Anti-Anginal Treatment Flashcards
What is angina
An inbalance of supply and demand in regards to oxygen. Ischemia occurs when demand is higher than supply. This inbalance can be a result of obstruction of blood flow in the coronary arteries (less supply), may also be induced by increased demand (exercise).
Three types of angina, type 1 is:
Unstable Angina: Recurrent angina associated with minimal exertion. Correlates with the fissuring of atherosclerotic plaque and the subsequent thrombus formation. Associated with MIs
Second type
Variant Angina: A reduction on coronary flow due to vasospasm. Has nothing to do with increased demand (exercise). Great prognosis
Third Type
Exertional: Exercise induced Angina, usually due to coronary vascular obstruction
Most effective way to treat Angina
Reduce demand….decrease HR, decrease contractility, reduce ventricular workload
Perfusion of the heart (blood supply to the heart…very important) occurs when?
During Diastole….So if you want to increase supply, you want more Diastole
What do Nitrates do?
Release Nitric Oxide
Nitrates are:
effective vasodilators, reduce afterload, one of the only veinodilators which means they also reduce pre-load and thus contractility (Frank starling)
How does Nitric Oxide work?
A nitrate is given (Nitroglycerine) and it is reduced to NO. NO is important because it activates Guanylyl cyclase. Guanylyl Cyclase is a cousin of adenyly cyclase which converts ATP to cyclic AMP. Guanylyl cyclase converts GTP to cyclic GMP. This is a potent vasodilator causing smooth muscle relaxation.
CV effects on nitrates
Decrease in preload, coronary vasodilation, Blood pressure unchanged or slight decrease, HR unchanged or slight decrease, Pulmonary vascular resistnance decreased, Cardiac output reduced
Adverse Effects on nitrates
Hypotension…seen with Higher doses of nitrates. This may trigger sympathetic stimulation of the heart (tacchycardia, increased contractility) and decrease coronary perfusion thus worsening angina
May also cause Headache, drug rash,
Important adverse Drug interactions
Sildenafil (Viagra) …too much cGMP can be made leading to profound hypotension, MI, etc..
What is important in regards to Nitrate metabolism
Rapidly absorbed orally, rapidly metabolized by hepatic enzymes, extensive first pass metabolism makes effective oral administration difficult
How do you overcome this rapid hepatic metabolism
1) Bypass the liver by bypassing portal circulation: sublingual, buccal, transdermal, intravenous administration
2) Alter the structure
3) Prodrugs
Force zero order kinetics
4) Extended Release
Continuous nitrate exposure leads to
tolerance
