Drugs for Heart Failure Flashcards
excitation - contraction coupling machinery of heart
primary defect
baroreceptor reflex, SANS, kidneys, AG2, aldosterone, apoptosis of cardiac cells
secondary defect
compensation in heart failure #1
Baroreceptor reflex increases sympathetic system:
1) increase contractility & HR (B1 adrenergic receptor)
2) increase vasomotor tone (A1 adrenergic receptor) to maintain systemic BP (inc. preload & inc. afterload)
compensation in heart failure #2
RAAS activated:
1) AG2 constricts artery - inc afterload & constricts vein - inc preload
2) aldosterone causes Na+/H2O retention - inc preload (edema)
3) AG2 increases fibrosis in heart (collagen)
Signs & Symptoms of Heart Failure
1) tachycardia
2) decrease exercise tolerance & SOB
3) peripheral & pulmonary edema (from LHF)
4) myocardial hypertrophy (initially helps maintain cardiac performance), [later leads to ischemic changes, impairment of diastolic filing, remodeling by local AG2 & aldosterone]
1) increases connective tissue proliferation
2) Beta myosin fetal cells
3) eventually apoptosis
remodeling
decrease ejection fraction
<50% (dilated/congestive)
systolic heart failure
loss of adequate relaxation
diastolic heart failure
Direct effects of Digoxin
- ** inhibition of cardiac Na+/K+ ATPase ***
1) Inc intracellular Na+
2) Dec Na+/Ca2+ exchange
3) Inc intracellular Ca2+
4) Inc Ca2+ release from sarcoplasmic reticulum
5) Inc actin - myosin interaction
6) Inc contractile force
Indirect effect of Digoxin
inhibition of neuronal Na+/K+ ATPase (results in increase vagal activity)
Decrease ESV
Increase SV & CO
Increase renal perfusion
First dose effect of Digoxin
Decrease EDV (preload) in continued use Continued large SV
Continued use of Digoxin
Autonomic Effects of Digoxin
Increase of intracellular Ca2+ –> Inc Ach in PANS (M2) –> Dec HR –> Dec SA, A-V conduction (Tx: SVT)
Effects of Digoxin on GIT (early signs)
Anorexia
Nausea
Vomiting
Diarrhea
Effects of Digoxin on CNS (late signs)
Disorientation
Visual Effects (hallucinations)
Altered color perception (blue/green)
ECG changes with Digoxin
1) Initial early shortening of AP
2) long term use - lengthening of AP
3) Increase PR interval d/t decrease AV cond vol
4) less -ve RMP - easy premature depolarization
toxic dose effects of digoxin
any cardiac arrhythmias, bigeminy ventricular premature contraction
What 3 factors cause - Increase Digoxin toxicity
hypokalemia
blood magnesium decrease
blood calcium increase
what 3 factors cause - decrease digoxin toxicity
hyperkalemia
blood magnesium increase
blood calcium decrease
Important key btwn K & digoxin
K & digoxin inhibit each other’s binding to Na/K ATPase b/c they compete with each other
management of digoxin toxicity
Fab antibodies
Quinidine interaction w/ digoxin
replaces digoxin from tissue protein binding & increases serum digoxin
verapamil interaction w/ digoxin
increase digoxin concentration by: 1) decrease its. clearance; 2) replaces it from tissue protein binding
Pharmacokinetics of digoxin
1) renal clearance- caution in renal impairment
2) long t1/2 - 1.5 days (min. 6 day -Css)
3) large vd - tissue protein binding
MOA: Increase cAMP
only given IV for short term therapy
Phosphodiesterase inhibitors: Inamrinone and Milrinone
Use for PDE inhibitors
Acute CHF
MOA of PDE inhibitors
Increase cAMP on heart - increase inotropy
Increase cAMP on smooth muscle - decrease TPR
ADR of PDE inhibitors
GI upset
Thrombocytopenia
liver toxicity
Sympathomimetics used for Acute CHF (systemic fxn decreases)
Dobutamine (B1 adrenergic agonist)
Dopamine
Drugs that decrease mortality in HF
1) ACE-I, ARB
2) B-Blocker
3) Spironolactone/Eplerenone
4) Carvedilol
5) Vasodilators: Nesiritide and Bosentan
recombinant human BNP, for acute decompensated CHF
ADR: decrease BP
Nesiritide (vasodilator)
Endothelin receptor blocker
Bosentan
decrease AG2 > + vasodilation
decrease aldosterone > decrease fluid retention
slows cardiac remodeling
angiotensin antagonist
Diuretics in HF
1) Furosemide - decrease volume immediately in pulm congestion and severe edema secondary to acute HF
2) Hydrochlorothiazide - mild chronic failure
3) Spironolactone/Eplerenone - long term benefits and decrease mortality in chronic HF
1) secreted by ventricular myocytes secondary to stretch
2) increase HF
3) binds to receptor on plasma membrane in vasculature, kidney and other organs
BNP
-ve Sa node funny channel > decrease HR but does not suppress heart contraction
Ivabradine
enzyme to degrade BNP and bradykinin
neprilysin
neprilysin derivative
decreases morbidity and mortality
sacubitril
symptoms of acute LHF
orthopnea dyspnea pink sputum sweating anxiety
sign of LHF
whole lung rales
Gallop HR
cyanosis
CXR of LHF
cardiomegaly
butterfly infiltration
management of acute LHF
1) O2
2) morphine
3) furosemide
4) digoxin
5) nitroprusside
6) life support
7) treat the cause
Stages of HF
1) SOB with heavy exercise
2) SOB with ordinary activities
3) SOB with less than ordinary activities
4) SOB at rest
