[Show abstract][Hide abstract] ABSTRACT: Hypercapnic respiratory failure is common in advanced chronic obstructive pulmonary disease and is usually treated by nasal ventilation. Not all patients requiring such ventilation can tolerate it, with anxiety and phobia influencing their reaction, along with treatment failure. We report the case histories of six patients with hypercapnic respiratory failure who were at risk of death due to refusal of nasal ventilation or its failure despite ongoing treatment. We report their improvement with oral modafinil 200 mg tablets used as a respiratory stimulant, which led to discharge, improved arterial blood gases, and offset further admissions with hypercapnic respiratory failure. This drug is licensed for narcolepsy and is said to stimulate the respiratory system via the central nervous system. Its use in respiratory failure is an unlicensed indication, and there are no case reports or studies of such use in the literature. Its respiratory stimulant effects appear better than those with protriptyline, which was a drug previously used until its production was discontinued. Our findings suggest that a study of modafinil in hypercapnic respiratory failure would be warranted, especially for patients with treatment failure or intolerance to nasal ventilation. This may offer a way of shortening hospital stay, improving outcome and quality of life, and reducing death and readmissions.
International Journal of COPD 04/2014; 9:413-9. DOI:10.2147/COPD.S54507
[Show abstract][Hide abstract] ABSTRACT: Seizures occur when the excitability of brain circuits is not sufficiently restrained by inhibitory mechanisms. Although modafinil is reported to reduce GABA-activated currents and extracellular GABA levels in the brain, the drug exerts anticonvulsant effects in animal studies.
The aim of this study was to determine the effects of modafinil and its metabolites (sulfone and carboxylic acid) on the anticonvulsant action of four classical antiepileptic drugs (AEDs)-carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA).
Anticonvulsant activity was assessed with the maximal electroshock seizure threshold (MEST) test and MES test in mice. Brain concentrations of AEDs were measured to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects.
Intraperitoneal injection of 75 mg kg(-1) of modafinil or its metabolites significantly elevated the threshold for electroconvulsions in mice, whereas 50 mg kg(-1) of each compound enhanced the anticonvulsant activity of CBZ, PHT, and VPA, but not that of PB. A 25-mg kg(-1) dose of modafinil or its sulfone metabolite enhanced anticonvulsant activity of VPA. Modafinil and its metabolites (50 mg kg(-1)) did not alter total brain concentrations of PB and VPA but did elevate CBZ and PHT.
Enhancement of anticonvulsant actions of VPA by modafinil in the mouse MES model is a pharmacodynamic effect. Collectively, our data suggest that modafinil may be a safe and beneficial adjunct to the therapeutic effects of AEDs in human patients.
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