HF Pharmacology

heart failure

CO too low for needs of the body

systolic HF & most common cause

LV doesn’t squeeze well enough

most common cause: coronary artery disease

diastolic HF & cause

LV can’t fill as much → decrease CO

hypertrophy and stiffening cardiac muscle

extrinsic neuro-hormonal compensation

RAAS and SNS sense decreased CO and try to compensate

RAAS response to decreased CO

increase ATII → vasoconstriction → increased afterload (resistance)

SNS response to decreased CO

increase NE → increased BP → increase contractility

long term effect of extrinsic neuro-hormonal compensation

cardiac performance weakens over time

(body constantly trying to compensate and increase cardiac performance, ends up overworking itself)

intrinsic compensation

myocardial hypertrophy

long term effect of intrinsic compensation

myocytes die, which further stresses alive myocytes & makes them work harder

effect of decreased CO on HR

HR increases as compensatory mechanism

How do SGLT2i impact HF

decreases risk of HF decompensation

SGLT2i impact on natriuresis

increases natriuresis → decreases plasma volume and systemic BP

increases vasculature function

SGLT2i impact on glycosuria

increases glycosuria → decreases body mass and visceral fat

decreases oxidative stress and inflammation

cardiac glycoside drug

digoxin (Lanoxin)

NOT FIRST LINE

digoxin MoA

positive inotrope

inhibits Na/K-ATPase → increases Na in cell → increases activity of Na/Ca exchanger → increases Ca → more Ca gets released from SR → increases force of contraction

digoxin SEs

NB, narrow therapeutic index

atrial arrhythmia

A-V conduction block

gynecomastia

HCN channel blocker drug

ivabradine (Corlanor)

ivabridine (Corlanor) MOA

blocks pacemaker current (funny current) in SA node passed by HCN4 channels → decrease HR

ivabridine (Cornalor) SEs

bradycardia

HTN

vision changes

PDEi MOA

increase cAMP → vasodilation, increase contractility and HR

sGC stimulator drugs (which one is first in class)

vericiguat (first in class)

riociguat

vericiguat MOA

synergies NO to stimulate sCG → increase cGMP → relaxes vascular smooth muscle; decreases PVR

vericiguat SEs

hypotension

anemia

synthetic natriuretic peptide

Nesiritide (Natrecor)

no effect/benefit

nesiritide (Natrecor) SEs

hypotension

headache

bradycardia

kidney failure

what happens when A and B-type natriuretic receptors are activated?

GC activated → increase cGMP → induce smooth muscle relaxation

Neprilysin inhibitor (only drug approved for this class)

Entresto (sacubitril/valsartan)