Drugs for Heart Failure Flashcards
Give the 9 drug classes / drugs that are used for heart failure
- ACE-Is / ARBs
- Beta blockers
- Loop diuretics
- Sacubitril-Valsartan
- Mineralocorticoid receptor antagonists
- Nitrates
- Hydralazine
- Ivabradine
- Cardiac glycosides (digitalis)
Name 4 beta blockers that can be used to treat heart failure and state their cardioselectivity
- Carvedilol: Non selective
- Bisoprolol: Beta-1 selective
- Metoprolol XL: Beta-1 selective
- Nebivolol: Mixed selectivity
Give 3 other features of carvedilol use besides its use in hypertension and heart failure
- Can bind to alpha-1 receptors to reduce peripheral vascular resistance
- Antioxidative
- Anti-ischaemic
Name the natriuretic peptide that increases with heart failure
Brain natriuretic peptide (BNP)
Give 4 effects of BNP
- Promotes vasodilation
- Promotes natriuresis
- Promotes diuresis
- Antagonises RAAS which has favourable effects on heart failure
Name the enzyme that breaks down NPs
Neprilysin
Name 3 molecules that are broken down by neprilysin
- Natriuretic peptides eg BNP
- Angiotensin II
- Bradykinin
Intended MOA of sacubitril
Inhibits neprilysin leading to prolonged BNP effects which is good for HF
Why must valsartan be given with sacubitril?
Since neprilysin also breaks down Ang II, valsartan is given to act as an Ang II blocker which can reduce the side effects of prolonged Ang II, which is bad for HF
Sacubitril-Valsartan is known as an ___ inhibitor
ARNi: Angiotensin receptor/neprilysin inhibitor
Clinical use of sacubitril-valsartan
Heart failure with reduced ejection fraction (HFrEF)
*Can replace ARB / ACEIs
State 5 ADRs of sacubitril-valsartan use
- Hypotension
- Hyperkalemia
- Dry cough (due to increase in bradykinin)
- Renal failure
- Angioedema
Name 3 loop diuretics
- Furosemide
- Bumetanide
- Ethacrynic acid
Describe MOA of loop diuretics
Inhibit the luminal Na+/K+/2Cl- ion transporter in the thick ascending limb of the loop of Henle.
This increases the excretion of Mg2+ and Ca2+ (loss of lumen positive electric potential that decreases reabsorption of cations)
Also induces renal PG synthesis and increases renal blood flow (furosemide)
____ interfere with the actions of loop diuretics by ____ PG synthesis
NSAIDs (eg aspirin)
Reducing
State 4 clinical uses of loop diuretics
- Acute pulmonary oedema and other edema
- Acute hyperkalemia
- Acute renal failure
- Anion overdose: toxic ingestions of bromide, fluoride, iodide
State 4 ADRs of loop diuretic use
- Hypokalemic metabolic alkalosis
- Ototoxicity
- Hyperuricemia
- Hypomagnesemia
Loop diuretics should not be given together with ____ antibiotics (due to increased risk of ototoxicity)
Aminoglycosides
Where in the nephron do mineralocorticoids primarily work at
Collecting duct cells (specifically principal cells)
Name 4 potassium-sparing diuretics (mineralocorticoid receptor antagonists)
- Spironolactone
- Eplerenone
- Triamterene
- Amiloride
MOA of spironolactone and eplerenone
Binds and blocks the aldosterone receptor
MOA of triamterene and amiloride
Binds and blocks the sodium channel
2 clinical uses of potassium-sparing diuretics
- Diuretic
- Hyperaldosteronism
Does spironolactone have a slow or fast onset of action?
Slow
Triamterene is metabolised in the ___
Liver
Compared to amiloride, triamterene has a shorter or longer half-life?
Shorter
State 5 ADRs of potassium-sparing diuretic use
- Hyperkalemia
- Metabolic acidosis
- Gynacomastia (spironolactone use)
- Acute renal failure (triamterene with indomethacin)
- Kidney stones (triamterene)
Name a potassium-sparing diuretic associated with gynaecomastia
Spironolactone
Name a potassium sparing diuretic associated with acute renal failure and kidney stones
Triamterene
Name an NSAID when used with triamterene that increases the risk of acute renal failure
Indomethacin
MOA of hydralazine
Direct arteriole vasodilator.
Inhibits the inositol triphosphate (IP3) induced release of calcium from the smooth muscle sarcoplasmic reticulum.
This reduces peripheral resistance causing compensatory release of NE and E leading to increased venous return and cardiac output
2 clinical uses for hydralazine
- HFrEF
- Acute onset severe peripartum and postpartum hypertension
Route of administration of hydralazine for HFrEF
Oral
Route of administration of hydralazine for acute onset severe peri and postpartum HTN
IV
In treating HFrEF with hydralazine, combination therapy with ____ should be used.
Isosorbide dinitrate (ISDN)
Hydralazine is a good second line medication for what condition?
Hypertension
2 ADRs of hydralazine use
- Baroreflex associated sympathetic activation symptoms: Flushing, hypotension, tachycardia
- Hydralazine-induced lupus syndrome (HILS)
State 4 clinical presentations of hydralazine induced lupus syndrome (HILS)
- Arthralgia
- Myalgia
- Serositis
- Fever
Treatment for HILS
Discontinue hydralazine therapy
Hydralazine is contraindicated in patients with
Coronary artery disease
(because hydralazine stimulates sympathetic nervous system causing increased CO / O2 demand, thus causing myocardial ischaemia)
Name 2 forms of digitalis (which are cardiac glycosides)
- Digoxin
- Digitoxin
Route of administration of digitoxin and digoxin
Oral
Digitoxin is extensively metabolised in the ___ and excreted in the ___
Liver
Feces
Is digoxin extensively metabolised?
No
Primary excretion route for digoxin
Unchanged by the kidney
MOA of digitalis
Directly inhibits the Na+/K+ ATPase pump in the cardiac myocytes, thus increasing intracellular sodium concentration
This leads to less Ca2+ efflux by the Ca2+/Na+ exchanger, leading to higher intracellular calcium concentration, causing stronger systolic contractions
2 clinical uses of digitalis
- Systolic dysfunction
- Atrial fibrillation
3 ADRs of digitalis use
- Progressively more severe dysrhythmia: AV block, AF, VF
- GI effects: nausea, anorexia, vomitting
- CNS effects: fatigue, confusion, headache, blurred vision
4 treatment for digitalis toxicity
- Discontinue cardiac glycoside therapy
- Correction of potassium or magnesium deficiency
- Antiarrythmic drugs (if automaticity predominant, use lidocaine or propranolol)
- Digoxin antibody (eg FAB fragments, digibind)
