flunarizine and Intermittent-Claudication

The authors report a randomised double-blind clinical study on the efficacy and tolerability of flunarizine. Two groups of patients with obliterating peripheral arterial disease (stage II) were treated for 3 months either with 10 mg flunarizine or with placebo and were examined monthly as to subjective symptoms, laboratory and instrumental parameters. Findings were evaluated by analysis of variance and Student's t-test. After three months, the flunarizine group had a greater increase of the distance walked before the onset of claudication and of maximum post-ischemic blood flow. No changes were observed in laboratory tests and central hemodynamics. The score of subjective symptoms was improved in the flunarizine treated group. Tolerance was good, side effects requiring withdrawal of treatment were not observed.

Topics: Aged; Arteriosclerosis Obliterans; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Intermittent Claudication; Male; Middle Aged; Random Allocation; Regional Blood Flow

Topics: Arterial Occlusive Diseases; Cardiovascular Agents; Cinnarizine; Clinical Trials as Topic; Dihydroergotamine; Dihydroergotoxine; Drug Combinations; Exercise Test; Flunarizine; Humans; Intermittent Claudication; Nafronyl; Pentoxifylline; Placebos; Pyrrolidines; Secologanin Tryptamine Alkaloids; Yohimbine

Flunarizine, a long-acting calcium antagonist, was studied in patients with peripheral vascular disease in order to assess its effects on blood viscosity, erythrocyte deformability, platelet activity and some clinical parameters. A randomized double-blind study was performed; all patients were given a standard diet, invited to abstain from smoking and to carry out a regular daily exercise (walking). After a 2-month run-in period the patients were divided into two groups: one was treated with flunarizine 10 mg/day and the other with placebo. The group treated with flunarizine presented marked and significant reduction of erythrocyte filtration time and blood viscosity and an improvement of the treadmill-free interval with a correlation between the parameters considered.

Topics: Aged; Blood Viscosity; Calcium Channel Blockers; Cinnarizine; Double-Blind Method; Erythrocyte Deformability; Flunarizine; Humans; Intermittent Claudication; Middle Aged; Piperazines; Platelet Aggregation; Rheology

Thirty-one patients, mean age 60 years (range 45-80 years), with a typical history and objective symptoms of intermittent claudication with a reported maximal walking distance less than 500 m, were included in a cross-over study. After a one month's run-in period on placebo, the patients were randomized into two groups: one group started with flunarizine (5 mg t.i.d.) and the other with pentoxifylline (400 mg t.i.d.). The treatment lasted 3 months, whereafter the medications were changed. The trial followed a double-blind design. The median of the maximal walking distance was 255 m after the placebo period, increasing significantly (p less than 0.01) during both medication periods: by 43% and 18% during flunarizine and pentoxifylline, respectively. No changes were recorded in the ankle systolic blood pressure ratio ( ASBP -ratio) after placebo or either medication period. Red cell rigidity (Pmax), which was initially elevated, decreased significantly (p less than 0.05) during both medication periods, but there were no significant differences between the two drugs. No changes were found in whole blood or plasma viscosity. We conclude that the decrease in red cell rigidity may have contributed to the increased walking distance.

Topics: Aged; Arteriosclerosis; Blood Pressure; Blood Viscosity; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Erythrocytes; Exercise Test; Flunarizine; Humans; Intermittent Claudication; Leg; Middle Aged; Osmotic Fragility; Pentoxifylline; Physical Exertion; Piperazines; Regional Blood Flow; Rheology; Smoking; Theobromine; Vasodilator Agents

The clinical significance of drugs improving red cell deformability is not confirmed. We established the effect of physical training alone and combined with flunarizine on intermittent claudication. Twelve patients aged 48-73 years were included in the study. Pain-free walking distance on treadmill, ankle/arm pressure ratio and transcutaneous oxygen tension were measured. Walking distance increased significantly (p less than 0.05) by 130% from 75 m to 173 m during the first year when the patients were on programmed physical training. Ankle/arm pressure ratio also increased significantly (p less than 0.05) from 0.46 to 0.55 during this period. The increase in walking distance ceased when the programmed physical training was discontinued for 6 months. During the following double-blind, cross-over medication period the patients were given flunarizine 5 mg b.i.d. and placebos in randomized order for 3 months each. They also continued the same programmed physical training as during the first year. Walking distance increased, albeit not significantly, with time to 392 m after the second medication period. There was no difference, however, between flunarizine and placebo. Ankle/arm pressure ratio was of the same magnitude as at the beginning of the trial. Oxygen tension measurements did not give consistent results. We conclude that programmed physical training increased walking distance as a function of time. Flunarizine had no effect on the performance of patients with intermittent claudication.

Topics: Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Female; Flunarizine; Humans; Intermittent Claudication; Locomotion; Male; Middle Aged; Physical Education and Training; Piperazines

Topics: Aged; Cinnarizine; Doppler Effect; Double-Blind Method; Female; Flunarizine; Humans; Intermittent Claudication; Leg; Male; Middle Aged; Physical Exertion; Piperazines; Ultrasonography

Drugs such as dipyridamole (200 micrograms/kg/min), an adenosine uptake inhibitor, and theophylline (300 micrograms/kg/min), an adenosine receptor antagonist, respectively increased and decreased postischemic hyperemia in normal subjects, as well as in POAD patients. Moreover, dipyridamole pretreatment was able to antagonize the reduction of peak flow induced by nifedipine, and the potentiating effect of flunarizine on postischemic hyperemia was affected significantly by theophylline, thus suggesting a possible interference of calcium entry blocker drugs with the endogenous adenosine system. In a cellular model (polymorphonuclear leukocytes--PMN) the inhibitory effect of calcium entry blockers on stimulated functions (degranulation and free radical production) was highly antagonized by theophylline. Finally, a 1H-NMR spectroscopy study showed a binding interaction between adenosine and flunarizine on the cell membrane. An adenosine-receptor coupling to the calcium entry blocker channels is suggested.

Topics: Adenosine; Arterial Occlusive Diseases; Calcium Channel Blockers; Dipyridamole; Female; Flunarizine; Humans; Intermittent Claudication; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neutrophils; Regional Blood Flow; Superoxides; Theophylline