BACKGROUND AND OBJECTIVE: Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert®) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo. METHODS: In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments. RESULTS: Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients. CONCLUSION: The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders. STUDY REGISTRATION: EudraCT No. 2011-004025-27.

• MeSH
• betahistin škodlivé účinky   terapeutické užití   MeSH
• cinarizin škodlivé účinky   terapeutické užití   MeSH
• dimenhydrinát škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fixní kombinace léků MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vertigo farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

• MeSH
• difenhydramin terapeutické užití   MeSH
• kinetózy * etiologie   farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• samoléčba MeSH
• Check Tag
• lidé MeSH

• MeSH
• analgetika * škodlivé účinky   terapeutické užití   MeSH
• antiemetika škodlivé účinky   terapeutické užití   MeSH
• antiflogistika nesteroidní škodlivé účinky   terapeutické užití   MeSH
• dimenhydrinát terapeutické užití   MeSH
• farmakoterapie metody   MeSH
• kodein škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• metoklopramid terapeutické užití   MeSH
• migréna * farmakoterapie   MeSH
• paracetamol terapeutické užití   MeSH
• plod účinky léků   MeSH
• sumatriptan terapeutické užití   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Organophosphorus (OP) is a large group of compounds with a wide variety of applications. The group comprises insecticides, pesticides and nematicides etc. in addition to deadly poison OP warfare chemicals like sarin and tabun. Thousands of casualties have been reported globally each year by the unintentional and intentional use of OP compounds. Uses of deadly poison OP like sarin by terrorists groups and irresponsible regimens have been documented as well. The threat always exists. The mainstream therapy includes administration of atropine, pralidoxime and bezodiazepines in addition to general supportive measures. Despite this standard therapy, the mortality rates of OP poisoning are still high. Different approaches and methodologies have been postulated and introduced as an alternative to standard therapy but none could replace the existing standard therapy. The present short review examined the possibility of usage of antihistamines as alternate to atropine. Pros and cons have been discussed. The study suggests that some of the first generation antihistamines like promethazine and diphenhydramine may be effectively used as antidote for OP poisoning depending upon the degree of poisoning. They may have several advantages like inexpensive, systematically and centrally acting anticholinergic antihistamines, readily crosses bloodbrain barrier, and large quantities of the drug exist in most hospitals and pharmacies, providing a reservoir in the event of a mass casualty event. However, further clinical studies and evidences are warranted.

