Anti-Anginal

Drugs
→ Angina is characterized by transient episodes of pressure like discomfort resulting from myocardial ischemia that do not cause cell death [MI] and last for 15 seconds to 15 minutes
→ Results from an imbalance b/w the O2 demand of the heart and the O2 supplied to it via the coronary vessels
→ Different types include:
o Stable: d/t narrowing of coronary arteries; pain usually associated w/ a predictable threshold of physical activity
o Unstable: d/t clots that form in response to plaque rupture (coronary thrombosis) OR diseased endothelium can’t produce NO & prostacyclin which inhibit aggregation & clots
o Variant [Prinzmetal]: d/t coronary vasospasm; enhanced sympathetic activity such as emotional stress coupled w/ dysfxnal endothelium and precipitate variant angina
→ Treatment rationales include increasing O2 delivery through coronary vasodilators or antithrombotic agents, or decreasing O2 demand via vasodilators and cardiac depressants
→ Decreasing the O2 demand is the only therapy that can be used in Prinzmetal angina, but stable and unstable can use either method
Drug Name Class Description MOA Uses PK Adverse Effects
Longer onset and duration than HA→ cerebral vasodilation
nitroglycerin Postural hypotension
Isosorbide
Indicated for ALL anginas Oral prophylaxis of angina t1/2 = 2-8 min Flushing
Mononitrate
Metabolites are active Onset > 1 Reflex tachycardia
Mimic the action of endogenous Nitrates activate guanylyl cyclase! converts hour
NO GTP into cGMP! ↑cGMP aids in the de- Similar to nitroglycerin but Desensitization/overcome
Isosorbide tolerance → “nitrate free
phosphorylation of myosin light chains→ Ongoing attack longer action- 100%
Dinitrate interval” of 10-12 hours needed
Rapid reduction in myocardial O2 smooth muscle relaxation bioavailability
Organic demand [via systemic
IV→ unstable angina and High 1st pass metab.→
Nitrates vasodilation] and relief of ↓coronary vasoconstriction→ ↑myocardial Contraindicated in pts taking
acute HF parenteral admin
symptoms perfusion Sildenafil!Inhibits PDE5
Nitroglycerin
which breaks down
Sublingual→ 1st line Onset in 2-5min
Functions of NO: Large venous dilation→ ↓preload and work cGMP leading to an even greater
treatment of acute SXS and lasts for 30min
Vasodilation of the heart increase in cGMP
Anti-thrombotic t½ = < 3min
Direct NO donor→ HTN
Sodium Anti-inflammatory Continuous IV infusion Severe nausea, vomit, HA
emergencies & severe HF in
Nitroprusside Protect from light due to cyanide poisoning
emergency settings
conversion to Cyanide
Rebound HTN or angina if drug is
Propranolol is NOT cardioselective discontinued abruptly [upregulate
↓ heart rate and contractility
Acebutolol Metoprolol and atenolol are β1 receptors]
↓ O2 demand Recommended in ‘all’ pts
Atenolol cardioselective
β-blockers ↓ frequency and severity of stable/unstable with stable angina who have
Metoprolol Contraindicated in asthma, COPD,
angina attacks [RAAS not as important here LV dysfunction
Propranolol No reflex tachycardia d/t inotropic Diabetes, PVD
as in HTN]
& chronotropic actions Sinus bradycardia/partial AV block
& Prinzmetal angina
-Minimal effect on conduction or heart rate!more selective for vascular
Flushing, Reflex tachycardia, HA,
smooth muscle
Hypotension, Peripheral edema,
Amlodipine Ca2+ is increased in ischemia -Entry of Ca2+ via L-type channel blocked→ ↓smooth muscle tone & PVR→
Oral (sustained release not the Constipation, Bradycardia, AV
Felodipine due to hypoxia induced arteriolar vasodilation→ ↓BP
short acting) block, anorexia, constipation,
Nifedipine membrane depolarization -used in combo with B-blockers when B-blockers are not successful or is
Calcium edema
contraindicated
Channel
Angina is improved by -Nifedipine should always be used with B-blocker to avoid reflex tachycardia
Blockers Verapamil/Diltiazem:
coronary and peripheral -Slows AV conduction directly→ ↓HR, contractility, BP, O2 demand
Verapamil Contraindicated in pts w/
vasodilation and reducing -cardioselective!greatest depressant effect on heart
Cardioselective preexisting depressed cardiac
contractility
function or AV conduction

abnormalities
Diltiazem DOC for Variant Angina Slows AV conduction similar to Verapamil, but decreases HR to a lesser extent
Use with caution in pts taking
digoxin
QT prolongation
Na+/Ca2+ exchanger reverses Nausea, constipation
direction in ischemia Dizziness
(Indirectly ↓Ca2+ levels by
↓ contractility Prophylaxis for pts in which
Na+ Channel blocking this exchanger)
Ranolazine ↓ O2 demand all other antianginal Metabolized by CYP3A4 Contraindicated in pts with
Blocker
May modify fatty acid oxidation therapies have failed prolonged QT! torsade’s de
May also produce myocardial
pointes and ventricular
relaxation
tachyarrhythmia





Treatment strategies:
Stable/Unstable:
→ Acute attacks are promptly relieved by rest or nitroglycerin

→ Maintenance therapy is best with long acting nitrates and β
blockers

→ Ca2+ channel blockers are used when β-blockers are not
successful or contraindicated
→ Ranolazine is a last ditch effort when all else fails
→ Patients should also take aspirin and modify their lifestyle

Prinzmetal[Variant]:
→ symptoms respond to nitroglycerin and Ca2+ channel
blockers [all types]; choice of drug based on the patient