Diuretic Pharmacology Flashcards Preview

CVPR: Renal > Diuretic Pharmacology > Flashcards

Flashcards in Diuretic Pharmacology Deck (21)
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1

Loop diuretics (Furosemide): Site/MOA @ nephron

  • Inhibit NaCl transport (Na+-K+2Cl- transporter) in the ascending limb of the loop of henle – more Na+, K+, and Cl- are retained in the urine

  • Associated with increased Mg2+ and Ca2+ excretion

  • Increase renal blood flow (via effect on renin-angiotensin system) 

2

Loop diuretics (Furosemide/Ethacrynic acid): Pharmacokinetics

  • Furosemide
    • Rapid oral absorption; extremely rapid IV response
    • Excreted by renal secretion and filtration 
  • Ethacrynic acid:
    • IV
    • renal secretion
    • rapid onset

3

Loop diuretics (Furosemide): uses

  • edema due to CV, renal, hepatic disease
  • Used in HF patients with volume overload in conjunction with salt restriction
  • Acute pulmonary edema
  • hypercalcemia

4

Loop diuretics (Furosemide): Adverse effects

  • metabolic alkalosis 
  • Hypokalemia
  • Hyponatremia
  • Ototoxicity
  • Hyperuricemia
  • Hypomagnesemia/Hypocalcemia
  • Overdose --> rapid blood volume depletion 

 

5

Thiazides: Examples & Site/MOA @ nephron

  • hydrocholorothiazide, chlorthalidone, metolazone
  • Inhibit the Na+/Cl- cotransporter and increase urinary excretion of NaCl (a modest diuretic effect since only 5-10% of filtered Na+ is reabsorbed here)
    • less effective than loop diuretics
  • metolazone: potent thazide; combo w/furosemide
  • Increase reabsorption of Ca2+ (lowering of intracellular Na+ drives Ca2++ exchanger) 

6

Thiazides (Hyrdrochlorothiazide): Pharmacokinetics

  • Oral absorption, best tolerated early in the day
  • Hydrochlorothyozide – twice daily dosing
  • Secreted by organic acid secretory system @ PT; competition with uric acid secretion may precipitate gout attacks 

7

Thiazides (Hyrdrochlorothiazide): Uses

  • First line for mild hypertension
  • Tx for Hypercalcuria – increased reabsorption of Ca2+ --> reduced urinary excretion --> decreases incidence of kidney stones
  • edema (primarily metolazone): synergistic diuretic effect with loop diuretics

8

Thiazides (Hyrdrochlorothiazide): Adverse effects

  • Hypokalemia, hypomagnesaemia 
  • Hyperuricemia – avoid in patients with gout
  • hyponatremia/chloremia
  • Impaired carbohydrate tolerance (hyperglycemia, glucosuria) and hyperlipidemia 
  • hypercalcemia

9

Potassium-sparing diuretics: Site/MOA @ nephron

  • Diuretics that block the Na+ channel or antagonize the aldosterone receptor will decrease Na+ reabsorption and decrease K+ excretion 
  • Spironolactone = antagonsits of aldosterone; bind receptors @ ald-dependent Na-K exchange site @ DCT
  • Eplerenone = binds mineralcorticoid receptor => blocks binding of aldosterone

10

Aldosterone Antagonists (Sprionolactone): Site/MOA

  • competitive antagonist at aldosterone receptor
  • prevents enhancement of protein synthesis; blockade of aldosterone effect at collecting tubule
  • --> less Na+ is reabsorbed, lumen potential becomes more positive, and less K+ ions move into the urine
  • Promotes only moderate increase in Na+ excretion; mild diuresis when used alone 

 

11

Aldosterone Antagonists (Sprionolactone): Pharmacokinetics

  • oral

  • renal, biliary excretion

  • dosed 1-2x/day with slow onset of action 

12

Aldosterone Antagonists (Sprionolactone): Clinical uses

  • Congestive heart failure
  • Raises serum potassium to counter risk of hypokalemia-induced arrhythmias resulting from K+ wasting diuretics
  • Hyperaldosteronism
  • HTN 

 

13

Aldosterone Antagonists (Sprionolactone): Adverse Rxns

  • Hyperkalemia --> arrhythmias
  • Endocrine abnormalities: gynecomastia with spironolactone, amenorrhea

14

Osmotic diuretics: examples/MOA

  • mannitol = sugar that's not metabolized + not reabsorbed @ PT
  • induced diuresis via elevation of osmolarity of glomerular filtrate = decreased tubular reabsorption of water
  • increased Na & Cl excretion

15

Osmotic diuretics: pharmacokinetics

  • IV administration
  • ECF distribution
  • Renal excretion

16

Osmotic diuretics: uses

  • prevent AKI
  • glaucoma
  • elevated intracranial pressure

17

Osmotic diuretics: adverse effects

  • acute increase in ECF volume
  • nausea, headache
  • prolonged => hypovolemia, hypernatremia

18

Carbonic anhydrase inhibitor: examples/MOA

  • acetazolamide
  • weak diuretic
  • inhibits regenration of bicarb @ PT => sodium bicarbo loss
  • produces metabolic acidosis

19

Carbonic anhydrase inhibitor: pharmacokinetics

  • oral
  • 90% protein-bound
  • not metabolized; renal excretion
  • half-life: 5 hr

20

Carbonic anhydrase inhibitor: uses

  • glaucoma
  • metabolic alkalosis
  • mountain sickness

21

Carbonic anhydrase inhibitor: adverse effects

  • metabolic acidosis
  • drowsiness, fatigue
  • CNS depression