Hydrochlorothiazide/Triamterene

Caring for the elderly nursing home patient has never been more clinically complex or administratively more troublesome. Patients carry with them a greater burden of disease with increasing frailty and vulnerability. More drugs are being used for more problems. Combination drug therapy (and by this we mean 2 or more drugs in the same pill or capsule) was not common or recommended even just a few years ago. Acceptable combinations for a long time were limited and they were represented by drugs such as hydrochlorothiazide/triamterene (Dyazide; GlaxoSmithKline, Research Triangle Park, NC) and carbidopa/levodopa (Sinemet; Merck & Co, Inc, Whitehouse Station, NJ). Other fixed combinations were generally unavailable because of the significant side effect profiles of individual agents and a relatively poor understanding of drug-drug interactions. A lot has changed in a very short period of time. In an effort to extend patent protection, drug manufacturers are offering a wider array of products in combination dosage forms. Now we have available to us amlodipine/atorvastatin (Caduet; Pfizer US Pharmaceuticals, New York, NY) and ezetimibe/simvastatin (Vytorin; Merck & Co, Inc, and Schering Plough, Kenilworth, NJ) to really push the envelope on the management of cardiovascular disease, affecting blood pressure/angina and lipids at the same time. As we have come to understand the physiologic changes that come with aging (more fat, less muscle mass, and decreased albumin), today’s drugs are designed to be excreted unchanged and with mixed metabolic pathways to avoid total dependence on 1 route of elimination. Ideal pharmacokinetic characteristics of drugs in the elderly are water soluble for ease in absorption, short to intermediate half-life for once daily administration, moderate protein binding, and combined elimination by hepatic and renal routes with an emphasis on glucuronidation and sulfation, rather than oxidative metabolism. Where possible, drug manufacturers are bringing new chemical entities to market that maximize safety and efficacy. Combination drug therapy now offers physicians the opportunity to better comply with OBRA ‘87 and the 9-drug

Noncardiogenic pulmonary edema is a rare but potentially life‐threatening complication of hydrochlorothiazide therapy. We describe three patients who developed this serious adverse reaction. A 64‐year‐old woman developed dypsnea and hypotension within 60 minutes of taking a single dose of hydrochlorothiazide 25 mg. She was admitted to the critical care unit with acute respiratory failure and subsequent multiple‐organ dysfunction. The second patient was a 56‐year‐old woman who experienced sudden onset of shortness of breath that developed 10 minutes after taking a single dose of hydrochlorothiazide 25 mg. The third was a 59‐year‐old woman who developed sudden onset of shortness of breath, nausea, vomiting, and diarrhea after her first dose of hydrochlorothiazide‐triamterene. All three women had a history of a similar, albeit minor, reaction to a thiazide diuretic. Review of the literature identified 36 additional cases of noncardiogenic pulmonary edema after thiazide use. The patients developed symptoms 10–150 minutes after ingestion of hydrochlorothiazide or another thiazide. Symptoms can occur on first exposure to the drug or in patients taking the drug intermittently. Of interest, 90% of documented cases occurred in women. With the increasing use of thiazide diuretics in the treatment of hypertension, clinicians need to be aware of the possible association of these drugs with the development of noncardiogenic pulmonary edema.