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이뇨제:학습목표

신장의해부,생리및체액조절기전을설명한다.

이뇨제를nephron의주요작용부위에따라분류한다.

이뇨제를작용기전에따라분류하고각각의작용부위를기술한다.

각이뇨제의약리효과,약동학적특징,유해작용,치료용도를설명한다.

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Collecting tubule

2-5% of NaCl reabsorption

principal cells ; Na+, K+, H2Otransport; Na+ reabsoption,K+ secretion

; aldosterone

intercalated cell ; proton secretion

antidiuretic hormone (ADH) :reabsorption of water

Potassium -sparing

diuretics

Potassium -sparing

diureticsPharmacodynamics

reduce Na+ absorption in thecollecting tubules and ducts

aldosterone antagonists

direct interfere with Na+ entrythrough the sodium-selectiveion channels

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Clinical indicationhyperaldosteroidosm

; primary hypersecretion, secondary aldosteronism

conjunction with a thiazide or loop diuretics

Toxicityhyperkalemia, hyperchloremic metabolic acidosis

gynecomastia, acute renal failure, kidney stone

Distal convoluted tubule

Only 10 % filtered NaClreabsorbed

impermeable to water

Na/Cl cotransporter

Ca++ actively reabsorbed;parathyroid hormone

thiazide diuretics

Thiazide

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Thiazide

Chemistry & pharmacokinetics

can be administered orally

Mechanism of action

inhibit NaCl reabsorption from the luminal side of epithelial cell in thedistal convoluted tubule by blocking the Na+/Cl- transporter

enhance Ca2+ reabsorption

Loss of K+

Clinical indication

hypertension

heart failure

nephrolithiasis due to idiopathic

hypercalciuria

nephrogenic diabetes insipidus

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ToxicityHypokalemicmetabolicalkaloisisHyperuricemiaImpaired carbohydratetoleranceHyperlipidemia,HyponatremiaAllergic reaction

Loop of Henledescending loop of Henle

: water extraction by osmoticforces created in thehypertonic medullaryinterstitium

Thick ascending limb

; actively reabsorbed NaCl (35%)

; impermeable to water : diluting

segmentNa+/K+/2Cl-cotransporter

reabsorption of cations;Mg2+, Ca2+

loop diuretics

Loop diuretics

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Loop diureticsadministered orally or parenterally

rapid onset

inhibit the luminal NA+/K+/Cl-transporter in the thick ascendinglimb of Henle’s Loop

induce renal prostaglandinsynthesis

Loop diuretics

Clinical indicationdrug of choice for acute pulmonaryedema

acute hypercalcemia

hyperkalemia, acute renal failure, anionoverdose

Toxicityhypokalemic metabolic alkalosis

ototoxicity

hyperuricemia

hypomagnesemia

allergic reactions

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Proximal tubule

sodium bicarbonate (85%), sodiumchloride (40%), glucose, amino acidand other organic solute arereabsorbed ; water (60%)

osmotic agent, carbonic anhydraseinhibitor

organic acid secretion ; S2 segment

; uric acid , NSAIDs, diuretics,

antibiotics

Carbonic anhydrase inhibitoracetazolamide

well absorbed after oral administration

renal insufficiency

depress bicarbonate reabsorption in the proximal tubule

hyperchloremic metabolic acidosis, decrease diureticefficacy following several days of therapy

Clinical indication

• glaucoma

•

urinary alkalinization• metabolic alkalosis

• acute mountain sickness

Toxicity

• hyperchloremic metabolic acidosis

• renal stone

• renal potassium wasting

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Agent that alter water excretion

Osmotic diureticsproximal tubule, descending limb of loop of Henle ; majoraction

oppose the action of ADH in the collecting tubule

mannitol ; nonreabsorbable solute

Clinical indication

• to increase urine volume

• reduction of intracranial and intraocular pressure

ADH antagonists

inhibit effects of ADH in collecting tubule

lithium, demeclocycline ; reduce cAMP

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