• MeSH
• antagonisté histaminu H1 terapeutické užití   MeSH
• antidota * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• antihistaminika * farmakologie   metabolismus   škodlivé účinky   terapeutické užití   MeSH
• difenhydramin škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• otrava organofosfáty * farmakoterapie   MeSH
• promethazin škodlivé účinky   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND OBJECTIVE: Vertigo may arise from dysfunction in the peripheral and/or the central vestibular system. Simultaneous activity of a medication at both sites will serve to improve the efficacy of antivertigo treatment. The aim of this study was to compare the efficacy and tolerability of a fixed combination of the peripherally acting cinnarizine (20 mg) plus the centrally acting dimenhydrinate (40 mg) with those of equally dosed monotherapies in the treatment of vertigo of various origins. METHODS: This prospective, randomized, double-blind, active-controlled, multicentre study included patients who assessed at least one vertigo symptom as being of at least medium intensity (≥2) on a 5-point visual analogue scale (VAS; ranging from 0 = not present to 4 = very strong) and who had pathological vestibulospinal movement patterns and/or nystagmus reactions. Patients were randomly assigned to receive either cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination, cinnarizine 20 mg as monotherapy or dimenhydrinate 40 mg as monotherapy, each three times daily for 4 weeks. Patients were examined at baseline (t(0)), and after 1 week (t(1w)) and 4 weeks (t(4w)) of treatment. The primary efficacy endpoint was the decrease in mean vertigo score (MVS) at t(4w), which was calculated by averaging the total score for 12 individual vertigo symptoms, each assessed using the 5-point VAS. RESULTS: The study included 182 patients, of whom 177 were evaluable for efficacy. The mean ± SD reduction in MVS after 4 weeks of treatment with the fixed combination (-1.44 ± 0.56) was significantly greater than the reductions with each of the active treatments alone (cinnarizine -1.04 ± 0.53; dimenhydrinate -1.06 ± 0.56; p = 0.0001, both comparisons). Cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination was associated with a significantly higher responder rate (78% of patients with MVS ≤0.5 at t(4w)) than the monotherapies. The odds ratios for MVS ≤0.5 at t(4w) in the cinnarizine or dimenhydrinate groups versus the fixed combination group were 0.345 and 0.214, respectively. The fixed combination reduced concomitant vegetative symptoms significantly more effectively than cinnarizine at both t(1w) (p < 0.05) and t(4w) (p < 0.01). Nine patients reported 15 adverse events (AEs) [three AEs for the fixed combination, six AEs each for cinnarizine and dimenhydrinate]. At t(4w) the tolerability of the treatments was rated as very good or good by almost all patients in all groups (fixed combination and dimenhydrinate 96.6% each; cinnarizine 98.3%). CONCLUSION: The fixed combination of cinnarizine 20 mg/dimenhydrinate 40 mg was an effective and well tolerated treatment for patients with vestibular vertigo of central and/or peripheral origin. The efficacy of the fixed combination exceeded that of each of the equally dosed active substances given as monotherapy, leading to higher responder rates, and showed a very good and comparable tolerability with a similar or even smaller rate of adverse events than the active substances given alone.

• MeSH
• antagonisté histaminu H1 aplikace a dávkování   terapeutické užití   MeSH
• cinarizin aplikace a dávkování   terapeutické užití   MeSH
• dimenhydrinát aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fixní kombinace léků MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vertigo farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Previous studies have demonstrated that central injection of L-carnosine (ß-alynyl-L-histidine), dipeptide synthesized in mammalian muscles, affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in anesthetized rats. In the present study, using urethane-anesthetized rats, we examined the dose-dependent effects of intravenous (IV) injection of various doses of anserine, dipeptide of similar structure to L-carnosine, on RSNA, BP and heart rate (HR). We found that injection of a low dose of anserine (1 µg) significantly suppressed RSNA, BP and HR. Conversely, a high dose (1000 µg) of anserine significantly elevated RSNA, BP and HR. Pretreatment with lateral cerebral ventricular (LCV) injection of thioperamide, a histaminergic H3-receptor antagonist, eliminated the effects of a low dose of anserine on RSNA, BP and HR. LCV injection of diphenhydramine, a histaminergic H1-receptor antagonist, abolished the effects of a high dose of anserine on RSNA, BP and HR. These findings suggest that anserine affects RSNA, BP and HR in a dose-dependent manner, and that the histaminergic nerve may be involved in the dose-different effects of anserine in rats.

• MeSH
• anestetika intravenózní MeSH
• anserin farmakologie   MeSH
• antagonisté histaminového receptoru H3 farmakologie   MeSH
• antagonisté histaminu H1 farmakologie   MeSH
• difenhydramin farmakologie   MeSH
• dipeptidy farmakologie   MeSH
• ethyl-karbamát MeSH
• injekce intravenózní MeSH
• krevní tlak fyziologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• ledviny fyziologie   inervace   krevní zásobení   MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• srdce fyziologie   účinky léků   MeSH
• sympatický nervový systém fyziologie   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

