9. Drugs for Regional Ischemia CAD Flashcards
What is angina?
What is cardiac ischemia?
The result of decreased blood supply to the heart due to an imbalance of reduced oxygen supply and increases oxygen demand
Cardiac ischemia occurs due to narrowing of the coronary arteries, a coronary artery disease (CAD)
What are the 2 ways to treat ischemia?
- Reduce oxygen demand and work load on the heart- by decreasing cardiac contractility, heart rate, and venous return
Ex: nitrates, β blockers, Ca2+ channel blockers (CCBs) - Increase oxygen supply- coronary vasodilation
Ex: nitrates and Ca2+ channel blockers (CCBs)
What are the 3 groups of drugs used to treat ischemia?
- Nitrates- increase cGMP levels in arteries and veins, potent vasodilator has rapid action, best for acute angina, tolerance develops
Ex: nitroglycerin, isosorbide dinitrate - β-adrenergic blockers- decrease O2 demand of heart, decrease heart rate, best for long term management, typical angina
Ex: metoprolol, atenolol - Ca2+ channel blockers (CCBs)- inhibit Ca influx via L type channels in heart and vessels, lowers load on heart and promotes coronary vasodilation, used for typical and atypical angina
Ex: diltiazem, verapamil, amlodipine
What is typical (exertional) angina vs atypical (vasoapastic) angina?
Typical/exertional/stable angina- discomfort that is noted when heart does not get enough blood or oxygen, typically caused by blockage or plaque buildup in coronary arteries, typically in men
Atypical/vasospastic/variant angina- more subtle presentation of localized symptoms mistaken for muscle pain of muscle pull, more common in women
What are organic nitrates?
What is their pattern of effects?
Prodrugs that mimic and act like nitric oxide
NO activates soluble guanylyl cyclase (sGC) which increases cGMP in smooth muscle cells which relaxes them
They relax vascular smooth muscle (vasodilation), bronchial, and GI smooth muscle
Increase myocardial O2 supply while decrease myocardial O2 demand (dominant action)
Nitrates->venodilation->⬇️venous return
- > ⬇️filling pressure->⬇️cardial wall tension
- > ⬇️oxygen consumption
Slides 4-11 CAD
How do nitrates help angina or ischemia?
The rapid relief of angina it ischemia is to decreased preload due to decreased venous return as a result of venodilation of capacitance vessels (resistance vessels dilate too but capacitance is more dramatic)
Rapid relief of acute angina is due to venodilation causing decrease venous return decreasing preload and work load on heart which decreases O2 consumption
Slides 7-8 CAD
What are the routes of administration for nitrates?
Rapidly activated in first pass metabolism in liver
Nitroglycerin given sublingually to act in 10-30 mins
Nitroglycerin given 2% ointment to act in 3-6 hours
Nitroglycerin given slow release transdermal to act in 8-10 hours
Isosorbide dinitrate given orally to act in 6-10 hours
Slide 11 CAD
What is the use of sodium nitroprusside (SNP)?
4 things
Used to treat hypertensive emergencies (primarily), not used long term for hypertension cause can cause cyanide poisoning
Also in many situations when short term reduction of cardiac preload and/or afterload is desired
Lower blood pressure durin lg acute aortic dissection
Improves cardiac output in congestive heart failure
Decreases myocardial oxygen demand after acute MI
What is the problem with nitrates and it’s tolerance?
Major problem
Nitroglycerin especially
Incidence of tolerance may be reduced by intermittent administration of nitrates
Ex: patch can be worn 12 hours on 12 off
Less tolerance with isosorbide dinitrate
Need drug holidays with nitrates to maintain advantage in overcoming acute ischemia
What are β-adrenergic antagonists (β1 blockers)?
Adverse effects?
Compete with Epi and NE at β1 rec No effect if their own Reduce heart rate, contractility, renin release in the kidney, RAS, afterload, TPR, BP, preload, VR, heart rate, cardiac output Decreases all these Saves lives
AE- lots. Reduced max exercise tolerance, asthma, PAD worsens, cold hands/feet, bad dreams, depression maybe, erectile dysfunction…
Slides 14-15 CAD
What are calcium channel blockers (CCBs)?
Block L-type Ca channels (in sinus, AV node, myocardium, peripheral vessels) to reduce Ca entry needed for contraction
Reduce heart rate, afterload
Negative ionotropic effects
CCBs are predominately arteriolar dilators
Dihydropyridines (DHPs) have higher affinity for smooth muscle than cardiac muscle (useful for treating hypertension)
Diltiazem, verapamil, DHPs
Slides 16-23 CAD
What are adverse effects of calcium channel blockers?
Constipation
Urinary retention
Headache
Bradycardia, AV block, heart failure with excess doses of verapamil and diltiazem
These two may also increase mortality in heart failure patients
What are the sites of action of calcium channel blockers?
4 drugs
Verapamil is more cardioselective L type CCB, useful in treating supreventricular tachycardia-arrhythmia
Diltiazem is a coronary artery selective L type CCB, useful in treatment of ANGINA
DHP amlodipine selectively block L type channels in peripheral vessels to decrease afterload and TPR and blood pressure
DHP cilnidipine blocks both L and N type channels to decrease blood pressure
Slide 18-20 CAD
What are the dihydropyridines (amlodipine), benzothiazepines (diltiazem), and phenylalkylamines (verapamil) affects on peripheral vasodilation, heart rate, myocardial contractility, nodal conduction?
DHPs:
PV- ⬆️ HR- ⬆️ MC- ⬇️ NC- ⬆️
Diltiazem:
PV- ⬆️ HR- ⬇️ MC- ⬇️ NC- ⬇️
Verapamil:
PV- ⬆️ HR- ⬇️ MC- ⬇️ NC- ⬇️
Slide 22 CAD
What type of calcium channel blockers would you use for hypertension, angina, and arrhythmia atrial flutter/atrial fibrillation/supraventricular tachycardia?
Hypertension- AMPLODIPINE, Nifedipine (peripheral vessel selective)
Angina- DILTIAZEM (preferably acts on coronary vessels
Arrhythmia atrial flutter/atrial fibrillation/supraventricular tachycardia- VERAPAMIL
