PHARMACOLOGY PRACTICAL

COURSE II
lec.11
Dr - KARRAR ALI ALARDAWEE
 Diuretics
Classification :
Loop diuretics (high efficacy) 10-15% of filtered
sodium is excreted
Thiazide (medium efficacy) 5-10% of filtered
sodium is excreted
Potassium-sparing (low efficacy) <5% of filtered
sodium is excreted
Non-classified include carbonic anhydrase
inhibitors and osmotic diuretics
Loop diuretics

These drugs are effective even when GFR is

<10mL/minute.

Examples: furosemide (Lasix)®, bumetanide (Burinex)®,

torsemide and ethacrynic acid.

The efficacy of these drugs is the same but the potency is

different. Bumetanide> furosemide

Torsemide acts as hypotensive drug at sub-diuretic dose

MOA:
- Inhibit Na+/K+/2Cl– transporter in thick ascending limb of loop of
Henle. Cause powerful diuresis and increased Ca2+ excretion.
Clinical Applications: Heart failure, pulmonary edema, severe
hypertension; other forms of edema
Pharmacokinetic: Oral, parenteral
Duration: 2–4 h (relatively short-acting)
Toxicities, Interactions: Metabolic hypokalemic alkalosis; ototoxicity;
hypovolemia; efficacy is reduced by nonsteroidal anti-inflammatory
drugs. Sulfonamide allergy (rare).
Thiazide diuretics

EX-- Hydrochlorothiazide, many other thiazides

MOA: Inhibit Na+/Cl– transporter in distal convoluted

tubule. Cause moderate diuresis with Na+,Cl–, K+ and
Mg++ excretion and reduced excretion of calcium

Clinical Uses: Hypertension, mild heart failure (Chronic

therapy of edematous conditions, although loop diuretics
are usually preferred), hypercalciuria with stones;
nephrogenic diabetes insipidus
Pharmacokinetic: Oral
Duration: 8–12 h (considerably longer than most loop
diuretics)
SE: Metabolic hypokalemic alkalosis; early hyponatremia;
increased serum glucose, lipids, uric acid; efficacy is
reduced by nonsteroidal anti-inflammatory drugs.
Sulfonamide allergy (rare). Volume depletion (this can cause
orthostatic hypotension, or light-headedness).
Chlorthalidone: Not a thiazide, but effects are
indistinguishable from those of thiazides
K+-sparing diuretics
1. Spironolactone, eplerenone

MOA: Steroid inhibitors of cytoplasmic aldosterone

receptor in cortical collecting ducts; reduce K+ excretion

Clinical Uses: - Excessive K+ loss when using other

diuretics; - aldosteronism

- spironolactone and eplerenone have been shown to

have significant long-term benefits in HF condition
Pharmacokinetic: Oral

Duration: 24–36, 48 h

SE: Hyperkalemia, gastric upset; gynecomastia

(spironolactone only)

2. Amiloride

Clinical Uses: Excessive K+ loss when using other diuretics;

usually in combination with thiazides

Duration: 10–12 h

SE: Hyperkalemia, leg cramps

Osmotic diuretics
 Mannitol

 MOA:

 - Osmotically retains water in tubule by reducing reabsorption in proximal

tubule, descending limb of Henle's loop, and collecting ducts;

 - in the periphery, mannitol extracts water from cells

 Clinical Uses: Solute overload in rhabdomyolysis, hemolysis; brain edema

with coma; acute glaucoma

 Pharmacokinetics: Intravenous; short duration

 SE: Hyponatremia followed by hypernatremia; headache, nausea, vomiting

Carbonic anhydrase inhibitors:
Acetazolamide

Mechanism of Action: Inhibits carbonic anhydrase.

- In glaucoma, secretion of aqueous humor is reduced,

Clinical Applications: Glaucoma, mountain sickness;

edema with alkalosis

Pharmacokinetics: Oral, parenteral

Diuresis is self-limiting, but effects in glaucoma and mountain

sickness persist
Duration: 12 h

Toxicities, Interactions: Metabolic acidosis; sedation,

paresthesias. Hyperammonemia in cirrhosis, Cross-
allergenicity between these and all other sulfonamide
derivatives (uncommon), calcium salts and formation of
renal stones

Dorzolamide, brinzolamide: Topical carbonic anhydrase

inhibitors for glaucoma only