Topic - Diuretics

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Sho wrav Roy – BPH 0 67 074 04
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Content
 Introduction
 Definition of Diuretics
 Classification of Diuretics
 Loop Diuretics
 Thiazides Diuretics
 Carbonic anhydrase inhibitor
 Potassium sparing diuretics
 Osmotic diuretics
 Conclusion
 Introduction
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure).
Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke &
myocardial infraction.
Examples –
Diuretics & ACE inhibitors,
Calcium Channel blockers & vasodilators,
Central sympatholytic,
β adrenergic blockers & α adrenergic blockers.
Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the
treatment of these disorders. Technically, a ‘diuretics’ is an agent that increase in renal sodium excretion
& an “aquaretic” increases excretion of solute free water.
 Definition & classification of Diuretics
 
Definition –
Diuretic is any substance that promotes, the increased production of urine. There are drugs which
cause a net loss of & water in urine.
Classification –
Diuretics are classified as –
 High ceiling/ Loop diuretics
 Thiazides diuretics
 Carbonic anhydrase inhibitors
 Potassium sparing diuretics
 Osmotic diuretics
 Low Ceiling Diuretics
 High Ceiling/ Loop Diuretics
High Ceiling diuretics may cause a substantial diuresis – up to 20% of the filtered load of NaCl
(salt) & water. This is large in comparison to normal renal sodium reabsorption which leaves
only about 0.4% of filtered sodium in the urine. Loop diuretics have this ability, & are therefore
often synonymous with high ceiling diuretics. 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, whereas water normally follows sodium back into the extra
cellular fluid.
Example of High ceiling/ Loop diuretics –
Furosemide
Torsemide
Bumetanide
Ethacrynic acid
High Ceiling/ Loop Diuretics (Cont.)

Furosemide Torsemide

Ethacrynic acid
Bumetanide
High Ceiling/ Loop Diuretics (Cont.)
Furosemide –
Mechanism of Action –
Furosemide acts by inhibiting the luminal Na – K – 2Cl cotransporter in the thick ascending limb
of the loop of the loop of Henle, by binding to the chloride transport channel, thus causes
sodium, potassium & chloride loss in urine.
Uses in Heart disease –
Furosemide is used to reduce extra fluid in the body caused by condition such as heart failure,
liver disease.
Side effects –
o Increased Urination
o Thirst
o Itching
o Dizziness
o Weakness
High Ceiling/ Loop Diuretics (Cont.)
Indication –
It is indicated in adult & pediatric patients for the treatment of edema associated disease.
Drug – Drug interaction –
Drug interaction of furosemide include –
o Aminoglycoside
o Ethacrynic acid
o Cisplatin
o Aspirin
o NSAID
o Steroids.

Dose –
 Injectable solution – 10mg/mL
 Oral Solution – 10 mg/mL & 8 mg/mL
 Table – 20 mg, 40 mg, 80 mg.
 Thiazide Diuretics
Thiazide type diuretics such as hydrochlorothiazide ac on the distal convoluted tubule & inhibit
the sodium chloride symporter leading to a relation of water in the urine, as water normally
follows penetrating solutes. Frequent urination is due to the increased loss of water that has not
been retained from the body as a result of a concomitant relationship with sodium loss from the
convoluted tubule. The short term anti-hypertensive action is based on the fact that thiazides
decrease preload, decreasing blood pressure. On the other hand, the long term effect is due to an
unknown vasodilator effect that decreases blood pressure. On the other hand, the Long term
effect is due to unknown vasodilator effect that decreases blood pressure by decreasing
resistance.
Examples of Thiazide Diuretics –
Chlorothiazide
Chlorthalidone
Hydrochlorothiazide
 Thiazide Diuretics (Cont.)

Chlorthalidone
Chlorothiazide

Hydrochlorothiazide
 Thiazide Diuretics (Cont.)
Chlorothiazide –
Mechanism of Action –
The mechanism of electrolyte reabsorption, thiazide increase excretion of Na & Cl approximately
equivalent amounts.
Uses in Heart disease –
• The medication is used to treat high blood pressure.
• Chlorothiazide is a water pill that causes to make urine.

Side effects –
o Dizziness
o Light head redness
o Headache
o Constipation
o Stomach upset
 Thiazide Diuretics (Cont.)
Indication –
It is indicated as –
 Adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis.

Drug – Drug interaction –

Some product that may interact with this drug are –
o Defoliate
o Lithium

Dose –
o Oral suspension – 250 mg/ 5 mL
o Powder for Injection – 500 mg
o Tablet – 250 mg & 500 mg
 Carbonic Anhydrase Inhibitor
Carbonic anhydrase inhibit the enzyme carbonic anhydrase which is found in the proximal
convoluted tubule. This results in several effects including bicarbonate accumulation in the urine
& decreased sodium absorption.
Examples of Carbonic anhydrase inhibitor –
Acetazolamide
Methazolamide
Brinzolamide
Dorzolamide
Carbonic Anhydrase Inhibitor (Cont.)

