Diuretics

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C
Proximal Convoluted Tubule
A Glomerulus B Loop of Henle C Distal
Convoluted Tubule D Collecting
Tubule, Collecting Duct
A
D
B
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??????????,?????????,???????????????,?????????????
??????????
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Kidney function in disease
???
???
????
???????????????
??
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?????

• ??????
• ???????????????????????,????????????????????
• ???
• ???????,??????????
• ?????
• ??????????????,?????
• ??????
• ??????,?? estrogen ???????????????

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Diuretic drugs ???

• ????
• ????????????????????????
• ?????????(??)????

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(No Transcript)
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????

• ?????????
• ?????????????????
• ????????????????
• 2/3 ???????,?????????????????????????

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??????

• ????????????????????
• ?????????,??????????
• ????????????

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??????

• ?????????????????
• Na/K/2Cl- cotransporter
• ?? 25-30 ??????????????????
• ????????? Loop diuretics ????????

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????

• ??????????
• 5-10 ?????????
• ???????? Apical Membrane ? Na/Cl- transporter
• Ca2?????????

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???

• ????
• ??????? aldosterone ???????????????
• ????????????????????(?? cAMP ??)

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ADH ?????
From Katzung 9th Ed
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Diuretic drugs

• Carbonic anhydrase inhibitors
• Loop diuretics
• Thiazide diuretics
• Potassium-sparing diuretics
• Osmotic diuretics

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Carbonic anhydrase inhibitors
From Lippincotts 3rd
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CARBONIC ANHYDRASE INHIBITORS

• Acetazolamide Diamox?
• Dichlorphenamide
• Dorzolamide
• Brinzolamide

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Pharmacokinetics

• Orally active and well absorbed
• Secreted by proximal tubule

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Mechanism of action inhibits carbonic anhydrase
From Lippincotts 3rd
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Action of carbonic anhydrase inhibitors

• ??????? carbonic anhydrase (????????????? H and
  HCO3-)
• ??????
• ?? HCO3- ?????? pH ???,?????????????

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Sites of action

• kidney - primarily in the proximal tubule
  (luminal gt cellular)
• ciliary body
• choroid plexus and CNS
• red blood cells
• gastric mucosa
• pancreas

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Medical indications

• ??????
• ???
• Acetazolamide ???????,????????,?????? pilocaroine
  (cholinergic agonist)
• ??
• ???

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Take home message-??????

• ???????,??????????,????????????,?????????,????
• ?????????? 1-3 ?,???????????????????,?????????????
  ????????
• Acetazolamide Diamox? ??????(?????)???,???????
  ??????????????????,????????,?????????,????????????
  ??????,?????????
• ???? ?????????(24????)???????,? 8 ? 12 ???? 250
  mg ?Acetazolamide??,????????????????
• ???????????????????????????125 mg Acetazolamide

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Side effects

• ?????
• ???
• ??
• ???
• ????

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Contraindications

• Carbonic anhydrase inhibitor-induced
  alkalinization of the urine will decrease urinary
  excretion of NH4 and may contribute to the
  development of hyperammonemia and hepatic
  encephalopathy in patients with cirrhosis

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Loop or high-ceiling diuretics
From Lippincotts 3rd
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Mechanism of loop diuretics

• ??????????????????????????,???????????
• ??????????
• ????????

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From Katzung, 10th edition
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Sites of action

• Thick ascending limb
• Macula densa
• A densely packed group of modified epithelial
  cells in the distal tubule of a nephron, adjacent
  to the juxtaglomerular cells
• Inner ear
• Vascular smooth muscle
• Renal-PGE2 mediated
• Pulmonary-PGI2 mediated and kidney-dependent

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Loop or high-ceiling diuretics

• Bumetonide furosemide (Lasix?) torsemide
  ethacrynic acid
• ?????????????
• Ethacrynic acid ?????,????
• Bumetanide ??? furosemide ??,???????

