo de dos grupos de pacientes con similar edad y sexo, con migraña cronica sin abuso, tratados preventivamente por primera vez con topiramato o flunaricina. Resultados. A 40 pacientes tratados con flunaricina se les asigno un paciente del mismo sexo y edad tratado con topiramato. La media de reduccion de las migrañas intensas en el grupo del topiramato fue del 59% y en el grupo de la flunaricina, del 58,5% (p = 0,9444); la tasa de respondedores al cuarto mes de tratamiento tampoco mostro diferencias significativas, ya que fue del 75% para el topiramato y del 70% para la flunaricina (p = 0,6236). La media de reduccion de otras cefaleas en el grupo del topiramato fue del 57%, y en el grupo de la flunaricina, del 64% (p = 0,4261); la tasa de respondedores al cuarto mes de tratamiento fue del 76%, similar en ambos grupos. El porcentaje de abandonos del tratamiento fue mayor con el topiramato (19,5%) que con la flunaricina (10%) (p = 0,3493). En ninguno de los dos grupos hubo efectos adversos graves. Un 78,9% de los pacientes que tomo topiramato presento satisfaccion con el farmaco frente al 75% del grupo de la flunaricina (p = 0,7903). Conclusion. La flunaricina mostro ser tan efectiva como el topiramato en el tratamiento de la migraña cronica sin abuso de farmacos.

Topics: Adult; Calcium Channel Blockers; Chronic Disease; Cognition Disorders; Fatigue; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Dropouts; Patient Satisfaction; Prospective Studies; Topiramate; Treatment Outcome

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Cinnarizine; Clinical Trials as Topic; Drug Tolerance; Female; Flunarizine; Humans; Male; Middle Aged; Piperazines; Placebos

94 patients with Stage II obliterating arteriopathy of the lower extremities, treated with Flunarizine (10-20 mg per diem), were checked every two months for a 6 month period. Of the 76 patients reaching the final check up, 58 had received no previous treatment and 18 had ischemias secondary to reconstructive vascular surgery. Clinical improvement in terms of increased independent mobility and improved Doppler flowmeter pressure readings were noted in both groups. In view of its beneficial effects on blood vessel function in other areas, Flunarizine is felt to be a valuable drug for the treatment of peripheral arteriopathies, both initially and in cases of ischaemia following vascular surgery.

Topics: Aged; Arterial Occlusive Diseases; Chronic Disease; Cinnarizine; Clinical Trials as Topic; Female; Flunarizine; Humans; Ischemia; Leg; Male; Middle Aged; Piperazines; Regional Blood Flow; Rheology; Time Factors; Ultrasonography; Vasodilator Agents

The anti-vertigo activity of flunarizine has been evaluated in a 16-week double-blind placebo-controlled cross-over trial involving 41 patients. After a 4-week open running-in treatment with 10 mg flunarizine daily, the 40 responders were either further treated with flunarizine--at the same dose--or given matching placebo. After another 6 weeks, they were switched to the alternative medication. Severity of vertigo, and frequency and duration of the attacks were quickly and significantly reduced with the open flunarizine dose. Continuation of the drug further produced a slight improvement whereas switching over to the placebo resulted in a significant deterioration of the patients' condition. Tinnitus seemed to be less responsive to treatment. The level of untoward effects (sedation) was low and similar for both medications.

Topics: Adult; Chronic Disease; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Flunarizine; Humans; Male; Middle Aged; Piperazines; Placebos; Tinnitus; Vertigo

Activation of peripheral and/or central trigeminovascular pain pathways are implicated in the pathogenesis of migraine. Small fibers mediate pain, thermal sensation, and autonomic functions. Axon flare response is correlated with local C-fiber activation and calcitonin gene-related peptide release. Laser speckle contrast analysis (LASCA) detects very subtle microcirculatory changes that are not visible to the naked eye.. Axon flare response was elicited by 0.01 mL intradermal (i.d.) histamine introduced to the left forehead, trigeminal nerve ophthalmic branch (V1) skin area. Skin microvascular blood flow data were recorded using a LASCA real-time microcirculation imaging system. In the healthy control, prick stimulus slightly elevated focal skin microcirculation only at the stimulated focal area. However, in our patient with chronic migraine, the unilateral prick stimulation transiently (over 10 to 12 seconds) increased ipsilateral skin microcirculation at all 3 branches of the trigeminal nerve, with a slight expansion across the midline. Left V1 stimulation by i.d. histamine induced not only prominent but also long-lasting (10 to 15 minutes of recording time) axon flare response at the ipsilateral V1, V2, and V3 areas, with an expansion to the contralateral V1 area and without any report of allodynia or hyperalgesia. The treatment decreased axon flare characteristics probably by inhibiting neurogenic inflammation.. The clinical characteristics and individual response to treatment vary widely across patients with pain. Here, we demonstrated the presence of transient spread of increased microcirculation at the ipsilateral trigeminal nerve, and also across the midline after prick stimulus, whereas a more prominent, widespread, and long-lasting histamine-induced axon flare response occurred in a rare subclass of patient who had chronic migraine with autonomic symptoms. The modulatory effect of the pharmacological intervention has also been objectively quantified by LASCA.

