Clinical medicine insights. Therapeutics最新文献

Nonalcoholic fatty liver disease (NAFLD) is on the rise and has become a major etiology for chronic liver disease. It is frequently associated with obesity, insulin resistance, hypertension, and dyslipidemia and is considered the hepatic manifestation of metabolic syndrome. In this review, we present a summary of the epidemiology and pathogenesis of NAFLD, and discuss the clinical evaluation and stratification of NAFLD patients into low, intermediate, and high risk with respect to liver-related outcomes. While diet and exercise are the cornerstone of treatment in all patients, the low rate of adherence and inadequacy of these recommendations necessitate pharmacologic intervention, especially in intermediate- and high-risk patients. We discuss vitamin E and pioglitazone which are often used as first-line therapy by many practitioners, with pentoxifylline and liraglutide as backup agents. Several drugs are in advanced-phase clinical trials and will likely change the landscape for management of NAFLD in the very near future.

Coronary heart disease is a global malady and it is the leading cause of death in the United States. Chronic stable angina is the most common manifestation of coronary heart disease and it results from the imbalance between myocardial oxygen supply and demand due to reduction in coronary blood flow. Therefore, in addition to lifestyle changes, commonly used pharmaceutical treatments for angina (nitrates, β-blockers, Ca²⁺ channel blockers) are aimed at increasing blood flow or decreasing O₂ demand. However, patients may continue to experience symptoms of angina. Ranolazine is a relatively new drug with anti-anginal and anti-arrhythmic effects. Its anti-anginal mechanism is not clearly understood but the general consensus is that ranolazine brings about its anti-anginal effects by inhibiting the late Na⁺ current and the subsequent intracellular Ca²⁺ accumulation. Recent studies suggest other effects of ranolazine that may explain its anti-anginal and anti-arrhythmic effects. Nonetheless, clinical trials have proven the efficacy of ranolazine in treating chronic angina. It has been shown to be ineffective, however, in treating acute coronary syndrome patients. Ranolazine is a safe drug with minimal side effects. It is metabolized mainly in the liver and cleared by the kidney. Therefore, caution must be taken in patients with impaired hepatic or renal function. Due to its efficacy and safety, ranolazine was approved for the treatment of chronic angina by the Food and Drug Administration (FDA) in 2006.

Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. Treatment is limited to chemotherapeutic approaches. Cisplatin is an established and effective treatment for R/M HNSCC, and many studies have investigated cisplatin treatment in combination with other agents. Even when being treated with first line therapy (cisplatin + 5-fluorouracil + cetuximab), overall survival is only 10 months, indicating the need for novel chemotherapeutics and treatment regimens. Current research is focused on molecular targeting therapies inhibiting epidermal growth factor receptor, phosphoinositide-3-kinase/Akt/mammalian target of rapamycin, and vascular endothelial growth factor pathways. A variety of clinical trials have been completed and are currently underway with encouraging results. Finally, future directions of cisplatin-based R/M HNSCC treatment may include targeting specific pathways known to induce cisplatin resistance, such as nucleotide excision repair and inhibition of apoptosis, in hopes to enhance response to cisplatin therapy.