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Medical indications

• ????????
• ????????????????
• ?????????
• ?????
• ?????????????

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Side effects of loop diuretics

• ???
• ???????????,?????????,???????,??? aminoglycoside
  ?????? streptomycin,??????
• ???????????????
• ?????? K?Cl- ??,??? Na-K ??,??????????,?K-H
  ???H ?????,??,??????????
• ???????
• loop diuretics??-COOH ????,????????????????????,??
  ,???????,????????

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???
??? (with aminoglycoside)
?????
???
???
Side effects of loop diuretics
From Lippincotts 3rd
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(No Transcript)
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Thiazides
From Lippincotts 3rd
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Thiazide and related agents

• ?????????
• ???????

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Thiazide and related agents

• Chlorothiazide
• ??????????????????????????????
• Hydrochlorothiazide
• ??? chlorothiazide ?,???????
• ????
• Actions ???????????(Na-Cl- cotransport system)
  ,??Na-Cl-????,??????????

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From Katzung, 10th edition
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??????

• ???
• ????????,TI ??,??????,???????,????,??????
• ??????
• ?????Ca2 ??,???????????????,???????????????????
• ??????Na???????
• ??????
• ?????,???????,?? ADH ???,??????

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Side effects of thiazides

• ???
• ?????????? renin-angiotensin-aldosterone
  ????????????
• ?????
• ??????????????,??????????
• ????
• ????????????
• ???
• ???????,????????????
• ???
• ???????????,?????,??,????????
• ???
• ?????????

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Thiazide-like analogs

• Chlorothalidone
• ?????
• ????????
• ???? ????
• Metolazone
• ???????????????????
• Indapamide
• ???? Thiazide ???
• ??????????????
• ???????????,???????????????,??????

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???
???
?????
???
???
Side effects of thiazide diuretics
From Lippincotts 3rd
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(No Transcript)
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?????

• ???? aldosterone ???,??????????? ???? thiazides
  ??
• Spironolactone
• Aldosterone ????? aldosterone ???????????
• Addisons disease ????????,???? aldosterone
  ????,???????????
• Triamterene amiloride
• ????????????????,??????aldosterone ??? Addisons
  disease

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(No Transcript)
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Take home message-- Addisons disease

• ?????????? (primary adrenal insufficiency),???????
  ? (Addisons disease),??????????????? (cortisol,
  aldosterone ?) ??????
• ??---??????????????????,???? ?????????????????????

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Relative changes in urinary composition induced
by diuretic drugs
From Lippincotts 3rd
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From Katzung 10th edition
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Osmotic diuretics

• Mannitol and urea
• ?????????
• ??gt??,??????????
• ?????????????????? ???????????????????????????
• Mannitol ????,??????

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From Katzung 9th Ed
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THIAZIDE DIURETICS
CARBONIC ANHYDRASE INHIBITORS
POTASSIUM SPARING DIURETICS
LOOP DIURETICS
OSMOTIC DIURETICS
Aldosterone ANH ADH
OSMOTIC DIURETICS
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ADH and ANH

• ADH
• Antidiuretic hormone (?????) ????????
• ?????,????????
• ANH
• Atrial natriuretic hormone (???????) ????
• ?????,??????????,????

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Take home message
From Wikipedia
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Take home message

• ?????????? B1??
• ???????????,?????????????????????,????? B1???????
• ??? B1????
• ???????????????????
• ? 40??????B1?????

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Take home message-??????

• ?????????????????????????????????????
• ??????????????????????,?????????????????,????????
  ?????????????
• ???,?????????????,???????????????????????????,????
  ?????????????????,??
• ?????,?????????????????? ?????????????????????????
  ?
• ?????,???????????????????
• ?????,?????????????????????????????
• ?????,??????????????????????????????
• ??????????,???????????????????

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Study question

• ??????????????????????
• A. Amiloride
• B. Chlorothiazide
• C. Tiamterene
• D. Spironolactone
• E. Torsemide
• Answer D

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The End