Heart Failure II Flashcards
Dr. Roane EXAM II
MOA of Ivabradine (Corlanor)
-inhibition of “Funny” Na HCN channels on the SA node
-controls the heart rate –> slows the heart, “giving the heart a break”
-Heart failure drug for pts who don’t tolerate ß-blockers
What is the consequence of HFrEF?
-Cardiomegaly - the heart is getting bigger (to pump more blood)
-also after MI (compensation of tissue loss)
-Law of LaPlace
-harder to squeeze due to increased wall tension
Which enzyme is mainly responsible for vascular smooth muscle CONTRACTION?
-MLCK
-activated by Ca2+
-deactivated by Protein Kinase G - cGMP
-deactivated by Protein Kinase A - cAMP
How does cGMP/cAMP get activated?
-GTP is converted to cGMP by the Guanylate cyclase (GC) -> drug target
-ATP is converted to cAMP by the Adenylate cyclase
Which drug targets the soluble Guanylate cyclase?
-Guanylate cyclase activator
-Riociguat
-Vericiguat
-Nitrates activate Nitric oxide (gaseous NT)
-> ADE: flushing due to VASODILATION
What is the indication of Guanylate cyclase activators?
-Pulmonary hypertension
-Riociguat
-Vericiguat
-Hydralazine
MOA of PDE5 inhibitor
-PDE5 breaks down cGMP
-inhibition of PDE5 -> higher level of cGMP and PKG -> VASODILATION
Which effect does Vasodilation of vascular smooth muscles in blood vessels have on the heart’s work rate?
it reduces the work the heart has to overcome to achieve appropriate ejection fraction (pump blood)
-Afterload reduction
Nitrate drug
-Nitroglycerin
-rapid onset, short-acting
-treats angina, to some extent for HF
-causes VENODILATION -> reduces Preload
-Nitroprusside (IV)
-> decompensated HF
Nitrate drug used for decompensated HF
Nitroprusside (IV)
-short half-life
The enzyme that converts Nitrate to nitric oxide
mitochondrial aldehyde dehydrogenase
nitric oxide (NO) stimulates the soluble guanylate cyclase
MOA of Hydrazaline
-used in combination with Isosorbide Dinitrate (ISDN)
-activation of the soluble guanylate cyclase (like NO)
-causes VASODILATION of the veins
-approved for use in African-American
-Nitrates show rapid tolerance -> prevented by hydralazine
How might SGLT2 reduce the risk of HF?
-indicated for diabetes -> blocking the SGLT2 transporter -> more Glucose in the urine (ADE: UTI)
-Glucose attracts water molecules and thereby has a small osmotic and diuretic effect - pulling water into the urine
-diabetic is a risk factor for HF, so lowering blood glucose might help in reducing the risk of HF
SGLT2 blocker drug
-Sotagliflozin (Inpefa)
-blocks SGLT1 and SGLT2
-recommended as the first-line drug for HFrEF
-others like Dapagliflozin are more specific to SGLT2 but still useful in HF
Which curve illustrates the contractility in heart failure?
-Frank-Starling curve
-Ventricular performance (how well the blood pumps blood)
-Ventricular end-diastolic volume
Acute decompensated heart failure
-sudden or gradual onset of symptoms of HF requiring hospitalization of the patient
What is the best way to increase Cardiac output?
Heart failure: the heart doesn’t pump enough blood
-> need to increase CO
-increasing CO by increasing stroke volume -> requires less O2 as if CO was increased solely by increasing HR
Which drugs increase cardiac output by increasing stroke volume?
-increase SV = increase in ionotropy (strength in contraction)
-Milrinone (Primacor) -> increases contractility without increasing HR
-PDE3 inhibitor
-also has effects on blood vessels causing Vasodilation
How is this drug different from Vericiguat or Riociguat???
-Vericiguat block PDE5
-They work on vascular smooth muscles causing Vasodilation
-Milrinone (Primacor) worse directly on the heart and blocks PDE3 and increasing levels of cAMP -> more Ca2+ -> stronger contraction of the heart
ß1-Agonists
-bind to ß1-receptors attached to the heart
-Dobutamine (also has ß2 agonist activity -> vasodilation, which also lowers the work the heart has to do)
-Dopamine:
binds to ß1-cardiac receptors -> heart beats harder and faster
binds to D2 receptors -> increases renal blood flow
-Epinephrine: agonist at all sympathetic receptors
-Norepinephrine: like EPI but with more alpha1 effects -> dangerous (too much vasoconstriction???)
Ionotropic agents
-Cardiac glycoside (ATPase inhibitor): narrow therapeutic window, long halflife
-Digoxin: long half-life (1-5d) depending on renal function, narrow therapeutic window, overdose is often a concern
MOA of Digoxin
-works on the heart muscle cells
-ATPase blocker that increases intracellular Ca2+
-after depolarization (Na+ influx) -> Ca2+ enters the cell -> followed by repolarization (K+ leaving)
-ATPase uses K+(outside) to exchange Na+
-Na+ (outside) is used to get Ca2+ out of the cell (Na+ gets in)
-Digoxin blocks the ATPase so Na+ levels outside stays low -> enables Antitransport with Ca2+ -> Ca2+ levels insight stays high -> greater heart muscle contraction
ADE of Digoxin
-Atrial fibrillation
-AV conduction block, other electrical abnormalities
-Bradycardia
-nausea
-altered color perception and visual halos
What is the Antidote of Digoxin?
-Digoxin immune antigen-binding fragments (Fab, antibody)
-binds Digoxin and takes it out of circulation
