Antianginal Drugs Flashcards
What are the risk factors for CAD
- Advanced age (> 55 y for men; > 65 y for women) • Family history of premature cardiovascular disease • Hypertension • Cigarette Smoking
- Diabetes Mellitus • Dyslipidemia • Kidney disease • Obesity • Physical inactivity
What are the common features in Angina Pectoris?
- Angina pectoris is the principal clinical manifestation of CAD
- Characterized by pre-cordial pressure-like discomfort resulting from myocardial ischemia
- Transient episodes that don’t cause cellular death (MI) & last 15 to 15 min)
- Immediate cause of angina pectoris = imbalance between myocardial O2 supply and demand
What is the Pathophysiology of Angina?
Features of Chronic Stable Angina?
- Relative ischemia occurs when oxygen demand increases.
- Pain is usually associated with a predictable threshold of physical activity
What are the common features of Unstable Angina?
Clots often form in response to plaque rupture in atherosclerotic coronary arteries; however can also form because diseased coronary artery endothelium is unable to produce NO and prostacyclin that inhibit platelet aggregation and clot formation
What are the common features of variant Angina?
- Enhanced sympathetic activity (eg, emotional stress) especially when coupled with a dysfunctional coronary vascular endothelium (reduced NO) can precipitate vasospastic angina
What are the treatment rational when treating Angina?
• Increase oxygen delivery
• Coronary vasodilators
• Anti-thrombotic drugs
• Decrease oxygen demand
- Vasodilators (reduce afterload & preload)
- Cardiac depressants (reduce heart rate & contractility)
What is the Nitrates Mechanism of Action?
Nitrates mimic the actions of endogenous NO
Rapid reduction in myocardial O2 demand (systemic vasodilatation) & relief of symptoms
• In CV system, nitrous oxide (NO) is primarily produced by vascular endothelial cells
• NO functions: • vasodilation • anti-thrombotic • anti-inflammatory
(all involve NO-stimulated formation of cGMP)
Nitrates Mechanism of Action MAP?
What is the Cardiovascular Action of Nitrates?
Systemic Vasculature
• Vasodilation (venous dilation > arterial dilation)
- Decreased venous pressure
- Decreased arterial pressure (small effect)
Cardiac
- Reduced preload & afterload (decreased wall stress)
- Decreased oxygen demand
Coronary
- Prevents/reverses vasospasm
- Vasodilation
- Improves subendocardial perfusion
• Increased oxygen delivery
Nitrates - Clinical Application?
- IV nitroglycerin = unstable angina & acute heart failure
- Nitroglycerin (sublingual or spray) = first-line therapy for treatment of acute anginal symptoms
- Isosorbide mononitrate = orally for prophylaxis (sustained release preps available)
Why use Isosorbide Mononitrate?
- Longer onset of action & duration of action than nitroglycerin (more useful for long-term prophylaxis)
- Isosorbide mononitrate = >1 h (time to onset of action) & nearly 100 % oral bioavailability
- Metabolites have longer t1/2’s and significant activity
What are the adverse effects of Nitrates?
- Headache (cerebral vasodilation)
- High doses = postural hypotension, facial flushing, reflex tachycardia
Contraindications • Sildenafil
Common features of Sodium Nitroprusside?
- Direct NO donor = very effective, immediate vasodilator
- Clinical Applications • ICU & emergency settings • Used to treat severe hypertensive emergencies &severe heart failure
- Pharmacokinetics • IV only (t1/2 < 3min) • Continuous infusion is required
Sodium Nitroprusside Adverse effects?
• Severe nausea
- Vomiting
- Headache etc
• High doses = cyanide intoxification (nitroprusside releases cyanide along with NO)
B-Blockers Mechanism of action?
- Block b1 receptors
- Reduce both heart rate & contractility
- O2 demand is reduced during exercise and at rest
• Reduce frequency and severity of angina attacks
Drugs
- Propranolol = non-selective
- Metoprolol & atenolol = b1 selective
What are the Clinical Application of B-Blockers?
