Understanding Cholesterol Absorption Inhibition and When Ezetimibe Therapy Is Considered

Cholesterol management involves two main sources of cholesterol production: the liver's internal manufacturing process and dietary cholesterol absorbed through the intestines. Statins primarily address liver-based cholesterol production, but for patients who absorb cholesterol efficiently from the gut, targeting intestinal absorption offers a complementary or alternative treatment pathway. Ezetimibe, marketed as Zetia, works specifically on the absorption side of cholesterol management. The intestinal transporter protein NPC1L1 moves cholesterol from the gut lumen into intestinal cells, where it enters the bloodstream and travels to the liver. Ezetimibe binds to this transporter and blocks its function, reducing how much dietary and bile cholesterol crosses into circulation. This mechanism reduces LDL cholesterol by fifteen to twenty-five percent on its own and adds a further fifteen to twenty percent reduction when combined with statin therapy. Ezetimibe becomes relevant in several clinical scenarios. Patients who cannot tolerate statins due to muscle side effects may use ezetimibe alone as a primary LDL-lowering agent. Patients who are already on statin therapy but have not reached target LDL levels despite dose optimization can add ezetimibe to achieve the remaining reduction needed without increasing statin dose and associated side effect risk. High-risk cardiovascular patients requiring very low LDL targets benefit most clearly from combination therapy. The IMPROVE-IT trial, a landmark cardiovascular outcome study, demonstrated that adding ezetimibe to simvastatin reduced heart attacks and strokes more than simvastatin alone in patients with recent acute coronary syndrome. This trial established ezetimibe as a medication with evidence-based cardiovascular outcome benefit, not just cholesterol lowering effect. Patients with rare genetic disorders causing very high cholesterol absorption sometimes achieve their best results with ezetimibe included regardless of baseline statin use. Sitosterolemia, a condition involving excessive plant sterol absorption, responds particularly well to ezetimibe due to its direct action on the NPC1L1 transporter affecting all sterols. Tolerability of ezetimibe is generally favorable. Common mild side effects include headache, diarrhea, and occasional stomach discomfort. Significant liver enzyme elevation is uncommon. Because ezetimibe does not cause muscle-related side effects, it is frequently the first-choice add-on for patients who had to reduce or stop statin therapy due to myalgia. For patients whose current cholesterol regimen is not meeting LDL goals and who want to explore their options, discussing zetia ezetimibe for cholesterol management with a provider helps clarify when adding this medication makes the most clinical sense. Ezetimibe is available as a standalone tablet and also as the fixed-dose combination pill Vytorin, which combines ezetimibe with simvastatin. The combination product simplifies pill burden for patients needing both agents. For a thorough foundation in cholesterol treatment strategies including how different drug classes work and when combination approaches are appropriate, reviewing cholesterol treatment options and clinical guidance supports informed patient participation in lipid management decisions.

Antibiotic Overuse Behind 'Superbug' Outbreak

By www.webmd.com

Researchers analyzed hospital data related to the outbreak of Clostridium difficile, a "superbug" gut infection. The investigators concluded that reducing the use of fluoroquinolones -- antibiotics such as ciprofloxacin (Cipro) and levofloxacin (Levaquin) -- curbed the outbreak.

"These findings are of international importance because other regions, such as North America, where fluoroquinolone prescribing remains unrestricted, still suffer from epidemic numbers of C. difficile infections," said study co-author Derrick Crook. He is a professor of microbiology at the University of Oxford in England.

Overuse of fluoroquinolones enabled antibiotic-resistant C. difficile to thrive because non-resistant bugs in the gut were killed off by the antibiotics. This left the way clear for rapid growth of antibiotic-resistant C. difficile, the researchers explained.

"Emergency measures -- such as 'deep cleaning' and careful antibiotic prescribing -- were introduced [after the outbreak began] and numbers of C. difficile infections gradually fell by 80 percent, but no one was sure precisely why," Crook said in a university news release.

"Our study shows that the C. difficile epidemic was an unintended consequence of intensive use of an antibiotic class, fluoroquinolones, and control was achieved by specifically reducing use of this antibiotic class, because only the C. difficile bugs that were resistant to fluoroquinolones went away," he explained.

Meanwhile, the smaller number of cases of diarrhea caused by C. difficile bugs that were not resistant to fluoroquinolone antibiotics stayed the same.

"Reducing the type of antibiotics like ciprofloxacin was, therefore, the best way of stopping this national epidemic of C. difficile, and routine, expensive deep cleaning was unnecessary," Crook said.

"However, it is important that good hand hygiene continues to be practiced to control the spread of other infections," he added.

The study was published Jan. 24 in The Lancet Infectious Diseases journal.

According to the U.S. Centers for Disease Control and Prevention, C. difficile sickened almost half a million Americans in 2011. An estimated 29,000 of those patients died within a month.

Most of these infections happen in the hospital, the CDC says.

Source: http://www.webmd.com/digestive-disorders/news/20170125/antibiotic-overuse-behind-superbug-outbreak-in-uk-hospitals

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