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