Current clinical pharmacology
-
Curr Clin Pharmacol · May 2011
ReviewDesigner drugs on the internet: a phenomenon out-of-control? the emergence of hallucinogenic drug Bromo-Dragonfly.
Based on the material available in both the scientific literature and on the web, the present paper provides an updated pharmacological, chemical, toxicological and behavioural overview of Bromo-Dragonfly (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane; 'B-fly'). B-Fly is a powerful, long lasting, LSD-like, hallucinogenic drug, which has been associated with a number of acute intoxications and fatalities in a number of countries. ⋯ It is concluded that the availability of online information on novel psychoactive drugs, such as B-fly, may constitute a public health challenge. Better international collaboration levels may be needed to tackle this novel and fast growing phenomenon.
-
Curr Clin Pharmacol · Feb 2011
ReviewBronchodilator combination therapy for the treatment of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, and its prevalence is rising worldwide. Bronchodilators remain the cornerstone of COPD treatment, especially inhaled β2-adrenergic receptor agonists and inhaled anticholinergics. Long-acting bronchodilators are considered more effective and convenient than short-acting bronchodilators for the maintenance treatment in patients with moderate to very severe COPD. ⋯ The combination of β2-adrenergic receptor agonists and anticholinergics has been shown to provide superior bronchodilatory effect than either agent alone, possibly because of different mechanisms of action of these agents. The current treatment guidelines recommend the use of one or more long-acting bronchodilators for patients with moderate to severe stable COPD who remain symptomatic with single-agent bronchodilator therapy. The objective of this article is to review clinical data on combined bronchodilator therapy with β2-adrenergic receptor agonists and anticholinergics in patients with COPD.
-
The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
-
Curr Clin Pharmacol · Aug 2010
ReviewMolecular targeted therapy in prevalent tumors: learning from the past and future perspectives.
Important advances have been achieved with molecular targeted agents in clinical oncology. Breast, colon, and lung cancer, are now commonly treated with a combination of chemotherapy and targeted agents. In this article the authors discuss the limitations of targeted therapy development, failures of previous studies, and possible strategies for an intelligent drug development. Initial attempts to block mTOR in breast cancer, the magnitude of benefit obtained with anti-EGFR therapy in lung cancer, and the narrowing use of anti-EGFR therapy in colon cancer based on KRAS status are discussed.
-
Curr Clin Pharmacol · Feb 2010
ReviewHyperhomocysteinemia and cardiovascular risk: effect of vitamin supplementation in risk reduction.
Homocysteine is a sulfur-containing aminoacid produced during metabolism of methionine. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis has been known; in recent years experimental evidences have shown that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed, including impairment of endothelial function, production of Reactive Oxygen Species (ROS) and consequent oxidation of low-density lipids. ⋯ Recently, large-scale intervention trials have been conducted to determine whether lowering homocysteine concentrations through B vitamins supplementation can decrease cardiovascular risk in healthy subjects or improve survival in patients with coronary heart disease. Some of these trials found no significant beneficial effects of combined treatment with folate and vitamin B(12), with or without vitamin B(6), in spite of adequate homocysteine lowering. In conclusion, it is still unclear whether decreasing plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk.