PMT, Kruse - Drugs for Heart Failure Flashcards
What type of agent is best used in systolic failure? wHy?
Inotropic agents (digoxin) directly treat myocardial dysfunction by increasing cardiac contractility.
What agents DO NOT improve survival?
Diuretics (except aldosterone does) and inotropic agents.
What are the three types of inotropic agents?
1) Cardiac glycosides - digoxin
2) Bipyridines - inamrinon and milrinone
3) B-agonists - dobutamine and dopamine
Digoxin:
- Agent and class
- Used for
- Pharmacokinetics
- Agent and class - Inotropic, cardiac glycoside
- Used for HF and afib
- Pharmacokinetics - oral and 1/day dose
Digoxin:
- MOA
- Desired physiological effects
- 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
Digoxin:
- Cardiac toxicity
- Other toxicity
- Cardiac - Arrhythmias and Tachycardia deteriorating into fibrillation is fatal.
- GI - anorexia/N/V/D
- CNS - hallucination, vision
Does SNS or PSN-mimetic effects dominate cardiac tissue at therapeutic levels of digoxin? What drug inhibits theses effects?
Parasympathomimetic effects.
Atropine inhibits
What electrolyte binds to the same sites as digoxin on Na/K ATPase? So, can use this electrolyte to do what?
Potassium. Use K to reduce digoxin toxic effects.
What increases risk of digoxin induced arrhythmias?
What do you give for a digoxin induced arrhythmia?
HyperCa and HypoMg
Mg
Inamrinone and milrinone
- Agent and class
- Used for
- Pharmacokinetics
- Agent and class - Cardiac glycoside, bipyridine
- Used for SHORT TERM support of circulation in SEVERE HF
- Pharmacokinetics - parenteral.
Inamrinone and milrinone
- MOA
- Desired physiological effects
- MOA - inhibition of PDE3, which increases cAMP
- Desired physiological effects - stimulate myocardial contractility and decrease LV afterload, which INCREASES CO
What two things have the same MOA as bipyridines?
Caffeine and theophylline (asthma meds, bronchodilator).
Inamrinone and milrinone toxicity, respectively.
Inamrinone - N/V/D, thrombocytopenia, liver enzyme changes.
Milrinone - arrhythmias
Dobutamine
- Agent and class
- Used for
- Pharmacokinetics
- MOA
- Desired physiological affects
- Toxicity
- 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
Dopamine
- Agent and class
- Used for
- Pharmacokinetics
- MOA
- Desired physiological affects
- Toxicity
- Agent and class - cardiac glycoside, D1-receptor agonist
- Used for raising BP (limited use in HF patients)»_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
What is the MOA of both stimulation of B1 and D1 receptors (dobutamine and dopamine)?
Stimulation of Gs-AC-cAMP-PKA pathway, which enhances Ca-dependent contraction and speeds relaxation.
What are the four types of diuretics used in HF?
1) Loops - bumetamide, furosemide, torsemide
2) Thiazide - HCTZ
3) Aldosterone antagonists - eplerenone, spironolactone
4) ADH antagonists - Conivaptan, tolvaptan
What is each type of diuretic used for most?
Which improves survival?
Tx congestive symptoms - dec. preload.
- Loop - HF
- Thiazide - systemic HTN
- Aldosterone antagonists - advanced HF **improves survial
- ADH antagonists - HF
What is conivaptan toxicity.
MOA of this ADH antagonist.
Toxicity of conivaptan - hyperNa, nephrogenic DI.
V1a and V2 receptor antagonist in CCT.
Other than Na and water retention, what else does Ald do that spironolactone and eplerenone inhibit?
Myocardial and vascular fibrosis/remodeling.
MOA of ACEi (-ipril)
What does this result in?
- Inhibit Ang2, which is a vasoconstrictor and increases Na/water retention.
- Ang2 inhibition results in decreased preload (dec fluid) and afterload (vasodilates)
ACEi does what three things?
- Suppresses Ang2»ald
- Dec. SNS activity
- Reduces remodeling of heart and vessels
MOA of ACEi reducing remodeling.
stops ACE degradation of bradykinin, which stimulates NO production. Increased bradykinin stops remodeling.
MOA of ARBs (-sartan)
Antagonizes AT1
Types of vasodilators and what vessels they affect.
1) Isosorbide dinitrate - venodilator (dec preload)
2) Hydralazine - arteriolar dilator (dec BP and afterload = inc CO)
3) Nitroprusside - veno and arteriolar dilator (inc. CO)
Isosorbide dinitrate is used for what?
AE?
- acute and chronic HR
- Angina
- AE - postural hypotension, tachy, HA
Venodilator = use for dyspnea
Hydralazine is used for what?
AE
- Use with nitrates to reduce mortality in patients with HF.
- AE - tachycardia, fluid retention, Lupus-like syndrome
Use nitroprusside for what?
Acute cardiac decompensation and HTN emergencies (malignant HTN).
Nesiritide
- Agent and class
- Used for
- Pharmacokinetics
- MOA
- Desired physiological affects
- Toxicity
- 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
BBlockers
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
First line of therapy for chronic HF.
ACEi and diuretics
What do you initiate to antagonize cat effects?
BB
What do you give if ACEi and diuretics fail to control symptoms?
digoxin
Give what to:
1) Patient with dyspnea with high filling pressures
1) Venodilator - isosorbide
Worsening HF due to cat effects, initiate what?
BB
Do not combine what drug with a loop?
Digoxin - due to K loss with Loop.
What four things reduce mortality?
1) Aldosterone antagonists
2) Hydralazine + nitrate
3) BB
4) ACEi
