RESUMEN
BACKGROUND: About 10% of all schoolchildren are suffering from migraine and 50% from tension-type headache. Headache of acute onset usually will be treated with analgesic substances like paracetamol, acetylsalicylic acid or ibuprofen, the first one being the reference drug for tension-type headache in childhood. In case of lacking improvement or side-effects there is demand for an alternative safe substance for the acute analgesic therapy. METHODS: In a double-blind randomised investigation flupirtine and paracetamol were given in two consecutive attacks of episodic tension-type headache. 30 children, 6-12 years old, were included. Dosage was determined according to age and weight. The children documented the acute headache intensity and duration in a special diary. RESULTS: Headache intensity was reduced during 2 h after intake in 89% of the 19 children treated. The reduction was 6,5 to 3,1 for flupirtine and 6,9 to 3,3/10 for paracetamol. There was no statistically significant difference between the two substances. Relevant side-effects could not be observed. CONCLUSION: Flupirtine has shown a convincing clinical effect treating acute episodic tension-type headache for children. The substance was well tolerated by the patients. In addition, flupirtine provides a high degree of safety.
RESUMEN
Short-term trials with the antioxidant thioctic acid (TA) appear to improve neuropathic symptoms in diabetic patients, but the long-term response remains to be established. Therefore, Type 1 and Type 2 diabetic patients with symptomatic polyneuropathy were randomly assigned to three treatment regimens: (1) 2 x 600(mg of TA (TA 1200), (2) 600)mg of TA plus placebo (PLA) (TA 600) or (3) placebo and placebo (PLA). A trometamol salt solution of TA of 1200 or 600 mg or PLA was intravenously administered once daily for five consecutive days before enrolling the patients in the oral treatment phase. The study was prospective, PLA-controlled, randomized, double-blind and conducted for two years. Severity of diabetic neuropathy was assessed by the Neuropathy Disability Score (NDS) and electrophysiological attributes of the sural (sensory nerve conduction velocity (SNCV), sensory nerve action potential (SNAP)) and the tibial (motor nerve conduction velocity (MNCV), motor nerve distal latency (MNDL)) nerve. Statistical analysis was performed after independent reviewers excluded all patients with highly variable data allowing a final analysis of 65 patients (TA 1200: n = 18, TA 600: n = 27; PLA: n = 20). At baseline no significant differences were noted between the groups regarding the demographic variables and peripheral nerve function parameters for these 65 patients. Statistically significant changes after 24 months between TA and PLA were observed (mean +/- SD) for sural SNCV: +3.8 +/- 4.2 m/s in TA 1200, +3.0+/-3.0m/s in TA 600, -0.1+/-4.8m/s in PLA (p < 0.05 for TA 1200 and TA 600 vs. PLA); sural SNAP: +0.6+/-2.5 microV in TA 1200, +0.3+/-1.4 microV in TA 600, -0.7 +/- 1.5 microV in PLA (p = 0.076 for TA 1200 vs. PLA and p < 0.05 for TA 600 vs. PLA), and in tibial MNCV: +/- 1.2 +/- 3.8 m/s in TA 1200, -0.3 +/- 5.2 m/s in TA 600, 1.5 +/- 2.9 m/s in PLA (p < 0.05 for TA 1200 vs. PLA). No significant differences between the groups after 24 months were noted regarding the tibial MNDL and the NDS. We conclude that in a subgroup of patients after exclusion of patients with excessive test variability throughout the trial, TA appeared to have a beneficial effect on several attributes of nerve conduction.
