Heart failure pharmacotherapeutics

Question 1

what drug classes are used for removing compensation?

Answer 1

• RAAS inhibitor
• ß-adrenoceptor antagonists (ß-blockers)
• ​ diuretics
• Vasodilators/venodilators

Question 2

Compensatory mechanisms in chronic/congestive heart failure are intended to

Answer 2

Cause venoconstriction + raise extracellular fluid volume, increasing central venous pressure, diastolic filling pressure and cardiac stretch. Cause vasoconstriction / rise in total peripheral resistance (which increases blood pressure and therefore tissue perfusion pressure). Increase heart rate (tachycardia) and force of contraction.

Question 3

How is compensation achieved?

Answer 3

• Sympathetic nervous system stimulation (NA and Ad release)
• RAAS activation (AII, aldosterone and ADH release)

Question 4

What is Sympathetic nervous system stimulation?

Answer 4

Responsible for vasoconstriction + venoconstriction (-vascular adrenoceptors), tachycardia and positive inotropy (cardiac ß-adrenoceptors)

Question 5

What is RAAS activation

Answer 5

Responsible for vasoconstriction + venoconstriction (vascular AII AT1-receptors + ADH V1-receptors) and salt and fluid retention (renal aldosterone mineralocorticoid type 1 receptors + ADH V2 receptors)

Question 6

which raas inhibitors are used to remove compensation?

Answer 6

ACE inhibitors (ACEIs) e.g. perindopril, ramipril, captopril, enalapril, lisinopril, quinapril, fosinopril​ angiotensin II AT1-receptor blockers (ARBs) e.g. candesartan, losartan, valsartan​ angiotensin receptor neprilysin inhibitors (ARNIs) – sacubitril with valsartan​ aldosterone receptor blockers e.g. spironolactone, eplerenone

Question 7

which ß-adrenoceptor antagonists (ß-blockers) are used to remove compensation ​

Answer 7

specific examples indicated in heart failure e.g. bisoprolol, carvedilol, nebivolol​ ​

Question 8

which diuretics are used to remove compensation

Answer 8

loop diuretics e.g. furosemide, bumetanide, torasemide​ thiazides and related diuretics e.g. bendroflumethiazide, chlortalidone​

Question 9

which Vasodilators/venodilators are used to remove compensation?​

Answer 9

• organic nitrates e.g. glyceryl trinitrate (GTN), isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN) ​
• directly acting agents e.g. hydralazine
• ​ alpha-adrenoceptor blockers e.g. prazosin (alpha1-adrenoreceptor selective) ​

Question 10

what are positive inotropes

Answer 10

Positive inotropes strengthen the heart’s contractions, so it can pump more blood with fewer heartbeats. This medicine is usually given to patients with congestive heart failure or cardiomyopathy. These medicines may also be given to patients who have had a recent heart attack.

Question 11

list the drugs used to achieve positive inotropy in the heart.

Answer 11

• Cardiac glycosides e.g. digoxin​ ​
• ß-adrenoceptor agonists e.g. dobutamine, dopamine
• Phosphodiesterase type III (PDE III) inhibitors e.g. milrinone, enoximone​

Question 12

explain the actions of Cardiac glycosides as a positive inotrope

Answer 12

inhibit Na/K-ATPase in cardiac sarcolemma to ultimately cause increased calcium accumulation in sarcoplasmic reticulum available for calcium-induced calcium release and myocardial contraction

Question 13

explain the actions of ß-adrenoceptor agonists as a positive inotrope

Answer 13

• ß-sympathomimetic agents​
• cardiac ß1-adrenoceptor signalling leads to raised cAMP and increased force of contraction​

Question 14

explain the actions of Phosphodiesterase type III (PDE III) inhibitors as a positive inotrope

Answer 14

• inhibit enzyme (PDE III) responsible for metabolising cardiac cAMP, thus raising myocardial cAMP and force of contraction
• ​ also raise cAMP in blood vessels, leading to vaso- and venodilation
• ​ known as inodilators in respect of these multiple cardiac and vascular effects ​

Question 15

fill this in

Answer 15

Question 16

fill in the blanks

Answer 16