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Drug Intelligence & Clinical Pharmacy May 1987Almitrine bismesylate is a pharmacologically unique respiratory stimulant. It enhances respiration after both acute and chronic administration by acting as an agonist of... (Clinical Trial)
Clinical Trial Review
Almitrine bismesylate is a pharmacologically unique respiratory stimulant. It enhances respiration after both acute and chronic administration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. In comparison with traditional central-acting respiratory stimulants, almitrine has advantages of oral activity, prolonged duration of effect, and an improved adverse effect profile. Almitrine is generally well tolerated, with headache and minor gastrointestinal disturbances being the most frequently observed side effects. This investigational agent has been shown to increase arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease both at rest and during exercise through increased ventilation and improved ventilation/perfusion matching. It may also prove useful in the treatment of nocturnal oxygen desaturation because of its ability to reduce the frequency and severity of nocturnal hypoxemia without impairing the quality of sleep. Additional research is needed to further define the role of almitrine in the relief of hypoxemia.
Topics: Adult; Aged; Almitrine; Chemoreceptor Cells; Clinical Trials as Topic; Double-Blind Method; Humans; Kinetics; Lung Diseases, Obstructive; Middle Aged; Piperazines; Respiratory Insufficiency
PubMed: 3556128
DOI: 10.1177/106002808702100503 -
The Cochrane Database of Systematic... Mar 2011Almitrine-raubasine combination (brand name Duxil), has been considered as an alternative treatment for dementia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Almitrine-raubasine combination (brand name Duxil), has been considered as an alternative treatment for dementia.
OBJECTIVES
To determine the clinical efficacy and safety of Duxil in the treatment of patients with dementia.
SEARCH STRATEGY
We searched the Cochrane Dementia and Cognitive Improvement Group Specialised Register (now known as ALOIS) (September 2009), the China Biological Medicine Database (CBM-disc 1979 to December 2009), the Chinese National Knowledge Infrastructure (www.cnki.net 1979 to December 2009), the Stroke Trials Registry at www.strokecentre.org/trials/index.aspx. We searched identified citations for additional trials, contacted the first author of identified trials for additional references and unpublished data. We also contacted the pharmaceutical company manufacturing Duxil (Servier Pharmaceutical Co Ltd) for additional unpublished data.
SELECTION CRITERIA
Randomised controlled trials studying the efficacy and safety of Duxil for dementia were included, irrespective of blinding, publication status, or language. If the trial was cross-over in nature, only data from the first period were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data.
MAIN RESULTS
Three trials involving a total of 206 participants were included, all patients with vascular dementia. All three included studies were assessed as being at high risk of bias. When analysing these trials together, there was significant beneficial effect of Duxil on the improvement of cognitive function measured by MMSE (WMD 2.04, 95% CI 1.43 to 2.66). No data on behaviour and death at the end of treatment and follow-up were available from the included trials. Two trials failed to show an improvement of functional performance measured by ADL (WMD -1.68; 95% CI -3.70 to 0.35). Of the three included trials, all described the adverse events in detail, there were no statistically significant differences across the trials (OR 4.84, 95%CI 0.55 to 42.67). Behaviour disturbance, quality of life, caregiver burden were not undertaken in the included trials.
AUTHORS' CONCLUSIONS
Due to the low methodological quality of included trials, small number of trials and probable publication bias, this review did not provide sufficient evidence to support the routine use of Duxil for the treatment of patients with dementia. High-quality and large-scale randomised controlled trials are needed to confirm or refute these results.
Topics: Aged; Almitrine; Dementia; Drug Combinations; Humans; Middle Aged; Neuroprotective Agents; Yohimbine
PubMed: 21412915
DOI: 10.1002/14651858.CD008068.pub2 -
Zeitschrift Fur Erkrankungen Der... 1987There is a place in therapy for an orally active respiratory stimulant. Almitrine bismesylate is a respiratory agonist which: 1. Effectively increases PaO2 in a unique... (Review)
Review
There is a place in therapy for an orally active respiratory stimulant. Almitrine bismesylate is a respiratory agonist which: 1. Effectively increases PaO2 in a unique way, principally by stimulation of the peripheral chemoreceptors. 2. Appears to have an effect on blood gases through mechanisms other than stimulation of ventilation which could be on ventilation-perfusion relationships, or even metabolic, for which there is as yet no firm evidence. 3. After chronic administration has a plasma elimination half-life of 20-30 days. This could result in plasma accumulation of the drug, and means that drug intolerance problems are not readily resolved by stopping the tablets. Special dosing schedules may be required. 4. Has an action on the pulmonary vasculature which is mainly vasoconstrictor (and vasodilator in acute hypoxia in animal studies). Present evidence regarding the effect of long-term administration on pulmonary haemodynamics is conflicting. 5. May have an adverse, possibly dose-related effect on dyspnoea in some patients - more work is needed on patient characteristics associated with good drug tolerance. 6. Has an adverse effect on peripheral nerve function in some patients. Whether this is de novo, or aggravation of a preexisting lesion has yet to be established. Thus, although almitrine is effective in increasing PaO2 and as an experimental drug is fascinating, its clinical use remains to be clearly defined. The most powerful argument for the therapeutic use of almitrine would be the demonstration of a beneficial effect on mortality; either in acute exacerbations of respiratory failure, or in the same way as LTO2 exerts an effect in chronically hypoxaemic patients.