Methazolamide
Acetazolamide

Brinzolamide
Dorzolamide
Carbonic Anhydrase Inhibitor (Cont.)
 Acetazolamide –
Mechanism of action –
Inhibition of the enzyme prevents dehydration of & hydration of in the proximal convoluted
tubule.
Uses in Heart Disease –
• Acetazolamide is used as a diuretic in people with congestive heart failure to reduce the build
up of fluid in the body.
Side effects –
o Dizziness
o Light head ness or increased urination may occur specially during the first few day as body
adjust to the medication.
Carbonic Anhydrase Inhibitor (Cont.)
Indication –
It is used for the treatment of –
 Glaucoma drug induced edema
 Heart failure epilepsy &
 In reducing intraocular pressure after surgery

Drug – drug interaction –

Acetazolamide interact with tiapride, methenamine, Anti – convulsant, others diuretics.
Dose –
o Tablet – 125 mg, 250 mg.
o Powder for Injection – 500 mg.
 Potassium Sparing Diuretics
These are diuretics which do not promote the secretion of potassium into the urine; thus
potassium is retained & not lost as much as with other diuretics. The term “potassium sparing’
refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers
to two specific classes that have their effect at similar locations:
 Aldosterone antagonists: Spironolactone, which is a competitive antagonist of aldosterone.
Aldosterone normally adds sodium channels in the principal cells of the collecting duct & late
distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal
cells, preventing sodium reabsorption. Similar agents are eplerenone & potassium cameronite.
 Epithelial sodium channel blockers.

Examples of Potassium Sparing Diuretics –

Amiloride
Eplerenone
Spironolactone
Potassium Sparing Diuretics (Cont.)

Amiloride
Eplerenone

Spironolactone
 Potassium Sparing Diuretics (Cont.)
Amiloride –
Mechanism of Action –
Blocks epithelial sodium channels in collecting tubules.
Uses in Heart Disease –
It has been shown to decrease mortality in such patients who are heart associated.
Side effects –
• Drowsiness
• Dizziness
• Nausea
• Vomiting
• Headache
 Potassium Sparing Diuretics (Cont.)
Indication –
• Bronchopulmonary diphase
• Hyperaldosteronism test

Drug – drug Interaction –

Concomitant administration of ACE inhibitors with potassium sparing diuretics has been
associated with severe hyperkalemia.
Dose –
o Tablet – 25 mg, 50 mg, 100 mg.
o Oral Suspension – 5 mg/mL
 Osmotic Diuretics

Osmotic diuretics are substances that increase osmolarity but have limited tubular epithelial cell
permeability. They work primarily by expanding extracellular fluid & plasma volume, therefore
increasing blood flow to the kidney, particularly the peritubular capillaries. This reduces
medullary osmolality & thus impairs the concentration of urine in the loop of Henle.
Furthermore, the limited tubular epithelial cell permeability increases osmolality & thus water
retention in the filtrate.
Example of Osmotic Diuretics –
Mannitol
Osmotic Diuretics (Cont.)

Mannitol
 Osmotic Diuretics (Cont.)
Mannitol –
Mechanism of Action –
Physical osmotic effect on tissue water distribution because it is retained in the vascular
compartment.
Uses in Heart Disease –
The potential uses of mannitol in the care of the patient with coronary artery disease or other
cardiac diseases.
Side effects –
o Reduced brain volume
o Initial hyponatremia
 Osmotic Diuretics (Cont.)

Indication –
Renal failure due to increased solute load, increased intracranial pressure, glaucoma.
Drug – drug Interaction –
Mannitol interacts with acetaminophen, acetazolamide etc.
Dose –
o IV Injection – 500 – 2000 ml/day.
 Conclusion
Diuretics have been recommended as first-line treatment of hypertension and are also valuable in
the management of hypervolemia and electrolyte disorders. Compared to other classes of
medications, thiazide diuretics are at least as effective in reducing cardiovascular events (CVEs)
in patients with hypertension and are more effective than β-blockers and angiotensin-converting
enzyme inhibitors in reducing stroke. The benefit of eplerenone following acute myocardial
infarction (MI) is limited to administration within 3 to 6 days post-MI. Aldosterone antagonists
have been shown to lower the incidence of sudden cardiac death and to reduce proteinuria. In the
setting of heart failure, long acting loop diuretics azosemide and torsemide are more effective in
improving heart failure outcomes than the far more commonly used short acting furosemide.  In
conclusion, diuretics are a diverse class of drugs that remain extremely important in the
management of hypertension and hypervolemic states.
 Reference

https://en.wikipedia.org/wiki/Diuretic#High_ceiling/loop_diuretic
https://www.slideshare.net/rezahei/diuretics-72238716
https://www.slideshare.net/Pharmacologist/diuretics-36415790
https://pubmed.ncbi.nlm.nih.gov/24243991/#:~:text=In%20conclusion%2C%20diuretics%20are
%20a,heart%20failure%3B%20diuretics%3B%20hypertension.
https://pubmed.ncbi.nlm.nih.gov/24243991/
Thank You