Diuretics and Dehydrants
§1
Diuretics
• Abnormalities in fluid volume and electrolyte
composition are common and important clinical
problems. Drugs that block the transport functions of the
renal tubules are valuable clinical tools in the treatment
of these disorders. It was not until 1957 that a practical
and powerful diuretic agent (chlorothiazide) became
available for widespread use.
• Technically, the term "diuresis" signifies an increase in
urine volume, while "natriuresis" denotes an increase in
renal sodium excretion. Because natriuretic drugs
almost always also increase water excretion, they are
usually called diuretics.
• Most diuretics act upon a single anatomic
segment of the nephron. Because these
segments have distinctive transport
functions, the first section of this chapter is
devoted to a review of those features of
renal tubule physiology that are relevant to
diuretic action.
Renal Tubule Transport
Mechanisms
1. Proximal
tubule
2. thick ascending
limb of Henle’s loop
3. Distal tubule and
collecting ducts
Proximal Tubule
acetazolamide
Loop of Henle
loop diuretics
Distal Convoluted
Tubule
thiazide
Collecting Tubule
Triamterene
※Common diuretics
Common diuretics
• exert effects on specific membrane transport
proteins in renal tubular epithelial cells (loop
diuretics, thiazides, amiloride, and triamterene)
• exert osmotic effects that prevent water
reabsorption (mannitol)
• exert effects by inhibiting enzymes
(acetazolamide)
• exert effects by interfering with hormone
receptors in renal epithelial cells (spironolactone)
Ⅰ. High –ceiling diuretics
(loop diuretics)
Furosemide,
Ethacrynic acid,
Bumetanide
[Pharmacological actions]
 Site of action:
thick ascending limb of Henle’s loop
 Mechanism:
competing with Cl－ for Cl－ joint-part of
Na+ -K+ -2Cl－ cotransporter
 Effects
1. Diuresis: Na+, K+, 2Cl－, Mg2+, Ca2+ excretion↑
2.↑renal blood flow: ↓renal vescular resistance
pharmacokinetics
• 1. p.o. & intravenous administration
• 2. excretion: by organic acid secretion
route in the proximal tubule
uric acid (尿酸) ↑
gout
indomethacin( 吲哚美辛)
probenecid (丙磺舒)
Clinical uses
• 1. Acute and Severe edema
• Acute pulmonary edema
cerebral edema
Clinical uses
• 3. acute renal failure: early
stage
• 4. Hypercalcemia :
• 5. Overdose of some toxicants:
bromide , fluoride , iodide
Adverse reactions
1. Electrolyte disorders:
• hypochloremia, hypomagnesemia,
hypokalemia※
 CHF: ↑intoxication with
digitalis
 Hepatic cirrhosis: coma
2. Ototoxicity: dose-related hearing impairment:
tinnitus, hearing loss, etc.
Adverse reactions
3. hyperuricemia
• (1) hypovolemia: reabsorption of uric acid
• (2) competing with diuretic for organic acid
secretion route →secretion of uric acid↓
4. Others: GI reactions, allergic reactions
Ⅱ.Moderate efficacy diuretics
• Thiazides: ※Hydrochlorothiazide
(氢氯噻嗪), chlorothiazide (氯噻嗪)
• Indapamide (吲哒帕胺)
• chlortalidone(氯酞酮)
Pharmacological actions
 Site of action: proximal end of
distal tubule
 Mechanism: inhibit Na+ -Cl－
cotransporter
 Effects
1) Diuresis: Na+ , K+ , 2Cl － ,
Mg2+excretion↑
2) ↑Ca2+ reabsorption in distal tubules:
primary hypercalciuria
3) reduced peripheral vascular resistance
Clinical uses
1.

Chronic edema
mild to moderate cardiac edema:
first choice
 ascites(腹水)due to cirrhosis(肝硬
变)
2. hypertension
early stage: ↓ blood flow
late stage : excretion of Na+↑→ Na+-Ca2+
exchange↓ → ↓Ca2+ in cell → tension of
arterial↓
3. nephrogenic insipidus
1) ↓ PDE → intracellular cAMP↑→
water permeating the tubule↑ →
reabsorption of water↑
•
2) excretion of NaCl↑ → plasma
osmotic pressure↓ → thirst feeling↓ →
amount of drinking↓ → urine↓
4. Primary hypercalciuria
Adverse reactions
•
•
•
•
1. electrolyte disorders
2. retention of uric acid and calcium
3. hyperglycemia and hyperlipidemia
4. allergic reaction:
Ⅲ. Potassium-sparing
diuretics
• Site of action:
distal tubule and collecting duct
aldosterone antagonist:
Spironolactone (antisterone)
【 mechanism 】 : competing with ald.
for ald-R in distal tubule and collecting
duct → Na+-K+ exchange↓
【 characteristics 】
※ ineffective in adrenalectomized animal
※ slow onset ＆ long duration
Clinical uses
• 1. primary hyperaldosteronism
• 2. liver cirrhosis and nephritis syndrome
(1)inactivation of ald.↓
(2)circulation blood volume↓
Adverse reaction
• 1. hyperkalemia: renal insufficiency
• 2. endocrine abnormality:
impotence, gynecomastia,
nonaldosterone antagonists
※ triameterene(氨苯蝶啶)
※
amiloride (阿米洛利)
• Mechanism :
Block Na+ –channel → ↓ Na+ entry
→K+ secretion↓
• clinical uses :
• adverse reaction :
§2 dehydrants
•
•
•
•
Difficultly penetrate membrane
filtrated by glomerulus easily
Not be reabsorpted by renal tubules
Not be metabolized
mannitol（甘露醇）
• Pharmacological actions
• 1. dehydrant effect
• 2. diuretic effect
Cliniucal uses
• 1. Brain edema
• 2. Glaucoma
• 3. Prevent acute renal failure
Adverse reaction
• extracellular volume expansion
• contraindication: chronic heart failure