DIURETICS

Diuretics are drugs which increase the excretion of sodium and water from the body by an action on the kidney. Their primary effect is to decrease the reabsorption of sodium and chloride from the filtrate, increased water loss being secondary to the increased excretion of salt.

CLASSIFICATION

High effect diuretics: Lasix Mediate effect: Thiazide diuretics Mild (Low)effect: K+ sparing diuretics Osmotic diuretics: Mannitol Others

urine formation & the action sites of diuretics

Glomerulus and its filtration Tubules and its reabsorption and secretion Proximal convoluted tubule Na+-H+-antiporter axetazolamide H+

Ascending limb of the loop of Henle dilution & concentration K+-Na+-2Cl- -cotransporter Distal tubule and collecting duct Na+ - K+-exchanger

Na+

•Furosemide•Thiazides•Spironolactone•Trianterene

High effect diuretics High ceiling (loop) diuretics Agent furosemide (lasix) Action site thick ascending loop (AL) Mechanism 1. Cl K-Na-2Cl

High effect diuretics 2. PGE P.E. Cl Na Renal Blood Flow (RBF) ADR Ototoxicity (etacrynic acid>lasix>bumetanide) Disturbance of water and electrolyte Hyperuricemia Others toxicities: allergic reactions,nausea et al.

P.K.Onset in 5 min by i.v. 30 min by p.o. t 1/2=2hr last for 4-6 hr

Mediate effect diuretics Thiazides Agent Hydrochlorothiazide (HCT) Action site Distal convoluted tubule (DCT) Mechanism Na-K-2Cl; PDE

Mediate effect diuretics ADR Hypokalemia ---be careful when use wit

h digitalis. Hyperuricemia--- compete with uric acid Hyperglycemia--- insulin Hypercalcemia--- Ca

Low effect diuretics K+ sparing diuretics Agent Antisterone, Triamterene & amiloride Action site DCT & CT (Collecting Tubule) Mechanism 1. Ald-R 2. Na channel

Na K

Low effect diuretics ADR Hyperkalemia, sex hormone like effects (antisterone) Others Carbonic anhydrase inhibitors (acetazolamide) H2O + CO2 H + HCO3 -------- inside cell

Na ----- outside cell

CA

Osmotic diuretics Agents (characters) Mannitol, Glucose Action site PCT, AL; Vessels, gastrointestinal tract Mechanism 1. Hyperosmolarity 2. Blood volume RBF

Osmotic diuretics P.E. H2O ADR BV CHF Dehydration Hypernatremia

CLINIC USES of DIURETICS Edema CHF ARF Hypertension Poisoning Hypercalciuria Hypercalciumia Glaucoma Diabetes insipidus

ADR of DiureticsPla. K Pla.Uric

APla.Ca ototoxicit

yothers

H.D (Lasix) _ + _ + BV _

M.D (HCT) _ + + _ LDL +

L.D (antisterone)

+ + _ _ Sex Heffects

In

common Hyponatremia, electrolyte imbalances

Review & questions The classes of diuretics. The mechanisms of each. The Common ADR of diuretics The common P.E of diuretics The clinic uses of diuretics.