Download A. Diuretic drugs

基础医学各论II
Diuretics and dehydrant drugs
The Kidney:
•Excretion water,
ions, and toxic
metabolites
A
B
Renal structures for urine
generation (A) and
osmotic gradient (B)
10％Na+
65-70％Na+
Na+, Cl－
reabsorption in
the kidney
25％Na+
Reabsorption sites
of Na+, K+, Cl-, and
other ions
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.
A. Diuretic drugs
Classification of diuretic drugs
Loop diureticshigh efficacy
furosemide 呋塞米
thick ascending limb of Henle loop
inhibiting Na+-K+-2Cl- symport
Thiazide diuretics
moderate efficacy
hydrochlorothiazide 氢氯噻嗪
distal convoluted tubule
inhibiting Na+-Cl- symport
K+-sparing diuretics
low efficacy
spironolactone 螺内酯
late distal tubule and collecting duct
inhibiting renal epithelial Na+
channels
A. Diuretic drugs
Loop diuretics
Furosemide
呋塞米
Bumetanide
布美他尼
Etacrynic acid
依他尼酸
A. Diuretic drugs
Furosemide 速尿
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.
A. Diuretic drugs
 Blocking kidney’s ability to concentrate urine during
hydropenia, by decreasing the hypertonic medullary
interstitium.
 Impairing kidney’s ability to excrete a dilute urine.
 Also, increasing excretion of Ca2+, Mg2+ by abolition of
transepithelial potential difference.
urine dilute
loop diuretics
urine concentration
A. Diuretic drugs
(2) Vasodilatation
 Renal vasodilatation: renal blood flow 
 Dilating veins: cardiac preload 
A. Diuretic drugs
2. Clinical uses
(1)
(2)
(3)
(4)
(5)
Severe edema: ineffective by thiazides
Acute pulmonary edema: heart failure
Acute renal failure: combined with dopamine
Hypercalcemia
Detoxication of toxins or drug overdose
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 (尿酸增高),
arrhythmias, RAAS activity , etc.
A. Diuretic drugs
Other loop diuretic drugs
 Bumetanide 布美他尼：similar to furosemide, but less
adverse effects
 Torasemide 托拉塞米：stronger and longer actions
 Etacrynic acid 依他尼酸：weaker actions and more severe
adverse effects
A. Diuretic drugs
Thiazide diuretic drugs
苄氟噻嗪
氯噻嗪
氢氯噻嗪
氢氟噻嗪
甲氯噻嗪
泊利噻嗪
三氯噻嗪
A. Diuretic drugs
Thiazide diuretic drugs
1. Pharmacological effects and clinical uses
(1) Diuretic effects
• Acting on distal convoluted tubule, inhibiting Na+-Clcotransporter (symport)
• Decreasing kidney’s ability to dilute urine
• Increasing the excretion of Na+, Cl-, K+, Mg2+, HCO3-, but
increasing the reabsorption of Ca2+ in distal convoluted tubule
thiazides
urine
dilute
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 
A. Diuretic drugs
(3) Diabetes insipidus (尿崩症）
 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.
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.
A. Diuretic drugs
Potassium-sparing diuretics
Spironolactone 螺内酯
Triamterene
氨苯喋啶
Amiloride
阿米洛利
A. Diuretic drugs
Spironolactone
Spironolactone
螺内酯
Aldosterone
A. Diuretic drugs
Spironolactone 螺内酯
1. Pharmacological effects
• Blocking aldosterone receptor
• Decreasing Na+ reabsorption and K+ excretion
• Weaker, slow acting, and lasting duration
Action of
spironolactone:
Blocking the effects of
aldosterone
spironolactone
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
A. Diuretic drugs
Triamterene
Amiloride
triamterene
氨苯喋啶
阿米洛利
amiloride
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.
B. Dehydrant agents
Osmotic diuretics
Mannitol
甘露醇
OH
OH
OH OH
OH
OH
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
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
B. Dehydrant agents
Other dehydrant drugs





Sorbitol 山梨醇
Hypertonic glucose (50%) 高渗葡萄糖
Urea 尿素
Glycerin 甘油
Isosorbide 异山梨醇