【正文】 ? Typical symptoms: polydipsia and polyuria ? mechanism phosphodiesterase cAMP ADH action the secretion of NaCl plasma osmotic pressure less thirsty and desire to drink water 36 Side effects ? Electrolyte disturbances ? hypokalemia, magnesium deficiency ? Hyperuricemia and induced gout ? increases absorption of uric acid and petes for the transport mechanism with uric acid ? Hyperglycemia and hyperlipidemia ? decrease glucose tolerance, reduce insulin secretion and glucose utilization, aggravates preexisting diabetes ? increases plasma concentrations of LDLcholesterol, triglyeride and total cholesterol 37 Side effects ? Hypovolemia ? over treatment, acute loss of excessive fluid leads to postural hypotension and dizziness ? Others ? photosensitive, thrombocytopenia, agranulocytosis ? Thiazides binding with quinidine can lead to polymorphic ventricular tachycardia 38 Classification of Diuretics ? High efficacy diuretics (loop diuretics) ? Moderate efficacy diuretics ? Low efficacy diuretics (K+sparing diuretics) 39 Low efficacy diuretics ? act in the late distal tubules and collecting tubule to inhibit Na+ reabsorption and K+ secretion ? These drugs reduce potassium secretion, so term as K+ retention diuretics or K+ sparing diuretics ? High efficacy and moderate efficacy diuretics increase K+ excretion, so term as K+ lossing diuretics ? Major use is in bination with other diuretics to reduce sodium reabsorption and prevent potassium loss in the tubule. 40 Spironolactone ? Mechanism of action ? aldosterone regulate Na+ reabsorption and K+ secretion at late distal tubules and collecting duct ? Spironolactone is a petitive antagonist to aldosterone ? bind with cytoplasmic aldosterone receptors ? promotes Na+ excretion ? blunt the K+ secretion 41 42 lumen apical membrane interstitial fluid Collecting tubule Basolateral membrane AIP: aldosteroneinduced protein。Diuretics Yanna Wu ., . Associate Professor Department of Pharmacology School of Basic Medicine Tianjin Medical University Email: 1 introduction ? Diuretics ? act on renal tubules, promote the production of urine ? are used to treat edema and unedema diseases (hypertension, heart failure, renal failure, and cirrhosis) 2 glomerulus Proximal convoluted tubule Distal convoluted tubule collecting duct Loop of Henle Thick ascending limb Thin descending limb filtration secretion excretion reabsorption Physiology of Kidneys Process of urine formation 180 L filtrate 12 L final urine 99% nephron renal corpuscle 3 Reabsorption of tubules and collecting tubes ? Proximal convoluted tubules ? NaHCO3 (Na+, HCO3) are reabsorbed ? epithelium is permeable to ions and water, and permit passive flow in either direction N