Cardiovascular agents

1. Introduction

• Cardiovascular agents are drugs that act on the heart, blood vessels, and circulatory system.

• Used to treat cardiac disorders (e.g., heart failure, arrhythmias, ischemic heart disease) and vascular conditions (e.g., hypertension, hyperlipidemia, thromboembolic disease).

• Include multiple drug classes with diverse mechanisms, often used in combination for optimal cardiovascular outcomes.

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2. Major Therapeutic Categories

1. Antihypertensive Agents

• Diuretics (thiazides, loop diuretics, potassium-sparing): lower blood pressure by reducing plasma volume and vascular resistance.

• Beta-adrenergic blockers: decrease heart rate, cardiac output, and renin release.

• Calcium channel blockers: relax vascular smooth muscle (dihydropyridines) and reduce myocardial contractility (non-dihydropyridines).

• ACE inhibitors: block conversion of angiotensin I to angiotensin II; reduce vasoconstriction and aldosterone secretion.

• Angiotensin II receptor blockers (ARBs): block AT₁ receptors; similar benefits to ACE inhibitors.

• Alpha-adrenergic blockers: reduce peripheral vascular resistance.

• Central alpha-2 agonists: reduce sympathetic outflow.

• Direct vasodilators: relax arteriolar smooth muscle.

• Renin inhibitors: directly inhibit renin enzyme activity.

2. Antianginal and Anti-ischemic Agents

• Nitrates: cause venodilation and reduce myocardial oxygen demand.

• Beta-blockers: lower heart rate and contractility to reduce oxygen demand.

• Calcium channel blockers: dilate coronary arteries and reduce afterload.

• Ranolazine: inhibits late sodium current in cardiac cells to improve myocardial relaxation.

3. Antiarrhythmic Agents

• Class I (Na⁺ channel blockers): slow conduction (IA, IB, IC subtypes).

• Class II (Beta-blockers): reduce sympathetic effects on conduction system.

• Class III (K⁺ channel blockers): prolong repolarization (e.g., amiodarone, sotalol).

• Class IV (Ca²⁺ channel blockers): slow AV nodal conduction (verapamil, diltiazem).

• Other: adenosine, digoxin for specific arrhythmias.

4. Heart Failure Agents

• ACE inhibitors / ARBs / ARNI (angiotensin receptor-neprilysin inhibitor): reduce preload/afterload and remodeling.

• Beta-blockers: improve survival and reduce hospitalization.

• Mineralocorticoid receptor antagonists: decrease aldosterone effects.

• Loop diuretics: manage congestion.

• SGLT2 inhibitors: reduce hospitalization and mortality in HFrEF.

• Ivabradine: slows heart rate in patients with elevated resting HR despite beta-blocker therapy.

• Hydralazine + isosorbide dinitrate: useful in certain populations (e.g., Black patients with HFrEF).

5. Lipid-lowering Agents

• Statins: inhibit HMG-CoA reductase, reduce LDL cholesterol.

• Ezetimibe: inhibits intestinal cholesterol absorption.

• PCSK9 inhibitors: increase LDL receptor recycling.

• Fibrates: lower triglycerides, raise HDL cholesterol.

• Bile acid sequestrants: bind bile acids to reduce cholesterol absorption.

• Omega-3 fatty acids: lower triglycerides.

6. Antithrombotic Agents

• Antiplatelet drugs:

  • Aspirin (COX-1 inhibition).

  • P2Y₁₂ inhibitors (clopidogrel, prasugrel, ticagrelor).

  • GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban).

• Anticoagulants:

  • Vitamin K antagonists (warfarin).

  • Direct oral anticoagulants (dabigatran, apixaban, rivaroxaban, edoxaban).

  • Heparins (UFH, LMWH, fondaparinux).

• Thrombolytics: alteplase, tenecteplase, streptokinase (used in acute MI, stroke, massive PE).

7. Vasopressor and Inotropic Agents

• Catecholamines: norepinephrine, epinephrine, dopamine, dobutamine.

• Non-catecholamine inotropes: milrinone, levosimendan.

• Used in shock states and severe heart failure for temporary support.

8. Peripheral Vasodilators

• Hydralazine, minoxidil, nitroprusside.

• Reduce vascular resistance; used in hypertensive emergencies and severe heart failure.

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3. Clinical Uses Overview

• Hypertension: first-line therapy often with thiazide diuretics, ACE inhibitors, ARBs, or calcium channel blockers.

• Coronary artery disease: nitrates, beta-blockers, calcium channel blockers.

• Heart failure: combination of ACE inhibitor/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist, SGLT2 inhibitor.

• Arrhythmias: selection based on mechanism and origin (atrial vs ventricular).

• Hyperlipidemia: statins as first-line; add-on agents for high-risk patients.

• Thromboembolic prevention/treatment: anticoagulants and antiplatelets tailored to indication.

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4. Contraindications and Precautions (General)

• Drug-specific contraindications (e.g., beta-blockers in severe bradycardia, non-DHP CCBs in advanced heart block without pacemaker).

• Caution in pregnancy: some classes (ACE inhibitors, ARBs, warfarin) are teratogenic.

• Adjust dosing in renal or hepatic impairment where applicable.

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5. Adverse Effects (General Trends)

• Hypotension, dizziness, syncope.

• Bradycardia or tachyarrhythmias depending on drug class.

• Electrolyte disturbances (diuretics, RAAS inhibitors).

• Bleeding risk (antithrombotic agents).

• Organ-specific toxicities (e.g., amiodarone pulmonary toxicity, statin myopathy).

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6. Drug Interactions (General Trends)

• Pharmacodynamic: additive hypotensive, bradycardic, or bleeding effects.

• Pharmacokinetic: CYP450 metabolism competition (notably with statins, warfarin, certain antiarrhythmics).

• Protein binding displacement (e.g., warfarin).

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7. Monitoring

• Blood pressure, heart rate, and ECG where applicable.

• Electrolytes and renal function for RAAS inhibitors, diuretics, digoxin.

• INR for warfarin therapy.

• Lipid profiles for lipid-lowering therapy.

• Signs of bleeding for antithrombotic drugs.