Agents used in heart failure Flashcards
Meaning of Pre-load and after-load
P - how much blood comes to the heart
A - peripheral resistance
Compensatory responses that occur in heart failure
- Decrease cardiac output
- Decrease carotid firing
- Increase sympathetic discharge
- Increase cardiac output - force, rate, preload
- Decrease cardiac output
- Decrease renal blood flow
- Increase renin release
- Increase Angiotensin II
- Increase preaload, afterload, remodeling
Acute heart failure
-drugs
- Digoxin
- Beta adrenoreceptos agonists
- Milrinone
- Levosimendan
- Diuretics - increase H20 and sodium elimination
- Vasodilator drugs - increase preload and afterload
All increase inotropic function
Chronic heart failure
-drugs
- Digoxin
- Beta adrenoreceptos blockers
- Ivabradin
- ACEi and ARB
- Diuretics - increase H20 and sodium elimination
- Vasodilator drugs - increase preload and afterload
All decrease workload (preload and afterload)
DIGOXIN
-mechanism of action (6)
- it binds to sodium-potassium pump and competes with potassium for it
- it inhibits sodium-potassium pump
- increases intracellular sodium levels
- calcium-sodium pump recognizes that there is a lot of calcium intracellulary
- this pump is less active
- accumulation of calcium intracellulary –> beneficial to cause beta contraction
DIGOXIN
- principal effects
- why are there negative effects?
+ –> inotropic and bathmotropic effect –> parasympathetic system effect directly
- –> chronotropic and dromotropic effect –> parasympathetic system effect indirectly
Positive inotropic effects will cause a higher cardiac output
- more drugs goes to periphery
- more blood to carotid sinus
- N. vagus active
- Parasympathetic system activity is increased in the heart
- that’s how decrease heart rate is caused indirectly
DIGOXIN
- pharmacokinetics
- indications
- unwanted effects
- high volume of distribution, mainly eliminated by the kidneys
- to slow ventricular rate in rapid persistent atrial fibrillation, heart failure
- the effects increase if extracellular K+ is low, pro-arrhythmic effects, GI: nausea, vomiting, diarrhea, vision disturbances
Beta adrenoreceptos agonists used in acute heart failure
DOBUTAMINE
DOPAMINE
Dobutamine
- mechanism of action
- indications
- unwanted effects
- contraindications
- more inotropic effects –> less effect in heart rate, it mainly causes better contraction
- doesnt have effect to peripheral resistance
- cardiogenic shock, acute heart failure, after heart surgery
- tachycardia, dysrhythmia, increase of myocardial damage
- hypertension, narrowing of the aortic valve, atrial fibrillation
Dopamine
-mechanism of action
Low doses - D1 receptors (decrease intracellular cAMP) –> vasodilation of kidney, mesenteric, coronary vessels
Medium doses - B1-adrenoreceptors (increase intracellular cAMP) –> positive inotropic effects
High dose - B1-adrenoreceptors + alpha-adrenoreceptors –> peripheral vasoconstriction
Dopamine
- indications
- unwanted effects
- cardiogenic shock, other shock
- tachycardia, dysrhythmias, hypertension
Milrinone
- indications
- mechanism of action
- effects
-acute heart failure
- inhibit phophodiesterase-3
- prevents degradation of cAMP –> increase intracellular cAMP –> increase calcium –> better cardiac contractility
-increase heart contractility, vasodilator effect
Levosimendan
- effects
- mechanism of action
- increase cardiac output without increasing myocardial O2 demand, vasodilator (opens ATP sensitive K+ channels in vascular smooth muscle)
- calcium sensitizer (increases heart’s sensitivity to Ca2+) –> increases cardiac contractility without rise in intracellular calcium
Ivabradin
- indications
- effects
- mechanism of action
- contraindications
- unwanted effects
- chronic stable angina pectoris, chronic heart failure
- lowers heart rate
- inhibits If (funny channels) in the heart that controls the spontaneous diastolic depolarization in the SN without affecting any other cardiac ionic channels
- HR<70 bpm prior to treatment, cardiogenic shock, acute MI, hypotension, sick sinus syndrome, sino-atrial and AV block, unstable or acute heart failure
- luminous phenomena, blurred vision, bradycardia, AV block, arrhythmia, uncontrolled BP
Sacubitril/Valsartan
- mechanism of action
- indications
- contraindications
- unwanted effects
- angiotensin receptor and neprilysin inhibitor
- inhibition of neprilysin leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II.
- However, when combined with valsartan, would result in blocking of angiotensin II to its receptor, preventing the vasoconstrictive effects and resulting in a decrease in vascular resistance and blood pressure.
- chronic heart failure with reduced ejection fraction
- concomitant use with ACEi
- hypotension
