Heart Failure Treatment Flashcards
What is congestive heart failure?
condition where the heart cannot pump sufficient blood to meet the needs of the body
systolic dysfunction : impaired ventricular contraction
diastolic dysfunction : impaired ventricular relaxation
What are the features of chronic heart failure?
- progressive cardiac dysfunction
- breathlessness
- tiredness
- neurohormonal disturbances
- sudden death
CHF normally due to coronary artery disease. condition has poor prognosis as it is a progressive condition so treatment can only slow down progression but not cure heart failure.
What are the cardiovascular consequences of heart failure?
cardiac failure -> decreased cardiac output -> decreased BP causes increased sympathetic activity where there will be vasoconstriction of peripheral arteries -> decreased renal blood flow leading to RAAS activation -> fluid retention from aldosterone and ADH -> edema because heart is still unable to pump this increased blood volume
cardiac failure -> venous congestion especially in RHF -> edema
What drugs are used in heart failure?
- ACE inhibitors/AT1 Blockers
- Sacubitril-Valsartan
- Beta blockers
- Loop diuretics
- Mineralocorticoid receptor antagonists
- Hydralazine
- Ivabradine
- Nitrates (ISDN and ISMN)
What are the different ways that drugs can slow down progression of heart failure?
- in the initial stages of chronic heart failure when there isnt a very drastic decline in cardiac output yet, the aim of treatment is to relieve the burden on the heart and this is done by decreasing cardiac preload so that heart function can be preserved in the long run
- in the later stages of chronic heart failure where the EF is very low and the patient is end stage, inotropic drugs are given to increase heart contractility just to extend life for awhile until heart muscles fatigue as this is not sustainable in the long-run
What nitrates are used in chronic heart failure?
- For heart failure, ISDN has been more extensively studied than ISMN and ISMN is not FDA approved as heart failure medication yet but in angina pectoris, ISMN may be preferred because of its ease of administration as a once daily formulation and is also the more stable form.
- ISDN has onset of 60 mins but ISMN has onset of 30 mins. ISDN has better half life because even once its broken down to ISMN, it is still pharmacologically active so ISDN have 8 hr duration of action but ISMN has 6 hr duration of action so ISDN has longer therapeutic effect in heart failure
- at low plasma concentration, they cause venous dilation only but at high plasma concentration, there is also arterial dilation. there is also direct dilatory effect on coronary arteries so there is improvement in subendocardial blood flow. this decreases cardiac load on failing heart
What is the MOA of beta-blockers in heart failure?
- only non selective carvedilol, beta1 selective bisoprolol and metoprolol, mixed nebivolol which is beta 1 selective at low dose and nonselective at higher dose are approved for heart failure
- Blockade of beta-1 receptors in
cardiac myocytes leads to
decreased contractility and more heart muscle relaxation which is useful in decreasing the load on the heart and enabling it to relax so that heart function can be preserved in the long run - in addition to being beta blockers, carvdeilol is also able to block alpha 1 receptors causing reduced peripheral vascular resistance as there is now vasodilation. it is also speculated to have antioxidative and anti ischemic properties
What is the MOA of hydralazine in heart failure?
- also used as second line anti-hypertensive
- direct arteriole vasodilator by inhibiting IP3 induced release of calcium from smooth muscle cells sarcoplasmic reticulum
- this reduction in peripheral resistance leads to compensatory release of epinephrine and norepinephrine so there is increased venous return and cardiac output. this helps heart failure with reduced EF
When is hydralazine used?
- used in combination with isosorbide dinitrate in heart failure with reduced ejection fraction. given orally
- second line drug for hypertension
- first line drug for severe peripartum or postpartum hypertension (IV)
What are the adverse effects of hydralazine?
- symptoms associated with baroreceptor associated sympathetic activation : flushing, hypotension and tachycardia
- hydralazine induced lupus syndrome where there will be athralgia, myalgia, serositis and fever. it is present in about 6% of users and is dose dependent after around 6 months of use
- CONTRAINDICATED IN CORONARY ARTERY DISEASE BECAUSE OF HYDRALAZINE’s REFLUX SYMPATHETIC ACTIVATION WHICH LEADS TO INCREASED OXYGEN DEMAND AND MYOCARDIAL INFARCTION
What are some loop diuretics used in heart failure?
- Furosemide
- Bumetaminde
- Ethacrynic acid
What is the mechanism of loop diuretics?
thick ascending limb normal ion movement :
- there is an apical Na+/K+/2Cl- transporter in the thick ascending limb of Henle’s loop. this transporter contributes to excess K+ accumulation within the cell and these K+ ions then back diffuse into the lumen, generating an electrical potential that provides the driving force for reabsorption of Mg2+ and Ca2+ cations via paracellular pathway
- loop diuretics selectively inhibit the apical Na+/K+/2Cl- transporter in the thick ascending limb. so there is a blockage of K+ dependent reabsorption of Mg2+ and Ca2+ cations leading to their increased excretion so there is less water reabsorption at the collecting ducts as the lumen is hypertonic and this prevents edema formation during heart failure
- loop diuretics like furosemide also induce renal prostaglandin synthesis which increase renal blood flow so that RAAS will not be activated and further worsen the edema in heart failure. but NSAIDS interfere with the PG synthesis
What are loop diuretics used for?
- acute pulmonary edema and other edema
- acute hyperkalemia because of less K+ reabsorption at thick ascending limb
- acute renal failure because loop diuretics can induce increased renal blood flow via PG
- Anion overdose from toxic ingestion of bromide, fluoride and iodide can be treated with loop diuretics because less ions reabsorbed at thick ascending limb
What are the side effects of loop diuretics?
- hypokalemic metabolic alkalosis
- ototoxicity so avoid using together with aminoglycoside antibiotic which also causes ototoxicity
- hyperuricemia
- hypomagnesemia
What is the mechanism of action of potassium sparing diuretics?
normal ion movement at the collecting ducts :
- at the principal cells, Na+ and H2O are reabsorbed but K+ is secreted. at the basal membrane, Na+ reabsorption is coupled with K+ secretion because of the Na+-K+ ATPase channel and this is regulated by aldosterone. ADH causes increases aquaporin H2O channels on apical surface.
- at the intercalated cells, H+ is secreted while HCO3- is reabsorbed
-spironolactone and eplerenone inhibit aldosterone receptor so there is reduced sodium reabsorption and lesser osmotic movement of water as well
- triamterene and amiloride inhibit sodium channels so there is still reduced sodium reabsorption. so even if aldosterone activated, sodium channels are still blocked by these drugs.
