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Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
In the therapy based upon cell-replacement, transplanting the motor neurons which are derived from stem-cell is measured to be a probable move to treat ALS (Christou et al., 2007). These motor neurons may extend to axons which eventually form neuromuscular junctions (Thonhoff et al., 2009). These transplanted neurons may face the challenge due to inhibitory action of myelin associated proteins such as Nogo-A, myelin associated glycoprotein (MAG) and oligodendrocytemyelin glycoprotein (Omgp). Inhibition may also be due to inhibitory proteins specific for the neurite growth. A winning transplantation outcome came in to lime light a decade back, in which rat spinal cord was injected with motor neurons along with dibutyryl cyclic adenosine monophosphate (dbcAMP)(Deshpande et al., 2006).The systemic administration of phosphodiesterase 4 inhibitor was also performed to obstruct the repulsive outcome of myelin (Deshpande et al., 2006). These studies highlighted that the alteration of the proteins responsible for regulation of growth and guidance of axon is important to re-establish appropriate functioning of motor neurons subsequent to therapy by cell replacement.
Psoriatic erythroderma
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Apremilast: This is a selective phosphodiesterase 4 inhibitor that has been approved for moderate to severe psoriasis. There are no trials reporting its use in erythrodermic psoriasis. It is particularly useful when the patient has other comorbidities limiting the use of other conventional first-line drugs, and it does not require close laboratory monitoring [20,21].
Psoriatic Arthritis
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Enzyme Inhibitors Apremilast, an oral phosphodiesterase 4 inhibitor, was recently tested in PsA. A phase 2 trial of 204 patients randomized to receive either 20 mg twice daily or 40 mg once daily for 12 weeks demonstrated better improvement among patients treated with twice daily dosing. Diarrhea was the main side effect [86]. A phase 3 trial with apremilast was recently completed [87]. It included 504 patients randomized to receive either apremilast 20 mg bid or 30 mg bid or placebo. It was a 24-week trial but at 16 weeks placebo patients who did not achieve at least a 20% reduction in inflamed joint count were rerandomized to either dose of the active drug. This study also demonstrated efficacy of both apremilast doses compared to placebo. It was noted that patients who were biologic naïve or who received apremilast monotherapy had higher responses than those on previous therapy. Higher responses also occurred among patients treated with the higher dose, but that dose was slightly more toxic, although no major safety issues were raised.
Vehicles for atopic dermatitis therapies: more than just a placebo
Published in Journal of Dermatological Treatment, 2022
Simon G. Danby, Zoe D. Draelos, Linda F. Stein Gold, Amy Cha, Bonnie Vlahos, Laraine Aikman, Paul Sanders, Dan Wu-Linhares, Michael J. Cork
Looking to other anti-inflammatory treatment for AD, RCTs of calcineurin inhibitors tacrolimus and pimecrolimus appear to show a stronger vehicle effect for the ointment base of the former compared to the cream base of the latter (82). The strength of this response appears to reduce the perceived efficacy of the more potent tacrolimus compared with pimecrolimus. A particularly strong vehicle effect was also reported in the RCTs for the newly developed phosphodiesterase 4 inhibitor crisaborole in patients with mild to moderate AD, which appears to conceal the otherwise strong response to the drug treatment (97). These observations beg the question of whether drug effects always augment vehicle effects (the assumption that underpins the vehicle control design) or whether they in fact mask them by reducing the therapeutic window.
Current and future direct healthcare cost burden of chronic obstructive pulmonary disease in Alberta, Canada
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2020
Dat T. Tran, Nguyen Xuan Thanh, Arto Ohinmaa, Irvin Mayers, Phillip Jacobs
Using a prevalence-based approach, we included all hospitalizations and ambulatory care visits between April 2008 and March 2017 (fiscal years [FYs] 2008–2016) where COPD was coded as the primary diagnosis (International Classification of Diseases [ICD], 10th revision, codes J41–J44) and patient aged ≥ 35 years at time of health services use to create the study cohort. This case definition has a sensitivity of 85% and specificity of 78.4%.12 All practitioner claims where COPD was coded as the primary diagnosis (ICD, 9th revision, codes 491, 492 and 496) and COPD drug dispensing events of the study cohort during the study period were then retrieved. COPD medications include: 1) inhaled corticosteroids [ICS], 2) long-acting β-agonist [LABA], 3) long-acting muscarinic antagonist [LAMA], 4) combination of LABA/LAMA in one device, 5) combination of LABA/ICS in one device, 6) short-acting β-agonist [SABA], 7) short-acting muscarinic antagonist [SAMA], 8) combination of SABA/SAMA in one device, 9) methylxanthines and 10) phosphodiesterase-4 inhibitor.13 A list of medications is provided in Supplemental Table S1.
Roflumilast in patients with advanced chronic obstructive pulmonary disease: towards a better-targeted use
Published in Expert Opinion on Pharmacotherapy, 2019
Ioana Alexa, Teodora Alexa-Stratulat, Sabina Antoniu, Ileana Antohe, Oana Arghir, Cristina Grigorescu
Phosphodiesterase-4 inhibitors and roflumilast, in particular, were previously evaluated in asthma and their rather inconstant efficacy was probably the cause for compounds inability to progress to later phase clinical studies. However, there are reports of improvement of lung function, especially when roflumilast was given as an add-on therapy for inhaled corticosteroids [8]. The analysis of the pooled data was not done based on the eosinophil count so that in this setting it was not clear if this biomarker can be used to predict the efficacy of the compound. A recently published short-term study performed in COPD patients with various degrees of airways inflammation (i.e. including GOLD stage II and III patients) demonstrated that 16 week therapy with roflumilast was able to reduce eosinophil count in the airways, suggesting an increased efficacy in COPD with more prominent involvement of this cell at bronchial level [9].