Flashcards in Antianginal Drugs Deck (33)
What is the primary cause of angina?
Imbalance between the oxygen demand of the heart and the oxygen supplied to it via the coronary vessels
What is the cause of chest pain and discomfort in angina?
Coronary blood flow cannot deliver sufficient oxygen to support cardiac oxidative metabolism --- myocardium becomes hypoxic
--triggers pain receptors in the heart
There are three types of Angina. The first is chronic stable angina. What is this caused by?
Chronic narrowing of coronary arteries due to atherosclerosis
What is the classification system for chronic stable angina?
1: angina with strenuous exercise
2: Angina with moderate exercise
3: Angina with mild exertion: walking1-2 level blocks at a normal pace or climbing 1 flight of stairs at a normal pace
4. Angina at any level of physical exertion
The second type of angina is unstable angina. What is this caused by?
Transient formation and dissolution of a blood clot within a coronary artery
--in response to a plaque rupture in the coronary arteries
--coronary flow is reduced, leading to a reduction in oxygen supply
--if the clot completely occludes the coronary artery for a long period of time, the myocardium supplied by the vessel may become infarcted.
The third type of angina is Variant (Prinzmetal's) Angina. What is this caused by?
--reduces coronary blood flow
What are the principles of antianginal therapy?
Short term goals: reduce symptoms that impair quality of life and exercise
Long term goals: prevent cardiovascular events and extension of life
In order to alleviate anginal pain oxygen supply/demand ratio has to be raised. How can this be achieved?
Increase blood flow (increase oxygen delivery or supply)
Decrease oxygen demand (decrease myocardial oxygen consumption)
--coronary vasodilators or anti-thrombotic drugs (increase oxygen delivery)
--vasodilators or cardiac depressant drugs (decrease oxygen demand)
Now going through the drugs to treat angina. The first are the vasodilators, calcium channel blockers (CCB). What are the clinical applications of these drugs?
Tx: HTN, angina, arrhythmias, chronic stable, unstable and Prinzmetal's angina
--need to use beta blockers with CCB due to the reflex tachycardia
What is the MOA for CCB?
Block calcium channels on vascular smooth muscle, cardiac myocytes and cardiac nodal tissue
--reducing entry into the cells of Ca2+
vascular smooth muscle relaxation, decreased myocardial force and decreased heart rate
How do CCB drugs work for angina?
Vasodilator and Cardiodepressant Actions
--increase in oxygen supply
---reduction in oxygen demand
--dilate coronary arteries
The dihydropyridines are CCB. What is their role in angina control?
Little effect on cardiac conduction or heart rate
--used for their vasodilator effects
Used for variant angina
The non-dihydropyridines are Verapamil and Diltiazem. What is their role in angina control?
--weak vasodilator but strong negative inotropic action therefore reduces oxygen demand by decreasing heart rate and contractility
--used for chronic stable, unstable and variant angina
--relieve coronary vasospasm by dilating coronary arteries
--used for variant angina
What are the adverse effects of the dihydropyridines CCB?
Reflex tachycardia (nifedipine being the strongest)
Dizziness, flushing, headache, hypotension, constipation, and peripheral edema
What are the adverse effects of Verapamil and Diltiazem CCB?
Cardiac conduction abnormalities: bradycardia, AV block
Anorexia, nausea, edema, hypotension
What are contraindications when using a CCB?
Continuing with the vasodilating drugs are the nitrates (isosorbide dinitrate, isosorbide mononitrate, nitroglycerin and sodium nitroprusside). What are the clinical applications?
Stable and Unstable Angina
--nitroglycerin: first line therapy for tx of acute anginal symptoms
---isosorbide mononitrate: orally for prophylaxis of angina
--sodium nitroprusside: used in ICU and emergency settings
What is the MOA for the nitrates?
NO produced by the vascular endothelial cells --- activates cGMP --- inhibits Ca2+ entry into the cell --- decreases intracellular Ca2+ concentrations --- smooth muscle relaxation
What are the important functions of NO?
1. Relaxing vascular smooth muscle (Vasodilation)
2. Inhibiting platelet aggregation (anti-thrombotic)
3. Inhibiting leukocyte-endothelial interactions (anti-inflammatory)
Do nitrates have more effect on veins or arteries?
--decrease venous pressure and ventricular preload this results in a decrease in oxygen demand by the heart
Tolerance to nitrates develops rapidly, what is a way to help with tolerance?
Daily nitrate free interval of 10-12H
--removing the drug at night
What are the adverse effects of the nitrates?
Hypotension: most serious toxicity
Reflex tachycardia: worsens angina by increasing oxygen demand
Headache: cerebral vasodilation
Sodium nitroprusside: cyanide toxicity due to parent compound releases both NO and cyanide (tx with sodium thiosulfate infusion)
What are the contraindications in nitrates?
Should not be taken alongside sildenafil
--inhibits breakdown of cGMP leading to an increase in cGMP levels leading to hypotension and impaired coronary perfusion.
Moving on to the cardioinhibitory drugs are the beta blockers. Particularly in regards to angina, Propanolol, Metoprolol and Atenolol. What are the clinical applications?
tx: HTN, angina, myocardial infarction, arrhythmias and heart failure
Angina: beta blockers are recommended in all patients with stable angina who have had an ACS or who have left ventricular dysfunction.
What is the MOA of beta blockers?
1) decrease myocardial contractility, heart rate and cardiac output
2) Reduce renin secretion thus decrease circulating angiotensin II levels
--no reflex tachycardia
-due to the negative inotropic and antihypertensive actions
--reduce work load thus reduce oxygen demand
What are the adverse effects of beta blockers?
--abrupt cessation of beta blocker therapy may produce unstable angina, MI or even death in patients with coronary disease.
--without coronary disease: tachycardia, sweating and generalized malaise due to increased blood pressure
Disturb lipid metabolism
What are the contraindications of a beta blockers?
--due to an oxygen supply problem
Beta blockers work by reducing oxygen demand
Reactive Airway Disease
Patients with sinus bradycardia and partial AV block
The next cardioinhibitory drug is Ranolazine, an Na channel blocker. What is the clinical application?
Alternative option for patients with chronic angina that have failed all other therapies
What is the MOA for Ranolazine?
Blocks late inward Na channels
--prevents Ca2+ overload within the cell leading to improved coronary blood flow
NO effect on heart rate or arterial pressure
What are the pharmacokinetics, adverse effects and contraindications for Ranolazine?
--metabolized by CYP 3A4
QT prolongation: risk of torsades de pointes and ventricular tachyarrhythmias
The last few cards will just be an overview of angina treatment. What is the acute and maintenance therapy for stable angina?
Nitroglycerin or rest
Long acting nitrates plus beta blockers
--Ca2+ blockers are used when beta blockers are unsuccessful
--Ranolazine is used when all above fails
What is the treatment for unstable angina?
Relieve symptoms with rest or nitroglycerin
--long term therapy with nitroglycerin and beta blockers