Treatment of heart failure Flashcards
What are three main underlying causes of heart failure?
- high resistance to cardiac output, i.e. from aortic stenosis, arterial hypertension; therefore less blood is ejected per heartbeat
- heart valves not closing properly therefore less blood available to eject per heartbeat
- heart muscle disease such, i.e. cardiomyopathy, MI; therefore less blood is ejected per heartbeat
What are the principles of treatment?
- relieve underlying condition e.g. replace valve
- relieve aggravating conditions e.g. anaemia
- reduce central venous pressure to reduce oedema
- increase cardiac output (positive inotropes) to reduce skeletal muscle fatigue
- reduce resistance to cardiac output (vasodilation) to reduce skeletal and cardiac muscle fatigue
What are cardioglycosides and how do they treat heart failure?
A positive inotrope which increases the concentration of intracellular calcium ions (bind to troponin C which stimulates force of heart muscle contraction). They inhibit Na/K ATPase which causes intracellular Na+ to increase. Less Na+ is in the extracellular space meaning that less Ca2+ can be exchanged with Na+ (inhibition of Na/Ca exchanger.
How do B1 agonists (sympathomimetics) cause a positive inotropic effect?
They activate cardiac B1 receptors which then activates adenyl cyclase causing an increased synthesis of cAMP. cAMP inhibits the inactivation of the slow inward current (L-type Ca2+ channels open) leading to an increase of intracellular calcium ion concentration.
How does phosphodiesterase (PDE) inhibitors increase intracellular calcium ion concentration?
They inhibit the metabolism and degradation of cAMP caused by PDE therefore there is a higher concentration of cAMP which inhibits the inactivation of the slow inward current.
Why are venodilators used to reduce central venous pressure?
Ventilators dilate central veins which may reduce venous pressure and oedema. However, vein dilation may reduce left ventricle end diastolic pressure which lowers CO. Therefore, ventilators should be used with positive inotropes.
Why are diuretics used to reduce central venous pressure?
They reduce blood volume.
What effect does drugs that reduce afterload have and give an example?
Their effect is to reduce muscle fatigue. Hydralazine has a direct (receptor-independent) arteriolar dilation which is mediated by an increase in cell cGMP and fall in Ca2+.
What is the effect of drugs that reduce afterload and preload?
Their effect is to reduce oedema and muscle fatigue.
What is prazosin and what effect does it have on the body?
It reduces afterload and preload as it is a a1 adrenoceptor antagonist which blocks vasodilation and venoconstrictor effects of noradrenaline and adrenaline.
What effects do catopril, ramipril and enalapril have?
They block angiotensin converting enzyme causing there to be a lower concentration of angiotensin ii which is a vaso/venoconstrictor.
Less angiotensin ii also reduces blood volume as it has a diuretic effects.
What effects do angiotensin ii receptor blockers have and why are they preferable to ACE inhibitors?
Act like ACE inhibitors where there is less circulating angiotensin ii, but do not cause a cough like ACE inhibitors.
What is the paradoxical benefit of B1 antagonists?
Symptoms initially worsen but after long-term use symptoms lessen and risk of death is lowered. This is due to inhibition of adverse adaptive changes in heart (remodelling). The sympathetic drive to the heart is switched off after long-term use.