BACKGROUND AND OBJECTIVE: Vestibular dysfunction commonly leads to - often severe - vertigo symptoms. The objective of this study was to compare the antivertiginous efficacy and tolerability of a fixed combination of cinnarizine/dimenhydrinate with those of betahistine in patients with acute vertigo due to vestibular disorders. METHODS: Sixty-six patients experiencing acute vertigo attacks participated in this prospective, double-blind, three-centre, comparative study. Patients who assessed at least one vertigo symptom as being of medium intensity (> or =2) on a 5-point visual analogue scale (VAS; from 0 = no symptoms to 4 = very severe symptoms) were randomly allocated to treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg three times daily or betahistine 12 mg three times daily for 4 weeks. The primary efficacy endpoint was change in mean vertigo score, as determined by patients' assessments of 12 individual vertigo symptoms on the 5-point VAS after 4 weeks of treatment. RESULTS: Treatment with the fixed combination led to significantly greater improvements in mean vertigo scores than the reference therapy betahistine after 4 weeks of therapy (p = 0.013). The differences were clinically relevant, based on the Mann-Whitney estimator. Furthermore, the incidence of vertigo-associated vegetative symptoms was significantly reduced after 1 (p = 0.004) and 4 weeks (p = 0.023) in the fixed-combination group relative to the betahistine group. Three patients, all of them in the betahistine group, reported adverse events, none of which was considered serious. Almost all patients (n = 62) rated the tolerabilities of both medications as very good or good. CONCLUSION: The fixed combination of cinnarizine/dimenhydrinate was shown to be an effective and very well tolerated treatment option for patients with acute vertigo due to vestibular disorders. The combination proved to be significantly more efficient in reducing vertigo and associated vegetative symptoms than betahistine in such patients.

• MeSH
• akutní nemoc MeSH
• časové faktory MeSH
• cinarizin chemie   terapeutické užití   MeSH
• dimenhydrinát chemie   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• financování organizované MeSH
• fixní kombinace léků MeSH
• lidé středního věku MeSH
• lidé MeSH
• periodicita MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• tablety MeSH
• vertigo etiologie   farmakoterapie   MeSH
• vestibulární nemoci komplikace   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

From 2001 to 2006, we performed a retrospective study of patients suffering from chronic unilateral or bilateral tinnitus that was previously ineffectively treated by oral drugs [betahistine (Betaserc), extract of Ginkgo biloba (EGb 761), tanakan (Tebokan), and cinnarizine-dimenhydrinate (Arlevert), singly or in combination]. We divided 150 tinnitus patients (80 men, 70 women) into seven treatment groups. Treatments consisted of application of intravenous pentoxifylline, lidocaine, or vinpocetine (Cavinton) and combination of these agents with physiotherapy and soft laser. Mean duration (+/- standard deviation) of tinnitus in these patients was 7.4 +/- 6.0 years; their mean age was 55.6 +/- 12.5 years. The aim of our study was to compare treatment modalities and define their effectiveness for tinnitus relief. The most effective treatment was defined as a combination of Cavinton and physiotherapy. We evaluated pure lidocaine infusion therapy as ineffective. None of the treatment modalities had an objective correlate of improvement, though improvement was reported by a visual analog scale.

• MeSH
• betahistin terapeutické užití   MeSH
• chronická nemoc MeSH
• cinarizin terapeutické užití   MeSH
• dimenhydrinát terapeutické užití   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• kombinovaná farmakoterapie MeSH
• kombinovaná terapie MeSH
• laserová terapie s nízkou intenzitou světla MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidokain terapeutické užití   MeSH
• pentoxifylin terapeutické užití   MeSH
• retrospektivní studie MeSH
• rostlinné extrakty terapeutické užití   MeSH
• senioři MeSH
• techniky fyzikální terapie MeSH
• tinnitus rehabilitace   MeSH
• vinca alkaloidy terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

• Klíčová slova
• Migraeflux,
• MeSH
• analgetika terapeutické užití   MeSH
• antiemetika terapeutické užití   MeSH
• dimenhydrinát terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• migréna farmakoterapie   MeSH
• paracetamol terapeutické užití   MeSH
• prospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• Migraeflux,
• MeSH
• antirevmatika aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• dimenhydrinát aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• migréna farmakoterapie   klasifikace   prevence a kontrola   MeSH
• paracetamol aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• příznaky a symptomy MeSH
• propionáty aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• prospektivní studie MeSH
• spokojenost pacientů MeSH