Chracterized by a recent onset of SOB -- essentially pulmonary edema

Also consists of cardiogenic shock - circulatory shock due to peripheral vasoconstriction and accompanied by low (<90 mm Hg) systolic BP 

Increase contractility by using inotropic agents

Reduce afterload by using ACE inhibitors or vasodilators

Reduce preload by diuretics and vasodilators 

More of a secondary drug in treatment of CHF

Inhibit Na/K-ATPase --> increase resting Ca level -- increased force of contraction 

Effects on electrical activity of heart, mainly due to vagomimetic effects (bradycardia, slowing of AV nodal conduction) -- reduce oxygen demand and allow more efficient filing of the heart

Will also have some level of vasodilation 

anorexia, nausea, diarrhea, color vision abnormality, disorientation, gynecomastia (in males; rare) 

Therapeutic index is low therefore risk of toxicity is high 

Long half life; therapy usually done in titration to elevate serum levels gradually until least amount of toxic effects 

Quinidine causes a doubling of digoxin levels 

Diuretics which induce hypokalemia can increase risk of toxicity for both digoxin 

Elevation of cAMP

B1 - positive inotropic and chronotropic effect oheart

B2: peripheral vasodilation 

B1 selective agonist with high inotropic and low chronotropic activity

It's not orally active, and will show desensitization

Limited to IV use during heart failure

Lead to elevation in cAMP levels 

orally-active agents: amrinone (Inocor), milrinone (Primacor) 

Selective for cardiac isoform PDE3

Bypass receptor so desensitization problem from dopamine avoided

Amrinone is hepatotoxic and induces nausea (short term IV)

Milrinone (higher mortality) 

Also used to treat acute heart failure

Low doses will cause norepinephrine release at the heart -- B1 stimulation 

Dopamine receptors in periphery will lead to vasodilation (increased renal and cerebral perfusion) 

High doses will have a1 activity and lead to vasoconstriction 

Only can be given IV and used for acute HF 

Through reduction of salt/water retention, will reduce preload ==

Reduces edema, and reduces cardiac size (increased pumping efficiency)

Mild to moderate: dietary salt restriction and HCTZ might be enough

Severe CHF: high ceiling diuretic like furosemide might be needed 

Elevated aldosterone is one of the consequences of neurohormonal activation of compensatory response to low CO 

Blocking aldosterone will block additional effects of aldosterone like 

Fibrosis of myocytes

Increased vascular sensitivity to angiotensin

Inhibition of nitric oxide release 

Spironolactone/eplerenone: reduced mortality

In patients with high filling pressures and pulmonary congestion, you would want to reduce preload and might use nitrate

In patients with low ventricular output, you would use hydralazine to reduce afterload

Generally vasodilators for HF are only used when other drugs don't really work 

Combo isosorbide dinitrate and hydralazine

Self described AA with CHF

Hydralazine might potentiate nitrate by reducing tolerance 

Effective and reduces mortality 

Recombinant version of human B-type natriuretic peptide

Activates guanylyl cyclase like nitrates -- vasodilation 

May be increased short term mortality associated with use, but usefulness has not been proven

Useful in treatment of HF

Reduce peripheral resistance and thus afterload

Reduce aldosterone secretion, so they also reduce preload through reduction of salt/water retention 

Reduced ciruclating angiotensin levels can reduce sympathetic activity 

Reduce long term remodeling of heart seen in CHF 

**FIRST CHOICE TREATMENT OF HF**

Counteract some of effects of excess activation of sympathetic nervous system 

Carvedilol seems to be most effective, likely due to added alpha antagonist activity 

Step therapy is used (reducing activity --> pharm)

1. Reduce workload of heart through weight reduction, limit activity

2. Restrict sodium intake to help reduce fluid retention

3. Diuretics to reduce blood volume

4. ACE inhibitors (sometimes given before diuretics)

5. B blockers

6. Digitalis compounds

7. Vasodilators 

ACEi and ARBS

B blockers

Spironolactone or eplerenone

Isosorbide hydralazine (BiDil)

Diuretics

Low dose digoxin

Nitrates 

inotropes and inotropic dilators

antiarrhythmics

high dose digoxin 

calcium channel blockers