Current opinion in pharmacology
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β-Blockers are used for a wide range of diseases from hypertension to glaucoma. In some diseases/conditions all β-blockers are effective, while in others only certain subgroups are therapeutically beneficial. The best-documented example for only a subset of β-blockers showing clinical efficacy is in heart failure, where members of the class have ranged from completely ineffective, to drugs of choice for treating the disease. ⋯ A different subset was found to be effective for this clinical indication. These findings call into question the current system of classifying these drugs. To consider 'β-blockers', as a single class is misleading when considering their rigorous pharmacological definition and their appropriate clinical application.
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Curr Opin Pharmacol · Feb 2014
ReviewMultiple mechanisms have been tested in pain--how can we improve the chances of success?
Recent advances in understanding the pathophysiology of pain have led to a wealth of molecular targets for novel analgesic drugs and many clinical drug trials. There have been successes, like the gabapentinoids for neuropathic pain and calcium channel blockers for otherwise intractable pain states; and drugs which show promise in clinical trials, like nerve growth factor inhibitors and p38 kinase inhibitors. ⋯ We suggest factors which might predispose to success, for example some clinical precedence for the mechanism in pain or a genetic link for the mechanism, for example a mutation linked to a pain syndrome. We also stress the importance of demonstrating molecular target engagement with a novel compound and suggest pain biomarkers which can be used for mechanistic drug profiling.
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Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide. It is characterised by chronic inflammation in the lungs that leads to progressive chronic airflow obstruction. The main strategy for treating COPD is control of the chronic inflammation. ⋯ Research has been focused on identifying the key inflammatory regulators. CXCR2 antagonists inhibit neutrophilic inflammation; inhibitors of phosphodiesterase-4 (PDE4), p38 mitogen-activated protein kinase (p38), Janus kinases and IL-6 have also shown some promising effects. There is an emerging need for identification of key modulators of the oxidative stress-regulated corticosteroid function aiming the development of monotherapies which will resolve any side effects issues currently faced.