Pharm Positive Inotropes

Positive Inotrope: classes
Digoxin, Dobutamine, Inamrinone, Milrinone
Molecular effects of digoxin
membrane potential less negative, slows recovery of sodium channels, increases effective refractory period, slows conduction of the AP, predisposes to re-entry->cardiac arrythmias
Molecular effects of Hypoxic cardiac tissue
Hypoxic cells make less ATP than normal, Na/K ATPase pump is less active, membrane potential is less negative, Na channels inactivate more slowly, longer ERP, slows the AP conduction, predisposes to re-entry
Therapeutic [digoxin]
vagus mediates digoxins effects on the SA node, atrial muscle, and AV node->slows AV conduction, lowers ventricular rate during atrial tachycardia
Toxic [digoxin]
Ca overload–>DADs, shortened atrial refractory period (reentry arrhythmias), excessive AV block
Digoxin: target
Na/K ATPase
Digoxin: pharm effects
increased contractility, slowed AV node conduction (indirect, vagal)
digoxin: adverse effects
cardiac arrhythmias (hypokalemia due to diuretics, renal disease, CHF, quinidine decreases renal clearance), nausea, vomiting, visual abberations, vasoconstriction, diarrhea, AV block
digoxin: PK
renal clearance, narrow therapeutic window
digoxin: uses
CHF, atrial tachycardias
When sympathetic and RAAS tone are normal, digoxin:
Increases cardiac contractility, increases afterload, Decreases HR
–>Little net change in CO and hemodynamics
When SANS and RAAS tone is high (CHF), digoxin
increases contractility–> SANS and RAAS tone decrease, afterload decrease (improve CO), improved RBF (diuresis)–> relieves congestion and decreases heart size. HR slows, decreasing O2 demand
Dobutamine: pharm effects
increased contractility
Dobutamine: adverse effects
increased HR, lowers BP, arrythmias
Dobutamine: PK
IV, tachyphylaxis (only use in acute setting or receptor downreg occurs)
PDE 3 Inhibitors:
inamrinone, milrinone
Inamrinone, milrinone: target
Inamrinone, milrinone: pharm effects
increased contractility, arteriolar vasodilation
Inamrinone, mirinone: adverse effects
increased HR, cardiac arrhythmias, INCREASED mortality
Inamrinone, milrinone: PK
Inamrinone, milrinone: uses
acute CHF (not really used anymore), contraindicated for chronic CHF
CHF is characterized by
decreased CO, elevated filling pressure
Clinical manifestations of vasoconstriction
cool, pale skin; low urine output
Inotrope or vasodilator to increase CO
vasodilator: does not increase O2 consumption
Drugs to decrease chronic CHF remodelling
ACE inhibitors, aldosterone inhibitors, b-blockers
Low CO symptoms
fatigue, exercise intolerance, cool extremeties, low urine output
Pulmonary edema symptoms:
SOB, rales, peripheral edema
Treat warm/dry CHF pt:
observe, optimize preload (slow progression)
Treat warm/wet CHF pt:
High ventricular filling pressures–>Pulm edema; Reduce preload-diuretic (furosemide), venodilator (nitroglycerine, nitrate). Inotropes NOT indicated.
Treat cold/wet CHF pt:
Decrease pulm edema and increase CO: Nitroprusside (balanced vasodilation), inotrope if necessary
Treat cold/dry CHF pt:
if HR is low->atropine or pacing; if HR is high->expand volume
conditions associated with progressive CHF
Drugs to inhibit CHF remodeling
diuretic (reduces mortality), digoxin, ACE-I, b-blocker, Angiotensin RB