[Acute thrombopenia during treatment with digoxin in an infant].
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Digoxin↗
Biomedical subjects
C Dubray
Publications and source records attributed to C Dubray.
Long-term observation of atrial and ventricular rates in the unanesthetized dog with complete atrioventricular block.
The evolution of atrial and ventricular rates was studied in unanesthetized dogs with complete A-V block over a three-year period. During the first 40 days after A-V block, atrial rate far exceeded the sinus rate recorded before surgery, but had fallen progressively back to this level by the 41st day, and remained there until the end of the three-year period. Ventricular rate had settled down to a plateau by the 31st day. These findings explain certain differences among previously reported results, and have led us to use such animals for drug studies only after the beginning of the third month after creation of the complete A-V block.
Animals↗
Comparison of prizidilol, a new antihypertensive drug with combined arteriolar vasodilator and beta-adrenoceptor blocking actions, with hydralazine and propranolol in conscious dogs with chronic atrioventricular block.
The effects of prizidilol, a novel antihypertensive agent with vasodilator and beta-adrenoceptor blocking actions, were compared with those of hydralazine and propranolol in conscious dogs with chronic atrioventricular block. Prizidilol significantly increased atrial rate, mainly through reflex reduction of atrial vagal tone in response to its hypotensive effect. Hydralazine also significantly raised atrial rate, while propranolol did not affect it. Prior administration of pindolol, which raised atrial rate to a degree comparable to that achieved with prizidilol and hydralazine, entirely suppressed the atrial tachycardiac effects of both drugs. Prizidilol did not affect ventricular rate on average, whereas hydralazine raised it and propranolol lowered it, both significantly. In some dogs, prizidilol raised ventricular rate like hydralazine; in others, it lowered it like propranolol. In both cases, variation was related to basal ventricular rate. The pattern of these effects was the same as that observed with pindolol. Prior treatment with pindolol almost suppressed the ventricular chronotropic effects of prizidilol, apparently through beta-adrenoceptor blockade.
Adrenergic beta-Antagonists↗
Comparative effects of disopyramide and its mono-N-dealkylated metabolite in conscious dogs with chronic atrioventricular block: plasma concentration-response relationships.
In animals and humans, the antiarrhythmic agent disopyramide is primarily metabolized by mono-N-dealkylation. The effects of disopyramide and its N-dealkylated metabolite (MND) were investigated in 13 conscious dogs with chronic atrioventricular (A-V) block and implanted atrial pacing electrodes. Our data clearly show that both compounds used within the therapeutic plasma level range induced lengthening of the atrial effective refractory period (AERP) as reflected by the diminution of the maximal atrial frequency determined by pacing. However, at equivalent drug plasma concentrations, disopyramide induced a more marked decrease (1.2-1.7 times) in the maximal atrial frequency than did its metabolite. Both compounds increased mean arterial pressure (MAP) and atrial rate and decreased ventricular rate, but the effects on MAP and atrial rate were more marked with disopyramide than with MND. Thus, with regard to these cardiovascular parameters, the parent drug and MND possess distinct pharmacodynamic profiles, which may in part be related to their respective vagolytic power.
Animals↗
Pain and Alzheimer's disease.
Literature on pain management in Alzheimer's disease is slowly emerging and this review deals with different aspects of pain in this growing population. Clinical pain, experimental pain and assessment of pain in cognitively impaired patients are presented. Treatment of pain is also discussed. This review calls for more studies and clinical trials with a view to improve the comfort and quality of life of patients suffering from Alzheimer's disease.
Aged↗
[Clinical study of antalgic drugs].
The assessment of the clinical properties of analgesics is not easy. Some of the difficulties are due to the multiplicity of the aetiologies involved in the pain process, to the complexity of pathophysiological mechanisms modulating the nociception and to the subjectivity of painful sensation. All of these explain the fairly high variability of the criteria available for assessing pain level or pain relief. As a consequence, that variability directly interferes with the pharmacological effect of analgesics to be assessed in clinical trials. Furthermore, the lack of consensus concerning the evaluation criteria does not facilitate the choice of a study design or the comparison of data collected from different clinical trials. Clinicians have to choose between testing the analgesics in healthy volunteers (experimental pain) or in patients suffering from painful disease (spontaneous pain). These two approaches are often complementary for assessing the pharmacological profile of new analgesic compounds. Whatever the choice, the investigators have to pay attention to the methodological aspects to avoid pitfalls and bias in this difficult field of therapeutic research.
Analgesics↗
[Interest of the use of pindolol in the treatment of depression: review].
