1. Drugs for
Congestive Heart Failure

2. Learning Objectives:
List classifications of the agents for CHF, their general target and mechanisms of action.
Identify the positive inotropic effect of Cardiac glycosides/digitalis
List the treatment of the cardiac toxicity of Cardiac glycosides
Analyze the mechanism of RAASI on CHF
Discuss the therapeutic considerations of β-adrenoceptor blockers for CHF

3. Pathophysiology of CHF
Systolic/Diastolic dysfunction
Sympathetic Nerve System activation
β-adrenoceptor down-regulation
Renin-Angiotensin-Aldosterone System activation
Myocardial hypertrophy and remodeling

5. Strategy for the treatment of CHF
Increase the cardiac contraction
Decrease the heart load
Inhibit myocardial hypertrophy
How?

6. Classification of Drugs for CHF
Cardiac glycosides/digitalis
RAASI: ACEI/ARB
Diuretics
β-adrenoceptor blockers
CCB
PDEI (phosphodiesterase inhibitor)
Vasodilators

7. Ca++ Cardiac Glycosides Ca+-ECC Na + Na+/Ca++ exchanger
Positive inotropic effect
K+-Na+-ATPase Na
+ Na+/Ca++ exchanger
Ca++
Ca+-ECC

8. 苷

9. Cardiac Glycosides Effects on nerve
To inhibit sympathetic nerve activity
To enhance vagus nerve activity
results?

10. Electrophysiological effects
In therapeutic dose on sinoatrial node (negative frequency ):
K MDP automaticity
In toxic dose on Purkinje fiber:
K-Na-ATPase K MDP
Intracellular
automaticity

11. Electrophysiological effects
Decrease the conduction in atrioventricular node (negative conduction)
Shorten the ERP in atrium

12. 强心苷的电生理学作用
负性频率 A
负性传导 C
16 字诀
正性自律 B
缩不应期 D

13. Cardiac Glycosides Clinic uses ADR CHF
Arrhythmia： Atrial fibrillation, Atrial flutter
ADR
Gastrointestinal tract: anorexia, nausea, vomiting, and diarrhea
Central nervous system: chemoreceptor trigger zoon stimulation; disorientation; hallucination, visual disturbances including aberrations of color perception：xanthopsia，chloropsia

14. ADR OF DIGITALIS Cardiac:
Supra -/-Ventricular arrhythmia , Atrial Ventricular Block , ventricular premature beat
Therapy:
Drug withdrawal
K+ supplement
Phenytoin sodium/lidocaine
Digoxin antibody

15. Treatment of toxicity caused by cardiac glycoside 强心苷中毒的治疗停药 竞争 A C
Phenytoin sodium
Drug withdrawal
8字诀 B 补钾 强抢 D
Digoxin antibody
K+ supplement

16. Non-cardiac glycosides positive inotropic drugs
PDEI (milrinone, amrinone, vesnarinone)
cyclic adenosine monophosphate
Adenosine Triphosphate
PDEI
ATP cAMP ’AMP
Increase cardiac output
Increase mortality
adenyl cyclase
Ca++ influx

17. The renin–angiotensin–aldosterone system
juxtaglomerular (J-g) cells
The renin–angiotensin–aldosterone system

18. Ang Ⅱ & hypertrophy c-fos c-myc gene Ang Ⅱ + AT1, AT2
+ PLC-IP3(DAG-PKC ) Ca
PTK nuclear transcription factor
+MAPK nuclear protein phosphorylation
proto-oncogene:c-fos、c-jun、c-myc
Cell growth and proliferation
c-fos
c-myc + +
cellular cycle
gene

19. ADR of RAASI
hyperpotassemia
hypotension
Dry cough (ACEI+ ; ARB-)

20. β-adrenoceptor blockers
Attenuation of the adverse effects of high concentrations of catecholamines
Up-regulation of receptors to increase the sensitivity to catecholamines
Decrease oxygen consumption

21. Therapeutic considerations
Indication: Ⅱ-Ⅲ
Low dosage as possible
Combination therapy with positive inotropic drug
sufficiently long-term application

23. Others Diuretics CCB Vasodilators: sodium nitroprusside、nitroglycerin
prazosin、hydrolazine
Nesiritide(Brain natriuretic peptide)
Bosentan(Endothelin R Blocker)