Classification of diuretics

According to site of action and mechanism of action
1. Acting at proximal convoluted tubules
i. Osmotic diuretics
These drugs are ª mannitole and urea
ii. Carbonic anhydrase inhibitors
These drugs are ª Acetazolamide, methazolamide
iii. Acidifying drugs
These agents are ª ammonium chloride
iv. Others
like tea, coffee, theophylline etc.
2.Acting at loop of Henle
i. Loop diuretics
Furosemide, torsemide, Ethacrynic acid
ii. Mercurial agents
Mercaptomerin
3.Acting at distal convoluted tubule
i. Thiazides diuretics
ª Chlorothiazide, chlorothalidone, Hydrochlorothiazide
ii. Sulfonamides
ª Indapemide, Xipemide
4. Acting at collecting duct system
i. K- sparing diuretics
. Aldosterone antagonist ª Spironolactone
. Direct acting ª Triamterene, amiloride
ii. ADH antagonists
ª Lithium salts, demeclocycline

OTHERS
ª Na/K acetate
ªNa/K bicarbonate
ªNa/K Acetate
ª Albumin
ª Dextrose
V. Diuretics
1. General Considerations
A. These drugs promote a loss of Na+ and water from the body--increasing urine flow
B. Used for clinical management of many disorders
-Oedema, could be due to weak heart
-Hypertension
-Also used to reduce toxicity of substances--overdose
C. Drugs will alter kidney at
1) Proximal Loop
2) Loop of Henle
3) Distal Tubule
2 ) Drugs
A. Carbonic anhydrase inhibitors (first diuretics)- Acetazolamide
1. Inhibits enzyme carbonic anhydrase at proximal tubules
CA catalyzes in both directions
CA¯
HCO₃ ^- + H⁺ ---------------® H₂CO₃ ----------------®H₂O + CO₂
2. Inhibits HCO₃ ^- (ie CO₂ and H₂O) reabsorption
3. Also inhibits Cl- reabsorption, this prevents Na+ reabsorption, (always together)
Thus decreased Na, Cl and bicarbonate reabsorption--less water reabsorbed
[Also low reabsorption of bicarbonate, therefore lose bicarb. in blood]
Weak diuretics- but used for treating glaucoma because aqueous humor has a lot of bicarbonate - decrease bicarbonate (eliminate in urine)----decrease pressure.
B. Loop agents
Inhibit NaCl reabsorption in thick ascending limb of loop of Henle
1. Furosemide (Lasix), Ethacrynic Acid [(like the Thiazides, they are sulfonamide derivatives--antibacterial agent produced diuresis)]
Inhibit ATPase pump- for Na⁺, K⁺, 2Cl^-,

• Normally pump out Na⁺, K⁺ and 2 Cl^- - but K⁺comes back in - thus get positive lumen which drives Ca++ out, Furosemide blocks this - thus increased Ca⁺⁺ excretion -- because no reabsorption (due to reduced positive potential across tubule therefore Ca++ is not driven out)

-Lasix - give to horses-give to bleeders-reduces edema formation -- race horses have developed very large hearts that produce high pressures -- the lungs can not take the high pressures and thus they bleed into the lungs (nose) -- Lasix reduces the bleeding
2. Pharmacokinetics- rapidly absorbed after oral administration
3. Therapeutic uses - most effective oral diuretics
used for treating acute edema (Pulmonary) and edema after congestive heart failure -- also used to treat hypercalcemia
4. Untoward Effects – lose K+ - later
C. Thiazides:
Benzothiadiazine, chlorothiazide, hydrochlorothiazide
Inhibit NaCl reabsorption in early segments of distal tubule- mechanism is unknown
There is a slight stimulation of Ca⁺⁺ reabsorption
May stimulate active reabsorption -- controlled by parathyroid hormone
Drug is administered orally
Therapeutic uses: chronic edema, hypertension, kidney stones produced by calcium
Untoward effects
Lose K+
Secondary hyperaldosteronism due to fluid loss---turns on renin, angiotensin, aldosterone -- which in turn causes secretion of K+  - aldosterone leads to increased Na⁺ reabsorption and K⁺ secretion
D. Aldosterone antagonists- potassium sparing diuretics.
Spironolactone, Triamterene
Competitive antagonists of aldosterone
---Therefore interferes with aldosterone mediated Na-K exchange in distal tubule
Increase Na⁺ loss and decreases K⁺ loss
Used in combination with other diuretics to treat edema and hypertension
Administered orally