Cardiac Heart Failure Flashcards
Dec in renal bf are sensed by
JGC of the afferent arterioles
Heart remodelling from RAAS activation by myocardial and vascular fibrosis and baroreceptor fxn
Aldosterone
Compensatory responses in HF (2)
1 sympathetic activation
2 RAAS
cardenolide structure
steroid nucleus + lactone ring + sugar
cardenolides come from
digitalis fox glove
Digitalis Bioavailability and Half life
Elimination
60-75% bio
36-40h
Elimination: 60% renal 40% hepatic metab
Digoxin MOA
Inhibition of Na pump (Na/K ATPase) -> inc Intracell Na -> alters Na-Ca exchange (dec Ca excretion) -> inc intracytoplasmic Ca (inc contraction) by SERCA
Inc CO Inc ventricular ejection Inc renal perfusion Dec EDS Dec sympa tone
Digoxin
Digoxin during early response shows electrical changes (4)
1 inc PR interval
2 flat T wave
3 slowed ventricular rate
4 shortened QT interval, T wave inversion, ST depression late
Early brief prolongation of AP then shortening of plateau bec of K conductance!
Digoxin toxic response
1 inc automaticity (arrhythmia)
2 delayed afterdepolarization (Ca overload)
Digoxin indication
CHF with systolic dysfxn
Atrial fibrillation
Improves functional status only
Digitalis SE (4)
CNS , GI stimulation
Color perception aberration
Gynecomastia
Electrolyte (hypokalemia, hypomagnesemia, HYPERcalcemia)
Arrhythmia, arrest
Digitalis tox tx (3)
1 correct K and magnesium deficiency 2 antiarrhythmics (lidocaine, phenytoin, propanol) if not refractory to K severe acute overdose (artificial pacemaker) 3 Digoxin antibodies
Digoxin Minimum Effective Concentration
1 ng/mL
bipyridine that inhibits PDE3 leading to inc cAMP, inc intracellular contractility
Also promotes vasodilation
Cannot be used in chronic Hf bec of inc mortality
Milrinone
Theophylline
Aminophylline
Bipyridine SE (3)
N & v, arrhythmia
Thrombocytopenia
Liver enzyme
First line for both systolic and diastolic dysfxn
Diuretics
Immediately reduces pulmo congestion and severe edema
Furosemide
Diuretic For mild chronic HF
HCTZ
Diuretic that dec mortality in CHF
Aldosterone antagonist
Spironolactone
Eplerenone
First line drugs that dec morbidity and mortality in CHF
Dec aldosterone sec, salt water ret, vasoconstriction
ACEI
Drugs for ACUTE HF with marked depression of systolic dysfunction
Also for cardiogenic or hypovolemic shock
Beta1 Adrenoreceptor agonist
Dobutamine
Dopamine
Do not give to chronic bec of tolerance, lack of oral efficacy, significant arrhythmogenic effects
Selective B1 agonist that inc CO and dec ventricular filling pressure
Given intermittently
SE: tachy, angina and arrhythmia, inc O2 consumption
Dobutamine
If need to inc BP give Dopamine
Dec preload by vasodilation
Dec afterload by arteriolar dilation
Reduces remodelling
Vasodilators
For acute severe failure with congestion
Dec preload and afterload
Nitroprusside NTG
Promotes vasodilation and natriuresis for acute failure (renal toxicity)
Nesiritide
Dec mortality in African-American with CHF
Hydralazine and ISDN
Nesiritide MOA
BNP inc CGMP -> dec venous tone, dec arteriolar tone
Nesiritide SE
Hypotension
Renal toxicity
Degrades BNP and ANP
Sucabitril LCZ696
ARB + Neprilysin inhibitor
ACE MOA Dec afterload by Dec preload by Dec angiotenstin and sympathetic Dec remodelling by
Dec peripheral resistance arteriolar dilation
Dec salt and water retention
Dec NE release
Dec aldosterone activation
Steroid derivative inc contractility by inhibiting NaK ATPase pump
Facilitates sequestration of Ca by SR
Less arrhythmogenic
Istaroxime
Sensitizes troponin to Ca
Inhibits phosphodiesterase
Vasodilator
Levosirerdan
Activates myosin and prolongs systole without inc in O2
Omecamtir mecarbil
