• Approximately 16 to 20 percent of the blood plasma entering the kidneys is

filtered from the glomerular capillaries into the Bowman's capsule

• kidney regulates the ionic composition and volume of urine by the active
reabsorption or secretion of ions and/or the passive reabsorption of water at
five functional zones along the nephron namely, the PCT, the descending
loop of Henle, the ascending loop of Henle, the DCT, and the CT and
duct
Homeostatic Functions of Urinary System

1. Regulate blood volume and blood pressure:

• by adjusting volume of water lost in urine
• releasing erythropoietin and renin
2. Regulate plasma ion concentrations:
• sodium, potassium, and chloride ions (by controlling quantities lost in urine)
• calcium ion levels (through synthesis of calcitriol)
3. Help stabilize blood pH:
• by controlling loss of hydrogen ions and bicarbonate ions in urine
Homeostatic Functions of Urinary System

4. Conserve valuable nutrients:

• by preventing excretion while excreting organic waste products

5. Assist liver to detoxify poisons

• “Drugs that promote a net loss of water
and sodium ions from the body, resulting
in an increase in urine formation”

• Excludes water, ethanol and digitalis

Mode of action of Diuretics
A. Increasing GFR, or
B. Diminishing reabsorption of water in the tubules by acting-
i. On specific membrane transport system,
ii. On enzymes,
iii. By osmotic action, and
iv. By acting as antagonists to hormones
Classification

• High efficacy:
• High ceiling or loop diuretics
• Moderate efficacy:
• Thiazide and related diuretics
• Low efficacy:
• Potassium sparing diuretics
• Osmotic diuretics
• Miscellaneous:
• CA inhibitors, Xanthine diuretics, Mercurial Diuretics, Acidifying salts.
High ceiling/loop diuretics

• Inhibitors of Na+-K+-2Cl- co-transport

• Most efficacious

• Frusemide, Butenamide, piretanide, torsemide, ethacrynic acid,

ticrynafen, indacrynic acid
Loop Diuretics
Mechanism of Action
Kinetics
Furosemide has p.o. bioavailability 65% and t1/2 30–60 min. It
acts on the ascending limb of Henley's loop by increasing
urine excretion of Na+, Cl, Mg2+ and Ca2+. Its diuretic effect is
achieved in 20–30 min after p.o. administration and lasts 4–6 h.
Its effect after i.v. administration begins in 3–5 min and lasts 2
h. In low doses (5 to 10 mg p.o.) furosemide has
antihypertensive effect. It does not disrupt GF.
Therapeutic uses
• Acute pulmonary oedema
• Refractory oedema associated with CCF and renal disease
• Acute renal failure
• Hypercalcaemia
• Hyperkalaemia
• Poisoning with barbiturate (forced diuresis)
• In raised intracranial pressure
Not recommended for antihypertensive therapy
Furosemide – ARs:

Hypokaliemia, skin rashes, hyperglycemia, increased plasma levels of

uric acid. In fast i.v. administration – transient
hearing disturbances with temporary deafness and orthostatic
collapse. Ototoxic risk is increased in co-medication with
aminoglycosides, cephalosporines, polymyxins, sulfonamides or
quinolones.
Drug interactions
may occur when loop diuretics are coadministered
with (1) aminoglycosides (synergism of ototoxicity caused
by both drugs),
(2) anticoagulants (increased anticoagulant activity),
(3) cardiac glycosides and antiarrhythmic drugs that prolong
repolarization (increased arrhythmias),
(4) lithium (increased plasma levels of Li+),
(5) propranolol (increased plasma levels of propranolol),
(6) sulfonylureas (hyperglycemia),
(7) cisplatin (increased risk of diuretic-induced ototoxicity),
(8) NSAIDs (blunted diuretic response and salicylate toxicity when
given with high doses of salicylates),
(10) thiazide diuretics (synergism of diuretic activity of both drugs
leading to profound diuresis), and
(11) amphotericin B (increased potential for nephrotoxicity and
toxicity and intensification of electrolyte imbalance)