Pharmacology???

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??????II
Diuretics and dehydrant drugs
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• The Kidney
• Excretion water, ions, and toxic metabolites

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B
A
Renal structures for urine generation (A) and
osmotic gradient (B)
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10Na
65-70Na
Na, Cl- reabsorption in the kidney
25Na
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Reabsorption sites of Na, K, Cl-, and other ions
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A. Diuretic drugs

• A diuretic is any substance influence the rates
  of transport of Na, K, Cl-,HCO3- and urate,
  increases urine and solute excretion.

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A. Diuretic drugs
Classification of diuretic drugs Classification of diuretic drugs
Loop diuretics- high efficacy furosemide ??? thick ascending limb of Henle loop inhibiting Na-K-2Cl- symport
Thiazide diuretics moderate efficacy hydrochlorothiazide ???? distal convoluted tubule inhibiting Na-Cl- symport
K-sparing diuretics low efficacy spironolactone ??? late distal tubule and collecting duct inhibiting renal epithelial Na channels
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A. Diuretic drugs
Loop diuretics
Furosemide ???
Bumetanide ????
Etacrynic acid ????
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A. Diuretic drugs

• Furosemide ??
• 1. Pharmacological effects
• (1) Diuretic effects
• Inhibiting the Na-K-2Cl- cotransporter
  (symport) of the luminal membrane in the thick
  portion of the ascending limb of the loop of
  Henle, and reducing the reabsorption of Na, K
  and Cl-.
• Most efficacious among the diuretic drugs,
  because the ascending limb accounts for the
  reabsorption of 25-30 of filtered NaCl and
  downstream sies are not able to compensate for
  this increased Na load.

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A. Diuretic drugs

• Blocking kidneys ability to concentrate urine
  during hydropenia, by decreasing the hypertonic
  medullary interstitium.
• Impairing kidneys ability to excrete a dilute
  urine.
• Also, increasing excretion of Ca2, Mg2 by
  abolition of transepithelial potential difference.

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urine dilute
loop diuretics
urine concentration
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A. Diuretic drugs

• (2) Vasodilatation
• Renal vasodilatation renal blood flow ?
• Dilating veins cardiac preload ?

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A. Diuretic drugs
2. Clinical uses (1) Severe edema ineffective
by thiazides (2) Acute pulmonary edema heart
failure (3) Acute renal failure combined with
dopamine (4) Hypercalcemia (5) Detoxication of
toxins or drug overdose
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A. Diuretic drugs
3. Adverse effects (1) Imbalance of water and
electrolytes acute hypovolumia
hypokalemia etc. (2) Ototoxicity hearing
damage, contraindicated to combine with
aminoglycoside antibiotics (3) Other effects GI
reactions, hyperuricemia (????), arrhythmias,
RAAS activity ?, etc.
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A. Diuretic drugs

• Other loop diuretic drugs
• Bumetanide ????similar to furosemide, but less
  adverse effects
• Torasemide ????stronger and longer actions
• Etacrynic acid ????weaker actions and more
  severe adverse effects

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A. Diuretic drugs
Thiazide diuretic drugs
???? ??? ???? ???? ???? ???? ????
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A. Diuretic drugs

• Thiazide diuretic drugs
• 1. Pharmacological effects and clinical uses
• (1) Diuretic effects
• Acting on distal convoluted tubule, inhibiting
  Na-Cl- cotransporter (symport)
• Decreasing kidneys ability to dilute urine
• Increasing the excretion of Na, Cl-, K, Mg2,
  HCO3-, but increasing the reabsorption of Ca2 in
  distal convoluted tubule

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thiazides
urine dilute
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A. Diuretic drugs

• Used in treatment of mild and moderate edema in
  cardiac and renal diseases, and hepatic diseases
  with cautions
• Used in treatment of hypercalciuria and calcium
  oxalate stones in urinary tract.
• (2) Antihypertensive effects
• blood volume ?
• spasm responsiveness of arterial smooth
  muscles ?

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A. Diuretic drugs

• (3) Diabetes insipidus (???)
• Unique ability to produce a hyperosmolar urine,
  and can substitute for the antidiuretic hormone
  in the treatment of nephrogenic diabetes
  insipidus.
• The urine volume of such individuals may drop
  from 11 L/day to 3 L/day when treated with the
  drug.

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A. Diuretic drugs
2. Adverse effects (1) Imbalance of eletrolytes
hypokalemia
hypomagnesemia hyponatremia
hypochloremia cautions dose
individualization, K supplement (2) Dysfunctio
of metabolism hyperglycemia
hyperlipidemia hyperuricemia
contraindicated in diabetes and gout patients (3)
Hypersensitivity bone marrow supression,
dermatitis, necrotizing vasculitis, interstitial
nephritis, etc.
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A. Diuretic drugs
Potassium-sparing diuretics
Spironolactone ??? Triamterene
???? Amiloride ????
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A. Diuretic drugs
Spironolactone ???
Spironolactone
Aldosterone
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A. Diuretic drugs

• Spironolactone ???
• 1. Pharmacological effects
• Blocking aldosterone receptor
• Decreasing Na reabsorption and K excretion
• Weaker, slow acting, and lasting duration

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Action of spironolactone Blocking the effects of
aldosterone
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spironolactone
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A. Diuretic drugs

• 2. Clinical uses
• Edema with increased aldosterone levles
• Combined with other diuretic drugs
• 3. Adverse effects
• (1) Hyperkalemia
• (2) Sex hormone-like effects
• (3) GI reactions
• (4) CNS reactions

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A. Diuretic drugs
Triamterene ???? Amiloride ????
triamterene
amiloride
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A. Diuretic drugs

• 1. Pharmacological effects
• Blocking renal epithelial Na channels
  decreasing Na-K exchange
• 2. Clinical uses
• Similar to spironolactone
• 3. Adverse effects
• Hyperkalemia, GI reactions, etc.

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B. Dehydrant agents
Osmotic diuretics
Mannitol ???
OH OH OH OH
OH OH
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B. Dehydrant agents
1. Pharmacological effects (1) Dehydrant
effects (2) Diuretic effects (osmotic diuretic
effects) 2. Clinical uses (1) Brain edema (2)
Glaucoma (3) Acute renal failure prevention and
early treatment
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B. Dehydrant agents

• 3. Adverse effects
• (1) Elevated extracellular osmolality pulmonary
  edema, etc.
• (2) Hyponatremia and dehydration headache,
  nausea, vomiting, etc.
• Contraindicated in anuric due to severe renal
  diseases, active cranial bleeding, heart failure

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B. Dehydrant agents

• Other dehydrant drugs
• Sorbitol ???
• Hypertonic glucose (50) ?????
• Urea ??
• Glycerin ??
• Isosorbide ????