Why diuretics used in the treatment of hypertension:

1

 Diuretics can be classified into following criteria

2Types of diuretics According to their site of action and their mechanism of action
3Types of diuretics According to potency
4Mechanisms of loop diuretics, thiazide, spironolactone in the treatment of hypertension
5FAQ

First of all, we need to know what diuretics do and what is the role of diuretics in reducing hypertension. Diuretics are substances that increase the urine output from the body. Urine output means reducing fluid levels from body, which means reducing blood pressure. so with this knowledge, we can understand that diuretics can be used in the treatment of hypertension. Let’s know more about how diuretics are used in the treatment of hypertension. There is a scientific definition of diuretics: Diuretics: it may be defined as a drug which increases the rate of urine output, which mainly includes sodium ion excretion along with chloride ion, which reducing extracellular fluid volume by decreasing total body sodium chloride (NaCl) content.

Diuretics can be classified in following criteria:

According to their site of action and their mechanism of action :

A. Thiazide and thiazide like diuretics: It usually inhibits NaCI reabsorption from the early part of the distal convoluted tubule of the kidney by blocking the active Na+/CI- transporter. There are some examples of these diuretics: – 1. Chlorothiazide 2. Hydrochlorothiazide 3. Chlorthalidone 4. Indapamide 5. Metolazone б.Bendroflumethiazide 7. Hydroflumethiazide 8. Polythiazide 9. Trichlormethiazid

B. Loop diuretics: it inhibit a special type of transporter which is known as a Na+-K+-2Cl-transporter, which is located at the thick ascending limb of loop of Henle. There are some examples of these diuretics: – 1. Frusemide 2. Torsemide 3. Bumetanide 4. Ethacrynic acid

C. Potassium sparing diuretics: These Diuretics are special because of their mode of action. They act on the collecting tubules and sparing potassium, which prevents hypokalemia. There are some examples of these diuretics: – a.Aldosterone receptor antagonist 1.Spironolactone 2.Eplerenone b. sodium channel blockers 1.Amiloride 2.Triamterenee.

D.Sodium glucose co-transporter 2 (SGLT2) inhibitors: Inhibition of SGLT-2 in the proximal convoluted tubule which increase  glucose excretion of 30-50% of the amount filtered because glucose can’t be absorbed. As a result glucose excreted along with large volume of water. Four SGLT2 inhibitors are currently available that can be used as sodium glucose co-transporter 2 (SGLT2) inhibitors: – 1. Dapagliflozin 2. Canagliflozin 3. Empagliflozin 4. Ipragliflozin

E.Carbonic anhydrase inhibitors (they are rarely used): It inhibits carbonic anhydrase located in the tubular epithelium. 1. Acetazolamide 2. Dorzolamide 3. Methazolamide 4. Brinzolamide 5. Dichlorphenamide

According to potency:

1.High efficacy diuretics or it can be known as a high ceiling diuretic: It can cause up to 25% of filtered sodium to be excreted. a. Loop diuretics- Most effective diuretics

2.Moderate efficacy diuretics: Can cause 5-10% of filtered sodium load to be excreted. a. Thiazide diuretics b. Non-thiazide

3. Low efficacy diuretics: It Can only cause 5% of the filtered sodium excretion from the body. a.Carbonic anhydrase inhibitors b.Pottasium sparing diuretics c.Osmotic diuretics

C. According to potassium sparing capacity:

1. Potassium losing diuretics: They cause hypokalemia by renal potassium loss. a. Loop diuretics b. Thiazide diuretics c. Carbonic anhydrase inhibitors d. Osmotic diuretics

2. Potassium sparing diuretics: They do not cause hypokalemia. 1. Aldosterone receptor antagonist a. Spironolactone b. Eplerenone 2. Sodium channel blockers a. Amiloride b. Triamterene

All these diuretics are different from each other in terms of their mechanism of action. So let me explain shortly how this diuretic helps reduce hypertension.

Mechanisms of loop diuretics in the treatment of hypertension:

Frusemide inhibits the Na+-K+-2CI-transporter (NKCC2) at the thick ascending limb of loop of Henle which reduces the reabsorption of Na+, K+, CI- ions and along with this Loss of ions, there is also a loss of  iso-osmotic volume of water, which leads to dieresis.By inhibiting the Na+-K+-2CI -transporter, frusemide also diminishes the lumen-positive potential that comes from K* recycling, by reducing this potential, loop diuretics cause an increase in Mg and Ca ion excretion.Loop diuretics also stimulate the synthesis of renal prostaglandins, which participate in the renal actions of these diuretics to potentiate their effectiveness.Furosemide increases renal blood flow by prostaglandin actions on the kidney vasculature, which > increase Glomarular flitration rate.> increase Urine formation and increase diuresis.

Mechanisms of thiazide in the treatment of hypertension:

  • First, Thiazides inhibit NaCI reabsorption from the luminal side of epithelial cells in the distal collecting tubule by blocking the Na-CI transporter, which causes the loss of Na+ and CI- ions along with the iso-osmotic volume of water, which eventually leads to diuresis, > causes a decrease in blood volume in the body> and decreases blood pressure.In cases of long standing therapy, thiazide decreases the responsiveness of blood vessels to circulatory catecholamines, which cause vasodilation. This decreases peripheral resistance and decreases blood pressure.
  • Mechanism of action/diuretic action of spironolactone in the treatment of hypertension:

    Normally, aldosterone binds with cytoplasmic receptors in the collecting tubules (CT), and this leads toNa+ reabsorption, K+ ion and H+ ion excretion, but spironolactone reverses the action of aldosterone at the receptor level. Spironolactone and eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. This leads to Na+ excretion and, K+ and H+ retention.Spironolactone is weak diuretic because most of the filtered Na+ is reabsorbed before reaching the collecting tubule. Sodium bicarbonate reabsorption by the proximal convulated tubule is initiated by the action of a Na+/H+ exchanger (NHE3), which is a counter-transporter located in the luminal membrane of the proximal tubule epithelial cell.Mechanism of action of carbonic anhydrase inhibitors  in reducing hypertension: Carbonic anhydrase inhibitors inhibit carbonic anhydrase in the luminal membrane, and so there is less breakdown of carbonic acid into water and carbon dioxide, so there is an accumulation of H+ ions in the lumen, which impairs the transport action of the Na+/H+ counter-transporter, which causes decreased reabsorption of Na+  and bicarbonate ion and leads to dieresis.

    Question for co-relate: 50 years old businessman presents to emergency department with exertional dyspnoea, cough with frothy sputum. On examination he is oedematous, bilateral basal crepitations over lungs.

    1.What is your diagnosis?
    2.What other clinical findings will suggest 3 aetiology?
    3.Write down the initial treatment of this case.

    Answer
    1.Diagnosis: Congestive cardiac failure


    2.Other clinical findings that will suggest 3 aetiology:
    -Central chest pain that radiates to neck, jaw and arms – Ischaemic heart disease.
    -Heaving apex beat – Systemic hypertension.
    -Murmur – Valvular heart disease.

    3. Initial treatment:
    Propped up position.
    Oz inhalation.
    Intravenous Inj. Frusemide.
    Nitroglycerine.
    ACE inhibitor or ARB.
    Treatment of the cause.

    Q. A patient presented with generalized oedema, tender hepatomegaly & elevated JVP.
    What is your probable diagnosis?

    Answer
    Probable diagnosis: Right heart failure.

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