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DIURETICS

This document discusses different classes of diuretic drugs used to treat conditions related to fluid retention and electrolyte balance. It describes loop diuretics like furosemide that work by inhibiting sodium reabsorption in the loop of Henle. Thiazide diuretics like hydrochlorothiazide are also discussed, which act on the distal tubule. Potassium-sparing diuretics like spironolactone antagonize aldosterone, while carbonic anhydrase inhibitors and osmotic diuretics have other mechanisms of action. Clinical uses include treating edema, hypertension, heart failure and other conditions. Adverse effects can include electrolyte abnormalities like hypokalemia if not properly managed.

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HUZAIFA YAMAAN
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25 views

DIURETICS

This document discusses different classes of diuretic drugs used to treat conditions related to fluid retention and electrolyte balance. It describes loop diuretics like furosemide that work by inhibiting sodium reabsorption in the loop of Henle. Thiazide diuretics like hydrochlorothiazide are also discussed, which act on the distal tubule. Potassium-sparing diuretics like spironolactone antagonize aldosterone, while carbonic anhydrase inhibitors and osmotic diuretics have other mechanisms of action. Clinical uses include treating edema, hypertension, heart failure and other conditions. Adverse effects can include electrolyte abnormalities like hypokalemia if not properly managed.

Uploaded by

HUZAIFA YAMAAN
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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DIURETICS

Kidney

- the excretory organ

• Excretion of waste products,

• Regulation of fluid volume and electrolyte


CLASSIFICATION
1. High efficacy diuretics-

 Furosemide, bumetanide

2. Moderate efficacy diuretics

 Thiazides - Chlorothiazide, hydrochlorothiazide,

Chlorthalidone, indapamide,
CLASSIFICATION

3. Low efficacy diuretics

 Potassium sparing diuretics- Triamterene,

amiloride, spironolactone

 Carbonic anhydrase inhibitors- Acetazolamide,

 Osmotic diuretics Mannitol, urea, glycerol


HIGH CEILING OR LOOP
DIURETICS
Mechanism of Action

• Frusemide acts by inhibiting NaCl– reabsorption in


the thick ascending limb of the Henle’s loop.

• It blocks the Na+ K+ 2Cl– symporter in the thick


ascending limb of the Henle's loop because of which
it is called is a loop diuretic.
• It greatly increases the excretion of Na+ and Cl– in
the urine.

• As a large amount of NaCl– is absorbed in this


segment, loop diuretics are highly efficacious.
Other actions

• Loop diuretics also enhance the excretion of K+,


Ca++ and Mg++

• ROA- IV, Oral

• Loop diuretics reach the ascending limb of Henle's


loop as they are secreted by the organic acid transport
system.
Adverse Effects of Loop Diuretics
1. Hypokalaemia and metabolic alkalosis (due to loss of
H+)
2. Hyponatraemia, dehydration hypovolaemia and
hypotension
3. Hyperuricaemia may precipitate acute attacks of gout.
4. Hypocalcaemia and hypomagnesaemia - After
prolonged use this may result in osteoporosis.
5. Ototoxicity
Uses

1. Edema- Loop diuretics are highly effective for the

relief of edema of all origins like cardiac, hepatic or

renal edema. In chronic congestive cardiac failure

loop diuretics reduce venous and pulmonary

congestion.

2. Acute pulmonary edema


Uses
3. Cerebral edema- as an alternative to osmotic
diuretics.
4. Forced diuresis- In poisoning due to drugs like
barbiturates and salicylates.
5. Hypertension with renal impairment may be treated
with loop diuretics.
6. Hypercalcaemia and hyperkalaemia Loop diuretics
enhance excretion of Ca++ and K+.
THIAZIDES AND THIAZIDE-
LIKE DIURETICS
Actions and Mechanism of Action
• Thiazides act on the early distal tubule.

• Thiazides have a moderate efficacy because 90% of


the filtered sodium is already reabsorbed before
reaching the distal tubule.