Asunto(s)
Antioxidantes/administración & dosificación , Neuropatías Diabéticas/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ácido Tióctico/administración & dosificación , Potenciales de Acción/efectos de los fármacos , Adolescente , Adulto , Anciano , Antioxidantes/efectos adversos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Placebos , Estudios Prospectivos , Nervio Sural/fisiopatología , Ácido Tióctico/efectos adversos , Nervio Tibial/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy. RESEARCH DESIGN AND METHODS: In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168). Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS). Data analysis was based on the intention to treat. RESULTS: No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline. The TSS in the feet decreased from baseline to day 19 (median [range]) by -3.7 (-12.6 to 5.0) points in the group given alpha-lipoic acid intravenously and by -3.0 (-12.3 to 8.0) points in the placebo group (P = 0.447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (85.6 [0-219] vs. 95.9 [5.5-220]); P = 0.033). After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial. The NIS decreased after 19 days by -4.34+/-0.35 points (mean +/- SEM) in A-A and A-P and -3.49+/-0.58 points in P-P (P = 0.02 for alpha-lipoic acid versus placebo) and after 7 months by -5.82+/-0.73 points in A-A, -5.76+/-0.69 points in A-P, and -4.37+/-0.83 points in P-P (P = 0.09 for A-A vs. P-P). The rates of adverse events were not different between the groups throughout the study. CONCLUSIONS: These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study. However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions. Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy.
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Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Administración Oral , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
AIMS: To evaluate the efficacy and safety of short-term oral treatment with the antioxidant thioctic acid (TA) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: Patients were randomly assigned to oral treatment with 600 mg of TA t.i.d. (n = 12) or placebo (n = 12) for 3 weeks. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) in the feet were scored at weekly intervals and summarized as a Total Symptom Score (TSS). The Hamburg Pain Adjective List (HPAL) and the Neuropathy Disability Score (NDS) were assessed at baseline and day 19. RESULTS: At baseline the TSS, HPAL, and NDS were not significantly different between the groups. The TSS in the foot decreased from baseline to day 19 by -3.75 +/- 1.88 points (-47%) in the TA group and by -1.94 +/- 1.50 points (-24%) in the placebo group (P= 0.021 for TA vs. placebo). The total HPAL score decreased from baseline to day 19 by -2.20 +/- 1.65 points (-60%) in the TA group and by -0.96 +/- 1.32 points (-29%) in the placebo group (P = 0.072 for TA vs. placebo). The NDS decreased by -0.27 +/- 0.47 points in the TA group, whereas it slightly increased by +0.18 +/- 0.4 points in the placebo group (P = 0.025 for TA vs. placebo). No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These preliminary findings indicate that oral treatment with 600 mg of TA t.i.d. for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions.
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Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Anciano , Antioxidantes/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Placebos , Ácido Tióctico/administración & dosificaciónRESUMEN
The effects of flupirtine (CAS 56995-20-1, D-9998, Katadolon) on muscle force and related electromyographic (EMG) activity has been assessed in comparison to tetrazepam and placebo in 12 healthy male volunteers after oral single-dose administration and under steady-state conditions. Muscle functions primarily reflecting dynamic daily demands remained unaffected under flupirtine in contrast to tetrazepam, the latter exhibiting the typical signs of increased (co-)innervation which can be interpreted as a compensation of a decrease of muscle force. Under conditions that serve as a model for static-spastic situations, flupirtine showed a decrease, tetrazepam a typical increase in the force parameter. Under the same conditions, a decrease of the EMG-amplitude was observed for flupirtine and, to a lesser extent, for tetrazepam as well. With respect to its muscle relaxing property, flupirtine differs both, quantitatively and qualitatively from tetrazepam, which has shown effects common for benzodiazepines.
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Aminopiridinas/farmacología , Ansiolíticos , Benzodiazepinas , Benzodiazepinonas/farmacología , Relajantes Musculares Centrales/farmacología , Músculo Esquelético/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Adulto , Electromiografía/efectos de los fármacos , Reflejo H/efectos de los fármacos , Humanos , Contracción Isométrica/efectos de los fármacos , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Proyectos PilotoRESUMEN
Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.
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Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Adolescente , Adulto , Anciano , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Presión Sanguínea , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Placebos , Ácido Tióctico/administración & dosificación , Ácido Tióctico/efectos adversos , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Aminopiridinas/uso terapéutico , Analgésicos/uso terapéutico , Cefalea/tratamiento farmacológico , Adulto , Aminopiridinas/efectos adversos , Analgésicos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
STUDY DESIGN: In a multicentric double-blind trial, flupirtine was compared with tramadol in the treatment of cancer pain. METHODS: Over a period of four weeks, 4 (-6) capsules containing either 100 mg flupirtine (n = 35) or 50 mg tramadol (n = 36) were taken daily in accordance with a fixed time schedule. Severity of pain was scored on a weekly basis using a five-stage verbal scale. RESULTS: Initially comparable in the two groups, pain was more markedly reduced after four weeks of treatment with flupirtine than after tramadol, the need for additional analgesic drugs also being less in the flupirtine group. The final general assessment by the attending doctors of the results achieved was "good" to "very good" in 63% of the patients on flupirtine, and in 46% of those on tramadol. Undesired effects were observed in 6% of the flupirtine patients and in 19% of those taking tramadol.
