HEART FAILURE DRUGS Flashcards
What is congestive heart failure ?
it is a pathophysiological state in which the heart fails to pump blood at a rate equal to requirements by metabolising tissue
What does CHF cause
inadequate circulation ,fluid build up in lungs , reduced oxygenation of tissues
What is the systolic failure pathophysiolgy in chf?
reduced myocardial contractility , reduced Sv ,
Increased Ventricular pressure and residual blood volume
dilated ventricles
What is the diastolic failure pathophysiology ?
ventricular relaxation reduces and ventricular filling decreases
Drug for increased Preload caused by Na+ and H20 retention?
Diuretics
Drugs for increased preload caused by vasoconstriction
Venodilators
increased afterload drugs caused by arterial vasoconstriction ?
Arterial vasodilators
What is the pathophysiology response by kidney in chf
retains water and na
maintains sv
allows the heart to function at high end diastolic volumes because of extra cellular fluid volume
Pathophyiology of CHF
edema
increased wall stress
increased pulmonary congestion causing fluid build up
end diastolic volume leads to higher end diastolic filling
increased ventricular size
What cycle follows after heart damage / ventricular overload / decreased ventricular contraction ?
- tachycardia ,ventricular dilation , myocardial hypertrophy
- reduced CO
- reduced renal perfusion
- increased sodium retention and h20
5 .increased osmotic pressure
6 increased AdH
7 .increased h20 absorption
8 .fluid overload causimg edema
Class I ambulatory treatment
diuretics
Class II ambulatory treatment
aceis/arbs
class III ambulatory treatment
diuretics + aceis/arbs
class IV ambulatory
diurectics + aceis/arbs +digoxin
what do we use instead of aceis for pts intolerable
hydralazine/nitrates
For hospitalised chf what drugs do we use with their classes in order ?
- Diuretics , pref loop diuretics
- Vasodilators , sodium nitroprusside
3.sympathomimetics = dobutamine or dopamine - phosphodiesterase inhibitors amrinone
MOA for vasodilators eg sodium nitroprusside
reduce preload and afterload
both veno and arterial dilators
inotropes moa
increase CO
ACEIs MOA
reduce vasoconstriction and and sodium and water retention
diurectics moa
Reduce sodium & water retention
reduce preload
does not reduce mortality
use minimal dose to maintain euvolemia
control congestive symptoms
Loop Diurectics examples and bio availabilty
furosemide 40-70%
.bumetanide 80%
torsemide 80%
ethacrynic acid for people allerrgic to sulfonamides
Loop diuretics moa
inhibit the Na+K+CL- symporter in the ascending loop of henle
thiazide diuretics moa
inhibit the Na +Cl - transport in distal convuluted tubule
loss of k+
great synergism with loop diuretics
K+ sparing diuretics moa
amiloride acts as a Na + inhibitor absorption
Spironolactone / canrenone acts as aldosterone antagonists
What doe aldosterone antagonists do in heart failure
increase survival independent of diuresis
reverse pathologic remodelling that occurs in heart failure
what are the Angiotensin II uses or actions ?
potent vasoconstrictor
increases Na+ and H20 retention
arrythmogenic
stimulate release of catecholamines
What does RAAS inhibiotrs do e.g arbs and acies
myocytes death
promote vascular hyperplasia
pathological myocardial hypertrophy
Aceis reduce proload and afterload why ?
because is it both a venodilator and arterial dilators
what are the adverse effects of ACEIs ?
Cough
angioedema
Loss of taste
Proteinuria
renal impairment
rise in K+
Examples of ARBs and uses
losartan , candesartan , telmesartan
has similar mortality benefit as aceis
prevent adverse ventricular remodelling
What is the MOA of nitrates and their duration of action
Nitroglycerin …transdermal , iv , ointment and raipd acting tablets
isosorbide mononitrate orally are short acting
isosorbide dinitrate orally act long lasting
MOA = provide NO by binding to smooth muscle cells and releases NO which binds to nitrogen receptors which cause guanylate cyclase stimulation and cause cGMP increase which causes dephosphorylation of mysoin light chain kinase leading to relaxation of muscles causing vasodilation
What is the mechanism of action for vasodilator hydralazine?
arterial vasodilators which reduce the afterload , of right and left ventricles by reducing pulmonary and systematic and pulmonary vascular resistance
Write shorts notes on hydralazine except moa
increases renal blood flow
redices renal vascular resistance
effective with organic nitrates e.g isosorbide
Positive inotropic effect
Examples of B blockers and its MOA
metoprolol
carvedilol
bisoprolol
MOA= improvement of ventricular structure and function , reduces chambers size while ejection fraction increases .Also it reverses the cellular events that underlie the pathological remodelling
Write short notes on Bblockers
approach heart problem pts carefully
initiate at low dose
reduce oxidative stress in myocardium by improving myocardial energetics
Short notes on Sodium nitroprusside ?
reduces ventricular and systematic resistance
reduces PVR becauses preload & afterload reduces reducing wall stress
increases the venous capacitance
rapidly metabolised to NO and cyanide
increase CO and increased renal blood flow
what are the side effects of sodium nitroprusside ?
