Heart Failure Drugs

Question 1

Furosemide

Answer 1

• loop diuretic
• blocks NKCC2 in thick ascending loop
• most common
• monitor K+ levels
• induce prostaglandin and NO generation from endothelial cells
• 4-8 hrs duration

Question 2

Ethacrynic Acid

Answer 2

• loop diuretic
• indicated for patients allergic to sulfonamides
• can cause more ototoxicity than furosemide

Question 3

Torsemide

Answer 3

-loop diuretic

Question 4

Bumetanide

Answer 4

-loop diuretic

Question 5

Chlorothiazide

Answer 5

• thiazide diuretic
• blocks Na+/Cl- cotransporter NCC in distal convoluted tubule
• PO
• cause hypokalemia, metabolic alkalosis, hypomagnesemia, hyponatremia, hypercalcemia, hyperglycemia, hyperurecemia

Question 6

HCTZ

Answer 6

• thiazide diuretic
• blocks Na+/Cl- cotransporter NCC in distal convoluted tubule
• PO
• cause hypokalemia, metabolic alkalosis, hypomagnesemia, hyponatremia, hypercalcemia, hyperglycemia, hyperurecemia

Question 7

Chlorthalidone

Answer 7

• thiazide diuretic
• blocks Na+/Cl- cotransporter NCC in distal convoluted tubule
• PO
• cause hypokalemia, metabolic alkalosis, hypomagnesemia, hyponatremia, hypercalcemia, hyperglycemia, hyperurecemia

Question 8

Metolazone

Answer 8

• thiazide diuretic
• blocks Na+/Cl- cotransporter NCC in distal convoluted tubule
• PO
• cause hypokalemia, metabolic alkalosis, hypomagnesemia, hyponatremia, hypercalcemia, hyperglycemia, hyperurecemia

Question 9

Indapamide

Answer 9

• thiazide diuretic
• blocks Na+/Cl- cotransporter NCC in distal convoluted tubule
• PO
• cause hypokalemia, metabolic alkalosis, hypomagnesemia, hyponatremia, hypercalcemia, hyperglycemia, hyperurecemia
• UNIQUE VASODILATORY EFFECTS

Question 10

Triamterene

Answer 10

• K+ sparring diuretic
• blocks ENaC channel
• side effects: hyperkalemia, hyperchloremic metabolic acidosis

Question 11

Amiloride

Answer 11

• K+ sparring diuretic
• blocks ENaC channel
• side effects: hyperkalemia, hyperchloremic metabolic acidosis

Question 12

Spironoloactone

Answer 12

• K+ sparring diuretic
• direct aldosterone antagonist
• opposes aldosterone action in late distal tubule and collecting duct
• side effects: hyperkalemia, hyperchloremic metabolic acidosis, gynecomastia
• aldosterone antagonists may be preventing myocardial and vascular fibrosis

Question 13

Eplerenone

Answer 13

• K+ sparring diuretic
• direct aldosterone antagonist
• opposes aldosterone action in late distal tubule and collecting duct
• side effects: hyperkalemia, hyperchloremic metabolic acidosis
• aldosterone antagonists may be preventing myocardial and vascular fibrosis

Question 14

Vasodilators (ACEi)

Answer 14

• decrease afterload by lowering peripheral resistance
• reduce preload by reducing aldosterone secretion, thereby lowering salt and water retention
• can cause hyperkalemia
• decrease in the degradation of bradykinin, which stimulates NO output
• decrease sympathetic activity by reducing norepinephrine release
• decrease long-term remodeling of the heart vessels
• used in conjunction with diuretics and digitalis
• prolonged treatment reduces CHF and reduces mortality
• in acute MI, ACEi decrease LV diastolic volume, prevent further ventricular dilation, and improve exercise tolerance
• Side Effects: cough, angioedema, hypotension, hyperkalemia, increased fetal mortality

Question 15

ARBs

Answer 15

• block AT1
• decrease afterload by lowering PVR
• reduce preload by reducing aldosterone secretion, thereby lowering salt and water retention
• long-term therapy reduces the risk of death and other cardiovascular events in patients with HF
• does NOT effect bradykinin duration, or production of NO

Question 16

Aliskiren

Answer 16

• renin blocker
• binds to active site of renin
• similar side effects to ACEi

Question 17

Beta-Blockers

Answer 17

• suggested in patients with a decreased LVEF

- bisoprolol, carvedilol, metoprolol succinate

Question 18

Beta Adrenergic Antagonists

Answer 18

• attentuation of the adverse effects of high concentrations of catecholamines (including apoptosis)
• up-regulation of beta-1 receptors for increased catecholamine responsiveness
• decreased heart rate and decreased arrhythmogenesis
• reduced remodeling through inhibition of the mitogenic activity of catecholamines
• short term: no acute lowering of CO; myocardial depression is balanced with vasodilation
• long term: prevents deterioration of myocardial function and reverses adrenergically mediated myocardial dysfunction and remodeling in dilated caridomyopathy

