| What are positive inotropic agents? | Increase myocardial contractility and thus CO
all result from increased cytoplasmic Ca enhancing myocardial cotractility via different mechanisms
These agents are associated with reduced survival in pt w/HFrEF, so they are only used for a short period inpatients.
Indications (Decompensated congestive HF, Cardiogenic shock, septic shock, cardiomyopathy) |
| How is classification of positive inotrops? | Adrenergic (catecholamine and non-catecholamine )
Non Adrenergic (PDE inhibitors and Miscellaneous) |
| What are cardaic glycosides/Digitalis? | Group of substances increase contractility of heart muscle used in cardiac failure, influence sodium and calcium influx increase atrial and ventricular contractions.
Show a narrow therapeutic window, most widely used is digoxin (prototype) |
| How is mechanism of action of digitalis? | Inhibit Na+/K+ ATPase so Na+ movement is reduced, so Ca cannot be excreted outside increasing intracellularly, this change should be controlled and minimal, as it increases the resting potential may be affected and reduced (from -90 to -70) and thus make membrane more excitable increasing risk of arrhythmias (toxicity) |
| How is action of digoxin in increasing contractility? | Digoxin increases the force of cardiac contraction, causing cardiac output to more closely resemble that of the normal heart
Vagal tone is also enhanced, so both heart rate and myocardial oxygen demand decrease.
Digoxin slows conduction velocity through the AV node, making it useful for atrial fibrillation.
[Note: In the normal heart, the positive inotropic effect of digitalis glycosides is counteracted by compensatory autonomic reflexes.] |
| What are therapeutic uses of digitalis? | HF (increase inotropy, ejection fraction, decrease preload and edema)
Arrhythmias (decreasd AV node conduction and ventricular rate in atrial flutter and fibrillation) |
| How is Pharmacokinetcis of digitalis? | A: Oral absorption 60-80%, PRL for emergencies IV onset 15 min max 2 h)
D: wide distribution into organs including CNS
E: 80% unchanged in urine, small amount by active transport in kidney (important to know renal failure) |
| Comparison between digoxin and digotoxin? | . |
| How is digoxin toxicity? | Should be used with drugs slowing AV conduction (b blockers, verapamil, diltiazim)
GI (nausea, vomit, abdo pain)
Neuro (weakness, confusion)
Electrolyte (Hyperkalemia >5.5 poor prognosis)
Cardiac (bradycardia, block)
Therapeutic level is 0.8-2 ng/ml, toxic >2.4 ng/ml
Severe toxicity leads to V tach needs antiarrhythmatics and antibodies to digoxin (immune Fab) |
| How are Adrenergic receptor agonists use in cardiac contractility? | Dobutamine and Dopamine positive inotropic and vasodilation, most common is dobutamine other than digoxin by increasing cAMP and activating protein kinase to slow Ca channels increasing entry of Ca into cells
Given IV, for short term action for acute HF
Act on Beta 1 receptors, drugs of choice for shock given continuous infusion, raises BP and CO (Dopamine)
Dobutamine (same, increase CO but lesser extent on vessels and HR, for Congestive HF and inotropic support post cardiac surgery no increase in O2 demand of myocardium) |
| What are phosphodiesterase inhibitors? | Cyclic-AMP is broken down by an enzyme called cAMP-dependent phosphodiesterase (PDE)
The isoform of this enzyme that is targeted by currently used clinical drugs is the type 3 form (PDE3).
Inhibition of this enzyme prevents cAMP breakdown and thereby increases its intracellular concentration.
➔This increases cardiac inotropy, chronotropy and dromotropy
The cardiac and vascular effects of cAMP-dependent PDE inhibitors cause :
✓Cardiac stimulation= Increases cardiac output
✓Systemic vascular resistance decreases= Lower arterial pressure.
✓Moderate dilation of both artery and veins leading to decrease in afterload and preload
Because of the dual cardiac and vascular effects of these compounds, they are sometimesreferred to as "inodilators." |
| Give name of PDE inhibitor? | Milrinone is a phosphodiesterase inhibitor that increases the intracellular concentration of cAMP. Like β-adrenergic agonists, this results in an increase of intracellular calcium and, therefore, cardiac contractility.
Long-term, milrinone therapy may be associated with a substantial increased risk of mortality. However, short-term use of intravenous milrinone is not associated with increased mortality in patients without a history of coronary artery disease, and some symptomatic benefit may be obtained in patients with refractory HF. |
| Compare between dobutamine and Milrinone. | . |
