DIURETIC DRUGS

Welly Ratwita
Lab. Farmakologi FK UNJANI

Diuretics
Drugs inducing a state of increased urine flow Carbonic Anhydrase Inhibitors Loop Diuretics Thiazide Diuretics Potassium-sparing Diuretics Osmotic Diuretics

Normal Regulation of Fluid & Electrolytes by Kidney

Proximal Convulated Tubule 2/3 Na+, almost all glucose, bicarbonate reabsorbed Acid secretory system
Descending Loop of Henle Countercurrent mechanism [NaC] 3x

 Ascending Loop of Henle Impermeable to water Active reasorption of Na, K, Cl, Mg, Ca 25-30% NaCl reabsorbed Loop Diuretics Distal Convulated Tubule Impermeable to water 10 % NaCl reabsorbed Thiazide Ca++ excretion Collecting Tubule and Duct Na, water reabsorption, K secretion

Carbonic Anhydrase Inhibitors

MOA
Acetazolamide inhibits carbonic anhydrase intracellularly on apical membrane of proximal tubular epithelium

H2O + CO2 H2CO3 H+ + HCO3

HCO3 retained in lumen urinary pH Loss of HCO3 metabolic acidosis & diuretic efficacy folowing everal days of therapy

Therapeutic Uses
P.O. once daily Glaucoma Epilepsy Mountain sickness

Adverse Effects
Metabolic acidosis (mild), potassium depletion, renal stone formation, drowsiness

Loop/High-Ceiling Diuretics
Bumetanide, furosemide, torsemide, ethacrynic acid On ascending limb of the loop of Henle Highest efficacy in mobilizing Na & Cl

MOA Inhibit Na+/K+/Cl- cotransport Reabsorption of Na, K,Cl , Ca++ urine Most efficacious of diuretics Renal vasc. resistance , renal blood flow Good in poor renal function

 Therapeutic Uses DOC in acute pulmonary edema of CHD Hypercalcemia

Pharmacokinetics P.O., I.V., rapid onset, DOA 1-4 hrs Adverse Effects Ototoxicity Hyperuricemia Acute hypovolemia Potassium depletion

Thiazides & Related Agents

Sulfonamide derivates like acetazolamide, w/ greater activity Affect distal tubules, w/ equal max diuretic effect, differing on potency

A. Clorotiazide
Prototype thiazide diuretic MOA Inhibit Na/Cl cotransporter Na reabsorption very hyperosmolar urine Not effective in renal function impairment Loss of K+ Ca++ excretion peripheral vascular resistance

 Pharmacokinetics
Effective orally T1/2 40 hrs Secreted by rganic acid secretory system 1-3 weeks to stabilize blood pressure reduction

Therapeutic Uses
Hypertention CHD Renal impairment Hypercalciuria Diabetes insipidus

 Adverse Effects
Potassium depletion Hyperuricemia Vokume depletion Hypercalcemia Hyperglycemia Hypersensitivity

B. Hydrochlorotiazide
Thiazide derivative Less ability to inhibit carbonic anhydrase More potent, less dose than thiazide Same efficacy as thiazide

C. Chlorthalidone
Thiazide dervative Very long DOA once daily

D. Thiazide analogs Metolazone

More potent than thazide Unlike thiazide, causes Na excretion in advanced renal failure

Indapamide
A lipid soluble, non thiazide diuretic Long DOA Significant antihypertensive action w/ minimal diretic effects Used in advanced renal failure Metabolized & excreted by GIT & kidneys

Potassium-Sparing Diuretics
Act in collecting tubule Inhibit Na reabsorption, K secretion, H secretion Used primarily whwn aldosterone in in excess In combination w/ thiazide Stop exogenous potasium supplementation

A. Spironolactone
MOA A Synthetic aldosterone antagonist Compete w/ aldosterone for intracellular cytoplasmic receptor Prevents translocation of receptor complex into targets cell nucleus not bind to DNA Not produce protein that response to aldosterone Excretion of Na, retention of K, no diuretic effect