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Aminopiridinas/uso terapéutico , Analgésicos/uso terapéutico , Neoplasias/fisiopatología , Dolor/tratamiento farmacológico , Tramadol/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Aminopiridinas/efectos adversos , Analgésicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Tramadol/efectos adversosRESUMEN
METHOD: To answer the question as to whether the analgesic flupirtine is suitable for long-term treatment of chronic pain, its side effects and efficacy were investigated over a 12-month treatment period. A total of 191 patients with chronic pain of degenerative and/or inflammatory musculoskeletal diseases were admitted to the open, uncontrolled multicenter study. This was followed by a single-blind placebo follow-up period of two weeks aimed at detecting withdrawal phenomena as a sign of a possible addictive potential of flupirtine. RESULTS: On the basis of patient and investigator documentation, laboratory studies and clinical examinations, flupirtine was found to be both well tolerated and effective. No signs of tolerance, addiction or relevant interactions were observed. The side effect profile differed from that of the opioids or prostaglandin synthesis inhibitors (NSAIDs).
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Aminopiridinas/uso terapéutico , Analgésicos/uso terapéutico , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Dolor/tratamiento farmacológico , Adulto , Anciano , Aminopiridinas/efectos adversos , Analgésicos/efectos adversos , Enfermedad Crónica , Femenino , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Dimensión del DolorRESUMEN
Antagonism of neuromuscular block using cholinesterase inhibitors and atropine is charged with several risks, which are at least partly caused by pharmacological characteristics of the anticholinergic drugs, e.g. short duration of action causing secondary bradycardia. Compared to atropine, ipratropium bromide, a new anticholinergic drug, is--due to its quarternary ammonium compound--characterized by longer duration of action. In contrast to atropine, this substance does not penetrate the blood-brain and placental barrier. Our present study was designed to compare the haemodynamic effects of both substances, using invasive monitoring, during antagonism of neuromuscular block with pyridostigmine. In contrast to atropine, ipratropium bromide induced a higher degree of initial tachycardia but did not allow secondary reduction of heart rate by rebound vagal stimulation. While cardiac output was almost constant, ipratropium bromide caused changes in stroke volume, which were due to alterations in heart rate. There were no clinically relevant changes of the other haemodynamic parameters. Cardiac arrhythmia were observed more often after administration of atropine and were of longer duration. In conclusion, ipratropium bromide is a useful alternative to atropine in patients with pre existing low heart rate and bradyarrhythmia.
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Derivados de Atropina/farmacología , Atropina/farmacología , Hemodinámica/efectos de los fármacos , Ipratropio/farmacología , Bloqueantes Neuromusculares/antagonistas & inhibidores , Bromuro de Piridostigmina/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Venosa Central/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Circulación Pulmonar/efectos de los fármacos , Factores de TiempoRESUMEN
Continuous epidural opiate analgesia with an implantable, percutaneously refillable pump was induced in 6 patients with chronic pain of malignant origin. The efficacy of this method was compared with that of on-demand bolus-injections of epidural opiate. Side-effects and development of tolerance were not observed during a more than one year period of treatment. Increased daily doses for some days were only necessary in case of additional pain sources, e.g. induced by an intermediate operation. There were no hygienic problems (bacteriologic investigations) or problems due to technique of implantation (localisation of the implant, stability of the fixation, patency of the catheter). Examination of post mortem explanted pumps (determination of the flow rate, inspection for precipitation within the pump, testing of permeability of filters) and catheters (electron microscopy, testing of the material for surface conditions, tensile strength and elongation) as well as histological findings for local compatibility did not reveal adverse reactions after long-term treatment. Indications for this new method of pain treatment were established.