Topics: Adult; Chronic Disease; Female; Flunarizine; Histamine; Histamine H1 Antagonists; Humans; Hyperalgesia; Microcirculation; Migraine Disorders; Perfusion Imaging; Thermography; Trigeminal Nerve

To analyse the results of out-patient treatment with diminishing doses of oral dihydroergotamine for patients with chronic migraine resulting from ergotics abuse.. A prospective and descriptive intervention study.. County hospital. Neurology out-patient clinic.. All the patients with chronic migraine as a side-effect of abuse of ergotic preparations who were referred to neurology out-patients over 18 months.. 1) Patients were told verbally of the causes of their migraine; 2) suppression of the ergotics, using diminishing doses of dihydroergotamine (Dihydergot gotas); 3) Prophylactic treatment with flunarizine (Sibelium); 4) Symptomatic treatment with sodic naproxen (Antalgin 550); 5) monthly and three-monthly check-up.. Over 18 months 25 patients with migraines due to ergotic abuse (6.7% of total migraines) were included. 4 were men; 21 women. Their average age was 43 (SD: 13). At one month the response was excellent in 19 patients (76%), good in 3 (12%) and bad in 3 (12%). At three months, the response was excellent in 17 patients (68%), good in 4 (16%), bad in 2 (8%) and 2 did not attend for the check-up (8%).. 1) Out-patient treatment with diminishing doses of oral dihydroergotamine is effective in treating chronic migraine due to ergotics abuse. 2) The general practitioner should intervene in the identification and prevention of ergotics abuse.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dihydroergotamine; Ergot Alkaloids; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Naproxen; Prospective Studies; Substance-Related Disorders; Time Factors; Vasodilator Agents

In chronic experiments on rabbits, the effect of hyperthermia growing up to 41 degrees C upon the cerebral circulation system, was studied. Cortical blood flow decreased by 20-25% due to hypercapnia and constriction of arterioles whereas the blood flow in the thalamus and hypothalamus either remained the same as initial one or increased insignificantly. The reactivity of cerebral vessels in CO2 inhalation and orthostatic load decreased along with the rise of body temperature. The signs of lesion of the hemato-encephalic barrier and an increase of the water content by 3-4% in the cortex and white matter were revealed in hyperthermia. The impedance data corroborated extracellular character of cerebral oedema. Comparative study of vasodilators euphylline, cavinton and flunaresine has revealed that the calcium blocking agent flunaresine provides the best restoration of the cerebral blood flow level and the reactivity of cerebral vessels in hyperthermia.

Topics: Aminophylline; Animals; Blood-Brain Barrier; Body Temperature; Body Water; Brain; Carbon Dioxide; Cerebrovascular Circulation; Chronic Disease; Electrodes, Implanted; Fever; Flunarizine; Posture; Rabbits; Vasodilator Agents; Vinca Alkaloids

Fifty-two patients, most of whom had had daily headaches for years, were examined and treated. Among them there were 40 who originally had migraine, the others had vasomotor or post-contusional headaches. Average duration of the migraine was 21 years, of chronic headache 7.6 years. All patients had been taking analgesics of a mixed type regularly and for a long time, on average 35.6 tablets or suppositories weekly. All patients had taken more than three different drugs. After an observation period of 3-6 months for grading the headaches and registering the amount of drug intake, all patients were admitted to hospital when all analgesics were at once discontinued. Changing degrees of withdrawal symptoms were the rule: increased headaches, nausea, vomiting, tachycardia, sweating, sleep disorders, and in some also hallucinations and cerebral episodes. At the end of the hospital stay chronic headache had completely disappeared or markedly improved in 77% of patients. Even after an average of 16 months of subsequent observation, chronic headache continued to be significantly improved in 70% of patients. There was a significant reduction in frequency and intensity of attacks in the patients with originally typical migraine. Regular intake of analgesics of the mixed type induces chronic headaches. These are most commonly caused by ergotamine tartrate and aminophenol derivatives, while psychological and physical dependence on anti-migraine drugs is initiated and maintained by additional barbiturates, caffeine and codeine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analgesics; Chronic Disease; Cinnarizine; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Substance Withdrawal Syndrome