• This group of drugs block Na+/Cl– cotransport


system in the early distal tubule
Adverse Effects
• Hypokalaemia, metabolic alkalosis, hyperuricaemia,
hypovolaemia, hypotension, hyponatraemia,
hypomagnesaemia, hypercalcaemia similar to that
seen with loop diuretics.
• Hyperglycaemia induced by thiazides may precipitate
diabetes mellitus probably by inhibition of insulin
secretion.
Uses
1. Hypertension: Thiazides are the first line drugs

2. Congestive heart failure: Thiazides are useful in the


management of edema due to mild to moderate
CHF.

3. Edema: Thiazides may be tried in hepatic (cirrhosis)


or renal edema.
4. Renal stones: Hypercalciuria with renal stones can be
treated with thiazides which reduce calcium
excretion.

5. Diabetes insipidus: Thiazides reduce plasma volume


and GFR - a paradoxical effect - and benefit such
patients
POTASSIUM SPARING DIURETICS
• Aldosterone: enhances the Na+ reabsorption through
Na+ channels in the collecting tubule and enhances
K+ secretion.

• It binds aldosterone receptors on distal tubule and


collecting duct and competitively inhibits the action
of aldosterone.
POTASSIUM SPARING
DIURETICS
• Spironolactone is an aldosterone antagonist

• As major amount of Na+ is already reabsorbed in the


proximal parts, spironolactone has low efficacy.

• Spironolactone also reduces K+ loss due to other


diuretics.

• Adverse effects- gynaecomastia, hyperkalaemia


• Amiloride and triamterene: directly acting agents
which enhance Na+ excretion and reduce K+ loss

• act on ion channels in the distal tubule and collecting


duct.

• They block the Na+ transport through ion-channels in


the luminal membrane. Since K+ secretion is
dependent on Na+ entry, these drugs reduce K+
excretion.
Uses of K+ Sparing Diuretics
1. With thiazides and loop diuretics: prevent potassium
loss.

2. Edema: In cirrhosis and renal edema where aldosterone


levels may be high.

3. Hypertension: Along with thiazides to avoid


hypokalaemia and for additive effect.

4. Primary or secondary aldosteronism


CARBONIC ANHYDRASE
INHIBITORS
• Carbonic anhydrase is an enzyme that catalyses the
formation of carbonic acid which spontaneously ionises
to H+ and HCO3 – .

• This HCO3 – combines with Na+ and is reabsorbed.

• Carbonic anhydrase inhibitors block sodium


bicarbonate reabsorption and cause HCO3 – diuresis.
• Other Actions

1. Eye: The ciliary body of the eye secretes bicarbonate


into the aqueous humor.

 Carbonic anhydrase inhibition results in decreased


formation of aqueous humor and thereby reduces
intraocular pressure.

2. Brain: Bicarbonate is secreted into CSF and carbonic


anhydrase inhibition reduces the formation of CSF.
Uses
1. Glaucoma– Intraocular pressure is decreased by
acetazolamide

2. Alkalinization of urine–as required in overdosage of


acidic drugs.

3. Metabolic alkalosis–acetazolamide enhances HCO3


– excretion.
4. Mountain sickness–In mountain climbers who
rapidly ascend great heights, severe pulmonary
edema or cerebral edema may occur. Acetazolamide
may relieve symptoms by reducing the formation
and pH of CSF-it can also be used for prophylaxis.

5. Epilepsy–acetazolamide is used as an adjuvant as it


increases the seizure threshold.
OSMOTIC DIURETICS
• Mannitol is a pharmacologically inert substance.

• When given IV (orally not absorbed), mannitol gets


filtered by the glomerulus but not reabsorbed.

• It causes water to be retained in the proximal tubule


and descending limb of Henle’s loop by osmotic
effect resulting in water diuresis.
USES
1. To maintain urine volume and prevent oliguria in
conditions like massive haemolysis and shock.

2. To reduce intracranial and intraocular pressure–


following head injury and glaucoma respectively

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