Diuretics – Mechanism of Action, Types, Classification, Drugs

Introduction

A diuretic is any substance that promotes diuresis, the increased production of urine.

All diuretics increase the excretion of water from bodies.

Such as vasopressin (Antidiuretic Hormone), is an agent or drug which reduces the excretion of water in urine.

Mechanism of action

First, they effectively reduce blood pressure.

Thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+) K(+)-2CI(-) co-transporter.

As a diuretic is any substance that promotes the production of urine, aquaretics that cause the excretion of free water .

This includes all the hypotonic aqueous preparations, including pure water, black and green teas, and teas prepared from herbal medications.

Types

Ceiling/loop diuretic

Also called Inhibitors of Na+-K-2CI- Cotransport. High ceiling diuretics may cause a substantial diuresis – up to 20 to 30% of the filtered load of Nacl (salt) and water.

Loop diuretics, such as furosemide, inhibit the body’s ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine.

Bumetanide It is similar to furosemide in all respects, but is 40 times more potent. It induces very rapid diuresis and is highly effective in pulmonary edema.

However, the site of action, ceiling effect, renal haemodynamic changes and duration of action are similar to furosemide.

Torasemide (Torsemide) Another high ceiling diuretic with properties similar to furosemide, but 3 times more potent. Oral absorption is more rapid and more complete.

Thiazides

(Inhibitors of Na+Cl- cotransport)

hydrochlorothiazide act on the distal convoluted tubule and inhibit the sodium chloride symporter leading to a retention of water in the urine.

Chlorthalidone It is a particularly long acting compound, used exclusively as Antihypertensive.

Metolazone In common with loop diuretics, it is able to evoke a clinically useful response even in severe renal failure and has marked additive action when combined with furosemide.

Xipamide It has more pronounced diuretic action similar to low doses of furosemide. It is used both as Antihypertensive and for treatment of edema.

Indapamide It has little diuretic action in the usual doses, probably because it is highly lipid soluble.

Pharmacokinetics– All thiazides and related drugs are well absorbed orally. There are no injectable preparations of these drugs.

Uses=

1. Edema- They act best in cardiac edema, are less effective in hepatic or renal edema. Thiazides are powerless in the presence of renal failure, but metolazone may still act.
2. Hypertension– Thiazides and related diuretics, especially chlorthalidone are one of the first line drugs
3. Diabetes insipidus– Thiazides are the only drugs effective in nephrogenic diabetes insipidus.
4. Hypercalciuria– with recurrent calcium stones in the kidney.

Carbonic anhydrase inhibitors

They inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule.

This results in several effects including bicarbonate accumulation in the urine and decreased.

acetazolamide– Acetazolamide is well absorbed orally and excreted unchanged in urine.

Potassium sparing diuretics

Aldosterone antagonists and renal epithelial Na+ channel inhibitors indirectly conserve K+ while inducing mild natriuresis, and are called potassium sparing diuretics‘.

Aldosterone antagonist- Spironolactone– It is highly bound to plasma proteins and completely metabolized in liver

Use – Spironolactone is a weak diuretic and is used only in combination with other more efficacious diuretics.

Adverse effects= The side effects are drowsiness, mental confusion, epigastric distress and loose motions.

CLASSIFICATION OF DRUGS

• High efficacy diuretics (Inhibitors of Na+- K-2Cl- cotransport) Sulfamoyl derivatives Furosemide, Bumetanide, Torasemide

• Medium efficacy diuretics (Inhibitors of Na+-Cl- cotransport)

(a) Benzothiadiazine (thiazides) Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide

(b) Thiazide like (related heterocyclics) Chlorthalidone, Metolazone, Xipamide, Indapamide, Clopamide

• Weak or adjunctive diuretics

(a) Carbonic anhydrase inhibitors Acetazolamide

(b) Potassium sparing diuretics

(i) Aldosterone antagonist: Spironolactone, Eplerenone

(ii) Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride.

(c) Osmotic diuretics

Mannitol, Isosorbide

Osmotic Diuretic

An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium. They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate.

Two examples:- mannitol and isosorbide.

Mannitol is a type of sugar alcohol used as a sweetener and medication. As a sweetener it is used in diabetic food as it is poorly absorbed by the intestines.

Isosorbide and glycerol =These are orally active osmotic diuretics which may be used to reduce intraocular or intracranial tension. Intravenous glycerol can cause haemolysis.