Q: Ketoconazole is considered as first line of medical treatment for Cushing's syndrome. In ICUs what could be the biggest pitfall which may make this therapy ineffective? 


 Answer: Most ICU patients are by default on Gastrointestinal(GI) prophylaxis. Ketoconazole requires an acidic environment for absorption after oral intake. With the use of proton pump inhibitors (PPIs), antacids and H2 blockers, ketoconazole may become ineffective. All GI prophylaxis should be preferably discontinued if ketoconazole get used for the treatment of Cushing's syndrome. Usual dose of ketoconazole is 400-600 mg daily in divided doses, but can be used up to 1200 mg in divided doses daily. Ideally, all such therapies should be performed under the guidance of endocrinologists. 


Reference: 

Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 2010; 49:509.