positive inotropic drug Flashcards
Acute heart failure- positive inotropic drugs
- beta adrenergic receptor stimulants
- cardiac glycosides
- calcium sensitizers
- PDE3 inhibitors
beta adrenergic receptor stimulant- MOA
stimulate the beta1 receptor in the heart
- activate the adenylyl cyclase and increase in cAMP, increase in PKA function
- increase in calcium influx and CICR -> increase in intracellular calcium concentration
- increase in contractility
dobutamine
- (-) enantiomer is an agonist of alpha 1, (+) is partial agonist
both are non-selective agonist of beta receptors
the vasoconstriction effect is offset by the vasodilator effect -> reduction in peripheral resistance
dopamine
- only at intermediate dose, can have beta 1 agonist effect, if too low -> vasodilation , too high -> vasoconstriction
beta adrenergic receptor stimulant- good
rapid onset and short duration of action
beta adrenergic receptor stimulant- adverse effects
- pro arrhythmic, pro-angina, tachyphylaxis after 4 days (need to replace by PDE3 inhibitor)
PDE3 inhibitors- example
milrinone, enoximone
PDE3 inhibitor- MOA
- prevent the breakdown of cAMP by PDE3
- increase in intracellular ca level
- vasodilation effect
PDE3 inhibitor- side effects
- pro-arrhythmic
cardiac glycosides (digoxin)- MOA
- inhibit the Na K ATPase, therefore increase in intracellular Na conc -> increase the efflux of Na and influx of Ca by Na Ca exchanger
- increase in the Ca2+ storage in SR -> next contraction -> increase in intracellular Ca level
digoxin- side effects
- very narrow safety margin
- pro-arrhythmic
not 1st line treatment for heart failure (but can be used for chronic heart failure)
digoxin- good
anti-arrhythmic
calcium sensitizer- example
levosimendan
Calcium sensitizer- MOA
- stabilise the binding between troponin C and calcium
- increase troponin C affinity for calcium
- increase in contractility without increasing the intracellular Ca level
Calcium sensitizer- good
coronary and systemic vasodilation: activate the potassium channels in VSMC -> hyperpolarization -> prevent activation of voltage gated Ca channel and thus prevent vasoconstriction
- it is not pro-arrhythmic
Calcium sensitizer- contraindications and bad
- baseline hypotension/ low bp patient
- headache and hypotension
Calcium sensitizer- administration
IV
Chronic heart failure
Adaptive changes/ compensatory mechanism/ maladaptation
- increase in sympathetic output (increase in heart rate and force of contraction; vasoconstriction)
- increase in RAAS output to reabsorption more water and sodium -> increase in blood volume
these are trying to restore and increase the Cardiac output
- however, both lead to increase in arterial pressure and thus decrease in CO
- increase in cardiac workload and myocardial hypertrophy (both RAAS and sym)
- peripheral oedema (RAAS) -> lungs -> reduction in oxygenation of blood -> further increase cardiac workload cos more blood needed to carry enough oxygen
Chronic heart failure drugs
ivabradine
LCZ696
LCZ696- MOA
- dual angiotensin receptor neprilysin inhibitor
- 1:1 ratio of valsartan and sacubitril
- inhibition of neprilysin by sacubitril -> reduce the breakdown of vasoactive peptides (bradykinin and substance P) -> vasodilation
- reduce breakdown of natriuretic peptides to increase the excretion of Na and water, reducing the blood volume
- have to use with ang receptor blocker because it also blocks the breakdown of AngII
LCZ696- side effect
hypotension
angioedema
hyperkalemia, renal dysfunction (related to the Ang receptor blocker)
- > do not use with ACEI
- > correct and check the Na level volume depletion status before using this to minimise the effect of hypotension
