Positive Ionotropic Agents Flashcards
Main Modulator of Contractility (and 2 determinants of that)
Ca binding troponin - so Ca availability and TnC affinity for Ca (pH, temp)
Starling’s Law of the Heart and Rationale
Force increases in proportion to starting length of the muscle. Increased sarcomere length increases TnC Ca binding affinity
Beta1 AR Mech
Activate AC -> cAMP -> PKA. PKA inhibits PLB/SERCA, and stimulates RyR and L-type CCs, all 3 of which increase IC Ca (kinda on the PLB/SERCA front, discussed later)
Digoxin vs. Digitoxin vs. Ouabain
Digoxin is 1/day, digitoxin is 1/wk (so riskier), ouabain is irreversible so you can kill some motherfuckers
Digoxin Mech
Inhibits Na/K ATPase, so Na/Ca exchanger can’t work as well and Ca can’t leave. So SERCA goes to town and gives you a ton of IC stores for the next contraction
5 Contractile Parameters Digoxin Affects
Increase SV Increase peak systolic pressure Reduces end-systolic V Reduces EDFP Reduces pulmonary venous pressure Pretty much does everything good
Big Benefit and Drawback of Digoxin
Doesn’t seem to increase mortality over time - HUGE
Narrow therapeutic window, so have to dose annually or whenever change any meds
Telltale Sign of Digoxin OD’ing
Yellow-green disturbances
Positive Ionotropic Effect of Adrenergic Stim
Increase force/contraction at any starting length/volume
Adrenergic “Loose-itropy”/Relaxation via PLB and SERCA
PLB normally inhibits SERCA. When phospho’d by PKA, SERCA can go super fast and thus speed up relaxation (necessary) and also outcompete Ca/Na ATPase to build up IC stores more
Consequences of Beta1 Positive Ionotropy
Can get Ca overload, as well as increased O2 consumption and decreased energy efficiency. So that’s really shitty when energy is limited. Also it might not be entirely consistent so can develop arrhythmias
Amrinone and Milrinone
Anti PDE-III (the one in heart). So cAMP stays increased and activates PKA so it do what it do
Treatment Protocol for Acute CHF
Gotta save patient first, so use like sympathomimetics like anti-PDE-III and shit IV just to get the patient out of trouble (and then BBs to prevent damage), but gotta use as little as possible because even intermittent use of that shit worsens HF prognosis/increases ischemic damage
Ca Sensitizers
Theoretically might be able to have benefits of increased IC Ca without actually doing it, avoiding a lot of problems. But they don’t exist yet. So why the fuck are we learning about them
