Question
A 62-year-old male presents with exertional dyspnea and pedal edema. There is no significant medical or family history. Physical examination showed the presence of elevated jugular venous pulse and mild hepatomegaly. Echocardiography showed an ejection fraction of 35% (normal >50%), suggestive of heart failure.
- (a) Name two drug groups, with two examples for each, which are likely to slow down the disease progression in this patient. 2 mark(s)
- (b) Explain their mechanism of action in heart failure. 4 mark(s)
- (c) Which drug would be suitable to relieve the congestive symptoms in this patient. Explain. 2 mark(s)
- (d) Explain the role of phosphodiesterase 3 inhibitors in heart failure. 2 mark(s)
Answer
a) Two drug groups slowing disease progression (Goal B — disease-modifying)
| Group | Examples |
|---|---|
| ACE inhibitors / ARBs | Enalapril, Losartan |
| Beta-blockers | Carvedilol, Bisoprolol |
(Aldosterone antagonists — Spironolactone, Eplerenone — are a further disease-modifying option in this reduced-ejection-fraction patient.)
b) Mechanism of action in heart failure
- ACE inhibitors/ARBs — block angiotensin II formation/action, reducing both afterload (vasoconstriction) and preload (aldosterone-driven Na⁺/water retention), directly interrupting the RAS-driven vicious cycle of heart failure, and independently slowing maladaptive ventricular remodeling (hypertrophy, fibrosis) that angiotensin II otherwise drives.
- Beta-blockers — despite being negative inotropes acutely, specific agents (carvedilol, bisoprolol) reduce mortality in stable, compensated systolic heart failure by blunting chronic sympathetic overactivity, which itself drives remodeling, arrhythmia, and further beta-receptor downregulation; started at very low dose in stable patients only, never during acute decompensation.
c) Drug for congestive symptoms, with explanation Furosemide — a loop diuretic, reduces preload through natriuresis, directly relieving the pedal edema and elevated jugular venous pressure reflecting fluid overload in this patient. It provides symptomatic (Goal A) relief only, with no independent mortality benefit — distinct from the disease-modifying drugs above.
d) Role of phosphodiesterase-3 inhibitors in heart failure PDE-3 inhibitors (Milrinone) inhibit breakdown of cAMP in cardiac and vascular smooth muscle, producing a combined positive inotropic and vasodilator (“inodilator”) effect — increasing cardiac output while reducing afterload. Used only as short-term IV therapy for acute decompensated heart failure/cardiogenic shock, since — like other positive inotropes — chronic use has been shown to worsen long-term mortality despite improving symptoms acutely, the same Goal A/Goal B dissociation seen with digoxin but more pronounced.