Heart Failure drugs Flashcards
How to choose between drugs that reduce workload of heart vs drugs that increase workload?
- Drugs that reduced workload = compensatory stage of HF
- Drugs that increase workload = chronic HF
As the pump becomes less effective, more blood remains in the ventricles at the end of each cycle. Gradually, end-diastolic volume (preload) increases. Initially, increase in preload may promote increased force of contraction (Frank-Starling Curve)
But as preload increases, further, the heart is overstretched and contracts less forcefully (chronic HF)
Drugs used in HF
- Beta blockers
- Sacubitril-Valsartan
- Diuretics (Loop, K+ sparing)
- Hydralazine
- Isosorbide mononitrate/dinitrate
- Ivabradine
- Cardiac Glycosides
Examples of beta blockers
Non-selective: carvedilol
(Cardvedilol also blocks a1 receptors → reducing peripheral vascular resistance)
Beta-1 selective: bisoprolol, metoprolol XL
Dose-dependent: Nebivolol (b1 selective in low doses, non selective in high doses)
MOA of beta blockers
Beta-adrenoreceptor antagonists decreases the HR → more time for ventricular filling during diastole → increase CO
What classes of drugs ends with -lol?
beta blockers
Beta blockers contraindicated in?
- Contraindicated in asthmatic patients as they can cause bronchoconstriction (b1 selective only)
- Contraindicated in diabetics as they can mask the effects of hypoglycaemia (palpitations, tremors etc.) preventing them from getting appropriate intervention
Clinical uses of beta blockers
1.Hypertension
2.HF (slower HR → increase time for ventricular filling → increase CO)
3.Abnormal heart rhythms
4.Following myocardial infarction
5.Anxiety disorders
MOA of Sacubitril
BNP antagonise the RAAS and has favourable effects on HF
BNP are broken down by neprilysin
Sacubitril inhibits neprilysin → prolongs BNP effects (antagonise RAAS which is activated under HF)
Why is Valsartan added
Neprilysin also breaks down angiotensin II (Sacubitril inhibiting neprilysin prevents the breakdown of angiotensinII)
Therefore add Valsartan (a AT1 receptor blocker)
Valsartan avoids the negative effects of angiotensin II that is prolonged by Sacubitril
Clinical uses of Sacubitril- Valsartan
HFrEF (decreases workload of the heart → preserves the heart’s function and prevent further damage)
Adverse effects of Sacubitril- Valsartan
- dry cough and angioedema (Neprilysin is also involved in the breakdown of Bradykinin, which is inhibited by Sacubitril)
- Hypotension
- Hyperkalaemia
- Renal failure
Examples of Loop diuretics
Furosemide, Bumetanide, Ethacrynic acid, Sulfonamide derivatives
Which channels of the nephron do loop diuretics act on
Na/K/2Cl cotransporter at the thick ascending limb
Which ions are affected by loop diuretics
Reduce absorption of Na+, K+, Cl-, Mg2+ and Ca2+
Adverse effects of Loop diuretics
- Hypokalemic metabolic alkalosis
- Ototoxicity (avoid use with aminoglycosides)
- Hyperuricemia
- Hypomagnesemia
Clinical uses of Furosemide
- Acute pulmonary oedema
- Acute hyperkalaemia (reduces K+ absorption from lumen)
- Anion overdose
- Acute renal failure
Do the Nitrates reduce the workload of the heart directly or indirectly
Indirectly.
Donates NO which activates guanylyl cyclase, increasing cGMP and causing inactivation of myosin-LC
a. Vasodilation → venodilation (decrease preload)
b. Vasodilation → arteriolar dilation (decrease afterload)
Overall decreases workload of the heart
Potassium sparing diuretics and which part of the nephron they work on
Spironolactone, Epierenone: blocks aldosterone receptor –> no activation of Na+ channel –> no reabsorption of Na+ at the collecting duct –> no water retention
Triamterene, Amiloride: blocks Na+ channels at the collecting duct directly
Do they K+ sparing diuretics have a slower onset of action than loop diuretics?