Question 19

Digitalis, Digoxin, Digitoxin, Ouabain

Answer 19

• inotropic agents
• cardiac glycosides
• block the Na/K pump
• increased Na oppose action of Na-Ca exchanger NCX, thus raising intracellular cytosolic Ca++ concentration
• increased cytosolic Ca++ increases Ca++ levels in sacroplasmic reticulum
• action potential then release greater-than-normal Ca++ to increase contraction
• K+ antagonizes action of digitalis
• decrease sympathetic output (direct and reflex) and increased vagal activity
• decrease in HR and increased vasodilation
• increased renal perfusion
• some inhibition of renal Na/K ATPase promoting Na+ excretion and diuresis
• improved renal perfusion dynamics and reduced renin output

Question 20

Digoxin

Answer 20

• reduces morbidity and hosptializations in CHF
• fewer deaths from failure are balanced with more from sudden death
• does seem to support the ability of ACEi to retard progressive cardiac deterioration in CHF

Question 21

Effects of Ouabain

Answer 21

• increases calcium releasse
• at toxic levels, action potential shortens further and a oscillatory depolarization is evoked, causing a calcium increment and an additional contraction
• Ouabain has low lipid solubility and is almost never used

Question 22

Istaroxime

Answer 22

-investigational steroid derivative that inhibits Na/K pump, but in addition facilitates Ca++ sequestration by the SR, which may render the drug less arrhythmogenic than digoxin

Question 23

Digitalis on Cardiac Electrical Fxns

Answer 23

• enhances vagal tone and reduces sympathetic activity
• slows conduction velocity and increases refractoriness in AV node
• reduces rate of ventricular stimulation in patients with atrial fibrillation or flutter
• can convert some SVT reentrant arrhythmias to normal rhythm

Question 24

Digitalis at Toxic Levels

Answer 24

• AV block
• promotes many forms of arrhythmia due to enhancement of vagal tone and extreme inhibition of Na/K pump
• increases sympathetic outflow, sensitizing the myocardium
• nausea, vomiting, visual disturbances
• digitalis induced tachyarrythmias treated with K+ if hypokalemia present, lidocaine, or Digitalis antibody

Question 25

Milrinone

Answer 25

- bipyridines - selective for phosphodiesterase isozyme 3 (PDE3) - increased cAMP and phosphorylation/activation of L-type calcium channels, raising Ca++ and increasing myocardial contractility - increased cAMP --> vasodilation - safe and effective for short term (<24 hrs) support of decompensated HF or for an exacerbation of CHF - useful when other txts are failing - less prone to produce arrhytmmias than adrenergics or digitalis - more likely to promote fatal arrhythmias than Inamrinone - produces less bone marrow and liver toxicity

Question 26

Inamrinone

Answer 26

- bipyridines - selective for phosphodiesterase isozyme 3 (PDE3) - increased cAMP and phosphorylation/activation of L-type calcium channels, raising Ca++ and increasing myocardial contractility - increased cAMP --> vasodilation - safe and effective for short term (<24 hrs) support of decompensated HF or for an exacerbation of CHF - useful when other txts are failing - less prone to produce arrhytmmias than adrenergics or digitalis - increases mortality relative to placebo - tachyphylaxis (receptor desensitization) - toxicity includes nausea, vomiting, arrhythmias, thrombocytopenia, liver enzyme changes

Question 27

Dobutamine

Answer 27

- beta-adrenergic agonist - activates adenylate cyclase to make cAMP - increased Ca++ levels in the SR to increase contraction - useful in txt of HF not accompanied by hypotension - synthetic analog of dopamine that stimulates beta-1 and beta-2 and alpha receptors - incrases contractility thorugh beta-1 - does not increase peripheral resistance because beta-2 and alpha-1 balance each other out

Question 28

Norepinephrine

Answer 28

- acts at beta-1 and peripheral alpha-receptors | - used for "warm" septic shock (good PVR)

Question 29

Epinephrine

Answer 29

- acts at beta-1, beta2, and peripheral alpha-receptors - useful for increasing contraction and HR - used for cardiac arrest - contraindicated in pts receiving beta-blocker therapy because of risk of alpha-mediated severe hypertension