Cardiovascular: Diuretics Flashcards
Definition of heart failure
inability of the heart to pump sufficient blood to sustain normal function
What causes heart failure?
- impaired cardiac muscle ability
- increase workload
How are RAS system activated?
reduced BP or volume causes stimulation of baroreceptor in the carotid sinus & aortic arch
What does RAS activation result in?
- incrreased sympathetic activity
- ADH release by hypothalamus
- retention of Na+ & water
What is preload?
volume of fluid in the heart prior to contraction
What does excess preload cause?
congestion (edema, ascite, hepatic congestion)
What is afterload?
pressure that the heart has to push against
What does excess afterload result in?
- mitral valve regurgitation
- decreased cardiac output
What are the pharmacological objectives to treat heart failure?
- decrease preload
- decrease afterload
- alter heart contraction
- decrease sympathetic input
- address arrhythmia
How can preload be decreased directly?
- decrease blood volume
- increase venous capacity
How can the preload be decreased indirectly?
- increasing fill time
- increasing stroke volume/ cardiac output
What are the classes of drugs that can directly decrease preload?
- diuretics
- venodilator
Why does congestive heart failure lead to an increase in blood volume?
increased water & sodium retention
What happens during congestive heart failure?
- increased preload
- increased afterload
- increased vascular stiffness
Why does vascular stiffness occur during congestive heart failure?
- Na+ accumulation in vascular smooth muscle
- increased Ca2+ influx by Na-Ca exchanger
- increased Ca2+ increases contraction of smooth muscle
What do diuretics do?
- increase the volume and flow of urine; hence increasing the excretion of water
- increase Na+ excretion
Why are diuretics commonly used to manage congestive heart failure?
- directly decrease preload by decreasing blood volume
What are some other uses for diuretics?
- acute renal failure
- increased intracranial/ intraocular pressure
-increase excretion of toxin
What type of diuretic is furosemide?
- high-ceiling diuretic
- loop diuretic
- highly protein bound
- excreted by renal tubule
Mechanism of action of furosemide
- inhibit Na+/Cl-reabsorption by inhibition of the Na/K/Cl co-transporter in the ascending loop of Henle
- loss of Na+, Cl-, & water
- increase synthesis of local prostaglandin that causes renal vasodilation
Adverse effects of furosemide
- dehydration & volume depletion
- hypokalemia & hyponatremia
- exacerbation of respiratory disease
Contraindication of furosemide
- digoxin interaction
- NSAIDs
Mechanism of action Thiazide diuretics
- decrease permeability of distal tubule by inhibition of Na/Cl transporter in the distal convoluted tubule
- decrease NaCl and water reabsorption
What is Torsemide
- loop diuretic with higher bioavailability & longer duration of action than furosemide
- some aldosterone blocking effect to reduce chance of tolerance
Clinical effect of Thiazide diuretics
- increase Na+ and water elimination
- increase K+ loss
- increase Ca2+ absorption
- mild direct vasodilatory effect
How does Thiazide diuretics cause increase in Ca2+ absorption?
increase in extracellular Na leads to increased Na-Ca exchange;hence increase Ca reabsorption
What is special about thiazide diuretics regarding diabetes insipidis?
paradoxically reduce urine production
Adverse effects of thiazide diuretics
hypokalemia, hypercalcemia, hypotension
Mechanism of action for spironolactone
competitive inhibitor of aldosterone & K+ sparing
Special features of spironolactone
- minimal diuretic effect
- usually used in combination due to its K+sparing effect
Contraindication for spironolactone
animals recieving ACE inhibitor or other K+ sparing diuretics
What can result from giving spironolactone to animals receiving ACE inhibitor or other K+ sparing diuretics?
increase risk of hyperkalemia
What are the beneficial effects that spironolactone provide
decrease heart remodeling
Adverse effects of spironolactone
gastric upset, hyperkalemia
What type of diuretic is mannitol?
osmotic diuretic
Mechanism of action of mannitol
- pharmacological inert sugar that remains in the lumen of the renal tubules to draw water out
- small increase of Na/CL excretion
Clinical indication for mannitol
used with acute renal failure, treat increased ocular & intracranial pressure
Adverse effects of mannitol
- extracellular water expansion (extracts water from cell)
- hyper/hyponatremia ( water from cells dilute Na+)
Carbonic anhydrase inhibitors mechanism of action
- inhibit carbonic anhydrase in the proximal tubule, which decreases the intracellular H+
- decreases the exchange of Na+ for H+, which limits Na+ reabsorption
- decreases bicarbonate reabsorption
Adverse effect of carbonic anhydrase inhibitor
- metabolic acidosis
- decrease in K+
Indications for carbonic anhydrase inhibitor
glaucoma
