Introduction to Cardiovascular Pharmacology

Learning Objectives

• Understand the molecular mechanisms behind cardiovascular drugs.
• Learn routes of administration and elimination processes for these drugs.
• Identify main adverse effects associated with cardiovascular medications.
• Recognize clinically significant drug interactions.
• Recall pharmacological profiles of medications for cardiovascular disorders covered in prior studies.

Cardiovascular Diseases (CVDs)

• CVDs encompass various heart and blood vessel disorders:
  • Coronary heart disease affects vessels supplying the heart.
  • Cerebrovascular disease concerns vessels supplying the brain.
  • Peripheral arterial disease impacts vessels in limbs.
  • Rheumatic heart disease results from streptococcal fever damage to heart structures.
  • Congenital heart disease involves structural malformations present at birth.
  • Myocardial infarction (heart attack) is caused by reduced blood flow to the heart.
  • Arrhythmia indicates abnormal heartbeat patterns.
  • Hypertension is characterized by elevated blood pressure.

Regulation of Blood Pressure

• Blood pressure is defined as Cardiac Output (CO) multiplied by Total Peripheral Resistance (TPR).
• Cardiac Output (CO) comprises Stroke Volume (SV) and Heart Rate (HR).
• Factors influencing SV include:
  • Contractility
  • Preload
  • Afterload

Loop Diuretics

• Therapeutic applications include:
  • Management of acute pulmonary edema and heart failure.
  • Treatment of edema from renal failure or nephrotic syndrome.
  • Diuresis for ascites linked to liver cirrhosis or right-sided heart failure.
  • Control of hypertension and hypercalcemia.

Thiazide Diuretics

• Mechanism of action: Inhibit Na+-Cl- symporter, reducing NaCl reabsorption in the early distal convoluted tubule.
• Renal effects include increased excretion of numerous ions and decreased excretion of calcium.
• Diuretic efficacy is moderate, with maximum Na+ excretion being 5-10% of filtered load.

Thiazides: Metabolic Adverse Effects

• Can cause Hypokalemic metabolic alkalosis and may lead to hyperglycemia.
• Associated with hyperlipidemia, hyperuricemia, and hypercalcemia.
• Rare but serious effects include exfoliative dermatitis, Stevens-Johnson syndrome, and agranulocytosis.
• Sexual dysfunction seen in up to 30% of patients after long-term use.

Beta Blockers

• Metoprolol selectively blocks beta-1 receptors, resulting in decreased heart rate and contractility.
• Clinically used for hypertension, heart failure, myocardial infarction, angina, and arrhythmias.

Inhibitors of the Renin-Angiotensin-Aldosterone System (RAAS)

• Begins with renal renin release triggered by blood pressure reduction, leading to formation of angiotensin I and II.
• ACE-inhibitors (e.g., Lisinopril, Enalapril) reduce angiotensin II levels, a potent vasoconstrictor, ultimately decreasing afterload and preload.
• Indicated for hypertension, congestive heart failure, coronary artery disease, and myocardial infarction.

Heparin and Low Molecular Weight Heparins (LMWH)

• Administered via IV or SC, with IV onset in minutes.
• Used for both preventative and therapeutic applications against thromboembolic diseases and unstable angina.

Novel Oral Anticoagulants (NOACs)

• Include Apixaban (Factor Xa inhibitor), Dabigatran (direct thrombin inhibitor), Edoxaban (Factor Xa inhibitor), and Rivaroxaban (Factor Xa inhibitor).
• Used primarily for non-valvular atrial fibrillation and post-acute coronary syndromes.
• Specific reversal agents available for each NOAC.

Direct Thrombin Inhibitors

• Bivalirudin and Argatroban work by binding thrombin's active site, inhibiting its coagulation activity.