Pharmacology of Diuretics Flashcards
Diuretics do what?
Increase urine volume by altering ion transport in the nephron.
When and why do we use diuretics?
They are a first line defense in the treatment of HTN and edematous states such as CHF, nephrosis, and cirrhosis
What are our osmotic agents?
Mannitol and urea
Mechanism of Mannitol? Uses?
Mannitol is filtered into the tubular lumen but not reabsorbed, increasing osmotic pressure in the lumen and retaining water in the urine.
We do it in order to reduce intraocular or intracranial pressure. It increases excretion of water more than Sodium, urinary excretion and metabolic toxins
Side effects of osmotic agents like Mannitol and Urea
Dehydration if you don’t drink enough water
Increased ECF volume, leading to pulmonary edema
What is acetazolamide and how does it work
Carbonic Anhydrase Inhibitor
Blocks carbonic anhydrase primarily in the Proximal tubule, preventing reabsorption of sodium bicarbonate and leading to diuresis
What are the uses and side effects of acetazolamide?
We use acetazolamide for:
- Glaucoma to decrease production of aqueous humor
- Acute Mountain sickness to stimulate ventilation via metabolic acidosis
- Elimination of acidic toxins (Alkalinizes urine, leading to increased excretion of weak acids)
- Corrects Alkalosis
Side effects
- Renal stones: increases urine concentration of Ca2+ and phosphates
- Potassium wasting (increased HCO3- in tubules attracts K+)
- Hypercholemic metabolic acidosis
What are furosemide, bumetanide, ethacrynic acid and how do they work
They are loop agents .
They work by inhibitng Na+ K+ 2Cl- transporter in thick ascending limb. Decreases positive luminal potential, leading to increased excretion of calcium and magnesium
What do we use loop diuretics for and what are the side effects
Hypokalemic (low k+) alkalosis (low H+) Hyperuricemia Hypomagnesemia Severe Dehydration Allergic Reactions
What are HCTZ and Metolazone and how do they work?
Thiazide Diuretics
Work by inhibiting Na+-Cl- cotransporter in DCT
Uses and side effects of thiazide diuretics
First line agent for treatment of HTN, CHF, nephrosis, hypercalciuria, and nephrogenic DI.
Thiazides reduce ECF volume which activates RAAS which increases proximal reabsorption of NaCl and H2O which decreases delivery of fluid to distal nephron which decreases urine output
Side effects: Dehydration, hypokalemia, hypercalcemia, hyperglycemia, hyperlipidemia, hyperuricemia, hyponatremia, allergic reactions
Spironolactone, Eplerenone, are what? How do they work?
Potassium sparing agents
Spironolactone and eplerenone directly antagonize the mineralcorticoid receptor (target of aldosterone), thereby reducing Na+ reuptake in the late DCT and collecting duct. Both drugs prevent the aldosterone-mediated increase in apical membrane permeability to K+ (ROMK channels) and therefore are considered “potassium-sparing”
What do we use the potassium sparing agents spironolactone and eplerenone for?
Spironolactone and eplerenone we use primarily in hyperaldosteronism (Conn syndrome) and edematous states caused by secondary hyperaldosteronism like cirrhosis, nephrotic syndrome and cardiac failure. Antiandrogen activity can be useful for treatment of polycystic ovary syndrome and hirsutism
Amiloride and Triamterene are what? How do they work?
Amiloride and triamterene directly inhibit ENaCs in the late DCT and collecting duct which aso reduces Na+ reabsorption. This renders the charge in the lumen more positive, which is unfavorable for K+ secretion.
Hence, these ENaC antagonists are also considered “potassium-sparing”
What do we use amiloride and triamterene for?
Counteract the K+ loss caused by other diuretics, adjunct therapy to other diuretics to treat edema or HTN
