USMLE Step 1 Web Prep Heart Failure

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SLIDE 1 of 10

Drugs for Heart Failure

Heart failure is due to defects in cardiac contractility

CO

Signs & symptoms: e ercise tolerance & muscle fatigue! plus compensatory responses e"o#ed $y decreased %&' S()S acti"ity tac*ycardia! arteriolar tone + afterload! output! renal perfusion, & "enous tone + preload! fi$er stretc*,' (cti"ation of renin-angiotensin system edema & dyspnea .ntrinsic compensation myocardial *ypertrop*y'
SLIDE 2 of 10

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Fig III-4-2. Cardiac Output versus Left e!tricular Filli!g "ressure

2entricular function cur"es +cardiac output "s preload, s*o3 compensatory mec*anisms in untreated *eart failure increase preload to increase CO'

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SLIDE # of 10

Drug $ctio!s i! Heart Failure

Drugs t%at offset co&pe!sator' &ec%a!is&s act via(

preload - diuretics! (C4.s! (5-1 receptor antagonists & "asodilators afterload - (C4.s! (5-1 antagonists & "asodilators contractility 6 digitalis! $eta agonists! $ipyridines 7rugs useful in *eart failure s*ould displace "entricular function cur"es 8up3ard & to t*e left9

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SLIDE 4 of 10

$CEIs ) $*-1 $!tago!ists

%loc# formation of (.. aldosterone fluid retention "asodilation preload & afterload .mpro"e symptoms & e ercise tolerance! slo3 progression of failure & prolong sur"i"al &rop*ylactic "alue post-;. - oppose 8re-modeling9 t*at leads to failure )o3 primary drugs for management of *eart failure - (5-1 antagonists *a"e similar efficacy'
SLIDE + of 10

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Cardiac ,l'cosides

.n*i$it cardiac mem$rane )a<=<(5&ase Ca0<in S?! so e citation

)a<>Ca0< e c*ange

Ca0< release & $inding to troponin

5ropomyosin mo"es actin & myosin interaction contraction' < %inding of digitalis to t*e 8pump9 is in*i$ited $y = ! so *yper#alemia decreases effects & *ypo#alemia increases effects' 5*e increase in contractility impro"es cardiac output! re"ersing t*e compensatory tac*ycardia and increases in %& & &2? t*at occur in *eart failure' ?enal perfusion & diuresis are impro"ed' Cardiac glycosides do )O5 impro"e sur"i"al'
SLIDE - of 10

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Fig III-4-#. Effects .esulti!g fro& I!%i/itio! of Cardiac 0e&/ra!e 1a 232$*"ase

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SLIDE 4 of 10

Su&&ar' of Cardiac effects of Digitalis 5see *a/le III-4 i! te6t7.

I!%i/itio! of 1a232-$*"ase

(tria -

(&7 & 4?&!

a$normal automaticity

(2 node 2&&-

conduction "elocity

(&7 & 4?& +minor effects,

C%oli!o&i&etic 5 agoto&i&etic7 - I!direct

(tria -

S( nodal rate 4?&! conduction "elocity

(2 node -

S'&pat%o&i&etic 5 1- li8e7

(tria -

S( rate! 4?&

conduction "elocity a$normal automaticity

SLIDE 9 of 10

(2 node -

2 & & - conduction "elocity!

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Co&pariso! of Digo6i! ) Digito6i!

digo6i! Half-life +*r, 00-40 digito6i! 100-110 :0 0'1

Clearance +m@>min, 130 +renal, 3 +*epatic, &rotein $inding +A, 05 2d +@>#g, 1

2agotomimetic action of digo in is prop*ylactic in S25s +eg! (B, & slo3s increased (2 conduction due to Cuinidine'
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SLIDE : of 10

Digitalis *o6icit'

4arly: ) & 2! S5 depression! 5 3a"e in"ersion! &2%s! $igeminy @ater: C)S effects include disorientation! *alos & *allucinations ;ore se"ere: S25s! (2 nodal tac*ycardias or (2 $loc# & 25 or 2B ;anagement: electrolyte adDustment! antiarr*yt*mics +lidocaine! p*enytoin,! digitalis Ba$ anti$odies & pacema#ers 6 *old cardio"ersion for 2B' 5o icity increased $y: =<! ;g0<! Ca0< and $y Cuinidine! )S(.7s! amiodarone! "erapamil! sympat*omimetics & some anti$iotics
SLIDE 10 of 10

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Ot%er Drugs i! Heart Failure 5$7

(mrinone & milrinone

o o

.n*i$it &*osp*odiesterase+&74,

c(;&

<"e inotropy & "asodilation

(mrinone causes t*rom$ocytopenia! milrone sur"i"alE 7o$utamine & 7opamine - used in acute failure 6 tac*yp*yla is' Car"edilol 6 alp*a & $eta $loc#er 6 slo3s remodeling & (mlodipine 6 "ascular selecti"e CC( 6 Spironolactone sur"i"al mortality rate 3*en used 3it* (C4.s' sur"i"al