Heart Failure Drugs (details) Flashcards
What is the MOA of sacubitril?
It inhibits neprilysin (breaks down BNP) –> prolongs BNP effects (ie: vasodilation, natriuresis and diuresis) –> beneficial for heart failure
Why does sacubitril need to be combined with valsartan?
Because neprilysin also breaks down ANGII, so when sacubitril inhibits neprilysin, more ANGII would be broken down too –> bad for heart failure because more sodium and water retention occurs
What is the MOA of valsartan?
Valsartan is a angiotensin ii receptor blocker, thus, when combined with sacubitril, it helps to mitigate the negative effects of ANGII
What are the pharmacological features of sacubitril-valsartan?
- Can be used to replace ARB/ACE inhibitors and therefore can be combined with other drugs normally combined with ARB or ACE inhibitors
Because neprilysin also breaks down bradykinin, so sacubitril-valsartan will inhibit neprilysin and the break down of bradykinin will be inhibited
What are the adverse effects of sacubitril-valsartan?
1) Hypotension
2) Hyperkalemia
3) Renal failure (rare)
4) Cough (because bradykinin is not broken down)
5) Angioedema (because bradykinin is not broken down)
Which part of the loop of Henle does loop diuretics work on?
The thick ascending limb of the loop of Henle.
This is where NaCl is actively reabsorbed
What is the MOA of loop diuretics?
1) Selective inhibition of the luminal Na+/K+/2Cl- transporter in the thick ascending limb of the loop of Henle, and increases Mg+ and Ca2+ excretion
2) Furosemide increases renal blood flow
What drug class should be taken together with loop diuretics and why?
NSAIDs
Loop diuretics induce renal PG synthesis, so NSAIDs should be taken to offset this effect.
What are the PK properties of loop diuretics?
1) They are rapidly absorbed, and thus have short onset of action.
2) The duration of effect for furosemide is usually 2-3 hours.
3) They are eliminated by tubular secretion as well as by glomerular filtration
What are the clinical uses of loop diuretics?
1) Acute pulmonary edema and other edema (can be used for acute PE because of its rapid onset of action)
2) Acute hyperkalemia
3) Acute renal failure
4) Anion overdose - toxic ingestions of bromide, fluoride and iodide (since loop diuretics inhibit the luminal Na+/K+/2Cl- transporter and Cl- is affected, the other halogen ions would be affected as well since they all belong to the same valence group)
What are the adverse effects of loop diuretics?
1) hypokalemic metabolic alkalosis
2) ototoxicity
3) hyperuricemia
4) hypomagnesemia
5) hypocalcemia
What class of drugs should you avoid taking together with loop diuretics?
Aminoglycosides
because both aminoglycosides and loop diuretics cause ototoxicity
Which part of the nephron will potassium-sparing diuretics exert their influence on?
The collecting tubule
What is the MOA of potassium-sparing diuretics?
They block either the aldosterone receptor or the sodium channel.
Which of the potassium-sparing diuretics block the aldosterone receptor?
Spironolactone and eplerenone
Which of the potassium-sparing diuretics block the sodium channel?
Triamterene and amiloride
If you want to use 2 diuretics, what can you use?
1 potassium-sparing diuretic + 1 loop diuretic OR 1 thiazide
no point using spironolactone together with triamterene even though they block different receptors because they’re still in the same pathway.
Pharmaco principle: if you want to use combo therapy, NEVER use 2 drugs that work on the same pathway!
What is the effect of potassium-sparing diuretics on potassium?
Potassium secretion will be decreased since sodium reabsorption is decreased
Discuss the PK properties of spironolactone, triamterene and amiloride
Spironolactone: slow onset of action, requires several days before full therapeutic effect is achieved
Triamterene: metabolised in the liver, shorter half-life and must be given more frequently than amiloride
Amiloride: excreted unchanged in the urine
What are the clinical uses of potassium-sparing diuretics?
1) Diuretic
2) Hyperaldosteronism (ie: over-retention of sodium)
What are the adverse effects of potassium-sparing diuretics?
1) Hyperkalemia
2) Metabolic acidosis
3) Gynecomastia (only for spironolactone)
4) Acute renal failure (when triamterene is taken together with indomethacin)
5) Kidney stones (with triamterene)
What are the MOAs of hydralazine?
Direct arteriole vasodilator –> reduces peripheral resistance –> compensatory release of epinephrine/ norepinephrine –> increase venous return and cardiac output + reduces afterload (directly via arteriole vasodilation + indirectly through release of epinephrine and norepinephrine)
What are the clinical indications of hydralazine?
1) HFrEF (given PO in combination with ISDN)
2) Essential hypertension (ie: primary hypertension). Given PO
3) Acute onset, severe peripartum or post-partum hypertension (>15min). Given IV
What are the adverse effects of hydralazine?
1) Symptoms associated with baroreflex associated sympathetic activation (ie: flushing, hypotension, tachycardia)
2) Hydralazine-induced lupus syndrome (HILS): athralgia, myalgia, serositis, fever
- Dose dependent & higher chance with long-term use
- Can be resolved with hydralazine discontinuation
3) Contraindicated in coronary artery disease
- Hydralazine stimulates the sympathetic nervous system –> increased cardiac output/ oxygen demand –> myocardial ischemia
