Transcript Heart Failure

Renin inhibitors
 Renin
Heart Failure
Inotropic agents
-Blockers
ACE 
 Sympathetic activity
 Angiotensin II
ARBs
Vasoconstriction
 Aldosterone
Vasodilators
Spironolactone
Cardiac
remodeling
 CO
Na+, water
retention
Diuretics
 Cardiac filling
Role of sympathetic activation in CHF
CHF
Sympathetic activation
Inotropy
Chronotropy
( contractility)
( Heart rate)
Lusitropy
( Ventricular relaxation & filling)
-Adrenoceptor antagonists:
• agonists dobutamine as also dopamine provide relief in CHF but
their long term use increases mortality
•Long term administration of -antagonists reduce mortality rate in
CHF
•Initially the systolic function decreases but over 2-4 months it
recovers and improvement beyond baseline occurs
•Mechanism of beneficial effects in CHF not clear
By preventing myocardial ischemia without significantly
influencing serum electrolytes, they may decrease frequency of
unstable tachyarrhythmias
Betterment of left ventricular morphology by decreasing left
ventricular size and increasing ejection fraction
By inhibiting sustained sympathetic discharge, they reduce
catecholamine induced cardiomyote toxicity and prevent or delay
myocardial contractile dysfunction
Decrease cardiomyocyte apoptosis
May induce positive myocardial remodeling by decreasing
oxidative stress on myocardium
•Drugs used: metoprolol, carvedilol, bisoprolol- other -blockers
are not effective
•Combined  and  blocker is preferred
•Carvedilol has additional advantages that it reduces free radical
induced lipid peroxidation and prevents cardiac and vascular
smooth muscle mitogenesis independent of its  or  receptor
blocking activity
• Adrenoceptor blockers have proven utility in improving
symptoms, hospitalization and mortality in patients of CHF
•They are recommended for use in patients along with ACE
inhibitors or ARBs
•Recommended only when the ejection fraction of heart is
<35% to counter the deleterious effects of circulating
catecholamines
•They are usually given in small doses initially, less than 1/10th
of the final dose and gradually titration of dose is done
•Not recommended for use in patients with severe, new onset
or acutely decompensated CHF
Heart Failure
Inotropes- for increasing ventricular contractions:
•Cardiac glycosides- digitalis, digoxin, oubain
• Adrenergic and dopaminergic agonistsdobutamine
•PDE inhibitors- Inamrinone, milrinone
Cardiac cell
Ca2+
3
Na+
Ca2+
Cations
NCX
Ca2+
Depolarised
ATPase
Ryanodine
receptor
(RyR2)
K+
SR
SERCA2
Na+
Ca2+
Ca2+
NCX
2 K+
Ca2+
Na+K+
(LType)
ATPase
3 Na+
Polarised
Na+
•Na+K+ATPase
•H+K+ATPase
•Cardiac glycosides bind and inhibit the phosphorylated 
sub unit of sarcolemal Na+K+ATPase
•They  Na+ extrusion from cell and  its level in cell
•At therapeutic serum levels they:
Increase vagal tone and decrease sympathetic tone
Decrease automaticity
Increase maximal diastolic resting membrane potential in
atrial and AV nodal tissues
Prolongs ERP and slows conduction in AV nodal tissues
These effects result in sinus bradycardia or arrest,
prolongation of AV nodal conduction and AV block
•In higher concentrations it increases sympathetic activity.
Simultaneously, there is Ca2+ overload which together
may cause development of cardiac arrhythmias
•Non-cardiac effects:
Blood vessels- constriction (direct) in normal; in CHF
vasodilatation due to decreased sympathetic activity
Kidney- Diuresis
GIT- anorexia, nausea,vomiting (CTZ)
CNS- disorientation, hallucinations, visual & colour
disturbances
•Uses:
CHF
PSVT
Atrial flutter/Atrial fibrillation
ADRs:
• Cardiac
• CNS- fatigue, neuralgia, blurred vision
• GIT- anorexia, nausea, vomiting, abdominal
cramps
• Endocrinal- gynaecomastia in males
Contraindications: Hypokalemia, children
below 10 years age, elderly with renal/hepatic
impairment
MI, hypothyroidism, myocarditis
Dobutamine:
•Racemic mixture that stimulates both 1 and 2 receptors and
(-) enantiomer that is agonist and (+) enatiomer that is partial
agonist of  adrenoceptors
•1-positive ionotropic and increase in stroke volume
•Relatively little increase in heart rate
•Vasoconstriction by (-) enantiomer is countered by (+)
enatiomer and 2 agonist activity- ultimate result is a decrease
in PVR and mild decrease in systemic blood pressure
•Continuous infusion 2-3 g/kg/min
•Tolerance may occur after some time
•ADRs: tachycardia, arrhythmias
PDE Inhibitors: Inamirinone, milrinone
•Decrease cellular degradation of cAMP resulting in increased
levels in cardiac and smooth muscle myocytes
•Produces positive inotropic effect on heart and dilatation of
resistance and capacitance vessels
•Nett effect: positive ionotropy and decrease in pre and after
load resulting in improvement in cardiac output
•Also called “inodilator” (inotropy + vessel dilatation)
•Theophylline, caffeine have low cardiac specificity and side
effects, so are not used
•Inamirinone and milrinone are selective PDE3 inhibitors
•Directly stimulate myocardial contractility & relaxation
Shock
•Haemorrhaegic (hypovolemic): replace with blood
or plasma expanders
•Anaphylactic :
Adrenaline
 agonist-  BP
1 agonist- +ve ino &
chronotropy
2 agonist- bronchial
relaxation
Physiological antagonist
of histamine
Corticosteroids
Antihistamine
•Cardiogenic:
Dopamine hydrochloride 2-5 g/kg/min i.v.
infusion till a maximal dose of 20-50 g/kg/min is
achieved
Dobutamine
NE- rare- reserved for patients with refractory
hypotension
•Septicemic (warm shock):
Dopamine hydrochloride
Chemotherapeutic agent
Recombinant activated protein- C known as
drotrecogin alpha (activated)- continuous infusion 24
g/kg/hr for 96 hrs, improves rate of mortality
Vasopressin (ADH)- peripheral vasoconstriction by
V1 receptors
Corticosteroids
Adrenaline, dobutamine