Diuretics Flashcards
Carbonic anhydrase inhibitor
Acetazolamide
NaK 2Cl symport inhibitor
Furosemide
Na Cl symport inhibitors
Hydrochlorthiazide
Chlorothiazide
2 groups of K sparing diuretics
Epithelial Na channel inhibitors
Aldosterone antagonists
Epithelial Na channel inhibitors
Amiloride
Triamterene
Aldosterone antagonists
Spironolactone
Eplerenone
Osmotic diuretics
Mannitol
Vasopressin receptor antagonists
Demeclocycline
Tolvaptan
Endogenous OAT substrates (4
Urate
Bile acids
Oxalate
Prostaglandins
Exogenous OAT substrates (6)
Hydrochlorothiazide Furosemide Acetazolamide Probenecid Pencillin Aspirin
OCT endogenous substrates (3)
Creatinine
Epinephrine
Histamine
OCT exogenous substrates (5)
Amiloride Triamterene Cimetidine Atropine Quinine
Site of action is in proximal tubule, where it competitively inhibits carbonic anhydrase
Acetazolamide
Carbonic anhydrase is responsible for ___ reabsorption and __ secretion
NaHCO3, acid (H+)
Control vs. \_\_\_\_ Vol: 1 vs 3 (ml/min) pH: 6 vs 8 Na+: 72 vs. 302 K+: 22 vs. 260 Cl-: 85 vs. 95 HCO3-: 1 vs. 120
Acetazolamide (CA inhibitor)
Acetazolamide effect on renal hemodynamics
Increases NaCl delivery to macula densa, reducing RBF (afferent arterioles constricted) and GFR
Uses=
Open-angle glaucoma
Altitude sickness
Epilepsy
Acetazolamide
ADEs=
Renal stone formation (urinary alkalinization)
Potassium wasting
Worsens hepatic encephalopathy (diversion of ammonia into systemic circulation)
Acetazolamide
Site of action is in thick ascending limb of the loop of Henle, inhibits Na+-K+-2Cl- symporters
Furosemide (also abolishes trans-epithelial potential difference that drives paracellular transport of Ca and Mg)
Control vs. \_\_\_\_ Vol: 1 vs 8 (ml/min) pH: 6 vs 6 Na+: 72 vs. 1615 K+: 22 vs. 115 Cl-: 85 vs. 990 HCO3-: 1 vs. 1
Furosemide
Urinary effects:
Increase in Ca and Mg excretion
Decreased uric acid excretion (chronic effect, exacerbates gout)
Reduces ability of kidney to dilute urine when over-hydrated and concentrate urine during dehydration
Furosemide
Furosemide renal hemodynamic effects:
- Increases RBF and redistributes it to cortex (prostaglandin-mediated)
- Stimulates release of renin (blocks TGF by inhibiting salt transport into the macula densa)
Acutely increases systemic venous capacitance and decreases left ventricular filling pressure
May be beneficial to patients with pulmonary edema
Furosemide (prostaglandin mediated)
PK= highly protein bound
Delivered to apical membrane by OAT
Short half-life
“Post-diuretic” sodium retention
Furosemide
Uses=
- Hyponatremia + IV hypertonic saline
- Hypercalcemia + IV isotonic saline
- Edema of nephrotic syndrome
- Congestive heart failure
- Acute pulmonary edema
Furosemide
ADEs= boxed warning for electrolyte and fluid loss
Hyponatremia, hypokalemia, hypocalcemia (cause in osteoporosis)
Hyperuricemia
Furosemide
ADEs= ototoxicity (tinnitus, vertigo, deafness)
Hyperglycemia (caution in co-admin with sulfonylureas)
NSAIDs reduce diuretic effect
Furosemide
Site of action is in distal convoluted tubule, where it inhibits Na+-Cl- symporter
ALSO weak inhibitor of carbonic anhydrase in PCT
Hydrochlorothiazide (chlorothiazide)
Moderate efficacy (5% of filtered load) Shallow dose-response Efficacy substantially reduced when GFR is low (<30-40 mL/min)
Hydrochlorothiazide
Control vs. \_\_\_\_ Vol: 1 vs 3 (ml/min) pH: 6 vs 7.4 Na+: 72 vs. 650 K+: 22 vs. 110 Cl-: 85 vs. 650 HCO3-: 1 vs. 25
Hydrochlorothiazide
DECREASES excretion of Ca
Decreases kidney’s ability to dilute urine during water diuresis (concentration ability is OK)
No effect on renal hemodynamics
Hydrochlorothiazide
Protein bound and delivered by OAT
Longer half-lives
Hydrochlorothiazide
Uses=
- Hypertension
- Mild edema
- Nephrogenic diabetes insipidus (paradoxical effect)
- Calcium nephrolithiasis and osteoporosis
Hydrochlorothiazide
ADEs= Hyponatremia, hypokalemia Hyperuricemia Hyperglycemia & hyperlipidemia Erectile dysfunction
Hydrochlorothiazide
DDIs of HCT (2)
- NSAIDs reduce diuretic efficacy
2. Quinidine- hypokalemia increases risk of torsades de pointes (arrhythmia)
Site of action is the late DCT and collecting duct, where they block epithelial Na+ channels on the apical membrane of principal cells
Triamterene and amiloride (ENaC inhibitors)
Site of action is the late DCT and collecting duct, where they block CYTOSOLIC mineralocorticoid receptors in principal cells, reducing expression of some proteins
Spironolactone and eplerenone (Aldosterone antagonists)
Abolish the trans-epithelial potential that drives tubular secretion of K+ and H+
ENaC inhibitors and aldosterone antagonists (ROMK channels and Type A intercalated cell H+-ATPase)
Control vs. \_\_\_\_ Vol: 1 vs 2 (ml/min) pH: 6 vs 7.2 Na+: 72 vs. 375 K+: 22 vs. 15 Cl-: 85 vs. 345 HCO3-: 1 vs. 15
Triamterene (SOME ACTION ON CARBONIC ANHYDRASE)
Potassium-sparing diuretics’ effect on renal hemodynamics
None
Uses:
Prevent K+-wasting
Liddle syndrome
Cystic fibrosis
ENaC inhibitors (triamterene and amiloride, K-sparing diuretics)
Uses: Prevent K+-wasting Primary hyperaldosteronism Hepatic cirrhosis CHF
Aldosterone antagonists (spironolactone, eplerenone)
ADEs= boxed warning for hyperkalemia (use cautiously with ACE inhibitors and NSAIDs)
Potassium sparing diuretics (triamterene, amiloride, spironolactone, eplerenone)
ADEs= gynecomastia, impotence, hirsutism, decreased libido
Aldosterone antagonists (spironolactone > eplerenone)
Site of action is entire tubule
Reduces renal medullary tonicity, which reduces the passive reabsorption of NaCl in the ascending limb
Mannitol (osmotic diuretic, increases the osmolarity of the tubular fluid)
Expands ECF volume
Increases excretion of ALL electrolytes
Mannitol (osmotic diuretic)
Increases RBF
GFR is unchanged
Inhibits release of renin
Mannitol
Given IV for dialysis disequilibrium syndrome, reducing CSF and intra-ocular pressure, and minimizing acute tubular necrosis
Mannitol
Contraindicated in heart failure (edema) and active cranial bleeding
Mannitol
