DIURETICS

This presentation is for the diploma students and it covers the topic diuretics. This course is designed to introduce to the students the concept of diuretics, summation of such search and writing a brief report based on collected information in student’s own words.
Completion of graduation project in the form of a report / essay is an essential requirement for obtaining the degree of D.Pharm.

1. DIURETICS PRESENTATION ON DIURETICS FOR DIPLOMA 1 ST YEAR STUDENTS GURU GOBIND SINGH COLLEGE OF PHARMACY, YAMUNA NAGAR SHIKHA KAMBOJ ASSISTANT PROFESSOR

2. DIURETICS A diuretic is a drug that increases the secretion of urine ( i.e , water, electrolytes, and waste products) by the kidneys or diuretics are the chemical agents which increase the excretion of urine by kidneys. They lead to the secretion of excess water and salt that accumulates in tissues and urine, results in decrease in body fluids especially the extracellular fluid. Many conditions or diseases, such as hypertension, congestive heart failure, endocrine disturbances, and kidney and liver diseases can cause retention of excess fluid (edema). A diuretic is used when the patient shows signs of excess fluid retention. Reabsorption of Na in the kidney results in the reabsorption of water. It follows that inhibition of Na reabsorption will result in diuresis. Because of this, the term diuretic has come to mean any a gent that will inhibit the tubular reabsorption of sodium.

3. Different sites for diuretics

4. Classification of drugs

5. 1. CARBONIC ANHYDRASE (CA) The carbonic anhydrases form a family of enzymes that catalyze the rapid inter-conversion of carbon dioxide (CO 2 ) and water to bicarbonate (HCO 3 ) and protons (or vice versa).

6. Uses: 1. It is used in treatment of glaucoma and drug induced edema. 2. It is also used as anticonvulsant for the treatment of epilepsy. 3. It is also used in the treatment of Menieres disease (disorder of inner ear) and neuromuscular disorders. 4. It is used in the treatment of moderate congestive heart failure, and in the treatment of glaucoma . Acetazolamide Chemical name: N -(5-sulphomoyl-1, 3, 4 thiadiazole-2-yl) acetamide. Properties: It is a sulfonamide derivative. It occurs as white to yellowish white crystalline powder, slightly soluble in water and alcohol. It is preserved in tight light-resistant containers. It is rapidly absorbed by the stomach, reaches peak level within 2 hours and is eliminated unchanged. Formulations : Actazolamide Tablets B.P, L.P, Actetazolamide CapsulesIt is used in the form of tablets, usual dose is 250 mg daily. Its sodium salt is official in U.S.P. and used parenterally. Intravenous or intramuscular dose is 250 mg of acetazolamide base. Storage: Store in air tight light resistant container.

7. Formulations: Actazolamide Tablets B.P, L.P, Actetazolamide CapsulesIt is used in the form of tablets, usual dose is 250 mg daily. Its sodium salt is official in U.S.P. and used parenterally. Intravenous or intramuscular dose is 250 mg of acetazolamide base. Brand name: Zolamide Diamos

8. Thiazides Thiazide diuretics are a type of diuretic (a drug that increases urine flow). They act directly on the kidneys and promote diuresis (urine flow) by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron (the functional unit of a kidney). Thiazides decrease sodium reabsorption which increases fluid loss in urine, which in turn decreases extracellular fluid and plasma volume. This reduces cardiac output (how hard the heart has to work to pump blood around the body) and lowers blood pressure. Thiazides also work in other ways to lower blood pressure. Thiazides also cause potassium loss while retaining calcium.

9. Metolazone Common name: 7-chloro-2-methyl-4-oxo-3-o-tolyl-1,2,3,4-tetrahydroquinazoline-6-sulfonamide. It is a long action quinazolone based sulphonamide thiazide like diuretic. Properties: - It occurs as a crystalline powder. It is tasteless and odourless , insoluble in water and alcohol. It is light sensitive. It is polymorphic. Storage:- Store in a air tight. Light resistant container. Uses -( i ) It is used to reduce the swelling and fluid retention caused by heart failure or kidney diseases. (ii) It is also used alone with other medications to treat high B.P

10. Formulations: Metolazone is a  thiazide-like diuretic  marketed under the brand names  Zytanix ,  Metoz ,  Zaroxolyn , and  Mykrox . Metolazone tablets, USP, for oral administration contain 2½, 5, or 10 mg of metolazone, USP, a diuretic XIPEMIDE (DIUREXAN, AQNAPHOR) Common name: 4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy-5-sulfamoylbenzamide Diurexan Xipamid Aquaphor Diurex (lacer) Aquaphor (diuretic) Aquaphoril Zipix It is a sulphonamide diuretic Properties:- It occurs as white to beige colored crystalline powder. It is lipophilic poorly soluble in water and highly soluble in polar organic solvents.