hypotension
cyanide toxicity in hepatic and renal failure
methemoglobinemia due to oxidation of Hb BY NO
Nitroglycerin short notes ?
short acting with tablets
used for lvf in MI
adverse effects : headache , nitrate tolerance , increases blood alcohol because administered in ethanol
Nesiritide short notes
recombinant dna Brain natriuretic peptide form
increases cGMP in soomth muscles and reduce after/pre load
vasodilation occurs in arterial and venous dilation
nesiritide deactivated by NEP
BNP deactivated by clearance receptors facilitating internalisation and enzymatic degradation
What are cardiac glycosides (digitalis) and give examples ?
these are drugs that contain a steroid nucleus combined with unsaturated lactone ring and series of sugars
e.g Digoxin and digotoxin
what is the molecular mode of action of digitalis?
inhibit the sodium potassiu m pump whic causes an increase in intracellura Na + whic initiates Na+ and Ca2+ exchange mechanism which causes a rise in Ca2+ .CA2+ influx too through voltage gated calcium channels
this increase in calcium ions causes an trigger in sarcoplasmic reticulum to release Ca2+ whic initiates a excitation contraction coupling
What is the main action of Digoxin ?
increased contraction of the heart
Inhibit the sympathetic activation and raas
decreased HR
increased Cardiac output
decreased salt and water rentention reducing edema
decreased preload which reducing pulmonary congestion
decreased afterload which increases tissue perfusion
What are the electrophysiological effects of digoxin ?
decreases sympathetic activity and increases vagal tone
1. decreases hr
2. decreases afterload and preload
3. decreased refractory period in atrial & ventricular tissues
What are the effects of digoxin at higher doses ?
increases K+ serum
increases automaticity and sympathetic activation
causes arrhythmia
What are the toxic effects of digoxin ?
overloading of intracellular Ca2+ which increases systoles which may lead to pulsus bigeminy then trigeminy which leads to tachycardia and ventricular fibrillation
What is the pharmacokinetics of digoxin ?
lipophilic
70% bioavailability
,plasma protein binding is 30%
t1/2 is 36-48hrs
excreted unchanged however renal impairment increases half life
What are the therapeutic uses of cardiac glycosides ( digoxin ) ?
1.heart failure patient who are asymptomatic or are on therapy with aceis or are in atrial fibrillation
2. atrial fibrillation with rapid ventricular response. Blocks AV node thereby protects ventricle from rapid atrial rate
3. atrial flutter , turns atrial flutter to atrial fibrillation which in turn goes back to normal rhythm after digoxin withdrawal
What are the contraindications of Digoxin ?
1.partial heart block
2. rheumatic fever
3. acute myocardial infarction
4.hypertrophic obstructive cardiomyopathy
What are the drug interactions of digoxin ?
1.cholestyramine , neomycin and antacaids decrease and plasma level by decreasing the absorption , while thyroxin increases renal clearance and increased volume of distribution
2.erythromycin , tetracycline and omeprazole increases plasma level by increasing absorption while quinidine , verampil , diltiazem , captopril and amiodarone reduces clearance
Phamacodynamic interaction of digoxin
with other drugs
1.k+ diurectics reduce k+ which increases automaticity and (-) na+/k+ which causes toxicity
2. sympathometics increases automaticity
3.b blockers block avn and san leading to bradycardia and heart block .Also decrease myocardial conduction therefore antagonising positive inotropic effects
What are the adverse effects of digoxin / digitalis toxicity ?
arrhythmias
blurred vision
dizziness
anorexia ,nausea , vomiting
abdominal pain
abnormal dreams , malaise
What is the treatment of digitalis toxicity
stop taking digoxin and K+ diuretics
atropine treats bradycardia & 2/3 degree hear block
lidocaine for ventricluar arrhythmia
administer k+ in tachyarrhythmia
k+ admin contraindicated in Av block
What are the parenteral drugs used in hospitalized heart failure ?
- diuretics by Iv
2.sodium nitroprusside reduces both afterload and preload - nitroglycerine decreases preload because its a venodilator so reduced venous congestion , edema reduced and pulmonary congestion
- Dopamine increase myocardial contractility and renal venodilator used in acute heart failure
- (In)amrinone milrinone prefferd reduces thrombocytopenia ,liver toxicity REDUCED PRE AND AFTER
stimulate myocardial contractility used IV for short term
.What is the MOA of dopamine or dobutamine ?
stimulation of cardiac myocyte dopamine D1 receptor & and B adrenergic receptor by stimulating D1 receptor muscles on smooth muscles and d2 receptors on sympathetic nerves
where does dopamine act
splanchnic and renal arterail beds and increase renal blood flow therefore maintaing GFR
INCREASES Cardiac output
Explain the different effects of the dose of dobutamine or dopamine
low dose causes vasodilation less than 2
intermediate increase the b receptor stimulation on the heart and vascular sympathetic neurons
high doses causes vasoconstriction which is used in circulatory failuure
