Diuretics Flashcards
Osmotic Diuretic drugs
Mannitol
Urea
Glycerin
Isosorbide
Site of action of Osmotic diuretics
Acts on both the Loop of Henle, which is the primary site, and in the Proximal Tubule, which is the secondary site
Therapeutic uses of Osmotic diuretics
Treatment of cerebral edema (Mannitol is contraindicated in generalized edema) Treatment of glaucoma Treatment of acute renal failure Mobilization of edema fluid Used in patients with drug overdose
Osmotic diuretics pharmacokinetics
Mannitol and Urea are administered IV
Glycerin and Isosorbide are administered orally
Mannitol is not metabolized and is eliminated rapidly by the kidneys
Loop or High Ceiling Diuretic drugs
Furosemide
Bumetanide
Ethacrynic acid
Site of action of Loop Diuretics
Thick ascending limb of the Loop of Henle
MOA of Loop Diuretics at site of action
Inhibit the Na+-K-2Cl symporter at the luminal membrane in the thick ascending limb of the Loop of Henle
Also results in inhibiting the paracellular reabsorption of Na+, Ca2+, and Mg2+
Loop diuretics are the most efficacious because about 25% of filtered Na+ is reabsorbed in the thick ascending limb
MOA of Loop Diuretics at the Distal Tubule and Collecting Duct
Increase Na+ delivery to the distal tubule and collecting duct which increases depolarization of the luminal membrane, creating a negative lumen
This facilitates K+ excretion in principal cells and H+ secretion in type A intercalated cells into the lumen
This results in hypokalemia and systemic alkalosis
MOA of Loop Diuretics elsewhere
Stimulates the Renin-Angiotensin-Aldosterone system, contributing to hypokalemia and systemic alkalosis
Increase total renal blood flow by a mechanism which may involve prostaglandins
Increase systemic venous capacitance which may be mediated by prostaglandins
Edema therapeutic uses of Loop Diuretics
Treatment of acute pulmonary edema and pulmonary congestion
Treatment of generalized edema associated with congestive heart failure, chronic renal failure, and liver cirrhosis
Treatment of increased intracranial pressure and udder edema
Treatment of edema of nephrotic syndrome which is usually refractory to other diuretics
Therapeutic use of Furosemide
Loop Diuretic
Used for treatment of exercise-induced pulmonary hemorrhage in horses
Therapeutic uses of Loop Diuretics combined with saline
Combined with isotonic saline to treat hypercalcemia and to prevent volume depletion
Combined with hypertonic saline for the treatment of life-threatening hyponatremia because loop diuretics inhibit the kidney from producing concentrated urine
Pharmacokinetics of Furosemide
Loop Diuretic
Administered intravenously and orally
Onset of action is rapid and duration is short
Partly metabolized by conjugation and partly excreted unchanged in urine, and actively secreted in urine by the organic acid secretory mechanism
Adverse effects of Loop Diuretics
Ototoicity Hypokalemia Hypomagnesemia Acute hypovolemia Hypotension Hyperglycemia Systemic alkalosis
Thiazide Diuretic drugs
Hydrochlorothiazide
Chlorothiazade
Site of action of Thiazide Diuretics
Distal convoluted tubule
MOA of Thiazide Diuretics
Inhibit the Na+-Cl symporter in the distal convoluted tubule resulting in inhibition of tubular reabsorption of Na+,Cl, and diuresis
Diuretic efficacy is moderate because 5% of Na+ occurs in the early distal tubule
Inhibit K+ and Mg2+ reabsorption but increase reabsorption of Ca2+
This causes hypokalemia and systemic alkalosis by mechanisms similar to Loop Diuretics
Therapeutic uses of Thiazide Diuretics
Treatment of edema of CHF, liver cirrhosis, nephrotic syndrome, and acute glomerular nephritis
Treatment of nephrogeni diabetes insipidus
Treatment of calcium nephrolithiasis
Treatment of udder edema in cows
