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Flashcards in Diuretics Deck (36):
1

Osmotic Diuretic drugs

Mannitol
Urea
Glycerin
Isosorbide

2

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

3

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

4

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

5

Loop or High Ceiling Diuretic drugs

Furosemide
Bumetanide
Ethacrynic acid

6

Site of action of Loop Diuretics

Thick ascending limb of the Loop of Henle

7

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

8

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

9

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

10

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

11

Therapeutic use of Furosemide

Loop Diuretic
Used for treatment of exercise-induced pulmonary hemorrhage in horses

12

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

13

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

14

Adverse effects of Loop Diuretics

Ototoicity
Hypokalemia
Hypomagnesemia
Acute hypovolemia
Hypotension
Hyperglycemia
Systemic alkalosis

15

Thiazide Diuretic drugs

Hydrochlorothiazide
Chlorothiazade

16

Site of action of Thiazide Diuretics

Distal convoluted tubule

17

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

18

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

19

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

20

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

21

Potassium-sparing Diuretic drugs

Spironolactone
Triamterene
Amiloride

22

Site of action of Potassium-sparing Diuretics

Late distal tubule and collecting duct

23

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

24

Therapeutic uses of Spironolactone

Potassium-sparing Diuretic
Diuretic
Treatment of primary and secondary hyperaldosteronism

25

Adverse effects of Spironolactone

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

26

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

27

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

28

Therapeutic uses of Trimterene and Amiloride

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

29

Adverse effects of Trimterene and Amiloride

Potassium-sparing diuretics
Hyperkalemia
Systemic acidosis

30

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

31

Carbonic Anhydrase Inhibitor drugs

Acetazolamide
Methazolamide
Dorzolamide and Brinzolamide (topical ophthalmic)

32

Site of action of Carbonic Anhydrase Inhibitors

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

33

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

34

Therapeutic uses of Carbonic Anhydrase Inhibitors

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

35

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

36

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