• Recommended in all patients (unless contraindicated) with stable angina who have had an ACS or who have left ventricular dysfunction
What are the adverse effects of B-Blockers?
- Bradycardia
- Conduction disturbances
- Bronchoconstriction
- Worsening of symptoms of peripheral vascular disease • Fatigue,
- CNS effects
- Impotence etc.
Contraindications of B-Blockers?
- Variant angina (treated by Ca2+ channel blockers or nitrates)
- Use with caution in patients with obstructive airway disease or peripheral vascular disease and, initially at very low doses in patients with heart failure
- NEVER discontinue abruptly (can cause rebound hypertension or angina)
What is the mechanism of actin of Ca2+ Channel Blocker?
- Ca2+ is essential for muscular contraction
- Ca2+ is increased in ischemia due to hypoxia-induced membrane depolarization
- L-type Ca2+ channel is dominant in cardiac & smooth muscle
Ca2+ channel blockers improve angina symptoms by: • Coronary & peripheral vasodilatation • Reducing contractility
WHat is the Clinical Application of Ca2+ Channel Blocker?
- Used in combination with b-blockers when initial treatment with b-blocker is not successful or, as a b- blocker substitute when b-blockers are contraindicated
- Relieve symptoms of variant angina
What is Nifedipine and Amlodipine Mechanism of Action, adverse effects and Class?
Ca2+ Channel blocker
- Minimal effect on cardiac conduction or HR
- Short-acting dihydropyridines should be avoided unless combined with b-blocker (increased mortality)
Adverse Effects
• Flushing • Headache • Hypotension • Peripheral edema (eg, pedal edema) • Constipation
What is Verapamil Mechanism of Action, Adverse effects, contrainidications and Class?
Ca2+ Channel Blocker
- Slows AV conduction directly à HR, contractility, BP & O2 demand
- Has greater inotropic effects than dihydropyridines (weaker vasodilator)
Adverse Effects- Same as other Ca2+ channel blockers • Constipation
Contraindications: • Preexisting depressed cardiac function or AV conduction abnormalities, • Use with caution in patients taking digoxin (increases digoxin levels)
What is Diltiazem Mechanism of Action, Adverse effects, contrainidications and Class?
Ca2+ Channel Blocker
• Similar effects to verapamil (slow AV conduction) • HR (lesser extent than verapamil) & BP
Adverse Effects • Same as other Ca2+ channel blockers but incidence is low
Contraindications • Same as verapamil
What is Ranolazine Mechanism of Action and Class?
Na+ Channel Blocker
- Blockade of Na+ current that facilitates Ca2+ entry via Na+/Ca2+ exchanger
- Decreased intracellular Ca2+ reduces ventricular tension & myocardial O2 demand
- Thought to also produce myocardial relaxation
- May modify fatty acid oxidation
What is the clinical applications, PK, and Adverse effects of Na+ Channel Blocker?
• Option for patients who have failed all other antianginal therapies
Pharmacokinetics - Metabolized by CYP 3A4
Adverse Effects - QT interval prolongation (main concern with this new drug), Nausea ,Constipation , Dizziness
Stable Angina Treatment?
• Acute attacks: promptly relieved by rest or nitroglycerin
- Maintenance therapy: long-acting nitrates & b- blockers are preferred
- Ca2+ channel blockers: when b-blockers are not successful or are contraindicated
• Ranolazine: when nitrates, b-blockers & Ca2+-blockers are unsuccessful
Unstable Angina Treatment?
- The link between stable angina & MI. Chest pains occur more frequently & precipitated more easily.
- Symptoms relieved by rest or nitroglycerin
- In addition, therapy with nitroglycerin & b-blockers should be considered
Variant Angina Treatment?
Episodic angina due to coronary artery spasm. Unrelated to activity, HR or BP.
Symptoms respond to nitroglycerin & Ca2+ channel blockers
All available Ca2+ channel blockers appear to be equally effective.
• Choice of drug is based on each individual patient
