南开大学医学院.ppt

Diuretic Agents Hydrochlorothiazide (氢氯噻嗪) All are absorbed by given orally, Hydrochlorothiazide is absorbed slowly, less than 10 %, t1/2=1.5 hr, excreted unchanged in the urine and not effective when renal function is severely impaired. It is excreted competes with uric acid, so uric acid secretory rate may be reduced. Diuretic Agents Pharmacological effects Diuretic effect moderate, primary site of action is the distal convolute tubule, inhibit the Na+-Cl- co-transporter in the luminal basolateral membrane by a Na+ pump competing for the Cl- binding site which is distinct from the action of transporter in the loop of henle. Thiazides inhibit sodium absorption by exchanging of Na+-K+ and H+-Na+. Diuretic Agents The renal cortex has a high-affinity receptor for thiazide diuretics. Variably decrease the glomerular filtration rate, but do not affect renal blood flow. Enhance Ca2+ reabsorption in the distal convoluted tubule, decreases Ca2+ excretion from urine. Hypotensive effect Anti-diuretic effect Diuretic Agents Uses Edema: it is available used for mild and moderate cardiac edema (congestive heart failure). The diuretic effect for renal edema depends on the renal function. Hypertension Diabetes insipidus. Diuretic Agents Adverse effects Electrolyte disturbances hypokalemia, hypomagnesemia, hyponatremia, Hypovolaemia， Hyperuricemia and induced gout it increases absorption of uric acid and competes for the transport mechanism with uric acid Diuretic Agents Hyperglycemia and hyperlipidemia glycosuria, aggravates preexisting diabetes, increases concentrations of cholesterol and triglycerides, total cholesterol increases. Thiazide diuretic decrease glucose tolerance, reduce insulin secretion and glucose utilization. Diuretic Agents Others photosensitive, thrombocytopenia, agranulocytosis, thiazides with quinidine can lead to polymorphic ventricular, tachycardia. Diuretic Agents Low efficacy diuretics Spironolactone (螺内酯，antisterone 安体