11. Combinations requiring special precautions The product information requests special precautions for these combinations: The antihypertensive effect can be increased by  ACE inhibitors ,  barbiturates ,  phenothiazines ,  tricyclic antidepressants ,  alcohol , etc. (Classified as  minor .) NSAIDs  can reduce the antihypertensive and diuretic effects. Xipamide increases the neurotoxicity of high doses of salicylates. (Classified as  minor .) Toxicity of  cardiac glycosides  is increased due to hypokalemia and  hypomagnesemia .(Classified as  minor .) Antiarrhythmic agents  (classes Ia and III), phenothiazines and other antipsychotics increase the risk of  torsades de pointes  due to hypokalemia.

12. Chlorthalidone Storage: Store in air tight, light resistant containers Uses: ( i ) It is used to treat mild hypertension (ii) It is used as diuretic in patient with renal failure (3) cardiac  oedema caused by  decompensation of heart failure (4) hypertension in combination with chronic renal disease Formulations: Xipamide is a sulfonamide  diuretic  drug marketed by  Eli Lilly  under the trade names Aquaphor (in Germany) and  Aquaphoril  (in Austria). It is used for the treatment of  oedema  and  hypertension . Common name: 2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide chlorthalidone Chlorothalidone It is thiazide diuretic. It occurs as white to yellowish white crystalline powder. It is practically insoluble in water, ether and chloroform and soluble in methanol. Storage: It should be stored in airtight container

13. Uses: It is used to treat high blood pressure and fluid retension Formulations: Chorthalidone tablets USP Potassium sparing diuretics Potassium-sparing diuretics are medicines that increase diuresis (urination) without the loss of potassium. They are generally weak diuretics and work by interfering with the sodium-potassium exchange in the distal convoluted tubule of the kidneys or as an antagonist at the aldosterone receptor. Aldosterone promotes the retention of sodium and water, so if potassium-sparing diuretics are used to block this effect, more sodium and water can pass into the collecting ducts of the kidneys, increasing diuresis. Because potassium-sparing diuretics do not promote the secretion of potassium during diuresis they do not cause  hypokalemia  ( low potassium  levels). However, there is a risk of  hyperkalemia  (high potassium levels) if they are used with other agents that also retain potassium, such as ACE inhibitors. Potassium-sparing diuretics may be used alone or in conjunction with loop or thiazide diuretics.

14. SPIRONOLACTONE It is aldosterone antagonist. Properties: It occurs as a buff coloured powder. It is odourless or has a slight odour of thioacetic acid. It is very slightly soluble in water. Storage: Protect from light Uses: It acts as a potassium sparing diuretic for the management of hypertension. It is used to control edema associated with hepatic cirrhosis and nephrotic syndrome off. It is used in conjugation with other diuretics to prevent excessive loss of potassium ions. Formulations: Spironolactone tablets B.P, I.P Brand name: (ALDECTONE®, LACTONE®, SPIROMIDE®)

15. Loop diuretics Diuretics are medicines that increase urine flow (cause diuresis). Loop diuretics are a powerful type of diuretic that work by inhibiting the sodium-potassium-chloride (Na+/K+/2Cl) co-transporter in the thick ascending loop of Henle (hence the name loop diuretic), which is located in the kidneys. This reduces or abolishes sodium, chloride, and potassium reabsorption, leading to increased loss of sodium, chloride, and potassium into the nephron (the functional unit of a kidney). As a result, water is also drawn into the nephron and urine volume increases. Loop diuretics also reduce the reabsorption of calcium and magnesium.

16. Bumetanide Bumetanide is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart, kidney, and liver disease. Bumetanide is in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine. Common name: 3-( butylamino )-4-phenoxy-5-sulfamoylbenzoic acid . Properties: - Bumetanide is a diuretic. It is a potent sulfamoylanthranilic acid derivative. It belongs to the class of loop diuretics. It occurs as a white crystalline powder. It has a bitter taste. It is relatively stable in light and at room temperature. It is very slightly soluble in water. Storage: Store in an airtight container. Uses: It is used for the treatment of oedema associated with CH, hepatic and renal disease. Formulations : Bumetanide Tablets B.P, Bumetanide Oral Solution B.P, Bumetanide Injection B.I Brand name: The brand name of this medication is  Bumex , BUMET, BURINEX.

17. BENZTHIAZIDE Properties: It occurs as a white crystalline powder with characteristic odour and a bitter taste. It is practically insoluble in water. It is stable in light and air. Storage: It should be stored in air tight container. Uses: (1) It is used in the treatment of oedema associated with CHF (ii) Hypokelaemia and other electrolyte imbalances may occur on prolonged use. It is used in the treatment of high blood pressure. Brand name: aquatag , fovane , exosalt , Dihydrex , Diucen , Edemax , Exna , Foven .