Diuretics

Question 1

Osmotic Diuretic drugs

Answer 1

Mannitol
Urea
Glycerin
Isosorbide

Question 2

Site of action of Osmotic diuretics

Answer 2

Acts on both the Loop of Henle, which is the primary site, and in the Proximal Tubule, which is the secondary site

Question 3

Therapeutic uses of Osmotic diuretics

Answer 3

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

Question 4

Osmotic diuretics pharmacokinetics

Answer 4

Mannitol and Urea are administered IV
Glycerin and Isosorbide are administered orally
Mannitol is not metabolized and is eliminated rapidly by the kidneys

Question 5

Loop or High Ceiling Diuretic drugs

Answer 5

Furosemide
Bumetanide
Ethacrynic acid

Question 6

Site of action of Loop Diuretics

Answer 6

Thick ascending limb of the Loop of Henle

Question 7

MOA of Loop Diuretics at site of action

Answer 7

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

Question 8

MOA of Loop Diuretics at the Distal Tubule and Collecting Duct

Answer 8

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

Question 9

MOA of Loop Diuretics elsewhere

Answer 9

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

Question 10

Edema therapeutic uses of Loop Diuretics

Answer 10

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

Question 11

Therapeutic use of Furosemide

Answer 11

Loop Diuretic

Used for treatment of exercise-induced pulmonary hemorrhage in horses

Question 12

Therapeutic uses of Loop Diuretics combined with saline

Answer 12

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

Question 13

Pharmacokinetics of Furosemide

Answer 13

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

Question 14

Adverse effects of Loop Diuretics

Answer 14

Ototoicity
Hypokalemia
Hypomagnesemia
Acute hypovolemia
Hypotension
Hyperglycemia
Systemic alkalosis

Question 15

Thiazide Diuretic drugs

Answer 15

Hydrochlorothiazide

Chlorothiazade

Question 16

Site of action of Thiazide Diuretics

Answer 16

Distal convoluted tubule

Question 17

MOA of Thiazide Diuretics

Answer 17

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

Question 18

Therapeutic uses of Thiazide Diuretics

Answer 18

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

Question 19

Adverse effects of Thiazide Diuretics

Answer 19

Electrolyte imbalanes (hyponatremia, hypokalemia, hypomagnesemia) are less than with Loop Diuretis
Hyperglycemia
Hypersensitivity reactions in patients allergic to sulfonamides
Hyperlipidemia

Question 20

Pharmacokinetics of Thiazide Diuretics

Answer 20

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

Question 21

Potassium-sparing Diuretic drugs

Answer 21

Spironolactone
Triamterene
Amiloride

Question 22

Site of action of Potassium-sparing Diuretics

Answer 22

Late distal tubule and collecting duct

Question 23

MOA of Potassium-sparing Diuretics

Answer 23

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

Question 24

Therapeutic uses of Spironolactone

Answer 24

Potassium-sparing Diuretic
Diuretic
Treatment of primary and secondary hyperaldosteronism

Question 25

Adverse effects of Spironolactone

Answer 25

Potassium-sparing Diuretic Hyperkalemia Systemic acidosis Adverse effects on reproduction because it acts on progesterone and androgen receptors

Question 26

Pharmacokinetics of Spironolactone

Answer 26

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

Question 27

MOA of Trimterene and Amiloride

Answer 27

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

Question 28

Therapeutic uses of Trimterene and Amiloride

Answer 28

Potassium-sparing diuretics Treatment of hypokalemia and hypomagnesemia Occasionally used in edematous disorders and hypertensions (very weak diuretics)

Question 29

Adverse effects of Trimterene and Amiloride

Answer 29

Potassium-sparing diuretics Hyperkalemia Systemic acidosis

Question 30

Pharmacokinetics of trimterene and AMiloride

Answer 30

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

Question 31

Carbonic Anhydrase Inhibitor drugs

Answer 31

Acetazolamide Methazolamide Dorzolamide and Brinzolamide (topical ophthalmic)

Question 32

Site of action of Carbonic Anhydrase Inhibitors

Answer 32

Proximal Tubule (primary site) and collecting duct (secondary site)

Question 33

MOA of Carbonic Anhydrase Inhibitors

Answer 33

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

Question 34

Therapeutic uses of Carbonic Anhydrase Inhibitors

Answer 34

Treatment of open angle glaucoma | Acetazolamide has been used in udder edema

Question 35

Adverse effects of Carbonic Anhydrase Inhibitors

Answer 35

``` Mild systemic acidosis Hypokalemia Hyperglycemia Signs in dogs - vomiting, diarrhea, hyperventilation Polyuria and polydipsia Behavior changes pruritus of paws ```

Question 36

Pharmacokinetics of Carbonic Andhydrase Inhibitors

Answer 36

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