Treatment of hypertension alone or combined with other antihypertensive drugs
Adverse effects of Thiazide Diuretics
Electrolyte imbalanes (hyponatremia, hypokalemia, hypomagnesemia) are less than with Loop Diuretis
Hyperglycemia
Hypersensitivity reactions in patients allergic to sulfonamides
Hyperlipidemia
Pharmacokinetics of Thiazide Diuretics
Administered orally
Bind extensively to plasma proteins
Excreted mainly by the kidneys and actively secreted in urine by the organic acid secretory mechanism
Decreased renal blood flow decreases their effectiveness
Potassium-sparing Diuretic drugs
Spironolactone
Triamterene
Amiloride
Site of action of Potassium-sparing Diuretics
Late distal tubule and collecting duct
MOA of Potassium-sparing Diuretics
Competitively blocks aldosterone by binding to aldosterone receptor in the late distal tubule and collecting duct (=aldosterone antagonist)
This results in excretion of NaCl and diuresis, as well as retention of K+ adn H+
Diuretic efficacy depends on the levels of endogenous aldosterone
Diuretic efficacy is mild because only 2% of Na+ reabsorption occurs in the late distal tubule and collecting duct
Therapeutic uses of Spironolactone
Potassium-sparing Diuretic
Diuretic
Treatment of primary and secondary hyperaldosteronism
Adverse effects of Spironolactone
Potassium-sparing Diuretic
Hyperkalemia
Systemic acidosis
Adverse effects on reproduction because it acts on progesterone and androgen receptors
Pharmacokinetics of Spironolactone
Potassium-sparing diuretic
Administered orally
Readily absorbed and highly bound to plasma proteins
Extensively metabolized by liver and converted to an active metabolite
Onset of action is slow (2-3 days) and duration is long
MOA of Trimterene and Amiloride
Potassium-sparing diuretics
Block epithelial Na+ channels in the luminal membrane of the principal cells in the late distal tubule and collecting duct
This results in excretion of Na+ and diuresis, as well as retention of K+ and H+
The diuretic efficacy is mild, similar to Spironolactone
Therapeutic uses of Trimterene and Amiloride
Potassium-sparing diuretics
Treatment of hypokalemia and hypomagnesemia
Occasionally used in edematous disorders and hypertensions (very weak diuretics)
Adverse effects of Trimterene and Amiloride
Potassium-sparing diuretics
Hyperkalemia
Systemic acidosis
Pharmacokinetics of trimterene and AMiloride
Potassium-sparing diuretics
Administered orally
Amiloride is excreted by the kidneys
Trimeterene is converted to an active metabolite int he liver which is actively secreted in the urine
Carbonic Anhydrase Inhibitor drugs
Acetazolamide
Methazolamide
Dorzolamide and Brinzolamide (topical ophthalmic)
Site of action of Carbonic Anhydrase Inhibitors
Proximal Tubule (primary site) and collecting duct (secondary site)
MOA of Carbonic Anhydrase Inhibitors
Reversible inhibition of carbonic anhydrase which inhibits the exchange for Na+ in the proximal tubule
Carbonic anhydrase inhibitors lower intraocular pressure (IOP) by inhibition of CCA in the eye, decreasing formation of aqueous humor
Therapeutic uses of Carbonic Anhydrase Inhibitors
Treatment of open angle glaucoma
Acetazolamide has been used in udder edema
Adverse effects of Carbonic Anhydrase Inhibitors
Mild systemic acidosis Hypokalemia Hyperglycemia Signs in dogs - vomiting, diarrhea, hyperventilation Polyuria and polydipsia Behavior changes pruritus of paws
Pharmacokinetics of Carbonic Andhydrase Inhibitors
Acetazolamide is administered orally
Onset of action about 30 minutes and duration about 4-6 hours in small animals
Acetazolamide is eliminated mainly by the kidneys and is actively secreted in urine by the organic acid secretory mechanism
Dorzolamide and Brinzolamide are administered topically on the eye
