Being an outstanding physician and lifelong learner requires stoking the flames of clinical curiosity. In Chiefs’ Inquiry Corner (CIC) we attempt to succinctly answer actual clinical questions that have been raised on the wards and in the clinics of NYU’s teaching hospitals. Our answers are not meant to be all encompassing or practice changing but rather to serve as springboards for further exploration. For those of us with short attention spans, we hope CIC satisfies that craving for a morsel of knowledge in a digestible format.
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Digoxin is a cardiac glycoside that increases the force of myocyte contraction and slows cardiac conduction through the AV node. Its use is limited by a narrow therapeutic window – “therapeutic” and “toxic” serum concentrations often overlap and are affected by many factors including absorption, distribution, or elimination. Renal impairment results in decreased elimination and is a common cause for elevated blood levels. Drugs such as amiodarone, dronedarone, verapamil, diltiazem and quinidine also result in elevated digoxin blood levels by altering p-glycoprotein activity. P-glycoprotein is an efflux pump in the intestine and proximal renal tubule and acts to lower serum digoxin concentrations under normal conditions. Concomitant administration of amiodarone inhibits the p-glycoprotein and can increase serum digoxin concentrations. To prevent toxicity, providers should empirically reduce the dose of digoxin by 50% when starting amiodarone and should monitor closely for clinical and/or ECG signs of digoxin toxicity.
References: Digoxin and Amiodarone
There is a well described role for ACE inhibitors and angiotensin receptor blockers (ARBs) in the treatment of hypertensive patients with diabetes and microalbuminuria. There is similarly a robust body of literature supporting the use of these agents in the primary prevention of microalbuminuria in hypertensive patients with diabetes. However, whether ACE inhibitors or ARBs play a role in primary prevention of microalbuminuria in normotensive patients
with diabetes remains less well understood. One of the few studies that help address this question was comprised of almost 2000 patients with type 2 diabetes, all of whom were normoalbuminuric. Patients were randomized to receive candesartan or placebo, with a median followup of almost five years, the primary endpoint being development of new microalbuminuria. Among patients who were normotensive at baseline, there was no significant reduction in the progression to microalbuminuria in those treated with candesartan compared to placebo. Prior studies similarly have failed to show that ACE inhibitors or ARBs provide a significant, durable reduction in development of new microalbuminuria in normotensive patients with diabetes.
References: ARBs and Microalbuminuria in Normotension
Steven Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a continuum of life-threatening mucocutaneous disease that is often triggered by medications and involves extensive necrosis of the epidermis. Management of SJS/TEN involves rapid assessment of the extent of illness as well as prognostication using the SCORTEN Score. The SCORTEN score uses seven clinical and laboratory criteria to estimate mortality in patients with SJS/TEN. If the SCORTEN score is greater than 2, or if greater than 30% of body surface area is involved, patients should be promptly referred to a burn center. The other mainstays of management include discontinuation of the offending agent and supportive care with wound care, pain control, nutrition, fluids, and prevention of infection (though NOT prophylactic antibiotics). Additionally, focus should be placed on prevention of complications, particularly ophthalmologic and gynecologic sequelae. Systemic therapy is highly controversial, and currently there is no definitive role for interventions such as steroids, IVIG, plasmapheresis, or TNF-inhibitors, though in small studies cyclosporine has shown improvements in disease progression and mortality.
References: SJS TEN
New York City’s Bill de Blasio has called a state of emergency over the current outbreak of measles in Williamsburg, Brooklyn, which has mainly centered in the Orthodox Jewish community. There have been 555 cases of measles this year in New York state, a substantial proportion of which are adults. Measles is a highly contagious viral disease, with a secondary attack rate of greater than 90% in unvaccinated household contacts. The disease follows a typical pattern: initially a prodrome resembling an upper respiratory tract infection and lasting 10-12 days. It is characterized by malaise, fever, coryza, conjunctivitis and cough. Towards the end of the prodrome, fever intensity increases and pathognomonic Koplik spots can appear. After the prodrome, the classic measles exanthem appears, starting on the face and migrating to involve the entire trunk, arms, and legs. The rash typically lasts for 4-5 days and will fade in the order that it appeared. While the course of measles is benign in many, adults are particular susceptible to complications, the most serious of which include pneumonia, which is responsible for 60% of deaths from measles, and neurological complications such as encephalitis. Treatment is mainly supportive: Vitamin A is associated with improved outcomes in pediatric measles, and ribavirin shows in vitro activity against measles, and has been used in some small case series in adults with measles pneumonitis.