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2015-03-22 13:52:43
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  1. Carbonic Anhydrase Inhibitors
    Acts in the proximal tubule through inhibition of carbonic anhydrase that is present in both the luminal border and cytoplasm of the epithelial cell. - increases excretion of Na+, K+, HCO3 , and water; decreases excretion of H+
  2. Disadvantages CarbonicAI:
    mild, production of metabolic acidosis. Infrequent toxic effects: sulfonamide related adverse reactions - bone marrow depression, skin toxicity, allergic reactions. Kinetics: oral (or i.v.) administration, t 1/2 6-9 hrs., renal excretion. Dorzolamide topical Therapeutic uses: - short term diuretic therapy, alternative/adjunct to other diuretics - correction of diuretic-induced alkalosis - epilepsy - glaucoma
  3. (Dorzolamide (Trusopt)) weird use
    - acute mountain sickness
  4. Loop Diuretics agents
    • Furosemide
    • Bumetanide
    • Ethacrynic acid
    • Torsemide
  5. Loop diuretic MOA
    Inhibit na/kcl active co cotransporter in the thick ascending limb causing decreased absorption of NA/k/Cl, countercurrent conc collapses increases urine loss of ions, also pulmonary vasodilation, increased venous compliance
  6. Loop diuretics advatages/ disadvantages/ kinetics
    • High efficacy and prompt action
    • Hypo K M, alkalosis, hyper uric glycemic, ototox- watch out if impaired renal fn or coadmin of aminoglycosides
    • PO rapid on/ off, plasma protein bound, organic acid secretion
  7. Loop therapeutic uses
    • Acute pulmonary edema
    • Nephrotic syndrome edema
    • CHF
    • Hypercalcemia
    • Asthma
  8. Thiazides agents
    Chlorothiazide, hydrochlorathiazide, indpramide, metalozone
  9. Thiazide MOA
    • Inhibit NaCl cotransporrter causing decreased Na reabsorption in the early distal tubule
    • Some CAI
    • Vasodilation in HTN pts with extended treatment
    • Increased K excretion
    • Ca sparing
  10. Thiazide advantage. Dis/ kinetics
    • PO active, minimal tolerance to diuretic effect
    • Hypokal, dehydration, hypercalcemia, hyperureicemia, hyperglycemia, and hyperlipidemia
    • Range of half life, plasma protein bound, secreted into lumen in proximal tubule
  11. Thiazide therapeutic uses
    • HTN
    • CHF edema
    • Hepatorenal edema
    • Nephrogenic diabetes insipidus
    • Ca dynamics- ca wasting and stones
  12. Osmotic diuretics agents
    Mannitol, glycerin, isosorbide
  13. Osmotic agents
    • Free filtered at glomerulus, limited reabsorption, and are relatively inert
    • Increased renal tubular osmolarity
    • Interfere with na and h2o reabsorption in the nephron due to the osmotic effect of increased conc of solute in urone
    • Can sustain flow even with low GFR
    • Increased electrolyte excretion
  14. Osmotic agent disadvantage
    • EC volume expansion
    • CHF and pulmonary edema precipitation
    • Hyponatremic
    • Headache N/V
  15. Osmotic kinetics
    Glycerin and isosornbide PO, mannitol IV, renal and metabolic elimination
  16. Osmotic therapeutics
    • Acute renal failure
    • Prophylactic or acute elimination of toxins
    • Decrease cell volume from cerebral edema
    • Decrease aq humor in glaucoma
  17. K sparing diuretic agents
    • Spironolactone
    • Eplerrenone
    • Triamterene
    • Amiloride
  18. K sparing moa
    • Spironolactone competively antagonizes aldosterone binding to mineraloCC receptor decreasing transport proteins
    • Triamterene and amilioride directly inhibit na channel in the late distal tubule through an aldost independent mech- excretion pattern is similar to spironolactone
    • These agents increase NaCl excretion and decrease K excretion hence k sparing
  19. Amount of k reabsorbed and location
    90% in prox tubule, small amount is handled by distal nephron- this segment determines net gain or loss
  20. Factors that promote K secretion
    • Increase Na to the collecting duct
    • Elevated aldosterone
    • Enhanced Na reabsorption
  21. Why do most diuretics cause K loss?
    • Many have direct effects on nephron segments
    • Presentation of elevated Na, nd subsequent h2o to the collecting duct
    • Stimulation of aldo release
  22. Compared to other diuretics K sparing
    • mild diuretic due to indiviual effcts of Na reabsorption
    • do nto lose K
    • spirano blocks aldo
    • amilioride blocks diuretic enchanced activity of na reabsorb and k excretion
  23. K sparing Disadvantages:
    • - hyperkalemia
    • - CNS, GI, musculoskeletal, dermatological, and hematological effects
    • - Gynecomastia, menstrual irregularities, androgen-like side effects with
    • spironolactone
    • - Spironolactone efficacy related to levels of circulating aldosterone
  24. K sparing Kinetics:
    • orally available, variable half times, excreted through kidneys and
    • metabolism
  25. K sparing Therapeutic uses:
    • - rarely used alone
    • - very useful in combination with thiazides to provide additive increase in Na
    • excretion with moderation of K+ loss
    • - hypertension, edema
    • - spironolactone: primary and secondary aldosteronism
    • - spironolactone: diuretic of choice in patients with hepatic cirrhosis
  26. Spiranolactone and cardiac
    • Contractility
    • Angiotensin II
    • Fibrosis
    • Free radicals
  27. Causes of diuretic resistance
    • noncompliance
    • bioavailability impaired
    • secretion impaired
    • protein binding in tubule lumen
    • reduced gfr
    • enhanced nacl reabsorp
  28. In patients with CHF, cirrhosis with ascites, hypovolemia NSAIDS
    reduce RBF and GFR; promote Na+ and water retention