1-25-24 Diuretic.pptx

Diuretics Chapter 11 by Susan Hartfield PA-C, PharmD Overview We are going to review for cardiology Diuretics (“water pills) Carbonic anhydrase inhibitors Thiazides, loop diuretics, potassium sparing diuretics Drugs that interfere with the renin-angiotensin-aldosterone system Angiotensin-Converting...

Diuretics Chapter 11 by Susan Hartfield PA-C, PharmD Overview We are going to review for cardiology Diuretics (“water pills) Carbonic anhydrase inhibitors Thiazides, loop diuretics, potassium sparing diuretics Drugs that interfere with the renin-angiotensin-aldosterone system Angiotensin-Converting Enzyme Inhibitors Angiotensin II Receptor Blockers Selective Aldosterone Receptor Antagonists Direct Renin Inhibitors Calcium Channel Blockers Nitrates Other Direct Vasodilators Alpha and beta blockers (already covered) Review Mean Arterial Pressure = CO x Peripheral Resistance Cardiac output (CO) Increased HR Increased contractility Increased sodium and water retention Peripheral Resistance = Vasoconstriction Renal Function  Responsibilities of the kidney Regulation of electrolytes Water balance Regulation of plasma pH Regulation of blood pressure Hormone activation  Vitamin D  Erythropoietin Renal Function  Fluid filtered at the glomerulus enters tubule  Tubule contains transporters to reabsorb necessary substances  Anything not absorbed is excreted as urine  By blocking the reabsorption of Na+ water is removed www.medbullets.com www.quora.com Clinical Uses of Diuretics Hypertension Edema Heart failure Kidney disease Hepatic cirrhosis (except carbonic anhydrase inhibitors) Hypercalcemia/hyperkalemia Proximal Convoluted Tubule (PCT)  First and most important segment  Bicarbonate reabsorbed mostly here  If CA (carbonic anhydrase) inhibited ↓ ability to absorb bicarb to blood ↓Na+/H+ exchanger to reabsorb Na+ Lose more NaHCO3 in the urine Metabolic acidosis, hyperchloremia Hypokalemic (see figure 9-4) Figure 9-1  Due to distal nephron trying to absorb more Na > Principal cell in the collecting tubule Carbonic Anhydrase Inhibitors  Acetazolamide (Diamox®) and methazolamide (Neptazane®) Brinzolamide (Azopt®) and dorzolamide (Trusopt®) are available as an eye drop Bicarbonate is used by the ciliary epithelium to create aqueous humor  Not typically used for hypertension Metabolic acidosis can be profound Diuretic effect wears off once bicarbonate is depleted Uses Altitude sickness Alkalinization of the urine Acidic drug overdose Pseudotumor cerebri Side effects Ideopathic intracranial HTN Metabolic alkalosis Hypersensitivity (sulfa) Precipitation of calcium kidney stones Do not use in patients with acidosis or hyperammonemia Hyperchloremic, hypokalemic metabolic acidosis Carbonic Anhydrase Inhibitors Thick Ascending Limb of Loop of Henle (TAL)  Relatively impermeable to water  Reabsorbs: Na, K, Mg, Ca, Cl  Blocking NKCC causes Na-K-Cl cotransporter ↓Mg-less K extruded, ↓driving force ↓K-d/t distal Na reabs (principal cell) Metabolic alkalosis-d/t reabs of K  Exchanges for H+  In the intercalated cells Figure 9.2 Loop Diuretics  “Powerhouse” Diuretics Useful in hypertension and heart failure Useful in generalized edema, pulmonary edema Treatment of hyperkalemia, hypercalcemia  Fluid must be replaced Acute renal failure Useful in patient with low GFR < 30ml/min Loop Diuretics  Furosemide (Lasix®) Available as oral or IV Dosing:20-120mg po 1-2x/day Ethacrynic Acid (Edecrin®)  Is not a sulfa Torsemide (Demadex®)  10-200mg po once daily Bumetanide (Bumex®) Loop Diuretics  Side effects and Cautions ↓Mg ↓K Metabolic alkalosis Hypersensitivity due to sulfa (except ethacrynic acid) May precipitate gout-Increases uric acid (induced by hypovolemia) Ototoxic, particularly in combination with other ototoxic drugs  Following rapid IV administration, dose related Loop Diuretics  Drug Interactions Aminoglycoside antibiotics (renal damage, ototoxicity) Lithium NSAIDs may blunt the diuretic response Thiazide diuretics + loop diuretics = synergism of diuretic activity of both drugs leading to profound diuresis (often a desirable effect) Distal Convoluted Tubule  Small amount of Na/Cl reabsorbed ~10%  Hormonal regulation of Calcium Via parathyroid hormone  Blocking NCC may cause Na-Cl cotransporter Hypercalcemic, hypokalemic metabolic alkalosis Thiazides  Low potency agents Chlorothiazide: first to be developed  500mg-1gm by mouth OR IV once or twice daily (500mg-1gm po/IV qday to bid)  Intermediate potency agents Hydrochlorothiazide (HCTZ®)-12.5mg by mouth once daily Chlorthalidone-12.5mg-25mg by mouth once daily  Highest potency Metolazone, Indapamide  Not effective when GFR 5 mEq/L