ACE inhibitors, Beta blockers, Calcium channel blockers

What are the main indications for ACE inhibitors?

1) HTN

2) Chronic heart failure

3) Secondary prevention of CVD

4) Diabetic nephropathy

5) CKD with proteinuria

Why are ACE inhibitors beneficial in diabetic nephropathy and CKD?

They reduce proteinuria and slow progression of kidney disease.

How do ACE inhibitors work?

Inhibit conversion of angiotensin I to angiotensin II.

What are the effects of reducing angiotensin II?

↓ Vasoconstriction, ↓ aldosterone secretion → ↓ BP and ↓ sodium/water retention.

How do ACE inhibitors affect afterload and preload?

↓ Afterload via reduced peripheral resistance.

↓ Preload via reduced aldosterone.

How do ACE inhibitors protect the kidneys?

Dilate the efferent glomerular arteriole → ↓ intraglomerular pressure → slower CKD progression.

What common adverse effects occur with ACE inhibitors?

First-dose hypotension, hyperkalaemia, renal impairment, dry cough.

Why do ACE inhibitors cause a dry cough?

Increased bradykinin levels (normally inactivated by ACE).

What is an alternative if ACE inhibitor-induced cough occurs?

ARB

Why can ACE inhibitors worsen renal function?

Reduced efferent arteriole constriction lowers GFR, especially in renal artery stenosis.

What rare but serious adverse effects can occur with ACE inhibitors?

Angioedema and anaphylactoid reactions.

In which conditions should ACE inhibitors be avoided?

Renal artery stenosis, AKI pregnancy, breastfeeding.

Which drugs increase the risk of hyperkalaemia with ACE inhibitors?

Potassium supplements, aldosterone antagonists, potassium-sparing diuretics.

Which drugs increases nephrotoxicity risk with ACE inhibitors?

NSAIDs

What are "sick day rules" for ACE inhibitors?

Stop during vomiting/diarrhoea to prevent dehydration, hypotension, and AKI.

When should an ACE inhibitor be stopped due to renal function decline?

When creatinine ↑ >30% OR eGFR ↓ >25%.

How should hyperkalaemia be managed with ACE inhibitors?

1) 5.0 mmol/L: stop other K⁺-raising drugs, reduce dose

2) 6.0 mmol/L: stop ACE inhibitor and seek specialist advice

What are the main indications for β-blockers?

1) IHD: to improve symptoms in angina and ACS

2) Chronic HF

3) AF

4) SVT

5) Resistant HTN (4th line)

6) Migraine prophylaxis

7) Thyrotoxicosis

Which receptors mediate the main effects of β-blockers?

β₁-adrenoreceptors, primarily in the heart.

What cardiac effects do β-blockers have?

↓ Heart rate, ↓ contractility, ↓ conduction velocity.

How do β-blockers reduce myocardial oxygen demand in IHD?

By reducing cardiac work and prolonging diastole, improving perfusion.

How do β-blockers lower blood pressure?

Partly by reducing β₁-mediated renin secretion from the kidney.

How do β-blockers control ventricular rate in AF?

Prolong AV node refractory period → fewer impulses conducted.

What are common adverse effects of β-blockers?

Fatigue, cold extremities, headache, gastrointestinal upset.

What CNS-related adverse effects may occur with β-blockers?

Sleep disturbance, nightmares.

What sexual adverse effect is associated with β-blockers?

Impotence.

Why are β-blockers contraindicated in asthma?

β₂-receptor blockade can cause life-threatening bronchospasm.

Are β-blockers safe in COPD?

Usually yes; prefer β₁-selective agents (e.g. bisoprolol, metoprolol).

What cardiovascular conditions contraindicate β-blockers?

Heart block and severe hypotension.

When may β-blocker dose need reduction?

Significant hepatic failure.

Which calcium channel blockers must not be combined with β-blockers? Why?

1) Non-dihydropyridines (verapamil, diltiazem).

2) Risk of severe bradycardia, HF and asystole.

Which β-blockers are preferred in heart failure?

Bisoprolol and carvedilol.

Which β-blocker is preferred for migraine and thyrotoxicosis?

Propranolol.

What resting heart rate is targeted in IHD?

55-60 beats/min.

How should β-blockers be stopped after long-term use?

Gradually over 1–2 weeks to avoid rebound sympathetic stimulation.

What is the risk of abrupt β-blocker withdrawal?

Myocardial ischaemia due to catecholamine surge.

What is a useful clinical tip when starting β-blockers in ACS?

Use a short half-life drug (e.g. metoprolol) initially, then switch to once-daily therapy when stable.

What are the main indications for calcium channel blockers?

HTN, angina (IHD), and supraventricular arrhythmias.

How do calcium channel blockers help in angina?

Reduce myocardial oxygen demand by lowering heart rate, contractility, and afterload.

Which calcium channel blockers are used for supraventricular arrhythmias?

Verapamil and diltiazem.

Which arrhythmias can verapamil and diltiazem be used for?

SVT, atrial flutter, and atrial fibrillation.

How do calcium channel blockers work?

Reduce Ca²⁺ entry into vascular and cardiac cells → ↓ intracellular Ca²⁺.

What is the vascular effect of calcium channel blockers?

Arterial smooth muscle relaxation → vasodilation → ↓ blood pressure.

What are the cardiac effects of calcium channel blockers?

↓ Contractility, ↓ AV nodal conduction, ↓ ventricular rate.

How do calcium channel blockers prevent angina?

↓ Heart rate, ↓ contractility, and ↓ afterload → ↓ myocardial oxygen demand.

What are the two main classes of calcium channel blockers?

Dihydropyridines and non-dihydropyridines.

Which drugs are dihydropyridines?

Amlodipine, nifedipine, felodipine.

What are the main effects of dihydropyridines?

Predominantly vasodilation (vascular selective).

Which drugs are non-dihydropyridines?

Verapamil and diltiazem.

How do verapamil and diltiazem differ?

Verapamil is most cardioselective; diltiazem has mixed cardiac and vascular effects.

What are common adverse effects of amlodipine and nifedipine?

Ankle oedema, flushing, headache, palpitations.

Why do dihydropyridines cause palpitations?

Reflex tachycardia due to vasodilation.

What common adverse effect is associated with verapamil?

Constipation.

What serious cardiac adverse effects can verapamil cause?

Bradycardia, heart block, and heart failure.

What adverse effects can diltiazem cause?

Both vascular (oedema, flushing) and cardiac (bradycardia, heart block).

Why should verapamil and diltiazem be used cautiously in LV dysfunction?

They can precipitate or worsen heart failure.

Why should verapamil and diltiazem be avoided in AV nodal disease?

Risk of complete heart block.

Why should amlodipine and nifedipine be avoided in unstable angina?

Reflex tachycardia and increased contractility raise myocardial oxygen demand.

Why are dihydropyridines contraindicated in severe aortic stenosis?

Vasodilation may cause cardiovascular collapse.

How should MR calcium channel blockers be taken?

Swallowed whole; not crushed or chewed.

Why should MR CCBs sometimes be prescribed by brand name?

Different preparations may not be bioequivalent.