Cardiovascular: Diuretics

Question 1

Definition of heart failure

Answer 1

inability of the heart to pump sufficient blood to sustain normal function

Question 2

What causes heart failure?

Answer 2

1. impaired cardiac muscle ability
2. increase workload

Question 3

How are RAS system activated?

Answer 3

reduced BP or volume causes stimulation of baroreceptor in the carotid sinus & aortic arch

Question 4

What does RAS activation result in?

Answer 4

1. incrreased sympathetic activity
2. ADH release by hypothalamus
3. retention of Na+ & water

Question 5

What is preload?

Answer 5

volume of fluid in the heart prior to contraction

Question 6

What does excess preload cause?

Answer 6

congestion (edema, ascite, hepatic congestion)

Question 7

What is afterload?

Answer 7

pressure that the heart has to push against

Question 8

What does excess afterload result in?

Answer 8

1. mitral valve regurgitation
2. decreased cardiac output

Question 9

What are the pharmacological objectives to treat heart failure?

Answer 9

• decrease preload
• decrease afterload
• alter heart contraction
• decrease sympathetic input
• address arrhythmia

Question 10

How can preload be decreased directly?

Answer 10

• decrease blood volume
• increase venous capacity

Question 11

How can the preload be decreased indirectly?

Answer 11

• increasing fill time
• increasing stroke volume/ cardiac output

Question 12

What are the classes of drugs that can directly decrease preload?

Answer 12

• diuretics
• venodilator

Question 13

Why does congestive heart failure lead to an increase in blood volume?

Answer 13

increased water & sodium retention

Question 14

What happens during congestive heart failure?

Answer 14

1. increased preload
2. increased afterload
3. increased vascular stiffness

Question 15

Why does vascular stiffness occur during congestive heart failure?

Answer 15

• Na+ accumulation in vascular smooth muscle
• increased Ca2+ influx by Na-Ca exchanger
• increased Ca2+ increases contraction of smooth muscle

Question 16

What do diuretics do?

Answer 16

• increase the volume and flow of urine; hence increasing the excretion of water
• increase Na+ excretion

Question 17

Why are diuretics commonly used to manage congestive heart failure?

Answer 17

• directly decrease preload by decreasing blood volume

Question 18

What are some other uses for diuretics?

Answer 18

• acute renal failure
• increased intracranial/ intraocular pressure
  -increase excretion of toxin

Question 19

What type of diuretic is furosemide?

Answer 19

• high-ceiling diuretic
• loop diuretic
• highly protein bound
• excreted by renal tubule

Question 20

Mechanism of action of furosemide

Answer 20

• 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

Question 21

Adverse effects of furosemide

Answer 21

• dehydration & volume depletion
• hypokalemia & hyponatremia
• exacerbation of respiratory disease

Question 22

Contraindication of furosemide

Answer 22

• digoxin interaction
• NSAIDs

Question 23

Mechanism of action Thiazide diuretics

Answer 23

• decrease permeability of distal tubule by inhibition of Na/Cl transporter in the distal convoluted tubule
• decrease NaCl and water reabsorption

Question 24

What is Torsemide

Answer 24

• loop diuretic with higher bioavailability & longer duration of action than furosemide
• some aldosterone blocking effect to reduce chance of tolerance

Question 25

Clinical effect of Thiazide diuretics

Answer 25

- increase Na+ and water elimination - increase K+ loss - increase Ca2+ absorption - mild direct vasodilatory effect

Question 26

How does Thiazide diuretics cause increase in Ca2+ absorption?

Answer 26

increase in extracellular Na leads to increased Na-Ca exchange;hence increase Ca reabsorption

Question 27

What is special about thiazide diuretics regarding diabetes insipidis?

Answer 27

paradoxically reduce urine production

Question 28

Adverse effects of thiazide diuretics

Answer 28

hypokalemia, hypercalcemia, hypotension

Question 29

Mechanism of action for spironolactone

Answer 29

competitive inhibitor of aldosterone & K+ sparing

Question 30

Special features of spironolactone

Answer 30

- minimal diuretic effect - usually used in combination due to its K+sparing effect

Question 31

Contraindication for spironolactone

Answer 31

animals recieving ACE inhibitor or other K+ sparing diuretics

Question 32

What can result from giving spironolactone to animals receiving ACE inhibitor or other K+ sparing diuretics?

Answer 32

increase risk of hyperkalemia

Question 33

What are the beneficial effects that spironolactone provide

Answer 33

decrease heart remodeling

Question 34

Adverse effects of spironolactone

Answer 34

gastric upset, hyperkalemia

Question 35

What type of diuretic is mannitol?

Answer 35

osmotic diuretic

Question 36

Mechanism of action of mannitol

Answer 36

- pharmacological inert sugar that remains in the lumen of the renal tubules to draw water out - small increase of Na/CL excretion

Question 37

Clinical indication for mannitol

Answer 37

used with acute renal failure, treat increased ocular & intracranial pressure

Question 38

Adverse effects of mannitol

Answer 38

- extracellular water expansion (extracts water from cell) - hyper/hyponatremia ( water from cells dilute Na+)

Question 39

Carbonic anhydrase inhibitors mechanism of action

Answer 39

- 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

Question 40

Adverse effect of carbonic anhydrase inhibitor

Answer 40

- metabolic acidosis - decrease in K+

Question 41

Indications for carbonic anhydrase inhibitor

Answer 41

glaucoma