PMT, Kruse - Drugs for Heart Failure

Question 1

What type of agent is best used in systolic failure? wHy?

Answer 1

Inotropic agents (digoxin) directly treat myocardial dysfunction by increasing cardiac contractility.

Question 2

What agents DO NOT improve survival?

Answer 2

Diuretics (except aldosterone does) and inotropic agents.

Question 3

What are the three types of inotropic agents?

Answer 3

1) Cardiac glycosides - digoxin
2) Bipyridines - inamrinon and milrinone
3) B-agonists - dobutamine and dopamine

Question 4

Digoxin:

• Agent and class
• Used for
• Pharmacokinetics

Answer 4

• Agent and class - Inotropic, cardiac glycoside
• Used for HF and afib
• Pharmacokinetics - oral and 1/day dose

Question 5

Digoxin:

• MOA
• Desired physiological effects

Answer 5

• MOA - Inhibits membrane bound Na/K ATPase = increases Ca in SR
• Desired physiological effects: 1) increase contractility; 2) prolong AVN refractory period in supraventricular arrhythmias

Question 6

Digoxin:

• Cardiac toxicity
• Other toxicity

Answer 6

• Cardiac - Arrhythmias and Tachycardia deteriorating into fibrillation is fatal.
• GI - anorexia/N/V/D
• CNS - hallucination, vision

Question 7

Does SNS or PSN-mimetic effects dominate cardiac tissue at therapeutic levels of digoxin? What drug inhibits theses effects?

Answer 7

Parasympathomimetic effects.

Atropine inhibits

Question 8

What electrolyte binds to the same sites as digoxin on Na/K ATPase? So, can use this electrolyte to do what?

Answer 8

Potassium. Use K to reduce digoxin toxic effects.

Question 9

What increases risk of digoxin induced arrhythmias?

What do you give for a digoxin induced arrhythmia?

Answer 9

HyperCa and HypoMg

Mg

Question 10

Inamrinone and milrinone

• Agent and class
• Used for
• Pharmacokinetics

Answer 10

• Agent and class - Cardiac glycoside, bipyridine
• Used for SHORT TERM support of circulation in SEVERE HF
• Pharmacokinetics - parenteral.

Question 11

Inamrinone and milrinone

• MOA
• Desired physiological effects

Answer 11

• MOA - inhibition of PDE3, which increases cAMP

- Desired physiological effects - stimulate myocardial contractility and decrease LV afterload, which INCREASES CO

Question 12

What two things have the same MOA as bipyridines?

Answer 12

Caffeine and theophylline (asthma meds, bronchodilator).

Question 13

Inamrinone and milrinone toxicity, respectively.

Answer 13

Inamrinone - N/V/D, thrombocytopenia, liver enzyme changes.

Milrinone - arrhythmias

Question 14

Dobutamine

• Agent and class
• Used for
• Pharmacokinetics
• MOA
• Desired physiological affects
• Toxicity

Answer 14

• Cardiac glycosides, B1-receptor AGONIST
• Used for systolic dysfunction and HF
• Pharmacokinetics - parenteral
• MOA - B1 receptor selective stimulator
• Desired physiological affects are increased SV and CO
• Toxicity - tachycardia and arrhythmia

Question 15

Dopamine

• Agent and class
• Used for
• Pharmacokinetics
• MOA
• Desired physiological affects
• Toxicity

Answer 15

• Agent and class - cardiac glycoside, D1-receptor agonist
• Used for raising BP (limited use in HF patients)&raquo_space; sepsis or anaphylaxis - in which circ failure dt vasodilation)
• Pharmacokinetics - parenteral
• MOA - D1 receptor selective stimulator
• Desired physiological affects - 1) low doses vasodilate, 2) Intermediate doses stimulate B-receptors on heart 3) high doses cause peripheral vasoconstriction (stims alpha)
• Toxicity - tachycardia, ischemia in CAD

Question 16

What is the MOA of both stimulation of B1 and D1 receptors (dobutamine and dopamine)?

