Inotropic Agents - Digitalis Mechanism of Action Pharmacokinetics Therapeutic uses Adverse Effects

1. INOTROPIC DRUGS - DIGITALIS
Tural Abdullayev
Group 30

2. INOTROPIC AGENTS
 Positive inotropic agents enhance Cardiac Muscle
Contractility and, thus, increase Cardiac Output
 In each case the inotropic action is the result of an
increased cytoplasmic Ca concentration that enhances
the contractility of cardiac muscle

3. MECHANISM OF ACTION
 Inhibition of Na/K ATPase
 Blunting of Ca2+ extrusion
 Ca2+
 Sarcomere shortening

4. MECHANISM OF ACTION
 Regulation of cytosolic Ca concentration :
 Free cytosolic Ca concentrations at the end of
contraction must be lowered for cardiac muscle to relax
 Na+/Ca2+ - exchanger extruding Ca2+ from the
myocyte in exchange for Na+
 Cardiac glycosides inhibit the ability of the myocyte to
pump Na+ from the cell, consequently Ca2+ also cannot
be pumped out of the cell.

5. MECHANISM OF ACTION
 Higher cellular Nas is exchanged for extracellular
Ca by Na/Ca – exchanger increasing intracellular
Ca2+
 Na/K ATPase exchanges 2Na for 1K, it restores the
ion concentrations and the membrane RP.
 When the Na/K ATPase is inhibited by Digoxin,
RMP may increase, which makes the membrane
more excitable, increasing the risk of arrhythmias

6. MECHANISM OF ACTION
 Increased contractility of the cardiac muscle :
 As Digitalis increases myocardial contraction leads to
decrease in end-diastolic volume, thus increasing the
efficiency of contraction ( ejection fraction )
 Improved circulation leads to reduced sympathetic activity,
which reduces Peripheral resistance, together these effects
cause reduction in Heart Rate and myocardial oxygen
demand diminishes.
 Digoxin slows down conduction velocity through the AV node

7. EFFECTS
 Mechanical Effects :
 ↑ force of contraction ( Positive Inotropic Effect )
 Slower HR, via PNS stimulation ( Negative Inotropic Effect )
 Electrical Effects:
 ↑ activity of ectopic pacemakers ( Positive Inotropic Effect )
 Impairs AV nodes conduction ( Negative Inotropic Effect )

8. THERAPEUTIC USES
 Digoxin :
 Severe Left Ventricular Systolic Dysfunction after initiation
of ACE inhibitor and Diuretic therapy
 Heart Failure with atrial fibrillation
 Not indicated in patients with diastolic or Right-Sided HF
 Doputamine :
 Can be given IV in the hospital

9. PHARMACOKINETICS
 Absorption :
 Good, after oral administration
 Protein Binding :
 Low, ≈25% of absorbed drug
 Volume of Distribution :
 High, because it accumulates in muscle
 Half Life :
 Long, 36 hours
 Elimination:
 Excreted with urine

10. ADVERSE EFFECTS
 Cardiac Effects:
 Most common is arrhythmia, characterized by slowing of AV
conduction associated with Atrial Arrhythmias
 ↓ in intracellular K
 GI Effects :
 Anorexia
 Nausea
 Vomiting
 CNS effects :
 Headache
 Fatigue
 Confusion
 Blurred vision
 Alteration of color perception