Diuretics and vasodilators

Question 1

COLT Pee

Answer 1

Examples: C = acetazolamide, O = mannitol, L = furosemide, T = hydrochlorothiazide, P = Spironolactone

Question 2

What conditions is use of a carbonic anhydrase inhbitor contrainidicated?

Answer 2

• Severe hepatic disease
• Hepatoencephalopathy

worsens hyperammonemia

Question 3

Why is use of an osmotic diuretic contrainidicated in animals with cardiopulmonary disease?

Answer 3

May result in hypernatremia

-> may exacerbate pulmonary edema, ascites, etc.

Mannitol

Question 4

What are osmotic diuretics mainly used for?

Answer 4

Oliguric renal failure

Oliguria = low urine output

Question 5

What drugs are “high-ceiling” diuretics and what does it mean?

Answer 5

Loop Diuretics like furosemide –> Potency keeps increasing as you continue administering.

Also has dose-dependent diuretic effects

Question 6

MoA of loop diuretics

Answer 6

Decrease sodium and chloride reabsorption => decrease reabsorption, increased excretion

(inhibition of Na+/K+/2Cl- co-transporter in thick asc. loop of Henle_

Question 7

What species can a loop diuretic NOT be administered PO in?

Answer 7

HORSES (5% oral absorption)

Question 8

Duration of action and effect peaks of furosemide

Answer 8

duration: IV = 2hr, PO = 6hr
peak: IV = 30min, PO = 1-2hr

Question 9

How is furosemide cleared from the body?

Answer 9

Renal clearance with >90% bound to albumin in the urine//tubule (and not the plasma)

Proteinuria may decrease drug effectiveness (thus decreased urination)

Question 10

How is furosemide dosed?

Answer 10

To effect, with potentially higher doses with renal disease. Tolerance may develop and dose may need to be increased.

at 4mg/kg, think about adding in other drugs (K-sparing diuretics, ACEIs). STOP at 12mg/kg

Question 11

Potential electrolyte abnormalities seen with Furosemide (5)

Answer 11

Question 12

Pros/cons of torsemide (alternative to furosemide)

Loop diuretics

Answer 12

Pros: increased PO bioavail.; longer half life (q24 vs 12h dosing)

Cons: increased risk of renal effects

Question 13

MoA of thiazide diuretics

Answer 13

Inhibit Na/Cl- transporter on luminal side of proximal distal convulated tubule

Question 14

Clinical use of thiazide diuretics

Answer 14

Question 15

Contraindications of thiazide diuretics

Answer 15

hypercalemic or azotemic pts

enhances Ca reabsorption; decreases renal blood flow

Question 16

MoA of K-sparing diuretics (spironolactone)

Answer 16

competitive ANTAGONIST of aldosterone

spirono-LACKS-aldosterone!

Question 17

Why is spironolactone typically combined with other drugs?

E.g., pt in CHF needs effects asap

Answer 17

B/c its peak effect takes 2-3 days.

Question 18

What is a (rare) ADE of spironolactone in cats?

Answer 18

RARE, but can cause Facial dermatitis/pruritis - seen months after starting, goes away after stopping

Question 19

RAAS

Answer 19

The Renin-Angiotensin-Aldosterone System (RAAS) is a hormone system within the body that is essential for the regulation of blood pressure and fluid balance.

It regulates your blood pressure by increasing sodium (salt) reabsorption, water reabsorption (retention) and vascular tone (the degree to which your blood vessels constrict, or narrow). The RAAS consists of three major substances, including:

Renin (an enzyme) – vasoconstriction when inadequate salt available.
Angiotensin II (a hormone) – vasoconstriction & increases water/salt retention.
Aldosterone (a hormone) – increases sodium levels and SNS activity

Question 20

ACE

Answer 20

Angiotensin Converting Enzyme (converts angiotensis I into II)

Question 21

Most common ACEIs

Answer 21

Benazepril and Enalapril

“-PRIL” = Put Renin In Limbo

All ACEIs are PRODRUGS!

Question 22

PKs of Enalapril vs Benazepril (dog, cat, horse)

Answer 22

Enalapril
- dogs 60% bioavail., half life 11hr, cleared renally
- cats none
- horses poor PO absorption

Benazepril
- dogs concentrations peak @ 75 mins, cleared renally and hepatically
- cats halflife 16-23hr, hepatic clearance
- horse low fraction absorbed (F%) but effects still seen when used PO admin

Question 23

Clinical uses of ACEIs in dogs, cats and horses

Answer 23

Question 24

Common ADE of ACEIs

Answer 24

Overdose can lead to severe, persistent HYPOtension

Question 25

Sildenafil - drug class, moa, uses

Answer 25

PDE Inhibitors work in smooth muscle (blood vessels of heart, lungs)

Sildenafil works in smooth muscle of the small arterioles of the LUNGS –> causes relaxation // vasodilation; used in pulmonary hypertension

Question 26

Hydralazine - drug class, moa, uses

Answer 26

Aterial vasodilator; directly relaxes vasc. smooth muscle in systemic arterioles (inhibits Ca2+); not commonly used in dogs/cats, sometimes used PO and IV in horses with CHF to reduce afterload

Question 27

Why should NSAIDs not be used with diuretics and vasodilator drugs?

Answer 27

NSAIDS reduce their effects via inhibiting prostaglandin-mediated vasodilation and natriuresis

Question 28

Drug-drug interactions of diuretics and vasodilators with Digoxin

Answer 28

• Hypokalemia induced by diuretics (COLT only) -> potentiates digoxin toxicity (fewer Na/K ATP pumps = higher probability digoxin will bind)
• Spironolactone can increase digoxin levels b/c it competes with it for renal elimination)

Question 29

What drug interactions can cause hyperkalemia?

Answer 29