Cardiovascular Pharmacology

Cardiovascular pharmacology encompasses the drugs used to manage hypertension, heart failure, and arrhythmias — among the most commonly prescribed medicines in New Zealand.

Antihypertensive drugs act via multiple mechanisms. ACE inhibitors (ramipril, lisinopril, perindopril) block angiotensin-converting enzyme, preventing conversion of angiotensin I to angiotensin II. This reduces vasoconstriction and aldosterone secretion, lowering blood pressure and reducing cardiac afterload. A key adverse effect is dry cough (bradykinin accumulation) and hyperkalaemia. They are contraindicated in pregnancy due to fetal renal dysplasia.

Angiotensin receptor blockers (ARBs — losartan, irbesartan) block the AT1 receptor directly. They provide similar benefits to ACE inhibitors without the cough, making them the preferred alternative in ACE inhibitor intolerance.

Calcium channel blockers (CCBs) block L-type voltage-gated calcium channels. Dihydropyridines (amlodipine, felodipine) are selective for vascular smooth muscle, causing vasodilation with minimal cardiac effect. Non-dihydropyridines (verapamil, diltiazem) also affect the heart, slowing conduction and reducing contractility — useful in rate control for atrial fibrillation but contraindicated with beta-blockers.

Beta-blockers (atenolol, metoprolol, carvedilol) antagonise beta-adrenergic receptors. Beta-1 selective agents reduce heart rate and contractility, lowering cardiac output and blood pressure. Carvedilol is non-selective and also blocks alpha-1 receptors. Beta-blockers are first-line in post-MI patients and heart failure with reduced ejection fraction (HFrEF).

Thiazide diuretics (bendroflumethiazide, hydrochlorothiazide) inhibit the Na-Cl cotransporter in the distal convoluted tubule, initially reducing plasma volume and later causing vasodilation via unclear mechanisms. They commonly cause hypokalaemia, hyponatraemia, and hyperuricaemia.

Heart failure drugs include digoxin, loop diuretics, and neurohormonal blockers. Digoxin inhibits Na/K-ATPase, increasing intracellular calcium and myocardial contractility (positive inotrope). It also increases vagal tone, slowing AV conduction. Digoxin has a narrow therapeutic index (0.5–2.0 nmol/L) and toxicity manifests as nausea, visual disturbance (yellow-green halos), and arrhythmias. Loop diuretics (furosemide, bumetanide) inhibit the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle, producing potent natriuresis. They relieve pulmonary congestion rapidly in acute heart failure.

Antiarrhythmics are classified by the Vaughan Williams system. Class I agents (e.g., flecainide) block fast sodium channels, slowing phase 0 depolarisation. Class II (beta-blockers) reduce automaticity. Class III agents (amiodarone, sotalol) block potassium channels, prolonging the action potential and refractory period. Amiodarone is the most widely used antiarrhythmic in New Zealand due to its efficacy, but has extensive toxicity (pulmonary, thyroid, hepatic, corneal microdeposits). Class IV (verapamil, diltiazem) slow AV conduction by blocking calcium channels.

In clinical practice, most patients with hypertension require combination therapy. The Pharmac schedule in New Zealand provides preferred access to perindopril, amlodipine, and bendroflumethiazide, reflecting evidence from large cardiovascular outcome trials.