Pharmacology: Cardiovascular Drugs

Cardiovascular drugs form the backbone of modern care for hypertension, ischemic heart disease, arrhythmias, heart failure, and thromboembolic disorders. While individual medications differ, most aim to alter a small set of physiologic variables: vascular tone, heart rate, contractility, circulating volume, and the tendency of blood to clot. Understanding mechanisms and adverse effects is not just academic. It is central to safe prescribing, monitoring, and patient counseling, especially because many cardiovascular agents interact with each other and with common comorbidities such as diabetes, chronic kidney disease, and asthma.

Antihypertensives

Hypertension management often requires combination therapy because blood pressure is regulated by multiple overlapping systems: the autonomic nervous system, the renin-angiotensin-aldosterone system (RAAS), vascular smooth muscle, and renal sodium handling. Drug selection is guided by efficacy, comorbidities, and side-effect profiles.

RAAS inhibitors: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors reduce formation of angiotensin II, leading to vasodilation and decreased aldosterone. Angiotensin receptor blockers (ARBs) block the angiotensin II type 1 receptor and achieve similar hemodynamic effects.

Practical uses include hypertension, chronic kidney disease with proteinuria, and heart failure with reduced ejection fraction. Key adverse effects for ACE inhibitors include cough and angioedema, related to bradykinin accumulation. Both ACE inhibitors and ARBs can cause hyperkalemia and a rise in creatinine, particularly in renal artery stenosis or volume depletion. They are contraindicated in pregnancy.

Diuretics

Diuretics lower blood pressure primarily by reducing intravascular volume and, over time, decreasing peripheral vascular resistance.

• Thiazide-type diuretics are common first-line agents. They can cause hypokalemia, hyponatremia, hyperuricemia (worsening gout), and impaired glucose tolerance in some patients.
• Loop diuretics are more potent for volume overload, often used in heart failure rather than uncomplicated hypertension. Adverse effects include electrolyte depletion and ototoxicity at high doses or with interacting drugs.
• Potassium-sparing diuretics, including aldosterone antagonists, reduce potassium loss and are especially relevant in heart failure. Hyperkalemia is the major concern, and some agents can cause endocrine effects such as gynecomastia.

Calcium channel blockers

Calcium channel blockers (CCBs) reduce calcium entry through L-type channels. Dihydropyridines primarily dilate arterioles and lower blood pressure, while non-dihydropyridines also slow atrioventricular conduction.

Common adverse effects include peripheral edema, flushing, and headache with dihydropyridines. Non-dihydropyridines can cause bradycardia, constipation, and worsening of some conduction disorders, especially when combined with other rate-slowing drugs.

Beta blockers

Beta blockers decrease heart rate and contractility and reduce renin release. They are valuable in patients with coronary disease, certain arrhythmias, and heart failure (with specific agents). Side effects include bradycardia, fatigue, exercise intolerance, and sexual dysfunction. Nonselective beta blockade can precipitate bronchospasm in susceptible patients and can mask symptoms of hypoglycemia.

Antiarrhythmics

Antiarrhythmic therapy aims to suppress abnormal automaticity or interrupt reentry. In practice, the same drug that controls rhythm can also create arrhythmias, so monitoring and careful patient selection matter.

Sodium channel blockers

Sodium channel blockers reduce phase 0 depolarization in fast-response cardiac tissue. They can be effective for certain atrial and ventricular arrhythmias, but many carry proarrhythmic risk, especially in structural heart disease. Some agents also widen the QRS complex, which can serve as a marker of excessive effect.

Potassium channel blockers

Potassium channel blockers prolong repolarization and can extend the QT interval. The major hazard is torsades de pointes, a potentially fatal polymorphic ventricular tachycardia associated with excessive QT prolongation. Risk rises with electrolyte abnormalities such as hypokalemia and hypomagnesemia, bradycardia, and drug interactions.

Calcium channel blockers and beta blockers for rate control

Non-dihydropyridine CCBs and beta blockers are widely used to slow ventricular rate in supraventricular arrhythmias by reducing atrioventricular nodal conduction. Excessive dosing can lead to hypotension or bradycardia, particularly in older adults or in combination therapy.