YES
Clinical uses of K+ sparing diuretics
- diuretics
- hyperaldosteronism
Side effects of Spironolactone and Triamterene
- Hyperkalaemia (decreasing Na+ reabsorption decreases K+ secretion by the Na+/K+/Atpase pump)
- Gynecomastia (only spironolactone which may block the testosterone receptor)
- Acute renal failure (triamterene + indomethacin)
- Kidney stones (triamterene)
Clinical use of Hydralazine
Second line hypertensive, first line for HF
- Essential hypertension (2nd line)
- HFrEF (in combination with isosorbide dinitrate, orally)
- Acute-onset, severe peripartum or postpartum hypertension (IV)
Adverse effects of Hydralazine
- Baroreflex associated sympathetic activation: flushing, tachycardia
- Hypotension
- HILS – arthralgia, myalgia, serositis, fever
- Contraindicated in coronary disease due to stimulation of SNS → increase CO output → increase myocardial oxygen demand
MOA of hydralazine
Direct vasodilator → decreasing total peripheral resistance → decrease afterload
- Vasodilator by inhibiting IP3-induced Ca2+ release from the smooth muscle cell sarcoplasmic reticulum
- Can trigger compensatory release of NE/adrenaline → increase CO
MOA of Isosorbide dinitrate/ Mononitrate
Donates NO which activates guanylyl cyclase, increasing cGMP and causing inactivation of myosin-LC
a. Vasodilation → venodilation (decrease preload)
b. Vasodilation → arteriolar dilation (decrease afterload)
Overall decreases workload of the heart
Comment on the duration of action and onsent of action of ISDN and ISMN
- long duration of action and long onset of action
- ISMN has a faster onset of action (30-45 min) compared to ISDN (60 min)
Clinical uses of ISMN/ISDN
- Angina pectoris prophylaxis (decreasing workload of heart reduce oxygen consumption + decrease end diastolic pressure for better blood flow to coronary arteries)
- HF
Side effects of ISMN/ISDN
- Reflex tachycardia (due to baroreceptors picking up lower BP)
- Hypotension
- Headache (meningeal artery vasodiation)
MOA of Ivabradine
A heart rate lowering agent
Does not reduce preload, afterload or contractility, just reduces heart rate
Inhibits cardiac pacemaker I(f) current that controls the spontaneous diastolic depolarisation in the SA node → slows down/regulates heart rate
Clinical uses of Ivabradine
Useful in HFrEF, in patients in sinus rhythm whose heart rate > 75 bpm (increase time for ventricular filling, improving overall cardiac function )
Does Ivabradine reduce preload, afterload or contractility?
No. just reduces heart rate
Adverse effects of ivabradine
- Visual problems: Luminous phenomena, transient enhanced brightness in a limited area of the visual field
- Dizziness (bradycardia)
- Hypotension, fatigue, malaise (all related to bradycardia)
Examples of Cardiac glycosides
Faster onset, shorter half life: Digoxin
Slower onset, longer half life: Digitoxin
MOA of Digoxin
Inhibits the Na+/K+/Atpase pump in cardiac muscle cells
Prevents efflux of Na+ → increase Na+ intracellularly → decrease efflux of Ca2+ (through the Ca2+ Na+ channel) → increased CICR from sarcoplasmic reticulum → increased myocyte contraction → increase CO
Clinical uses of DIGOXIN
- Late stage HF
- Systolic dysfunction
- Atrial fibrillation
Adverse effect of cardiac glycosides
1.Progressive, more severe dysrhythmia (AV block, AF, VF)
2.GI effects: anorexia, nausea, vomiting
3.CNS: headache, fatigue, confusion, blurred vision
How to treat Digitalis toxicity
- Discontinue cardiac glycoside therapy
- Correction of K+ or Mg+ deficiency
- Antiarrhythmic drugs (as it can increase automaticity leading to AF or VF)
- if automaticity is predominant: lidocaine, propranolol
Digoxin antibody (FAB fragments, digibind)
Do ACE inhibitors, sacubitril and valsartan cause dry cough?
Only ACE inhibitors (e.g. Lisinopril) and Sacubitril
