Anti anginal Agents Flashcards
β-Adrenergic Antagonists (β-Blockers)
Drug list
- Atenolol
- Metoprolol
- Propranolol
- Timolol
Organic Nitrates
Drug list
- Nitroglycerin
- Isosorbide dinitrate
- Isosorbide mononitrate
Calcium Channel Blockers (CCBs
Drug list
- Dihydropyridines(DHPs)
- Amlodipine
- Felodipine
- Nicardipine
- Many others…
- Non-dihydropyridines
- Diltiazem
- Verapamil
Angina Pectoris
- The primary symptom of ischemic heart disease
- Coronary artery disease is usually the underlying cause
chest pain from ischemia
Types of Angina
- Effort angina (aka classic angina)
- Variant angina (aka vasospastic or Prinzmetal’sangina)
- Unstable angina (aka acute coronary syndrome)
•Effort angina (aka classic angina)
- Myocardial O2requirement increases during exercise, but coronary blood flow does not increase proportionately
- Resulting ischemia usually, but not always, leads to pain
•Variant angina (aka vasospastic or Prinzmetal’sangina)
•O2delivery decreases as a result of reversible coronary vasospasm
•Unstable angina (aka acute coronary syndrome)
•Angina at rest or an increase in the severity, frequency, and duration of chest pain in patients with previously stable angina
Molecular Mechanisms of Anti-AnginalAgents in the Vasculature
•Increase cGMP
- Nitroglycerin (NTG), other nitrates and nitrites
* Potentiated by PDE inhibitors (ed drugs)
Molecular Mechanisms of Anti-AnginalAgents in the Vasculature
•Decrease intracellular Ca2+
•Calcium channel blockers
Molecular Mechanisms of Anti-AnginalAgents in the Heart
- Decrease intracellular Ca2+
- Calcium channel blockers (reduces heart rate)
* Verapamil > diltiazem > DHPs - Beta blockers (reduces contractility and heart rate)
- Calcium channel blockers (reduces heart rate)
•Physiologic effect: decrease rate and contractility in cardiac myocytes
Organic Nitrates
Prototype
nitroglycerin (NTG)
- Available in many different formulations:
- Sublingual tablet or spray
- Sustained release oral capsules
- Buccal tablets or gel
- Ointment
- Transdermal patch
Organic Nitrates
Other Agents
- Isosorbide dinitrate
- Isosorbide mononitrate
- Sublingual, oral, or sustained release tablets
they are extended release
Organic Nitrates: Pharmacodynamics
- MOA: metabolism releases NO
- Dilates both arterial and venous vessels—decreases TPR and venous return
- Decreases both preload & afterload
- Mainly relaxation of large veins decreases venous return decreases preload decreases O2demand (major effect), smaller in afterload
- Primary antiischemic effect is to decrease myocardial O2demand by producing systemic vasodilation (more so than coronary vasodilation)
- Prevents coronary vasospasm (dialate coronaries)
Nitrate Use in Angina
- First-line therapy for an acute anginalattack (typically sublingual administration, spray equally effective)
- Long-acting oral and transdermal formulations improve exercise tolerance and time to onset of angina
- Improve antianginal and antiischemiceffects of beta blockers and calcium channels blockers
- Long-term utility is limited by tolerance
Nitrate Tolerance
- Effectiveness diminishes significantly with continuous use
- Multiple mechanisms proposed
- Generally not a problem with sublingual nitroglycerin (drug is only in body for short time)
- Limits the usefulness of oral and transdermal nitroglycerin and oral isosorbide mono-and dinitrate
Prevention of Nitrate Tolerance
- Intermittent therapy with a nitrate-free interval of at least 8 hours may prevent tolerance (for q 24 hour period)
- Angina frequency and silent ischemia may increase during off-patch hours
Nitrates: Adverse Effects
•Common: orthostatic hypotension, syncope, throbbing headache, flushing
- Drug-drug interaction: synergistic hypotension with phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) (bc both increase cgmp)
- Can lead to myocardial infarction and death
β-Adrenoreceptor Antagonists
Non-selective
Non-ISA
Propranol
carvedilol (also blocks a1 and has vasodilating activity)
nadolol
timolol
β-Adrenoreceptor Antagonists
Non-selective
ISa
labetalol (also blocks a1 and has vasodilating activity)
carteolol
penbutolol
pindolol