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Cardio –CHF
Trachte – 10.02.09
Characteristics of the disease state
– Cause can be left ventricular dysfunction
–Can be diastolic abnormality related to altered compliance
–Can be right ventricular problem
–Can be a problem with arrhythmias (lots of potential causes)
Cardiogenic
–Contractility decreased (stenosis, anemia, Infarction)
–Arrhythmias
–Hypertension
Be familiar with the therapeutic strategies in treating Congestive heart failure (CHF):
•Objective of Tx: improve myocardial performance (i.e., repress compensatory mechanisms and thereby
restore cardiac output and tissue perfusion)
Compensatory Mech
Tachycardia & sympt NS activation
Pharm Tx
Inhibit sympt NS
Arteriole constriction
Renal Na retention
Vasodilate
Inhibit aldosterone (Na retention & dec myocyte apoptosis)
-diet – dec Na intake
Water retention
Vol depletion (dec preload)
-diet – dec Na intake
Afterload inc relative to CO & VR
Vasodilate to dc afterload or preload (venous dilation), mimic NO
Renin-Ang Activation
----
Renin-Ang Inhibitors
Cardioselective – inc contractility (good acute, improves quality of
life)
–Other Therapies- Restrict salt intake to dec Na & water retention
Know the generic names and mechanisms of action of the six groups of drugs used to treat CHF.
-3 classes alt course: 1. Renin-Ang Inhibs, 2. Beta-recp antagonists, & 3. Aldosterone Recp Antagonist
-others are used to improve quality of life: Diuretics (SOB), venodilators, cardiac inotropes,
•cardiac inotropes – not that great
•Diuretics – key cuz pt vol loaded, edema – forozimide, don’t improve survival but do improve quality of life.
•Venodilators – dec CVP and preload, improve cardiac function, great in blacks!Vidole
Drug class
General MOA
Key Notes
Drugs
Drug specifics
CAPTOPRIL
»dec filling P
Renin-Ang system
Balanced Vasodilators* (both
Prolongs survival
(Capoten),
»inc CO
Inhibitors (ACE
veins & arts)
First line long term Tx
ENALAPRIL
»red heart size **
inhibitors)
-dec pre/afterload  inc CO
(Vasotec) &
LISINOPRIL
Losartan
Aldosterone Recp
Antagonist
ß receptor antagon.
Venodilators
Arterial
Vasodilators
Blocks Aldosterone Recp
-heart aldo recp encourage
apoptosis & CT
prevent deleterious effects of
catecholamines on the heart***
Dec preload/afterload to inc CO,
SV, EF
Dec afterload to inc CO (no
effect on preload!)
angiotensin recp
antagonist
Eplerenone
Spironolactone
Metoprolol
Carvedilol
Nitrovasodilators
(Isosorbide
Dinitrate,
Nitroglycerin)
Hydralazine +
isosorbide
dinitrate
Gynecomastia
B1 selective
Alpha 1 antagon.
activate soluble
guanylyl cyclase to
increase cGMP
Most effective in combo
(arterio +venodilator)
Was superior to ACE but now equal
Prolongs survival
3rd choice drug
Not used as often cuz of side effects
Prolongs survival
Prolongs survival
Best in blacks! Improves survival
-approved in pregnancy!