Answer 16

Stimulation of Gs-AC-cAMP-PKA pathway, which enhances Ca-dependent contraction and speeds relaxation.

Question 17

What are the four types of diuretics used in HF?

Answer 17

1) Loops - bumetamide, furosemide, torsemide
2) Thiazide - HCTZ
3) Aldosterone antagonists - eplerenone, spironolactone
4) ADH antagonists - Conivaptan, tolvaptan

Question 18

What is each type of diuretic used for most?

Which improves survival?

Answer 18

Tx congestive symptoms - dec. preload.

• Loop - HF
• Thiazide - systemic HTN
• Aldosterone antagonists - advanced HF **improves survial
• ADH antagonists - HF

Question 19

What is conivaptan toxicity.

MOA of this ADH antagonist.

Answer 19

Toxicity of conivaptan - hyperNa, nephrogenic DI.

V1a and V2 receptor antagonist in CCT.

Question 20

Other than Na and water retention, what else does Ald do that spironolactone and eplerenone inhibit?

Answer 20

Myocardial and vascular fibrosis/remodeling.

Question 21

MOA of ACEi (-ipril)

What does this result in?

Answer 21

• Inhibit Ang2, which is a vasoconstrictor and increases Na/water retention.
• Ang2 inhibition results in decreased preload (dec fluid) and afterload (vasodilates)

Question 22

ACEi does what three things?

Answer 22

• Suppresses Ang2»ald
• Dec. SNS activity
• Reduces remodeling of heart and vessels

Question 23

MOA of ACEi reducing remodeling.

Answer 23

stops ACE degradation of bradykinin, which stimulates NO production. Increased bradykinin stops remodeling.

Question 24

MOA of ARBs (-sartan)

Answer 24

Antagonizes AT1

Question 25

Types of vasodilators and what vessels they affect.

Answer 25

1) Isosorbide dinitrate - venodilator (dec preload) 2) Hydralazine - arteriolar dilator (dec BP and afterload = inc CO) 3) Nitroprusside - veno and arteriolar dilator (inc. CO)

Question 26

Isosorbide dinitrate is used for what? | AE?

Answer 26

- acute and chronic HR - Angina - AE - postural hypotension, tachy, HA Venodilator = use for dyspnea

Question 27

Hydralazine is used for what? | AE

Answer 27

- Use with nitrates to reduce mortality in patients with HF. | - AE - tachycardia, fluid retention, Lupus-like syndrome

Question 28

Use nitroprusside for what?

Answer 28

Acute cardiac decompensation and HTN emergencies (malignant HTN).

Question 29

Nesiritide - Agent and class - Used for - Pharmacokinetics - MOA - Desired physiological affects - Toxicity

Answer 29

- Agent and class - natriuretic peptide - Used in acutely decompensated HF with dyspnea at rest or minimal activity - Pharmacokinetics - given IV - MOA - type of BNP - Desired physiological affects - vasodilation, natriuresis, diuresis to counteract effects of angiotensin and NE - Toxicity - excessive hypotension, renal damage

Question 30

BBlockers

Answer 30

reduce mortality - Decrease SNS - Bisoprolol = B1antagonist - Carvedilil = NS B ant and A1 ant = mild to severe HF - Metoproplol = B1 sel antag - mild to severe HF

Question 31

First line of therapy for chronic HF.

Answer 31

ACEi and diuretics

Question 32

What do you initiate to antagonize cat effects?

Answer 32

BB

Question 33

What do you give if ACEi and diuretics fail to control symptoms?

Answer 33

digoxin

Question 34

Give what to: | 1) Patient with dyspnea with high filling pressures

Answer 34

1) Venodilator - isosorbide

Question 35

Worsening HF due to cat effects, initiate what?

Answer 35

BB

Question 36

Do not combine what drug with a loop?

Answer 36

Digoxin - due to K loss with Loop.

Question 37

What four things reduce mortality?

Answer 37

1) Aldosterone antagonists 2) Hydralazine + nitrate 3) BB 4) ACEi