Unit 2 Day 4 (Fri 4/10) Flashcards
3 Major Types of Angina
- stable- lumen narrowed by plaque, inappropriate vasoconstriction
- unstable- plaque rupture, platelet aggregation, thrombus formation, unopposed vasoconstriction
- variant angina- no overt plaques, intense vasoconstriction
Precipitating Cause of Angina
Imbalance between O2 demand of heart and O2 supply via coronary vessels - most often due to atherosclerotic obstruction of large coronary vessels that results in decreased blood supply
Three Major Pharmacological Classes of Antianginal Agents
- nitrates
- β-blockers
- Ca++ channel blockers
Nitrates- MOA
-nitrates are converted to nitric oxide
-NO activates guanulate cyclase, leading to inc. GTP to cGMP
-inc. cGMP leads to relaxation of smooth muscle (prevents vasospasm)
-results in reduction of LVEDP and systemic reduction vascular resistance
• Primary effect: decreased wall tension and decreased
myocardial O2 requirement-demand
• Secondary effect: improves perfusion of ischemic myocardium
Nitrates- Effect
- inc. HR (reflex tachycardia)
- dec. systolic pressure
- dec. LV volume
- dec. preload
- dec. afterload
Nitrates- Uses
- tx of acute angina: sublingual tablet bypasses 1st pass hepatic metabolism
- prophylaxis for chronic drug: control of BP in perioperative hypertension, congestive HF associated with MI
Nitrates- Adverse Rxns
- direct extension of therapeutic vasodilation
- throbbing headache
- orthostatic hypotension
- reflex tachycardia
- tachyphylaxis (tolerance) with contrinuous exposure (minimized by nitrate-free interval)
Calcium Channel Blockers
- Amlodipine
- Verapamil- block L type Ca channels at SA and AV node, and in cardiac myocyte
- Diltiazem- block L type Ca channels at SA and AV node, and in cardiac myocyte
- Nifedipine
- Felodipine
Ca Channel Blocker- MOA
- targets: vascular tone (vasodilators)
- mostly vascular effects: nifedipine, amlodipine, felodipine (dec. preload)
- mostly cardiac effects: verapamil and diltiazem (dec. afterload)
Ca Channel Blocker Effect
Nifedipine, Verapamil, diltiazem
- nifedipine: inc. HR, dec. systolic pressure, vasodilation
- verapamil: dec. HR, dec. myocardial contractility, dec. systolic pressure, antiarrhythmic, vasodilation
- diltiazem: dec. HR, dec. systolic pressure, antiarrhythmic, vasodilation
Ca Channel Inhibitors- Pharmacokinetics
- dipines may rapidly lower BP
- reflex actiation of the SNS leads to tachycardia, worse angina and inc. MI risk
- avoid use of rapid onset formulations
- oral bioavailability varies widely
- matbolized by cytochome P450
CCBs- Uses
- angina: long dec. in peripheral vascular resistance
- other uses: arrhythmias, hypertension, subarachnoid hemorrhage, inhibition of premature labor
CCBs- Adverse Reactions
- cardiac depression (more with verapamil and diltiazem)
- minor toxicities (dizziness, constipation, gingival hyperplasia)
Beta Blockers- Types
- metoprolol (tartrate and succinate forms): beta 1 selective
- propanolol: non-selective, acts on beta 1 and beta 2
Beta Blockers- MOA
- stable in stable angina: due to hemodynamic effects that dec. O2 requirements
- can block reflex tachycardia associated with use of nitrate vasodilators in chronic stable angina
- NOT direct vasodilators, so no role in variant angina
- olol = beta 1 selective
- dilol = dilates via alpha 1, beta 1, beta 2 block
- alol = alpha 1 and alpha 2