The principal stakes of depression treatment are to accelerate and enhance the clinical effects of antidepressant drug. The onset of antidepressant action of Serotonin (5HT) selective reuptake inhibitors (SSRIs) was attributed in part to the decrease in firing activity of serotonin neurons produced by the activation of raphe 5HT1A autoreceptors at the time of treatment initiation. Pindolol, an antagonist at somatodendritic pre-synaptic 5HT1A receptors has been investigated as a potential accelerator or potentialisator of antidepressant response. Six open label studies and 12 controlled studies were identified for revue. The first open-label pilot study was conducted by Artigas et al. They showed promising results with pindolol, both in the acceleration of antidepressant response and in improving the efficacy of antidepressant. On the basis of these results five open-label studies were conducted. The open label studies suggest that pindolol accelerate the antidepressant response of serotoninergics therapeutics. The augmentation of antidepressant response was not clearly demonstrated by these studies particularly in the treatment of refractory depression. For example, Dinan et Scott that found the addition of pindolol in association with SSRI therapy had a poor efficacy. In the twelve controlled studies, 4 tried to underscore the shortening of the onset and the augmentation of efficacy of SSRI by pindolol [Berman et al., Maes et al., Perez et al., Tome et al. ], 3 tried to underscore shortening of the onset [Bordet, Zanardi ] and 3 tried to underscore the augmentation of efficacy [Maes et al., Moreno et al., Perez et al. ]. One study tried to underscore the augmentation of efficacy of sleep deprivation by pindolol and another one the shortening of the onset of ECT. Six studies included depressive resistant patients. Three studies were carried out with fluoxetine, 1 with fluvoxamine, 3 with paroxetine, 1 with trazodone. Two -studies were investigated with several antidepressant treatments. The results of the studies indicate one acceleration of antidepressant response in 6 studies, one augmentation of efficacy in 5 studies. Two studies clearly demonstrate that pindolol may -augment and accelerate antidepressant response. Three studies did not confirm these observations. Several points can be examined. For pindolol: 3 authors have demonstrated that the effect of pindolol did not rely upon small antidepressant effect mediated by b-blockers properties, because anxiety was not predominantly improved by pindolol plus SSRI while depressive symptoms were clearly improved. On the basis of data issues from recent positron emission tomography (PET) studies, several authors suggested that the dose of pindolol used in most clinical trials (3 yen 2,5 mg day-1) might be insufficient to induce a substantial occupancy of 5-HTA receptors (Rabiner et al. It is possible that higher doses will show a more evident benefit. On the whole, pindolol seemed to be well tolerated. Adverse effects most commonly reported were increased irritability, insomnia and nausea. Pindolol had poor adverse effects in cardiovascular functions. The variation of the results of the controlled studies can be explained by different points: Firstly by difficulty to determine good criterion of resistance. The most simplistic definition of treatment resistance is the failure to achieve and sustain euthymia with adequate antidepressant treatment. Secondly by the fact that depressive patients who present antecedents of depressive illness seem to be worst responders to the association pindolol/serotoninergic antidepressant than patients suffering of first episode of depression. We observed one antecedent of depression in the group of resistant patients who were good responders to the association pindolol/antidepressant therapy. We observed three anterior episodes of depression in negatives studies of the association pindolol/antidepressant therapy. Thirdly by the fact that the failure of the antidepressant treatment at the time of earlier (or actual) episode seems to be a criterion for less responsiveness to the association of this antidepressant treatment with pindolol. In fact, the open label studies who demonstrated efficacy of the association between pindolol and serotoninergic therapy in major resistant depression were realized with new antidepressant molecule for the episode. Other controlled trials could confirm these facts. Most of the studies failed to retrace clearly the historicity of depression, and it may be interesting in future investigations to analyze the response of the association -compared to the status of the patient with the antidepressant therapy. Further perspective could be envisaged especially in the utilization of pindolol for the treatment of pathologies which are usually treated with a serotoninergic antidepressant -therapy. For example, the antagonist 5HT(1A) Way 100635 was experimented with success in animals in order to augment the efficacy of clomipramine in the treatment of chronic pain. In other respects several psychopharmacogenetics studies could be investigated to examine, for instance, the role of the 5-HT transporter and its implication in the response to pindolol and antidepressant association. In summary, pindolol accele-rates, and in some cases enhances the clinical action of antidepressant drugs. It appears that this augmentation strategy has more limited effect on treatment resistant patient but there is experimental evidence for using higher doses in future augmentation trial.
Major Depressive Disorder↗
[Caffeine poisoning in infants resulting from confusion between dosage forms. Apropos of 5 cases].
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Caffeine↗