Compelling evidence indicates that HAPE is a hydrostatic-induced permeability leak with mild alveolar hemorrhage.62,64,65 Two explanations have been suggested. The first is that that hypoxic pulmonary vasoconstriction is not homogeneous; consequently, pulmonary capillaries supplied by dilated arterioles are exposed to high pressures which cause damage to the capillary walls (stress failure) and leads to a leak of high-protein edema fluid with erythrocytes.4 The second explanation hypothesizes an

increase in pulmonary capillary pressures due to hypoxic pulmonary venous constriction.62,65 Regardless of the mechanisms, successful Inhibitors,research,lifescience,medical prophylaxis and treatment of high-altitude pulmonary edema using nifedipine, a pulmonary vasodilator, indicates that pulmonary

hypertension is crucial for the development of high-altitude pulmonary Inhibitors,research,lifescience,medical edema.63,66 There are no randomized controlled trials evaluating treatment strategies. Oxygen, rest, and descent are commonly agreed upon.59,66 When patients fail to respond to conservative measures or develop HAPE in remote settings, nifedipine is recommended, 10 mg orally initially and then 30 mg of the extended release formulation orally every 12–24 hours.66 Phosphodiesterase inhibitors such as tadalafil have been shown to prevent Inhibitors,research,lifescience,medical HAPE in susceptible individuals67 and may also be effective in patient management. Some physicians are now employing Inhibitors,research,lifescience,medical combination

therapy with nifedipine and phosphodiesterase inhibitors,68 although these are off-label uses. If descent is not possible, use of a portable hyperbaric chamber is recommended. AMS: PREVENTION AND TREATMENT Drugs used in the prevention and management of AMS click this include acetazolamide, Inhibitors,research,lifescience,medical dexamethasone, phosphodiesterase inhibitors, and analgesics. Strategies to prevent AMS include preacclimatization, copious water consumption, and a high-carbohydrate diet. ACETAZOLAMIDE Acetazolamide is a potent carbonic anhydrase inhibitor; AV-951 its efficacy in preventing and ameliorating AMS has been well demonstrated although there is still debate regarding the optimal dose.69–71 A recent double-blind, randomized, placebo-controlled study in the Everest region of Nepal showed that 125 mg twice a day was just as effective in preventing AMS as 375 mg twice a day.69 In this study, the incidence of AMS among subjects taking acetazolamide averaged about 22% compared to 51% for those taking a placebo. Acetazolamide is not a panacea; a substantial percentage of subjects taking acetazolamide still develop AMS. In fact, on Kilimanjaro, where the rate of ascent tends to be faster than in Nepal, the incidence of AMS in those taking acetazolamide (250 mg twice a day) was 55% versus 84% for a comparison/placebo group.