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
How do you avoid tolerance
Have an 8-12 hour nitrate free period each day (night usually)
Mechanism of tolerance
volume expansion, neurohormonal, depletion of cystein stores which are needs to reduce nitrates to NO
Anginal rebound is:
When you suddenly remove IV nitrate and coronary vasospasm occurs. Don’t do this. Overlap the withdrawl of IVs with a patch or oral form
Calcium channel blockers work on
L-type calcium channels
What are the two classes of calcium channel blockers according to this professor
dihydropyridine and non-dihydropyridine
Dilitazem and Verapamil are what type of CCB
Non-dihydropyridine, They work in a use dependent way, that is, the channel must be in use or open for them to bind
What tissues do Diltiazem and Verapamil bind?
Cardiac Cells!!!
What is the Dihydropyridine calcium blocker
Nifedipine
What tissues do the Dihydropyridine blockers target
smooth muscle
Dihydropyridines are voltage dependent binders,,,not use dependent
true
Effects of Non-dihydropyridne CCBs
Decrease heart rate, decrease contractility, slow AV conduction
Decreased MvO2 (cardiac oxygen demand) by lowering rate, contractility
Prevents and revereses vasospasm
Effects of Dihydropyridine Ca channel blockers
Vasodilators (heart rate and contractility unchanged)
Reduces afterload by decreaseing resistance, decreases coronary resistance.
Cram slide…look at it
ok
Adverse effects of dihydropyridines
excessive vasodilation leading to dizziness, hypotension, headache etc…
GI irritation
Peripheral edema
Non-dihydropyridines (Diliazem and Verapamil) side effects
Bradycardia, asystole, AV block
Obviously you shouldn’t give this in pts with CHF
Constipation
Mechanism of anti-anginal effects of Beta Blockers
Blunts heart rate and inotropic response to exercise
reduces afterload, does not reduce pre-load
Does not prevent coronary vasospasm
Beta blockers particularly useful when combined wit
CCBs and Nitrates
Beta blockers reduce herat rate and contractility in response to exercise particularly well
truth…makes them very useful in exertional angina by reducing the level of cardiac stimulation that they get
Beta blockers and nitrates are best used for
unstable angina
Beta blockers are ineffective in what type of angina
vasospastic
Beta blockers useful for MI?
Yes
Dihydropyridine CCB alone?
Not usually. Much better with Beta blocker
Non-dihydropyridine (with no beta blocker) much better when?
When patients have asthma or bronchospastic COPD, peripheral vascular disease, depression, insulin dependent diabetes
Ranolazine
Increases efficiency of O2 utilization on the heart