Topics: Almitrine; Central Nervous System Stimulants; Chemoreceptor Cells; Humans; Piperazines; Pulmonary Circulation; Respiration; Respiratory Insufficiency
PubMed: 2890242
DOI: No ID Found -
Thorax Apr 1989
Review
Topics: Almitrine; Humans; Hypoxia; Lung Diseases, Obstructive; Peripheral Nervous System Diseases; Piperazines
PubMed: 2548298
DOI: 10.1136/thx.44.4.247 -
Lancet (London, England) Apr 1985
Topics: Almitrine; Humans; Lung Diseases, Obstructive; Piperazines
PubMed: 2858674
DOI: No ID Found -
Anaesthesia, Critical Care & Pain... Aug 2020
Topics: Almitrine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Hypoxia; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory System Agents; SARS-CoV-2
PubMed: 32653550
DOI: 10.1016/j.accpm.2020.07.003 -
European Neurology 1998Different pharmacological properties of almitrine-raubasine show that this combination may be a good therapy for the treatment of age-related cerebral disorders and... (Review)
Review
Different pharmacological properties of almitrine-raubasine show that this combination may be a good therapy for the treatment of age-related cerebral disorders and functional rehabilitation after stroke. Many clinical studies have been carried out in France and in the rest of Europe, confirming the value of this compound in such situations. Without discussing the complexity of clinical trials in both the areas of cognitive disorders and stroke, we shall present two studies demonstrating the beneficial effects of almitrine-raubasine against cognitive impairments. The first is a double-blind controlled study versus placebo with a 3-month follow-up period involving patients (aged between 60 and 85) with memory loss, lack of concentration, impaired mental altertness, and emotional instability. The second is a controlled multicenter study of 155 outpatients (age 70-85) presenting with cognitive decline (assessed by MMSE, SCAG). In both these studies, almitrine-raubasine significantly improved symptomatology and was superior to placebo, especially in the vascular cases. This confirms the validity of previous studies and justifies the indication of these compounds in the treatment of age-related cognitive disorders. Other studies also demonstrated the beneficial effect of this compound on neurosensory vascular disorders, with specific studies carried out on chorioretinal dysfunctions (visual symptomatology) and in vestibular disorders (vertigo associated with electronystagmographic modifications). The appropriate and usual dosage (2 tablets per day) and the good tolerance of the compound have been confirmed in a French multicentric study in 5,361 outpatients.
Topics: Aged; Aging; Almitrine; Clinical Trials as Topic; Cognition Disorders; Drug Combinations; Humans; Ischemia; Neuroprotective Agents; Retinal Vessels; Treatment Outcome; Yohimbine
PubMed: 9516074
DOI: 10.1159/000052069 -
Anaesthesia, Critical Care & Pain... Aug 2020
Topics: Aged; Almitrine; Betacoronavirus; COVID-19; Case-Control Studies; Coronavirus Infections; Female; Humans; Hypoxia; Injections, Intravenous; Male; Middle Aged; Oxygen; Pandemics; Partial Pressure; Patient Positioning; Pneumonia, Viral; Prone Position; Respiratory Distress Syndrome; Respiratory System Agents; SARS-CoV-2
PubMed: 32505756
DOI: 10.1016/j.accpm.2020.05.013 -
Critical Care Medicine Feb 2021Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may... (Clinical Trial)
Clinical Trial Observational Study
OBJECTIVES
Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome.
DESIGN
Single-center retrospective observational study.
SETTING
ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020.
PATIENTS
Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events.
INTERVENTIONS
Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 μg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion.
MEASUREMENTS AND MAIN RESULTS
A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale.
CONCLUSIONS
Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.
Topics: Almitrine; COVID-19; Critical Care; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; COVID-19 Drug Treatment
PubMed: 33093279
DOI: 10.1097/CCM.0000000000004711 -
Frontiers in Medicine 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial dysfunction leading to particularly severe hypoxemia. We hypothesized that an impaired hypoxic pulmonary vasoconstriction aggravates hypoxemia. The objective of the study was to test the effect of two pulmonary vasoactive drugs on patient oxygenation. Observational, single-center, open-label study in one intensive care unit (ICU) of the Paris area, realized in April 2020. Eligible patients had coronavirus disease 2019 (COVID-19) and moderate to severe ARDS [arterial partial pressure of oxygen/fraction of inspired oxygen (PaO/FiO) <200 mmHg] despite conventional protective ventilation. Exclusion criteria included pulmonary artery hypertension defined by a pulmonary artery systolic pressure (PAPs) >45 mmHg. The assessment of oxygenation was based on PaO/FiO at (1) baseline, then after (2) 30 min of inhaled nitric oxide (iNO) 10 ppm alone, then (3) 30 min combination of iNO + almitrine infusion 8 μg/kg/min, then (4) 30 min of almitrine infusion alone. Among 20 patients requiring mechanical ventilation during the study period, 12 met the inclusion criteria. Baseline PaO/FiO was 146 ± 48 mmHg. When iNO was combined with almitrine, PaO/FiO rose to 255 ± 90 mmHg (+80 ± 49%, = 0.005), also after almitrine alone: 238 ± 98 mmHg (+67 ± 75%, = 0.02), but not after iNO alone: 185 ± 73 mmHg (+30 ± 5%, = 0.49). No adverse events related to almitrine infusion or iNO was observed. Combining iNO and infused almitrine improved the short-term oxygenation in patients with COVID-19-related ARDS. This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients.
PubMed: 34277653
DOI: 10.3389/fmed.2021.655763