Cardiovascular Therapeutics Midterm

Mean Arterial Pressure (MAP) Calculation

• MAP formula: ( \text{MAP} = \frac{(2 \times DBP) + SBP}{3} )

Introduction to Cardiovascular Medications

Beta-Adrenergic Agonists and Antagonists (Beta Blockers)

• Beta receptors are G-protein coupled, activating adenylyl cyclase for ATP to cAMP conversion.
• Vital for myocardium contractility and conduction velocity in heart function.
• Post-synaptic B-receptors lead to tissue-specific physiological responses.
• Beta blockers function by competitively inhibiting beta receptors.

Key Physiological Effects of Beta Agonism

• Mild agonism from acebutolol, penbutolol, and pindolol.
• Bisoprolol and nadolol require renal function considerations.

Clinical Indications for Beta Blockers

• Cardiac:
  • Angina prevention
  • Treatment of arrhythmias, including atrial fibrillation
  • Management of heart failure with reduced ejection fraction (EF)
  • Post-myocardial infarction care
• Non-cardiac:
  • Management of elevated intraocular pressure (timolol)
  • Treatment for essential tremor (propranolol)
  • Prophylaxis for migraines (propranolol, timolol)

Pharmacokinetics of Beta Blockers

• Generally well absorbed, peak peak levels within 1-3 hours after oral administration.
• Some, like carvedilol, require concurrent food intake to enhance bioavailability.
• Different formulations (IV solutions for metoprolol and propranolol; esmolol is IV only).
• Distinct lipophilicity: propranolol is highly lipophilic; atenolol is hydrophilic and renally dependent.
• Varying half-lives: esmolol (~10 minutes), others 3-30 hours depending on the specific beta blocker.

Class-Wide Adverse Drug Reactions

• Bradyarrhythmias (decreased heart rate)
• Drug-dose dependent bronchospasm
• Side effects like fatigue and sleep disturbances, especially common with lipophilic options.
• Risk of hypotension and potential masking of hypoglycemia symptoms.
• Metabolic effects include hypercholesterolemia and hypertriglyceridemia.
• Withdrawal effects can include rebound tachycardia and hypertensive crises.

Precautions and Contraindications

• Notably affected by CYP2D6 metabolism (e.g., carvedilol, metoprolol, propranolol).

Calcium Channel Blockers (CCBs)

Mechanism of Action

• Target L-type channels in myocardium, SA/AV nodes, and vascular smooth muscle for calcium influx management.
• CCBs decrease myocardial contractility and produce vasodilation.

Indications for CCBs

• Non-DHP:
  • Hypertension management
  • Ischemic heart disease treatment
  • Supraventricular tachyarrhythmias
• DHP: Primarily used for hypertension and ischemic heart disease.

Pharmacokinetics of CCBs

• Rapid onset for IV formulations (e.g., verapamil, diltiazem).
• Different half-lives observed (e.g., clevidipine ~15 minutes, amlodipine has longer duration).

Adverse Drug Reactions (ADRs)

• Gastrointestinal issues (constipation due to decreased GI motility)
• Peripheral edema from arterial vasodilation.
• Non-DHP versions more likely to induce bradycardia.

Drug-Drug Interactions (DDIs)

• Noteworthy interactions with anticoagulants and statins, especially involving CYP enzymes.

ACE Inhibitors, ARBs, and ARNI

Mechanism of Action

• ACE inhibitors block angiotensin-converting enzyme, preventing the breakdown of bradykinin.
• ARBs inhibit angiotensin II Type 1 receptors.
• Neprilysin inhibitors decrease the breakdown of bradykinin and natriuretic peptides, promoting vasodilation.

Indications

• ACEi/ARBs:
  • Used in acute coronary syndrome and heart failure with reduced EF.
  • Effective for hypertension and proteinuric chronic kidney disease.
• ARNI: Beneficial in both reduced and preserved EF heart failure.

Pharmacokinetics

• Specific pharmacokinetic profiles not provided; important for understanding drug actions and interactions.