Chapter 13 Diuretics Flashcards
Thiazide and related-diuretics names
Hydrochlorothiazide
Indapamide
Chlorthalidone
Metolazone
Thiazide and related diuretics names (ALT)
MoA: Acts on early portion of the distal tubule to inhibit the Na+ ,Cl- symporter that participates in the reabsorption of sodium and chloride from this segment of the nephron. This action leads to the delivery of a greater volume of sodium chloride-enriched tubular fluid to the late distal tubule and collecting duct, which in turn stimulates the exchange of sodium and potassium at these sites. In this process a small amount of sodium is reabsorbed as potassium is secreted into urine in the tubules, and this can cause hypokalemia. Thiazide also increase magnesium excretion, but decrease calcium excretion in the urine.
Clinical use:
-Hypertension
-Edema associated with heart failure, cirrhosis, corticosteroid therapy, estrogen therapy and Renal disorders such as nephrotic syndrome
-Nephrolithiasis associated with hypercalciuria and Nephrogenic diabetes insipidus (thiazide exert antidiuretic effect in these patients and reduce the excessive urine volume)
Adverse effects:
-Hypokalemia and hypokalemic metabolic alkalosis (Administer potassium chloride IV or orally for alkalosis)
-Elevated blood glucose, uric acid, lipid levels (Hyperuricemia may lead to gout)
-Decreased the insulin sensitivity (can contribute to development of diabetes)
Interactions:
-Increase serum levels of lithium
-Hypotensive effect decreased by NSAIDs and augmented by ACE inhibitors
Loop diuretics-names
Furosemide
Ethacrynic acid
Bumetanide
Torsemide
Loop diuretics (ALT)
MoA: Inhibit the Na+, K+, 2Cl- symporter in the ascending limb of loop of Henle and thereby exert a powerful natriuretic effect. Inhibit the reabsorption of a greater percentage of filtered sodium and produce a dose dependent diuresis throughout their clinical dosage range. They produce kaliuresis by increasing the exchange of sodium and potassium in the late distal tubule and collecting duct in the same manner as thiazides. They increase magnesium and calcium excretion by reducing the reabsorption of these ions in the ascending limb. They cause a reduction of potassium back diffusion, and this decreases transepithelial electrical potential that normally drives the paracellular reabsorption of magnesium and calcium and thus increases magnesium and calcium excretion.
Clinical use:
-Pulmonary edema,
-Preferred diuretics in the treatment of persons with renal impairment and nephrotic syndrome (creatinine more than 2,3 mg/dL)
-Edema caused by heart failure, Cirrhosis or other diseases
-Hypertension (but thiazide drugs are more preferred) and to treat hypercalcemia
Adverse effects:
-Electrolyte abnormalities; hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis.
-Increase blood glucose, uric acid and lipids
-Ototoxicity; tinnitus, ear pain, vertigo and hearing deficits (Ethacrynic acid is more ototoxicity than the others)
Interactions:
-Diuretic effect decreased by NSAIDs
-Hypotensive effect increased by ACE inhibitors
Specials:
-Bumetanide, furosemide, and torsemide are sulfonamide derivatives that are given oral or iv, and Torsemide has longer half-life then the others.
-Ethacrynic acid is the only loop diuretic that is not a sulfonamide
Potassium-sparing diuretics-names
Amiloride
Triameterene
Spironolactone
Eplerenone
Amiloride and triameterene (ALT)
MoA: Blocking the entry of sodium into the principal tubular cells of the late distal tubule and collecting duct. These drugs prevent sodium reabsorption at this site and indirectly reduce the secretion of potassium into the tubular filtrate and urine. They produce a modest amount of natriuresis but decrease kaliuresis.
Clinical use: Prevention and treatment of hypokalemia induced by thiazide and loop diuretics
Adverse effects: Hyperkalemia (Administer patiromer, a drug which binds to potassium in the GI tract. This drug is not absorbed and thus it reduces free potassium concentration in GI lumen and in the serum)
Interactions: Hyperkalemic effect increased by ACE inhibitors and potassium supplements
Spironolactone and eplerenone (ALT)
MoA: Block aldosterone binding to the mineralocorticoid receptor in epithelial cells of the late distal tubule and collecting duct. When activated the mineralocorticoid receptor interact with DNA to promote expression of genes for sodium channels and the sodium pump that enable sodium reabsorption and potassium secretion. Thus they lead to decreased sodium reabsorption and decreased potassium secretion.
