Diuretic Drugs

1-Overview 2-Classification 3-Indiviual drugs Lecture 1 1-Overview 2-Classification 3-Indiviual drugs

Lecture 2 1-Indications of Diuretics. 2-Adverse effects. 3-Manitol and Carbonic Anhydrase inhibitors.

Indications of Diuretics 1- Oedema States Sodium overload “Cardiac, Renal, Hepatic” “Acute pulmonary edema”

Oedema

Indications of Diuretics 2-Hypertension Reduction of: Intravascular volume and peripheral vascular resistance.

Indications of Diuretics 3-Hypercalcaemia Furosemide reduces calcium re-absorption in ascending limb of loop of Henle.

Indications of Diuretics 4-Idiopathic Hypercalciuria. A cause of renal stone disease, treated by Thiazide

Indications of Diuretics 5- The syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) May be treated with Furosemide.

Indications of Diuretics 6-Nephrogenic Diabetes Insipidus. My be paradoxically treated with diuretics by contracting vascular volume, increase salt and water reabsorption in proximal tubule.

Indications of Diuretics 7-Congestive cardiac failure. Reduction of oedema ,relief of dyspnea Should avoid overtreatment ! Dizziness tiredness, postural hypotension Monitor body weight !

Acute Pulmonary Oedema Potent Loop Diuretic ex Furosemide (Lasix) Used intravenously with combination of other drugs and oxygen

Indications of Diuretics 8-Hepatic ascites Portal hypertension Decrease in colloid pressure and hyperaldosteronism. “Spironolactone”

Indications of Diuretics Vigorous diuresis can cause encephalopathy! Paracentesis

Indications of Diuretics In secondary hyperaldosteronism of Nehrotic syndrome Spironolactone (Aldactone) is preferred.

Adverse effects 1-Potassium depletion: Increasing the sodium which reaches the exchange at the DCT and collecting duct. “Na exchanged for K”

Adverse effects This can lead to Arrhythmia especially in patient receiving Digoxin Safe lower limit of K = 3.5 mmol/L

Loop diuretics cause smaller loss in K than Thiazides: “For the same amount of diuresis”

Adverse effects But as loop is more potent They cause more diuresis they cause more hypokalemia !

Adverse effects Hypokalemia is more prone to occur in hyperaldosteronism whether primary or: More commonly Secondary to liver disease congestive cardiac failure or nephrotic syndrome.

Adverse effects Prevention of K depletion: 1-Good dietary intake. Vegetables and fruits 2-K depleting drug with sparing diuretic. 3-Intermittent diuretics. “Drug holidays”

Adverse effects 4-Potassium supplementation KCL because Cl is the principle ion excreted All K preparations are irritant to GIT and esophageal ulceration can result. Cupful of liquid preferably upright

Adverse effects 2-Hyperkalemia in potassium sparing diuretics ACE Inhibitors And can cause dangerous hyperkalemia if combined with K sparing diuretic

Adverse effects Treatment of hyperkalemia: 1-Stop any K sparing diuretic. 2-Meassures to move K rapidly into the cells including:

Adverse effects A-Sodium bicarbonate 50 ml of 8.4% solution. B- Glucose 50 ml 50 % solution +10 units of soluble insulin. C- Nebulised salbutamol (Beta 2 Agonist) 5-10 mg.

Adverse effects Calcium Gluconate 10 ml of 10 % solution. IV oppose the myocardial effects of raised serum K

Adverse effects 3-Hypovolaemia in overtreatment: Postural hypotension Dizziness Lethargy Somnolence “Usually Insidious”

4-Urinary retention: Sudden vigorous dieresis especially in elderly Adverse effects 4-Urinary retention: Sudden vigorous dieresis especially in elderly

Adverse effects 5-Hyponatremia especially in patient who drinks a lot of water. Large quantities of water. *Increase in ADH could be a mechanism.

Adverse effects In Hyponatremia Discontinue diuretic and water restriction. Elderly are more predisposed

Adverse effects 6-Urate retention Hyperuricaemia Increase in uric acid Thiazide and loop diuretics NOT Amiloride or Spironolactone

Adverse effects Mechanism of Hyperuricaemia could be: 1-Volume depletion and decrease in GFR. 2-Diuretics are organic acids that competes with the site of transport

Adverse effects 7-Magnesium deficiency in loop and Thiazides Loss of magnesium K sparing diuretics leads to Magnesium retention Cardiac arrhythmia

Adverse effects 8-Carbohydrate intolerance: Intracellular potassium is necessary in the formation of insulin Can change latent diabetes into overt diabetes.

