Pharm Anti-Anginal Agents Linger Flashcards
4 common β-Adrenergic Antagonists (β-Blockers) from the list
Atenolol Metoprolol Propranolol Timolol
Name the 3 Organic Nitrates
Nitroglycerin Isosorbide dinitrate Isosorbide mononitrate
Name the 2 sub-classes of Calcium Channel Blockers (CCBs)
Dihydropyridines (DHPs) Non-dihydropyridines
Name the Dihydropyridines (DHPs)
Amlodipine Felodipine Nicardipine
Name the Non-dihydropyridines
Diltiazem Verapamil
What is the primary symptom of ischemic heart disease?
Angina Pectoris
What are the types of Angina?
Effort angina Variant angina Unstable angina
What is effort angina?
Increased myocardial O2 demand (exercise) exceeds coronary flow abilities
What is variant angina?
Pain due to coronary artery vaso spasm (Prinzmetal’s angina)
What is unstable angina?
Chest pain at rest, typically a progression from effort angina.
Agents that decrease O2 demand
ß adrenergic antagonist, Ca entry blockers, organic nitrates,
Agents that increase O2 supply
Vasodilators, statins, anti-thrombotics
Nitrates and nitrites MOA
metabolized to NO which Increase cGMP
Which Ca blockers are cardio specific
Non-DHPs (Verapamil > diltiazem > DHPs)
Non-DHPs physiologic effect
decrease rate and contractility in cardiac myocytes
Organic nitrates prototype?
nitroglycerin (NTG)
NTG formulation?
- Sublingual tablet
- spray
- Sustained release oral capsules
- Buccal tablets
- gel Ointment
- Transdermal patch
NTG preferentially dilates which vessels?
Large veins
How does NTG relieve angina?
Primary antiischemic effect is to decrease myocardial O2 demand by producing systemic vasodilation (more so than coronary vasodilation)
First-line therapy for an acute anginal attack?
NTG typically sublingual administration, spray equally effective
NTG formulations that improve exercise tolerance and time to onset of angina?
Long-acting oral and transdermal formulations
NTG improves antianginal and antiischemic effects of?
beta blockers and calcium channels blockers
NTG Long-term utility is limited by?
tolerance
NTG tolerance is not a problem with which formulation?
Generally not a problem with sublingual nitroglycerin
How to prevent nitrate tolerance?
Intermittent therapy with a nitrate-free interval of at least 8 hours may prevent tolerance
Nitrates: Adverse Effects
Common: orthostatic hypotension, syncope, throbbing headache, flushing
NTG Drug-drug interaction?
synergistic hypotension with phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) Think viagra.
Can lead to myocardial infarction and death
ß blockers list the non-selective
Propranolol
Carteolol
Nadolol
Penbutolol
Timolol
Pindolol
Cardioselective ß blocker
Metoprolol
Acebutolol
Atenolol
Nebivolol
Esmolol
Bisoprolol
Betaxolol
Combined alpha beta blockers
Labetalol
Carvedilol
Beta Blockers: Pharmacodynamics
Reduce cardiac work (i.e., O2 consumption) by decreasing heart rate and contractility
Most are not vasodilators; no effect on O2 supply
Beta Blocker Use in Angina prototype
Propranolol
First-line therapy to reduce frequency of angina (i.e., prophylaxis) and improve exercise tolerance
Propranolol
Propranolol Reduce O2 requirement by?
reducing heart rate and contractility
ß blocker NOT effective in_____ angina.
variant
All types of ß blockers are equally effective in _______ angina; _______ often preferred
exertional
cardioselective (β1-selective)
Beta Blockers that Prolong Survival After MI
Timolol, propranolol, and metoprolol have been specifically studied in large-scale clinical trials
Use of other beta-blockers for this indication is less compelling
Why are ß blockers used in conjunction with ACE inhibitors for Tx of CHF
Combined effect on mortality is increased over using either alone
Beta Blockers Adverse Effects?
Most common: bradycardia and fatigue
ß blocker Relative contraindications
Asthma/COPD
Diabetes
Variant angina
Acute decompensated heart failure
ß blocker Can cause heart block, especially if combined with
other negative inotropes (e.g., verapamil, diltiazem)
Calcium Channel Blockers (CCBs) bind to?
L-type Ca++ channels
But the two classes bind to different sites, resulting in different effects on vascular versus cardiac tissue.
Non-dihydropyridines:
Prominent cardiac effects, but also act at vascular tissues
Verapamil > Diltiazem
Dihydropyridines (DHPs):
Predominantly arteriolar vasodilation effects
Amlodipine, Clevidipine, Felodipine, Isradipine, Nicardipine, Nifedipine, Nisoldipine
Pharmacokinetic Properties of CCBs
Good oral absorption but high 1st pass effect
Amlodipine, felodipine, isradipine slowly absorbed, long t1/2 is advantage
DHPs with long plasma half-lives preferred to minimize reflex cardiac effects; extended release preparations available
Nifedipine, clevidipine, verapamil, and diltiazem sometimes used IV
CCBs: Pharmacodynamics
Relaxation of vascular smooth muscle causes peripheral vasodilation
Arterioles are more sensitive than veins
Reduce afterload and decrease O2 demand
Little effect on preload
Also increase O2 supply due to dilation of coronaries
vasodilator that is most effective on
- large veins
- arterioles
- organic nitrates
- Ca channel blockers
Calcium Channel Blocker Use in Angina
Preferred agents: diltiazem, verapamil, amlodopine, or felodipine
Added to or substituted for beta blockers in chronic stable angina
Also effective in vasospastic angina
Reduce O2 requirement by reducing heart rate and contractility
Increase O2 delivery by vasodilation and reversal of vasospasm
CCBs: Adverse Effects & Toxicity
Generally very well tolerated
Excessive vasodilation – dizziness, hypotension, headache, flushing, nausea; diminished by long-acting formulations and long half-life agents
Constipation (esp., verapamil), peripheral edema, coughing, wheezing, pulmonary edema
Use of verapamil/diltiazem with a β-blocker is contraindicated because of the potential for AV block
Verapamil/diltiazem should not be used in patients with ventricular dysfunction, SA or AV nodal conduction defects and systolic BP< 90 mmHg
Short-acting dihydropyridines can cause reflex tachycardia
According to board exams constipation is always caused by?
verapamil
Relatively newer antianginal drug with a MOA: late sodium channel blocker
Ranolazine
Typically reserved for angina that is refractory to treatment with beta blockers, calcium channel blockers, and nitrates
Used either in combination with beta blocker or as a substitute in patients who cannot receive beta blockers
Angina Preventative Therapies
Regular aerobic exercise
Stress reduction
Smoking cessation
Weight control
Blood pressure control
Diabetes management
Pharmacotherapies to prevent cardiovascular events:
Aspirin (or clopidogrel)
HMG-CoA reductase inhibitors (the –statins)
ACE inhibitors (the –prils) and ARBs (the –sartans)
Three primary drug classes that are utilized in angina
beta blockers, calcium channel blockers, & nitrates
Nitrates are the mainstay of treatment for ____ symptoms
acute
Cardioselective beta blockers are often recommended as?
initial first-line therapy for long-term prophylaxis
Anti-anginal Combinations may be
more effective than monotherapy
Only CCBs or nitrates can be used to relieve
vasospastic angina by preventing coronary artery spasm