Clinical use: Hyperaldosteronism and reduce mortality in pat with heart failure
-Spironolactone-> used in polycystic ovary disease and hirsutism (Because of its antiandrogenic effect)
Adverse effects: Hyperkalemia, gynecomastia and impotence (Eplerenone have less endocrine side effects)
Osmotic diuretics-names
Mannitol
Glycerol
Osmotic diuretics (ALT)
MoA: After it is filtered through glomerulus they are not absorbed from the renal tubules, and thus they osmotically attract and retain water as they move through the nephron and into the urine. This action reduces the tubular sodium concentration and the gradient between the tubular fluid and cells and thereby retards the reabsorption of sodium. They increase osmotic pressure of the plasma and thereby attract water from interstitial and transcellular fluids (thus used in cerebral edema). They also attract water from ocular fluids into the circulation, and thus they reduce intraocular volume and pressure (thus used in acute glaucoma).
Clinical use:
Mannitol->Cerebral edema, acute glaucoma, as diuretic in renal failure, maintain renal function in antineoplastic therapy with platinum compounds (cisplatin) and promote renal excretion of toxic substances (such as drug overdose or poisoning)
Glycerol->Acute glaucoma
Adverse effects: Excessive plasma volume expansion which may lead to heart failure and pulmonary congestion and edema (esp. after rapid drug administration or administration of large doses)
Carbonic anhydrase inhibitors-names
Acetazolamide
Dorzolamide
Carbonic anhydrase inhibitors (ALT)
MoA: They inhibit carbonic anhydrase throughout the body. This enzyme catalyzes the conversion of carbon dioxide and water to carbonic acid, which spontaneously decomposes to bicarbonate and hydrogen ions. Effect of CA:
(1)When the ciliary process forms aqueous humor, CA participates by catalyzing the formation of bicarbonate, which is secreted into the posterior chamber of the eye, along with water and other substances that make up the aqueous humor.
(2)CA is also required for the reabsorption of sodium bicarbonate from the proximal tubule and for the secretion of hydrogen ions in the collecting duct (In the reabsorption of sodium bicarbonate, bicarbonate must be converted to carbon dioxide and water by CA, because the apical cell membrane of the tubular epithelial cells is impermeable to bicarbonate. The carbon dioxide and water can diffuse into the tubular cells, where CA converts them back to bicarbonate, which is then transported into the interstitial fluid for diffusion into the circulation. Inhibition of this process by CA inhibitors causes a marked reduction in the reabsorption of sodium bicarbonate and a corresponding increase in its renal excretion. This leads to alkalinization of the urine and produces a mild form of hyperchloremic metabolic acidosis. The hyperchloremia results from the increased reabsorption of chloride as a compensation for reduced bicarbonate reabsorption).
Clinical use:
-Treatment of chronic ocular hypertension and open-angle glaucoma (reduce aqueous humor secretion and intraocular pressure)
-Alkalinization of the urine
-Prevention and treatment of high-altitude sickness (counteracts respiratory alkalosis, by producing metabolic acidosis)
-Epilepsy (inhibition of CA in the CNS elevates seizure threshold)
Adverse effects:
Acetazolamide-> CNS effects (Drowsiness, paresthesia etc.), Hepatic insufficiency, Hypokalemia, hyperglycemia, metabolic acidosis and Less commonly hypersensitivity reactions and blood deficiencies
Dorzolamide->Blurred vision, bitter taste and allergic reactions
Interactions:
-Increase the pH in urine and thus decrease the excretion of weak bases (amphetamine, ephedrine and pseudoephedrine, and quinidine)
-Serum levels of CA inhibitors are increased by salicylates
ADH antagonists-names
Conivaptan
Tolvaptan
ADH antagonists (ALT)
MoA: V2 receptors are coupled with insertion of aquaporin channels in apical membranes of the renal collecting ducts, leading to reabsorption of water, and these receptors are usually activated by ADH. V1 receptors lead to vasoconstriction. Conivaptan antagonized both receptors while tolvaptan antagonized V2 receptors, which causes free water excretion or aquaresis (these drugs are thus called aquaretics).
Clinical use: Euvolemic and hypervolemic hyponatremia
