Phosphodiesterase Inhibitors in Congestive heart failure
These are some Phosphodiesterase Inhibitors used in treatment of Congestive heart failure in animals-
- Methyl Xanthine
- Bipyridine derivatives
- Pyridazone derivatives
1. Methyl Xanthine
Theophylline, Etamiphylline, Aminophylline are examples of Methyl xanthines. here bolow, functions of these drugs descried-
- Block all PDE isoforms – effect on heart, kidney, smooth muscle, lung
- Theophylline is a Cardio potent drug
- For cardiac disease accompanying respiratory problem
- Relieves cough in CHF in dogs
- Increases O2 in heart
- consumption and causes tachycardia and vomiting
2. Bipyridine derivatives
Amrinone (Inamrinone), Milrinone are the examples of Bipyridine derivatives. these are potent inotropic agents.
Mechanism of action of Bipyridine derivatives-
- Inhibit PDE III, Inodilator (dilates veins and arterioles)
- Decrease preload and afterload
- Increases CO
- Improves exercise capacity
Amrinone
Pharmakinetic of Amrinone
Effect in 2 minute after IV, peak in 10 minute, Conjugated in liver and some excreted unchanged through kidney, Half life increase in heart failure due to decreased hepatic blood flow.
Side effect of Amrinone
Hypotension, GI disturbances, long term therapy – thrombocytopenia, hepatotoxicity, hypersensitivity (occasional), CHF: may increase susceptibility to arrhythmia
Use of Amrinone
Short term IV use in severe / refractory CHF, 2nd line agent in CHF; Along with digoxin and diuretics
Milrinone
• Positive inotropic, Systemic arteriolar dilator, Inhibits PDE III, relaxes left ventricle by enhancing Ca2+ ATPase
• activity on sarcoplasmic reticulum
• Minimal chronotropic effect
• 20-30 x more potent than amrinone
• IV/ PO, TI: 100 (safer)
• High dose of Milrinone cause Arrhythmia
3. Pyridazone derivatives
Pimobendan is a Pyridazone derivative drug used in CHF. these are the features of pyridazone derivatives-
- Inotropic and vasodilator effect
- Calcium sensitizer – Increase the binding efficiency of Ca2+
- to
- myofibrils without increasing IC calcium / oxygen – less prone for
- arrhythmia
- PDE III inhibitor – Vasodilatation (potent inodilator)
- Anti-cytokine and anti-thrombotic property
Pimobendan – First choice
Use
Mitral valve disease (small breed), Dilated cardiomyopathy (medium to large breed), Combined with diuretics (Furosemide) and ACEI (Enalapril).
Dose
0.2-0.6mg/kg BID, before feeding (Dog) Improves quality of life
Side effects
Well tolerated, arrhythmia in some cases
Contraindications
Hypertrophic cardiomyopathy
Interactions
taking Ca2+ channel blockers and β blockers drugs along with Pimobendan decrease the effect