Diuretics and vasodilators Flashcards
COLT Pee
Examples: C = acetazolamide, O = mannitol, L = furosemide, T = hydrochlorothiazide, P = Spironolactone
What conditions is use of a carbonic anhydrase inhbitor contrainidicated?
- Severe hepatic disease
- Hepatoencephalopathy
worsens hyperammonemia
Why is use of an osmotic diuretic contrainidicated in animals with cardiopulmonary disease?
May result in hypernatremia
-> may exacerbate pulmonary edema, ascites, etc.
Mannitol
What are osmotic diuretics mainly used for?
Oliguric renal failure
Oliguria = low urine output
What drugs are “high-ceiling” diuretics and what does it mean?
Loop Diuretics like furosemide –> Potency keeps increasing as you continue administering.
Also has dose-dependent diuretic effects
MoA of loop diuretics
Decrease sodium and chloride reabsorption => decrease reabsorption, increased excretion
(inhibition of Na+/K+/2Cl- co-transporter in thick asc. loop of Henle_
What species can a loop diuretic NOT be administered PO in?
HORSES (5% oral absorption)
Duration of action and effect peaks of furosemide
duration: IV = 2hr, PO = 6hr
peak: IV = 30min, PO = 1-2hr
How is furosemide cleared from the body?
Renal clearance with >90% bound to albumin in the urine//tubule (and not the plasma)
Proteinuria may decrease drug effectiveness (thus decreased urination)
How is furosemide dosed?
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
Potential electrolyte abnormalities seen with Furosemide (5)
Pros/cons of torsemide (alternative to furosemide)
Loop diuretics
Pros: increased PO bioavail.; longer half life (q24 vs 12h dosing)
Cons: increased risk of renal effects
MoA of thiazide diuretics
Inhibit Na/Cl- transporter on luminal side of proximal distal convulated tubule
Clinical use of thiazide diuretics
Contraindications of thiazide diuretics
hypercalemic or azotemic pts
enhances Ca reabsorption; decreases renal blood flow
MoA of K-sparing diuretics (spironolactone)
competitive ANTAGONIST of aldosterone
spirono-LACKS-aldosterone!
Why is spironolactone typically combined with other drugs?
E.g., pt in CHF needs effects asap
B/c its peak effect takes 2-3 days.
What is a (rare) ADE of spironolactone in cats?
RARE, but can cause Facial dermatitis/pruritis - seen months after starting, goes away after stopping
RAAS
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
ACE
Angiotensin Converting Enzyme (converts angiotensis I into II)
Most common ACEIs
Benazepril and Enalapril
“-PRIL” = Put Renin In Limbo
All ACEIs are PRODRUGS!
PKs of Enalapril vs Benazepril (dog, cat, horse)
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
Clinical uses of ACEIs in dogs, cats and horses
Common ADE of ACEIs
Overdose can lead to severe, persistent HYPOtension
Sildenafil - drug class, moa, uses
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
Hydralazine - drug class, moa, uses
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
Why should NSAIDs not be used with diuretics and vasodilator drugs?
NSAIDS reduce their effects via inhibiting prostaglandin-mediated vasodilation and natriuresis
Drug-drug interactions of diuretics and vasodilators with Digoxin
- 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)
What drug interactions can cause hyperkalemia?
