flunarizine and Nervous-System-Diseases

Aged people are frequently the victims of iatrogenic diseases, especially adverse effects of drugs since they are affected by many age-related diseases and are given many drugs. Geriatric medicine in Japan has a bitter history of having produced many victims by adverse effects of cerebral vasodilators and cerebral stimulants; they included parkinsonism and depression induced by flunarizine and cinnarizine, and Reye-like encephalopathy induced by calcium hopantenate. Parkinsonism induced by sulpiride, tiapride, metoclopramide or atypical anti-psychotics, dyskinesia induced by anti-parkinsonian drugs or anti-psychotics, and psychotic symptoms induced by anti-parkinsonian drugs, anti-cholinergic drugs, anti-depressants or histamine H2 antagonists are still very common. Wernicke encephalopathy caused by intravenous glucose infusion without thiamine, central pontine myelinolysis by too rapid correction of hyponatremia are important though infrequent. Iatrogenic Creutzfeldt-Jakob disease by dura grafts is a warning against the easy use of medical materials produced with human organs or blood. Iatrogenic diseases are preventable, and geriatricians have to pay attention to the information on adverse effects of drugs and medical materials and carefully observe the early signs of iatrogenic diseases.

Topics: Aged; Cinnarizine; Creutzfeldt-Jakob Syndrome; Flunarizine; Humans; Iatrogenic Disease; Medication Errors; Nervous System Diseases; Parkinson Disease, Secondary; Psychoses, Substance-Induced; Wernicke Encephalopathy

Flunarizine is a class IV calcium antagonist with a pharmacological profile which suggests its therapeutic potential in a number of neurological and cerebrovascular disorders. It is an effective prophylactic treatment for common or classic migraine in children and adults, and it appears at least as effective as a number of other agents which act by different pharmacological mechanisms, including pizotifen (pizotyline), cinnarizine, methysergide, nimodipine, metoprolol, propranolol, aspirin and cyclandelate. Flunarizine is also effective in reducing the frequency of seizures, when used as an 'add-on' treatment, in some patients with partial or generalised epilepsy resistant to maximal therapy with a combination of several conventional antiepileptic drugs. Placebo-controlled studies show that flunarizine is effective in the treatment of vertigo and associated symptoms of either peripheral or central origin, and in the treatment of cerebrovascular insufficiency where psychological symptoms, rather than vertigo, are the primary symptoms. In the treatment of vertigo, flunarizine appears at least as effective as cinnarizine and more effective than nicergoline, betahistine dichlorhydrate, pentoxifylline (oxpentifylline) and vincamine. Flunarizine therefore is useful in the prophylaxis of migraine, an effective treatment for vertigo and a worthwhile alternative as 'add-on' therapy in patients with epilepsy resistant to conventional drugs.

Topics: Animals; Flunarizine; Humans; Nervous System Diseases

Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear.. Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated.. Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy.. The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Female; Flunarizine; Fructose; Hemiplegia; Humans; Intelligence; Longitudinal Studies; Male; Movement Disorders; Nervous System Diseases; Retrospective Studies; Surveys and Questionnaires; Topiramate

The lipophilic calcium channel antagonist flunarizine has been demonstrated to be neuroprotective in several models of cerebral ischemia. Ischemic spinal cord injury may have a similar pathophysiology and hence may respond in a similar fashion. This study was designed to investigate the effects of pretreatment with flunarizine on systemic hemodynamics, spinal cord blood flow, and neurological recovery in a rabbit model of ischemic spinal cord injury.. New Zealand White rabbits were anesthetized with ketamine and xylazine and instrumented for systemic blood pressure monitoring and spinal cord blood flow measurements using the microsphere method. After pretreatment with flunarizine or vehicle, ischemic spinal cord injury was created selectively in the caudal regions of the spinal cord by cross-clamping the abdominal aorta for a period of 25 minutes. Spinal cord blood flow was measured before, during, and 15 minutes after cross-clamp removal. Animals were allowed to recover and were graded neurologically at 18 and 24 hours after ischemia.. Flunarizine injection was associated with hypotension that was both transient and dose related. Animals pretreated with flunarizine 0.4 mg/kg had significantly improved neurological recovery scores at 18 hours after ischemia (P = .017) compared with vehicle controls. At 24 hours this effect was lessened (P = .095); however, 60% of flunarizine-treated animals retained their ability to hop, whereas all of the vehicle-treated animals were nonambulatory.. Flunarizine has a protective effect on neurological recovery after experimental ischemic spinal cord injury. The therapeutic window is narrow, and dosing is limited by untoward hypotension. The mechanism of protection likely involves inhibition of pathological cytosolic calcium accumulation rather than a direct effect on vascular smooth muscle.

Topics: Animals; Flunarizine; Ischemia; Male; Motor Activity; Nervous System Diseases; Rabbits; Regional Blood Flow; Spinal Cord

Perfusion of the cerebral cortex during closed chest CPR in dogs, generating systolic pressures of 60 to 70 mmHg, is only 10% of pre-arrest blood flow. In contrast, internal cardiac massage produces normal cortical perfusion rates. Following a 20-min perfusion arrest, during pressure controlled reperfusion, cortical flow rates decay to less than 20% normal after 90 min of reperfusion. This appears to be due to increasing cerebral vascular resistance, and is not due to rising intracranial pressure. The post-arrest cortical hypoperfusion syndrome is prolonged with cortical flow remaining below 20% normal up to 18 hr post arrest. The use of a variety of calcium antagonists, including flunarizine, lidoflazine, verapamil, and Mg2+, immediately post-resuscitation maintains cerebral vascular resistance and cortical perfusion at normal levels. A prospective blind trial of the calcium antagonist lidoflazine following a 15-min cardiac arrest in dogs and resuscitation by internal massage, demonstrates amelioration of neurologic deficit in the early postresuscitation period.

Topics: Adenosine Triphosphate; Animals; Brain; Calcium; Cell Membrane; Cerebral Cortex; Cerebrovascular Circulation; Cinnarizine; Dogs; Fatty Acids, Nonesterified; Flunarizine; Heart Arrest; Heart Massage; Hypoxia, Brain; Ischemia; Lidoflazine; Nervous System Diseases; Resuscitation