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Flashcards in E1. Diuretics Deck (37):
1

What are the different classes of diuretics? (7)

- Cardiovascular diuretics
- Physiological diuretics
-Osmotic diuretics
-Loop or high ceiling diuretics
-Thiazide diuretics
-Potassium – sparing diuretics
-Carbonicanhydrase inhibitors

2

What is a diuretic?

Diuretic is a drug that increases the rate of urine flow. They are also able to increase the rate of sodium excretion (usually as sodium chloride).

3

The 2 major types of cardiovascular diuretics?

Digitalis (digoxin)
Phosphodiesterase inhibitors
– aminophylline
– inamrinone
–milrinone

4

A dog came into your clinic with edema associated with congestive heart failure, what drug(s) should you use?
A.Sodium chloride
B. Digitalis
C. Digoxin
D. B and C
E. All of the above

D. B and C

5

What drugs are physiological diuretics? What can they be used in?

Water
– used to compensate chronic interstitial nephritis of dogs
Sodium chloride
– used in urolithiasis in sheep, calves and cats.

6

What drugs are osmotic diuretics?

Mannitol
Urea
Glycerin
Isosorbide

7

Where and how do osmotic diuretics work?

-They act in the loop of Henle which is the primary site and in the proximal tubule which is a secondary site.
-The may interview with transport mechanisms in the thick ascending limb and increasing the urinary excretion of sodium, potassium, calcium, magnesium, chloride, bicarb, and phosphate.
-It can also act by an osmotic effect medullary tenicity.
- They also increase renal blood flow and renal medullary blood flow by several mechanisms.

8

You have an animal with cerebral edema what class of diuretic should you use?
A. Cardiovascular diuretics
B. Physiological diuretics
C. Osmotic diuretics
D. Loop or high ceiling diuretics
E.Thiazide diuretics

C.Osmotic diuretics

9

You have an animal with glaucoma what class of diuretic should you use?
A. Physiological diuretics
B. Cardiovascular diuretics
C. Carbonic anhydrase inhibitors
D. Potassium – sparing diuretics
E. None of the above

E. None of the above

It should be osmotic diuretics.

10

You have an animal with acute renal failure, what class of diuretics should you use?
A. Osmotic diuretics
B. Thiazide diuretics
C. Carbonic anhydrase inhibitors
D. Potassium – sparing diuretics
E. None of the above

A. Osmotic diuretics

11

What class of diuretics should be used to treat the mobilization of edema fluid and patients with drug overdose?
A. Thiazide diuretics
B. Osmotic diuretics
C. Carbonic anhydrase inhibitors
D. Potassium – sparing diuretics
E. None of the above

B. Osmotic diuretics

12

What are the pharmacokinetics associated with osmotic diuretics? (3)

– Mannitol and urea are administered intravenously
– Glycerin and Isosorbide are administered orally
– mannitol is not metabolized and is eliminated rapidly by the kidneys

13

What are the drugs in your for high ceiling diuretic classifications? (3)

– Furosemide
–Bumetanide
–Ethacrynic

14

What are other names for furosemide? (2)

Lasix or Salix

15

What is the MOA of loop or high ceiling diuretics?

-It will inhibit the sodium potassium chloride symporter

16

Why are the loop diuretics considered to be the most efficacious diuretics?

Because approximately 25% filtered sodium is reabsorbed in the thick ascending loop.

17

When would you want to use a loop or high ceiling diuretic? (8)

– treatment of acute pulmonary edema and pulmonary congestion
– treatment of generalized edema associated with congestive heart failure, chronic renal failure and liver cirrhosis.
– combined with isotonic saline to treat hypercalcemia and to prevent volume depletion.
– may be useful in patients with acute renal failure.
– Treatment of increased intracranial pressure and udder.
– Drug overdose
– Combined with hypertonic saline for the treatment of life-threatening hyponatremia because loop diuretics inhibits the kidney from producing concentrated urine.
– it is effective in the treatment of edema of nephrotic syndrome which is usually refractory to other diuretics.

18

You have an horse that has exercise induced pulmonary hemorrhage, what drug(s) should you use?
A. Glycerin
B. Digoxin
C. Lasix
D. Furosemide
E. Mannitol

D. Furosemide
C. Lasix

19

What are the adverse effects associated with loop or high ceiling diuretics? (10)

– Ototoxicity
– hypokalemia
– Hypomagnesium
– acute hypovolemia
– hypotension
– cardiac arrhythmias
– hyperglycemia
– Hyperuricemia
– systemic alkalosis
– hypersensitivity reactions in patients allergic to sulfonamides

20

What is the pharmacokinetics of furosemide? (3)(administration, on set of action/duration, metabolism)

– Administered orally and intravenously
– onset of action is rapid and duration of action short
– Partly metabolized by conjugation and partly excreted unchanged in urine and is actively secreted urine by the organic acid secretory mechanism.

