DIURETICS

• Drugs which cause a net loss of sodium and water in urine

Diuretics

Classification

1. High efficacy diuretics (Inhibitors of Na+-K+- 2Cl- cotransport)

e.g. Furosemide , bumetanide , ethacrynic acid

2. Medium efficacy diuretics ( Inhibitors of Na+- Cl- symport) e.g. Chlorothiazide, benzthiazide , indapamide, chlorthalidone

Classification (contd..)

3. Weak or adjunctive diuretics

a) Carbonic anhydrase inhibitors :Acetazolamide

b) Potassium sparing diuretics :

Spironolactone, triamterene , amiloride

c) Osmotic diuretics : Mannitol, glycerol

HIGH-EFFICACY (LOOP) DIURETICS

Site of action – thick ascending limb of

Loop of Henle

•Inhibit the luminal Na+-K+-2Cl-

transporter - reduce reabsorption of

NaCl •Prevent reabsorption of Ca2+ and Mg2+

Therapeutic uses of loop diureticsAcute pulmonary edema – i.v. furosemide

Renal edemaHypertension associated with renal failure

& congestive heart failure

Hypercalcemia & renal calcium stones

Hyperkalemia

Forced diuresis – in cases of poisoning

• Medium efficacy diuretics

• Site of action – distal convoluted tubule

Block Na+/ Cl- transporter – inhibit NaCl reabsorption

Increase Ca2+ reabsorption

THIAZIDE DIURETICS

Uses

• Mild hypertension

• Edema associated with CHF/ kidney

disease

• Hypercalciuria /osteoporosis

Hypokalemia Hyponatremia Hyperuricemia - attacks of gout Hyperglycemia Hyperlipidemia Hypocalcemia – loop diuretics; hypercalcemia – thiazides Ototoxicity – esp. ethacrynic acid GIT disturbances Allergic reactions

Adverse effects of high ceiling &

thiazide diuretics

III. Carbonic anhydrase inhibitors Acetazolamide, dorzolamide Site of action – Proximal convoluted tubule Inhibits carbonic anhydrase activity -

decreases HCO3- reabsorption - alkaline

diuresis

Therapeutic Uses

• Glaucoma: acetazolamide, dorzolamide

• Urinary alkalinization : UTI ; to promote

excretion of certain acidic drugs

• Metabolic alkalosis

• Acute mountain sickness

Adverse effects

• Acidosis

• Renal stones

• Hypokalemia

• Drowsiness , fatigue

• Hypersensitivity reactions

POTASSIUM SPARING DIURETICS• Site of action - Late distal tubule & collecting duct

Spironolactone – aldosterone antagonist

Competitively inhibit the binding of

aldosterone to mineralocorticoid receptor

inhibits formation of aldosterone-induced

proteins (AIPs) – prevent sodium

reabsorption and potassium excretion

Therapeutic uses: Hyperaldosteronism (cardiac failure, liver and

kidney disease, Conn syndrome)

Hypertension (with thiazide /loop diuretics)

Adverse effects: Hyperkalemia Drowsiness, confusion Abdominal upset Impotence Menstrual irregularities

OSMOTIC DIURETICS

• Mannitol Freely filtered at the glomerulus Not reabsorbed at the renal tubulesRelatively inert pharmacologicallyNon - metabolizable Increases plasma osmolarity

• Decrease sodium reabsorption• Dilute tubular fluid and increase water

excretion

USES:

1.Head injury or stroke

2.Glaucoma

3. In cases of poisoning

3.To maintain g.f.r. and urine flow in patients with impaired renal function

A/E: Headache, nausea, vomiting

Excessive plasma volume expansion –

pulmonary edema

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