Adenosine and other acute agents

Adenosine transiently blocks atrioventricular nodal conduction and is used acutely for certain reentrant supraventricular tachycardias. It has a very short half-life but can cause chest discomfort, flushing, and bronchospasm in susceptible individuals.

Antianginals

Angina reflects a mismatch between myocardial oxygen supply and demand. Antianginal drugs work by reducing demand (heart rate, contractility, wall stress) or improving supply (coronary perfusion).

Nitrates

Nitrates generate nitric oxide, increasing cyclic GMP and relaxing vascular smooth muscle. Venodilation reduces preload and myocardial oxygen demand; some arterial dilation improves afterload. Patients often experience headache and flushing. Clinically important issues include orthostatic hypotension and reflex tachycardia. Tolerance can develop with continuous exposure, so regimens often include a nitrate-free interval. Concomitant use with phosphodiesterase-5 inhibitors can cause profound hypotension and is contraindicated.

Beta blockers and calcium channel blockers

Beta blockers reduce heart rate and contractility, lowering demand. CCBs can reduce afterload and, depending on type, slow heart rate. Choice depends on blood pressure, baseline heart rate, and conduction status.

Heart failure drugs

Heart failure pharmacology differs depending on whether the problem is reduced ejection fraction or preserved ejection fraction, but several core goals recur: reduce congestion, blunt maladaptive neurohormonal activation, and improve symptoms and survival where evidence supports it.

Diuretics for congestion

Loop diuretics are the mainstay for symptomatic fluid overload. They improve dyspnea and edema but require monitoring of renal function and electrolytes. Overdiuresis can lead to hypotension and kidney injury, while underdiuresis leaves patients congested and at higher risk of hospitalization.

RAAS inhibition and aldosterone antagonism

ACE inhibitors or ARBs reduce afterload and neurohormonal activation and are foundational for many patients with reduced ejection fraction. Aldosterone antagonists add benefit in appropriately selected patients but increase hyperkalemia risk, particularly with impaired kidney function.

Beta blockers in chronic therapy

Specific beta blockers improve outcomes in chronic heart failure by attenuating sympathetic overactivity. Initiation requires clinical stability, as acute decompensation can worsen with rate-slowing and negative inotropy. Dose titration is gradual, with monitoring for bradycardia and fluid retention.

Positive inotropes and rate control when needed

Some patients require agents that increase contractility or control rate in arrhythmia-associated heart failure. These drugs can improve symptoms but may increase arrhythmia risk, so they are typically reserved for selected situations and close monitoring.

Anticoagulants and antithrombotic therapy

Thrombosis underlies myocardial infarction, ischemic stroke, venous thromboembolism, and many complications of atrial fibrillation. Anticoagulants reduce clot formation, while antiplatelet drugs reduce platelet aggregation. The clinical challenge is balancing prevention of thromboembolism against bleeding risk.

Heparins and related agents

Heparins potentiate antithrombin activity, inhibiting key coagulation factors. They are used in acute coronary syndromes and venous thromboembolism. Major adverse effects include bleeding and, with some forms, heparin-induced thrombocytopenia, an immune-mediated prothrombotic complication that demands prompt recognition.

Vitamin K antagonists

Vitamin K antagonists reduce synthesis of several clotting factors. They are effective but require careful monitoring and have many drug and dietary interactions. Bleeding is the central risk, and dose adjustments are guided by coagulation testing.

Direct oral anticoagulants

Direct oral anticoagulants target specific coagulation factors and offer predictable dosing for many patients. They still carry bleeding risk and require attention to renal function, drug interactions, and perioperative management.

Putting it together: mechanisms, monitoring, and safety

Cardiovascular drug therapy succeeds when mechanism, patient factors, and monitoring align. A diuretic may improve breathlessness but cause electrolyte shifts that provoke arrhythmias. A potassium channel blocker may stabilize rhythm while prolonging QT and increasing torsades risk. A nitrate may relieve angina but trigger hypotension when combined with other vasodilators.

Practical safety habits include checking baseline kidney function and electrolytes when starting RAAS inhibitors or diuretics, monitoring heart rate and conduction when using beta blockers or non-dihydropyridine CCBs, and reassessing bleeding risk whenever anticoagulants are prescribed or combined with other antithrombotic agents. Cardiovascular pharmacology is ultimately about tailoring these powerful tools to the physiology in front of you, then following through with vigilant, patient-centered monitoring.