diuretics by siva

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Diuretics :

Diuretics Prepared & Presented by Dr. Siva Reddy Challa, Professor & HOD, Dept. of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences, Siddhartha Nagar, Vijayawada-520010 Andhra Pradesh, INDIA Email: sivareddypharma@gmail.com

Diuretics:

Diuretics Classification: Carbonic anhydrase inhibitors Loop diuretics Thiazides K+ sparing diuretics Osmotic diuretics

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Diuretic classes Drugs Site of action Carbonic anhydrase inhibitors PCT Loop diuretics ALH Thiazide diuretics DCT Potassium sparing diuretics Collecting duct Osmotic diuretics

Diuretics: Sites of Action:

Diuretics: Sites of Action 4 Na + Cl - K + Na + Cl - HCO 3 - Na + K + Carbonic Anhydrase Inhibitors Eg: Acetazolamide Loop Diuretics Eg: Furosemide Thiazides Eg: Chlorothiazide K + - Sparing Eg: spironolactone

Diuretics:

Diuretics

Carbonic anhydrase inhibitors :

Carbonic anhydrase inhibitors Drugs :Acetazolamide (oral), Dorzolamide(topical ) . Acts at Proximal convoluted tubule. Uses :Rx of 1) Glaucoma 2) Hydrocephalus 3) Metabolic alkalosis 4) Acute mountain sickness 5) Toxicity of acidic drugs Adverse effects 1 . Metabolic acidosis 2.Renal stones 3.Hypokalemia 4.Drowsiness 5.Paresthesia 6.Interstitial nephritis.

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Carbonic Anhydrase Inhibitors:

10 Carbonic Anhydrase Inhibitors Mechanism of action : Inhibition of Carbonic Anhydrase Enzyme in PCT results in no/less H + available for reabsorption of Na + , leading to Na + loss HCO 3- Excretion increases Causes mild diuresis

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11 Causes significant bicarbonate loss Hyperchloremic metabolic acidosis Limited effectiveness because: bicarbonate depletion increases sodium chloride reabsorption reduction in aqueous humor and cerebrospinal fluid production

Clinical Applications:

12 Clinical Applications Because of Mild diuresis , not much useful for HTN Are used to alkalinize urine

Other uses:

13 Other uses Glaucoma CAIs Reduces aqueous humor production and Decrease intraocular pressure Dorzolamide (topical application) Advantage: No diuretic or systemic metabolic effects (compared to acetazolamide) Acute Mountain Sickness Hydrocephalus Metabolic alkalosis Epilepsy: CA inhibitors increase the seizure threshold

ADRs:

14 ADRs Hyperchloremic metabolic acidosis due to reduction of body bicarbonate stores Renal stones : bicarbonate loss is associated with: phosphaturia hypercalciuria (calcium salts, relatively insoluble at alkaline pH) Renal potassium loss: Rx : Potassium chloride administration

ADRs:

15 ADRs Drowsiness, Parasthesias Hypersensitivity reactions CI : Hepatic cirrhosis Increases chances of hepatic encephalopathy

Carbonic anhydrase inhibitors:

Carbonic anhydrase inhibitors Drug interaction : Digoxin toxicity ( Due to Hypokalemia ). Cross allergy with other “sulpha” containing drugs. Precaution : 1.Hepatic cirrhosis 2.Chronic obstructive pulmonary disease.

Loop diuretics :

Loop diuretics Drugs : Furosemide,Ethacrinic acid, Bumetanide , Torsemide . Mech : Inhibits Na,k,2Cl Co-transporters in thick ascending loop. Uses :Rx of 1.Acute pulmonary edema 2.HTN 3.Acute renal failure 4.Anion overdosage 5.Heart failure 6.Hypercalcemia

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Loop diuretics:

Loop diuretics Adverse effects : 1. Hypokalemia 2.Metabolic alkalosis 3.Ototoxicity 4.Hyperuricemia 5.Hypocalcemia 6.Hypomagnesemia 7.Hypotension 8.Allergic reactions(skin rash,intertitial nephritis,esinophilia).

Loop diuretics:

Loop diuretics Drug interactions : 1. Aminoglycosides + Loop diuretics Ototoxicity 2.Increases toxicity of Digoxin ( Due to Hypokalemia). 3.Loop diuretics decreases excretion of Lithium.

Thiazide diuretics :

Thiazide diuretics Drugs : Chlorothiazide Hydrochlorothiazide Chlorthalidone Indapamide, Metolazone . Mech :Inhibits Na+,Cl-cotransporter in distal convoluted tubule. Uses :Rx of 1.HTN 2.Congestive Heart failure 3.Nephrolithiasis 4.Nephrogenic Diabetes insipidus.

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Thiazides:

Thiazides Side effects: 1. Hypokalemia 2.Metabolic alkalosis 3.Hyperuricemia 4. Hyponatremia 5.Hyperglycemia 6.Hyperlipidemia 7.Hypercalcemia. 8.Allergic reactions. Drug interactions : 1.Increases toxicity of Digoxin (Due to Hypokalemia). 2.Cross hypersensitivity with other drugs with sulfa group.

K+ Sparing Diuretics :

K+ Sparing Diuretics Spironolactone : Aldosterone antagonist Amiloride & Triamterene : Na channel blockers Acts at Collecting tubules. Uses : Rx of 1.Hyper Aldosteronism(Conn’s syndrome) 2.HTN 3.Heart failure. Adverse effects :Hyperkalemia, Metabolic acidosis, Gynecomastia Nephrolithiosis (Triamterene).

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K+ Sparing Diuretics :

K+ Sparing Diuretics Drug interactions : 1. Digoxin action (Hyperkalemia) 2.K+ sparing Diuretic + ACE inhibitors---> Severe Hyperkalemia

Osmotic diuretics:

Osmotic diuretics Mech : Decreases absorption of water in proximal convoluted tubules and descending limb of loop of Henle. Ex : Mannitol (iv),Glycerol (oral) Uses : Rx of 1.Cerebral edema. 2.Glaucoma Side effects : Dehydration, Hypernatremia Pulmonary edema.

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Diuretic Adverse effect Carbonic anhydrase inhibitors Hypokalemia, Metabolic Acidosis Loop diuretics Hypokalemia, Alkalosis Hypocalcemia,Ototoxicity. Thiazides Hypokalemia, Alkalosis, Hypercalcemia, Hyponatremia. K+ Sparing (or) Aldosterone antagonists Hyperkalemia ,Acidosis, Gynecomastia. Osmotic diuretics Dehydration,Hypernatremia

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This presentation is Dedicated to My parents

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