Clinical Pharmacology of Heart failure

Question 1

What are the strengths and weaknesses of diuretic therapy in heart failure?

Answer 1

✅ Strengths:

Rapid symptom relief (fluid overload, oedema, breathlessness)
Improves exercise tolerance
Reduces hospital admissions
❌ Weaknesses:

No mortality benefit
Risk of hypokalaemia, hyponatraemia
Worsens renal function (pre-renal AKI)
Activation of RAAS (long-term maladaptive response)

Question 2

What are the strengths and weaknesses of ACE inhibitors in heart failure?

Answer 2

✅ Strengths:

Mortality reduction (SOLVD, CONSENSUS trials)
Reduces afterload and preload
Slows progression of HF
Improves symptoms

❌ Weaknesses:

Cough (due to bradykinin accumulation)
Hyperkalaemia (due to aldosterone suppression)
Hypotension (first-dose effect)
Angioedema (rare but serious)
Contraindicated in bilateral renal artery stenosis

Question 3

How do renal and hepatic dysfunction affect drug metabolism in heart failure?

Answer 3

🩸 Renal dysfunction:

ACE inhibitors & diuretics – Risk of worsening renal failure
Digoxin & aminoglycosides – Accumulation → toxicity

🫁 Hepatic dysfunction:

Beta-blockers & statins – Altered metabolism in cirrhosis
Spironolactone – Risk of hepatic encephalopathy

Question 4

What are the hormonal and physiological responses to heart failure?

Answer 4

📈 Compensatory mechanisms (harmful long-term):
1️⃣ Renin-Angiotensin-Aldosterone System (RAAS) → Vasoconstriction, sodium retention
2️⃣ Sympathetic nervous system (SNS) → Tachycardia, vasoconstriction
3️⃣ Natriuretic peptides (ANP, BNP) → Vasodilation, diuresis (counteracts RAAS)
4️⃣ Endothelin → Vasoconstriction, fibrosis

🔹 Sites for therapeutic intervention:

ACE inhibitors/ARBs → Block RAAS
Beta-blockers → Reduce SNS overactivation
Diuretics → Reduce fluid overload

Question 5

What are the strengths and weaknesses of beta-blockers in heart failure?

Answer 5

✅ Strengths:

Mortality reduction (CIBIS II, MERIT-HF)
Reduces hospitalizations
Improves ejection fraction (EF) over time
Reduces arrhythmias

❌ Weaknesses:

May worsen symptoms initially
Contraindicated in acute decompensated HF
Risk of bradycardia, hypotension
Fatigue, dizziness, sexual dysfunction

Question 6

Mnemonic for Heart Failure Drugs

Answer 6

💊 “ABCD” for Heart Failure Treatment
A – ACE inhibitors / ARBs
B – Beta-blockers
C – Calcium channel blockers (not first-line)
D – Diuretics (for symptom relief)