Heart Failure pharm Flashcards
What are 8 classes of drugs used in HF?
1) ACEi
2) ARBs
3) ß-blockers
4) Sacubitril-Valsartan
5) Mineralocorticoid receptor antagonists
6) Hydralazine
7) Ivabradine
8) Nitrates
Which 4 ß-blockers are approved for HF treatment?
Cardio(ß1) selective:
1) Bisoprolol
2) Metoprolol XL
Non-selective:
3) Carvedilol
Mixed (3rd gen):
4) Nebivolol
What is the moa of Sacubitril-Valsartan?
Sacubitril is a neprilysin inhibitor (so prevents break down of natriuretics)
but neprilysin ↑AT2 so Valsartan added to prevent -ve effects of AT2 as a ARB
When is Sacubitril-Valsartan indicated?
Chronic HFrEF
What are 5 AEs of Sacubitril-Valsartan?
1) Hypotension
2) Hyperkalemia
3) Renal failure
4) Cough
5) Angioedema
What are 5 examples of loop diuretics?
ET is FABulous
Ethacrynic acid
Torasemide
Furosemide
Azosemide
Bumatanide
What is the moa of loop diuretics?
Inhibit luminal Na/K/Cl transporter in thick ascending limb of LoH
→ excess intracellular K+
→ K+ back diffusion
→ ↑Mg2+ and Ca2+ excretion
- furosemide also ↑renal blood flow
How do NSAIDs affect loop diuretics?
Loop diuretics induce renal PG synthesis (↓ by NSAIDs)
Loop diuretics are (slowly/rapidly) absorbed and the diuretic response is (slow/rapid) following IV injection.
Rapid absorption, extremely rapid response
What are 4 clinical uses of loop diuretics?
1) Acute pulmonary edema
2) Acute hyperkalemia
3) Acute renal failure
4) Anion overdose
What are 4 AEs of loop diuretics?
1) Hypokalemic metabolic acidosis
2) Ototoxicity
3) Hyperuricemia
4) Hypomagnesemia
What antibiotics should be avoided with loop diuretics?
Aminoglycosides (ototoxicity)
What are 4 K+-sparing diuretics?
1) Spironolactone
2) Triamterene
3) Amiloride
4) Eplerenone
What is the moa of K+-sparing diuretics?
Spironolactone, Eplerenone: inhibit aldosterone receptor on principal cells of collecting duct
Triamterene, Amiloride: inhibit Na+ channel
Both eventually ↓Na/water reabsorption → ↓K+ secretion
Spironolactone has a (fast/slow) onset of action.
slow
Where is triamterene metabolised?
Liver
Triamterene has a (longer/shorter) T1/2 than amiloride?
Shorter
How is amiloride excreted?
unchanged in urine
What are the clinical uses of K+-sparing diuretics?
1) Diuretic
2) Hyperaldosteronism
What are 2 AEs of K+-sparing diuretics?
1) Hyperkalemia
2) Metabolic acidosis
3) Gynecomastia (spironolactone)
4) Acute renal failure (triamterene + indomethacin)
4) Kidney stones (Triamterene)
What is the moa of hydralazine?
Direct arteriole vasodilator:
- inhibit IP3-induced Ca release from SER
→ ↓ peripheral resistance
- compensatory release of E/NE → ↑venous return and CO
What are 3 indications for hydralazine?
1) HFrEF (with ISDN): oral
2) essential HTN (when 1st line inadequate): oral
3) Acute severe peripartum/post-partum HTN: IV
What is the onset and duration of IV and oral hydralazine?
IV: onset 5-30min, duration 2-6hrs
Oral: onset 20-30min, duration 2-4 hrs
reaches peak Pc in 2.5 hrs, T1/2 ~ 7hrs
When is hydralazine contraindicated?
px with CAD
(SNS stimulation → ↑myocardial O2 Dd)
What are 4 AEs of Hydralazine?
1) Hydralazine-induced lupus syndrome (HILS
- Arthralgia, myalgia, serositis, fever
- dose dependent
- can be resolved w discontinuation
Baroreflex associated SNS activation:
2) Flushing
3) Hypotension
4) Tachycardia
What plant is digitalis derived from?
Foxglove
What is the moa of digitalis?
inhibits Ka/K exchanges → ↑intracellular Na
→ inhibit Ca2+ efflux by Ca/Na exchanger
→ ↑intracellular Ca
→ stronger systolic contraction
What are 3 cardiac effects of digitalis
1) Mechanical:
Contractility ↑ → ↑CO → ↓SNS + ↓ AT2 → ↓Afterload + preload
2) Electrical:
a) ↓QT, ST, T wave inversion
b) ↑PNS → ↑PR ↓Ventricular rate
3) Toxic
- ↑intracellular Ca → ↑ automaticity, extrasystoles, tachycardia, fibrillation
What are 2 clinical uses for digitalis?
1) Systolic dysfunction
2) Atrial fibrillation
What are 3 AEs of digitalis?
1) Progressive dysrhythmias: AV block, Afib, Vfib
2) GI effects: anorexia, nausea, vomiting
3) CNS: headache, fatigue, confusion, blurred vision
How is digitalis toxicity treated?
1) Discontinue
2) Correct K/Mg deficiency
3) Antiarrhythmics (eg. lidocaine, propanolol)
4) Digoxin Abs (FAB fragments, digibind)