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Cardio –CHF
Trachte – 10.02.09
Mixed Vasodilators
Dilate both arteries & veins
Cardiac Inotropes
Minoxidil
Brain natriuretic
peptide
ACE Inhbit,
Angiotensin recp
antagonist
Cardiac Glycosides
(Digoxin)
Dobutamine
Dopamine
Milrinone
Diuretics
Dec bld vol by dec Na & H20
Furosemide
Loop diuretics
(Ethacrynic acid)
No used often
Natural diuretic made
by failing heart
Dec survival, used in end stage CHF,
Best as a marker of CHF severity
Classics
-Blocks Na-K pump
Not that great
-Inc CO by inc SV
Best for failure caused by chronic
-dec HR & TPR by dec
overload (hypertension, valvular
sympts
lesions)
-dec heart size and wall -Don’t use in Diastolic failure
tension (T = P xr/2)
-inc mortality in women
dec O2 demand
-dec bld vol from inc
renal perfusion
-B1-agonist (positive inotrope)
IV (short ½ life) in acute
CHF management
-Untoward effects- Arrhythmias,
headache, palpitations, dyspnea,
nausea
-preferential dilation of the renal Not commonly used in
vasculature - diuresis
CHF for undesirable side
-increases contractility by acting
effects and IV admin
on ß1 receptors
-Odd – positive inotrope + dec
-approved for CHF
TPR via vasodialation
refractory to other
inotropic agents
-Phosphodiesterase inhibitor:
increases cAMP by inhibiting
-may worsen survival
phosphodiesterase (block degrad
of cAMP)
Improves quality of life but doesn’t
most common
prolong survival,
Strongest
Cautions - hypokalemia, alkalosis,
electrolyte imbalances
*-vasodil - inhibits Angiotensin II (constrictor) formation and inhibits the degradation of Bradykinin (dilator)
**reduces heart size (hypertrophic effect of angiotensin II – along with reducing preload, afterload)
***Beta recp desensitized oby specific kinases – blocking the Beta recp improves the situation.
Know this signaling pathway:
-NE/D  B1  Gprotein  cAMP is
degraded by PPE (block PPE, prolongs
cAMP life) similar to viagra. 5 -10 families
of PPE
-Cholera hits g protein.
Actual Treatment:
•Acute- must relieve symptoms
•Treat with:
–loop diuretics (Furosemide) to remove fluid
–Morphine sulfate (venodilation plus analgesic)
–Nitroprusside or Nitroglycerine (i.v.) (Hit arts and veins –
dilates)
–Oxygen
•Chronic- must relieve symptoms, reduce hospitalization & improve
survival
–Angiotensin converting enzyme inhibitor or receptor blocker-good for
improving survival
–Digoxin- improves quality of life (no evidence for survival effect, but can
prevent hospitalization); suspected to be less effective in women; falling out
of favor
–Furosemide- reduces fluid accumulation (no evidence for survival effect
but can prevent hospitalization)
–ß Blockers- good addition to ACE inhibitor & diuretic but must slowly
wean patient onto drug (Carvedilol [Coreg] -  & ß blocker best agent so
far); improves survival equally in either gender; Metoprolol (Lopressor)
also
–Spironolactone (Aldactone)- aldosterone receptor antagonist definitively
shown to improve survival
»Plus beta blockers & ACE = good
Cardio –CHF
Trachte – 10.02.09
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His big Qs: What do drugs do to CO & VR curves? And what drugs work in pairs or
antagonistically?
Furosemide -- dec vol to dec VR – Left shift
Enalapril– up & left
Digoxin – shift up
Phenylephrine – right shift from inc pressure
Propranolol – dec contractility
So, Left is C, Furosemide & Rights is Digoxin
Study Questions:
1.
Inhibitors of the Renin-Angiotensin System increase CO by
A. venodilation
B. arterial dilation
C. reducing afterload
D. reducing preload
E. All of the above
2. Activation of Aldosterone receptors on heart contribute to deleterious remodeling in congestive heart failure by:
A. Encouraging apoptosis
B. Too much CT disrupting cardiac function
C. Decrease coronary artery perfusion
D. A &B
3. Hydralazine & isosorbide dinitrate combination drug:
A. is approved for use only in blacks
B. is best at decreasing preload
C. improves CO by decreasing afterload
D. is a venodilator
4. Mixed vasodilators:
A. dilate a mix of central and peripheral arteries
B. dilate veins in a mixed population study
C. dilate both arteries and viens
D. include the drugs Minoxidil &Losartan
5.Digoxin’s effects include:
A. increasing CO by increased SV while decreasing TPR
B. targeting the Na-Ca ATPase pump
C. increasing HR
D. increase heart oxygen efficency by increasing wall tension
Answers:
1. E
2. D
3. C
4. C
5. A
Cardio –CHF
Trachte – 10.02.09
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