21

Name the thiazide diuretics. (2)

– Hydrochlorothiazide
– Chlorothiazide

22

What is the mechanism of action for the thiazide diuretics?

*They inhibit the sodium Chloride symporters in the distal convoluted tubule resulting in inhibition of the tubular reabsorption of sodium, chloride and diuresis.*
It also inhibits potassium and magnesium reabsorption, but *increases reabsorption of calcium.*

*Thiazide diuretics cause hypokalemia and systemic alkalosis by mechanisms similar to loop diuretics.

23

What are the therapeutic uses thiazide diuretics? (5) d

– *Treatment of edema from CHF*, liver cirrhosis, nephrotic syndrome, and acute glomerulonephritis
– treatment of hypertension alone or combined with other antihypertensive drugs
– treatment of nephrogenic diabetes insipidus and useful in *central diabetes insipidus.*
– Treatment of calcium nephrolithiasis and may be useful for the treatment of osteoporosis.
– Treatment of udder edema in cows.

24

What are the adverse effects of thiazide diuretics?(4)

–Electrolyte imbalances (hyponatremia, *hypokalemia (big issue)*, hypomagnesemia) are less than with diuretics.
– Hyperglycemia.
– Hypersensitivity reactions in patients allergic to sulfonamides.
– Hyperlipidemia.

*Hypertension is a risk factor for cardiovascular disease animals.

25

What is the thiazide diuretic pharmokinetics?

– Administered orally
– absorption is slow and incomplete
–*bind extensively to plasma proteins*
– *xcreted mainly by the kidneys and are actively secreted in urine by the organic acid secretory mechanism*.
– Decreased renal blood flow decreases their effectiveness.

26

Name the 3 potassium sparing diuretics.P

–Spironolactone
–Triamterene
–Amiloride

27

What is Spironolactone mechanism of action?

–*competitively blocks aldosterone binding to aldosterone receptor * (also called mineral or decoy receptor, MR) the late distal tubule and the collecting duct.
– This results in excretion of sodium chloride and diuresis as well as retention of potassium and hydrogen.

*Use when you have hyperaldosterone. Action can take a day or so to have diuretic effect. Can treat congestive heart failure.

28

What can dictate Spironolactone efficiency?

Levels and of endogenous aldosterone.

Diuretic effect is mild because only 2% of sodium reabsorption occurs in the late distal tubule and collecting duct.

29

When a therapeutic uses of Spironolactone? (2)

– Diuretic
– treatment of primary and secondary hyperaldosteronism

30

What are the adverse effects of Spironolactone? (3)

– Hyperkalemia
– systemic acidosis
– adverse effects on reproduction because it acts on progesterone and androgen receptors

31

What are Spironolactones pharmacokinetics?

–*oral administration*
– readily absorbed and is highly bound to plasma proteins
– extensively metabolized by the liver and is converted to an active metabolite
–*onset of action is slow (2 – 3 days) and duration of action is long*

*sodium channel antagonist, and preventsaldosterone remodeling in the heart

32

What are Tramterene and Amiloride mechanism of action?

–*lots of epithelial sodium channels in the luminal membrane of the principal cells in the late distal tubule and collecting duct*.
– This results in excretion of sodium and diuresis as well as retention of potassium and hydrogen.
– The diuretic efficiency is mild as Spironolactone

33

What are Tramterene and Amiloride therapeutic uses, adverse effects, and pharmacokinetics? (Not extremely important, know Spironolactone)

Therapeutic uses:
– treatment of hypokalemia and hypomagnesemia
– occasionally used in a edematous disorders and hypertension (very weak diuretics)
Adverse effects:
– hyperkalemia
– systemic acidosis
Pharmacokinetics:
– both are administered orally
–Amiloride is excreted by the kidneys
– Triamterene is converted to an active metabolite in the liver which is actively secreted in urine.

34

Name the 4 carbonic anhydrase inhibitors (CAIs)?
Is there a way to know which drugs fall into this category?

– Acetazolamide
– Methazolamide
--Dorzolamide
– brinzolamide

all end in zolamide

35

Give the mechanism of action for the CAIs.

– reversible inhibition of carbonic anhydrase which inhibits the exchange of hydrogen for sodium in the proximal tubule which is the primary site
– secondary site of CA is the collecting duct
– carbonic anhydrase inhibitors lower intraocular pressure (IOP) (Dorzolamide) by inhibition carbonic anhydrase in the eye decreasing formation of aqueous humor.

36

What are the therapeutic uses of CAIs?

–Treatment of open angle glaucoma (Dorzolamide)
–Acetazolmide has been used in udder edema.

37

What are the adverse effects of CAIs? (7)

What is their pharmacokinetics?

(not overly important)

Adverse:
– mild systemic acidosis
– hypokalemia
– hyperglycemia
– signs and dogs (vomiting and diarrhea, hyperventilation)
– PU/PD
– behavioral changes
– pruritus of the paws

Pharmacokinetics:
– Look at slide 61