Adverse effects 9-Calicium homeostasis Loop diuretics Increases renal calcium loss. Furosemide can be used to treat hypercalcaemia.

Adverse effects Thiazides decrease renal excretion of calcium Decreasing the risk of hip fracture in elderly!

Adverse effects 10-IV loop diuretics potentiate ototoxicity of aminoglycoside antibiotics and nephrotoxicity of cephalosporins

Osmotic diuretics Small molecular weight substances Filtered by glomerulus but: NOT Reabsorbed Increases osmolarity and prevent re-absorption of water and sodium “Proximal convoluted tubule”

Osmotic diuretics Mannitol is a polyhydric alcohol Given intravenously. 1-Reduction in intracranial pressure. 2-Maintain urine flow to prevent acute tubular necrosis and renal failure. Increase urine volume *Contraindicated in CHF and Pul Oedema

Carbonic Anhydrase Inhibitors CO2 + H2O → H2CO3 (CA) Carbonic Anhydrase enzyme THEN BREAKDS DOWN TO H ion + HCO3 Carbonic Anhydrase is present in: “GIT, Eye, Pancreas, kidneys”

C. A. Enzyme Carbonic Anhydrase

Carbonic anhydrase inhibitors Reduced hydrogen in PCT Na loss and diuresis Reduced HCO3 absorption “Metabolic Acidosis” *Not used as diuretic

Carbonic anhydrase inhibitors Acetazolamide is the most commonly used.(Diamox) *Reduction in intraocular pressure(IOP) (Glaucoma) Hypokalemia and Acidosis

Carbonic Anhydrase inhibitors Used also in treatment of mountain sickness High altitude Over 300 meters Nausea Lassitude Headache Pulmonary and cerebral edema

High altitude Mountain Sickness

Acetazolamide

Carbonic anhydrase inhibitors *Hypoxia *Hyperventilation *Alkalosis

Carbonic anhydrase inhibitors Acetazolamide Acidosis Increases respiratory drive 125-250 mg bid (Twice Daily)

Drowsiness Fever Rash Paresthesia Blood dyscrasia Adverse effects Drowsiness Fever Rash Paresthesia Blood dyscrasia

The Relation of serum creatinine with: 1-Renal function 2-GFR ***Final Remarks The Relation of serum creatinine with: 1-Renal function 2-GFR

MCQs A patient with ascites was receiving Thiazide & was stable until he developed hypersensitivity. His treatment was changed to Furosemide 40 mg every other day and the dose was tittered to produce the same previous clinical efficacy. By this the risk of K depletion and hypokalemia is: A-Increased. B- Decreased. C- Remained the same. D- Unpredictable.

MCQs A patient with oedema was receiving hydrochlorothiazide but his oedema did not resolve & that is why the treatment was changed to Furosemide tab. 40 mg /day which caused dramatic improvement. By this the risk of K depletion and hypokalemia is: A-Increased. B- Decreased. C- Remained the same. D- Unpredictable.

MCQs 60 years old lady with osteoporosis was in need for diuretic therapy and was prescribed Thiazide. she was worried about the effect of the drug on her bone density and likelihood of fractures. Your reply would be: A-It has no effect. B- It could be protective C- It could be harmful. D- Unknown effect.

MCQs A patient with congestive heart failure was receiving Furosemide diuretic every other day. His GP advised him that he could take the dose daily when he feels shortness of breath. He consulted you complaining of severe fatigue, dizziness, dryness of the mouth, and somnolence. The most likely cause of this could be: A-Hypokalemia. B-Hyperkalemia. C-Hypocalcaemia D- Dehydration and Overtreatment.

MCQs A patient with gout was prescribed some form of diuretic therapy which cause elevation of his serum uric acid and caused acute attack of gouty arthritis. This diuretic could be: A- Amiloride. B- Spironolactone. C- Triamterene. D- Bendrofluazide.

MCQs A patient with hypovolaemic shock & severe hypotension has developed oliguria & was in need for drug to maintain adequate renal function and increase his urine output, the best choice for this would be: A-Furosemide. B- Mannitol. C- Thiazide. D- Acetazolamide.

MCQs Which one of the following drugs increases the calcium loss in the urine? A-Hydrochlorothiazide. B- Amiloride. C- Furosemide. D- Triamterene.

MCQs Acetazolamide is known to cause: A- Metabolic Acidosis B-Metabolic Alkalosis. C- Hypokalemia & Metabolic Acidosis. D- Hypoglycemia.