Antianginal Drugs Flashcards
What is the difference between classic angina and variant angina?
classic = stable and unstable (inadequate blood flow in presence of CAD) varient = Prinzmetal or vasospastic
When does prinzmetal angina usually occur and why?
at night - recumbent position increases venous return, which triggers neurogenic alpha adrenergic coronary vasospasm leading to angina
What are the two main pharmacological goals in treating classic stable angina?
decrease cardiac work (and reduce O2 utilization)
shift myocardial metabolism
What are the two main pharmacological goals in treatment of variant angina?
reverse vasospasm
treat underlying atheroclerosis
What are the goals of treatment in unstable angina?
Do everything you can - so reverse spasm, treat the atherosclerosis, decrease cardiac work and shift myocardial metabolism
What are the 4 things that determin myocardial O2 demand?
ventricular wall stress
heart rate
contractility
basal metabolism
Describe how ventricular wall stress affects myocardial O2 demand?
ventricular wall stress is the tangible force acting on the myocardial fibers from stretch, tending to pull them apart - energy is expended to oppose that force and you have increased myocardial O2 demand
What relationship governs how ventricular wall stress affects myocardial O2 demand/
laplace’s relationship
ventricular wall stress :
σ = (P x r) / 2h
where P is intraventricular pressure
R is radius of the ventricle
H is ventricular wall thickness
What is the relationship between wall thickness and ventricular wall stress?
inversely proportional:
a thicker wall has a greater muscle mass over which to spread out the force, thus decreasing O2 consumption per gram of tissue (this is why hypertrophy results in response to chronic pressure overload - it’s a compensation to reduce O2 consumption)
In a normal heart, increased demand for oxygen is met by what?
increased coronary blood flow
What is the limiting factor for perfusion?
duration of diastole - flow drops to near sero during systole
Why does damage to endothelium of coronary vessels lead to poor O2 supply?
it alters the ability of the vessels to dilate and reduce resistance
coronary flow is inversely proportional to coronary vascular resistance
What are the three traditional used classes of drugs for angina?
- organic nitrates
- Ca2+ blockers
- betal blockers
All three classes can reduce HR, ventricular volume, blood pressure and contractility, but which two can also increase O2 supply to ischemic tissues?
nitrates and Ca2+ blockers - they lead to vasodilation, thus allowing increased blood flow
Nitrates cause dilation in what vessels?
veins and arterioles (but mostly veins)
Why do you get slight reflexive tachycardia wtih nitrates at high doses?
because you have vasodilation, you get a slight decrease in TPR. This drops blood pressure and signals the baroreceptors to increase sympathetic activity, thus increasing heart rate
(also slightly icnreases contractility)
this is less than ideal
How do nitrates also encourage the redistribution of coronary blood flow?
they decrease left ventricular end-diastolic volume and pressure by decreasing preload on the heart
this favors the distribution of the total coronary blood flow to the endocardium (which is the first to get ischemic in angina)
Why is sublingual nitroglycerin better than oral?
theres’ high first pass metabolism, so sublingual is more effectives
Why is there such rapid absorption of nitroglycerin?
it’s highly lipid soluble
What are the toxicities of nitroglycerin>
orthostatic hypotnesion, reflex tachycardia and headache
Nitroglycerin will cause synergistic hypotension with what class of drugs?
phosphodiesterase type 5 inhibitors like viagra, cialis and levitra
What are the other two nitrates besides nitroglycerin? How do they differ from nitro?
isosorbide dinitrate (longer duration) isosorbide mononitrate (can be used orally for prophylaxis)
What do Ca2+ blockers do in the context of angina?
they block Ca2+ channels, so you get slower depolarization in nodal cells, thus slowing heart rate
decreases myocyte contractility
it also causes muscle relaxation in vasculature to increase total coronary blood flow and decrease aortic diastolic pressure
What is the one negative thing Ca2+ channel blockers do in the ocntext of angina?
also increase left ventricular end-diastolic pressure
