RESUMO
Background: Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system inhibitors. Even though older adults are often at increased risk of adverse drug events, specific guidelines for choosing between different classes of antihypertensives are lacking. Given the prevalence of hypertension in older adults, clinicians should be aware of the increased risk of electrolyte disorders after the initiation of thiazide diuretics in this population. Case Presentation: A patient aged > 90 years fell getting out of his bed 2 weeks following initiation of hydrochlorothiazide 25 mg daily medication therapy. Laboratory tests revealed a urine sodium of 35 mmol/L most consistent with hypovolemic hypoosmotic hyponatremia secondary to thiazide initiation. Hydrochlorothiazide was discontinued and sodium gradually normalized over the next 2 weeks without any other intervention. Conclusions: Despite being recommended as first-line therapy for uncomplicated hypertension, thiazide diuretics may cause more harm than good in older adults with risk factors for thiazide-induced hyponatremia, which should be considered before initiation.
RESUMO
In vitro biochemical and cell-based small molecule screens have been widely used to identify compounds that target specific signaling pathways. But the identified compounds frequently fail at the animal testing stage, largely due to the in vivo absorption, metabolism and toxicity of chemicals. Zebrafish has recently emerged as a vertebrate whole organism model for small molecule screening. The in vivo bioactivity and specificity of compounds are examined from the very beginning of zebrafish screens. In addition, zebrafish is suitable for chemical screens at a large scale similar to cellular assays. This protocol describes an approach for in situ hybridization (ISH)-based chemical screening in zebrafish, which, in principle, can be used to screen any gene product. The described protocol has been used to identify small molecules affecting specific molecular pathways and biological processes. It can also be adapted to zebrafish screens with different readouts.