Cardiotonics
TomasGonec 14.11.2011
Heart failure
H
Signaling for Hypertropic growth and Remodeling
AT1 receptor antagonists ACE inhibitors Beta blockers
Left ventricular dysfunction
Hypertension Viral Infection Myocardial Ischemia
Inotropic agents
function
vasoconstriction Salt and water retention
j Left ventricular Left ventricular
í
ACE inhibitors AT^ antagonists Diuretics
Perceived reduction in circulating volume and pressure
ACE inhibitors AT1 antagonists
>
í ) ^function
t/-
(+)^ Sympathetic tone
w
renin-angiotensin-aldosterone (+) + Arginine vasopressin
\<->
AT1 rec eptor antagonists ACE inhibitors Beta blockers
Cardiomyocyte contraction
Extracellular space
Na'
Ma-.
Na~
Ptasma	Na+	i
membrane—.	I	J
		
'-~		K'
Ja'/Ca2*		
Sarcoglycan complex
changer
Junctin-triadin complex
L-typeCsi+| Ryanodine (Ca**-release)
channel ^Calsflquestrin
ises
a
Sarcomere (myosin, actin, troponin and titin)
I
Therapy of heart failure: inotropic agents
□ cardioglycosides
□ p-adrenergic agonists
□ phosphodiesterase inhibitors
□ Ca2+ channel senzitizers
Cardiac glycosides
B
kardenolid
bufenolid
Cardiac glycosides
Digoxin
I 11
Cardiac glycosides - mechanism of action
□ Na+/K+-ATPase inhibitors
□ Na+ ions intracelular retention
□ due to ion substitution also Ca2+intracelular retention
□ positive inotropic effect
11
Cardiac glycosides used in therapy
□ Lanatosides A, B, C; purpureaglycosides A, B digitoxin, gitoxin, digoxin - secundary glycosides with cleavaged terminal sugar
□ Ouabain, k-strophantoside
□ Proscillaridine, meproscillarine (buffadienolides)
Cardiac glycosides
B
□ narrow therapeutic-toxic window
□ high plasma proteins binding
□ monitoring during therapy necessary
□ long-term administration increases mortality -therapeutic use in future questionable
11
Pi-adrenergic receptor agonists
□ stimulation of adenylatecyclase, increase of intracelular cAMP, positive inotropic effect
OH
denopamin
oxyfedrin
Pi-adrenergic receptor agonists
		OR	
		Cf	
		CH2CH2NH-R1	
	R	R1	léčivo
	H	H	dopamin
	H H	-CHCH2CH2-/~Ty0H CH3 X==/ -(CH2)6NHCH2CH2-^^	dobutamin dopexamin
	-COCH(CH3)2 -COOCH2CH3	-CH3 -COCHNHCOCH, I CH2CH2-S-CH3	íbopamin dokarpamin
11
Phosphodiesterase inhibitors
□ xanthine derivatives
□ bipyridine derivatives
□ 3-pyridazinone derivatives
□ chinolin-2-one derivatives
Xanthine derivatives
B
□ Theophyline
□ Aminophyline
□ Etophyline
* see coronary vasodilatators presentation
uounxoug
H
UOUUÜIAI UOUUlilB
3-pyridazinone derivatives
Simendan
Chinolin-2-one derivatives
Cardioprotectives
B
□ detoxication of free radicals (NO, 00, OH)
ch.
*****
V
oh
hoco
r i
\)h
nh.
ch.
V
oh
■nh
fosfokreatin
fbsfbkreatinin
H
+ I (CH3)3N-CH2-C-CH2COO
OH
levokarnitih