Antianginal Medication Flashcards
What is the symptom of Angina Pectoris?
Tight chest
What is the underlying cause of Angina Pectoris?
Atherosclerosis
What causes Angina Pectoris?
Oxygen supply to the myocardium is insufficient for it’s needs
What can the chest pain be described as in Angina Pectoris?
Intense
Diffuse
Gripping
Constricting
Suffocating chest pain
Hard to distinguish from ‘heart burn’
Where can Angina pectoris pain radiate to?
Arms, Neck and Jaw
What is the lumen of an artery like in someone with Angina Pectoris?
Artery is smaller due to plaque growth.
What causes the artery to be blocked?
Rupturing of the plaque on an artery, platelet activation, thrombus, blood clot, blockage!
What is the aim of treatment for someone with Angina?
*Alleviate acute symptoms
*Minimise frequency of ischaemia
*Reduce progression of atherosclerosis
What secondary prevention measures can be put in place to reduce the progression of atherosclerosis?
Statins
Aspirin
ACEI in diabetes
What can increase a cardiac workload and trigger angina?
Exercise, Emotion, GI perfusion (heavy meals), Peripheral vasoconstriction
What can physically reduce the oxygen supply to the heart causing angina?
*Restricted coronary perfusion
* Narrowing of the coronary arteries (atheroma)
*Limits on dilation
*Aortic stenosis
*Atherosclerosis
How do we reduce the oxygen demand to the heart?
-Reduce perfusion demands
-Reduce pre-load
-Reduce afterload
-Reduce cardiac rate/contractability
-Improve efficiency of the heart
How can we reduce perfusion demands on the heart?
Rest, stress reduction, smoking, weight
How can we reduce the pre-load on your heart?
Venodilator - Nitrates!
How can we reduce afterload on the heart?
Arterial dilator
CCB, Nitrates
How can we reduce cardiac rate/contractilibility and cardiac workload?
Negative iontrope/chronotrope
-B-blocker
-CCB (Amlodipine etc)
How do we improve efficiency of the heart?
Exercise, stop smoking, lifestyle!!
How do we improve oxygen supply to the heart?
Increase coronary flow
Arterial dilator - more relaxed
-CCB
-Nitrates
Surgery - bypass, angioplasty, stent
What are the anti-anginal agents?
-Organic nitrates (acute attacks)
-CCB
-B-adrenoreceptor antagonists (b-blockers)
-Potassium channel activators - vasodilators
Why are b-blockers used for angina?
Slow heart rate so reduce metabolic demand
What are the long acting organic nitrates?
Isosorbide mononitrate
MOA of nitrates?
Nitric oxide is released from organic nitrates , this relaxes smooth muscle, decreasing pre-load.
What do lower doses of nitrates do?
-Marked dilation of large veins
-Reduction in central venous pressure (pre-load reduced)
-Reduction in cardiac output and oxygen consumption
-Little effect on arterioles/little change in BP
What do higher doses/chronic use of nitrates do?
-Arteriolar dilation
-Fall in BP
-Reduced cardiac output
-Headache
What is shear stress?
Shear stress is a frictional force parallel to the wall at the surface of the endothelium directly related to blood flow velocity
MOA of nitrates?
1) Nitrates
2) No radicals
3) Activation of guanylate cyclase
4) Accumulation of cGMP
5) Activation of cGMP dependent kinases
6) Dephosphorylation of myosin light chain
7) Vasodilation of smooth muscle
8) Reduced pre-load
9) Reduced workload and decrease O2 consumption
10) Relaxation!!
How do nitrates effect coronary circulation?
*Increase coronary flow - reducing vascular resistance
*Dilation of coronary arteries despite BP drop
*Divert blood from normal to ischaemic areas - by pass of narrowed segments
How does glycerol trinitrate work?
-Absorbed sublingually - rapid relief
-Rapidly metabolised in the liver (30 min activity)
-Can’t be swallowed 1st pass effect
-Sprays
-Tablets
-Patches
What does the action of a b-blocker, depressing the myocardium have on the heart?
-ve iontropy
*No effect on coronary arteries
*Provide secondary prevention
*Improve exercise capacity - reduce workload
*Contraindicated in coronary spasm
*Slow withdrawal as receptors upregulated
What are the three main classes of CCB?
*Phenylalkylamines - verapamil
*Dihydropyridines - nifedipine, amlodipine
*Benzothiazepines - diltiazem
Simple MOA of CCB?
Block calcium ions from entering cells through preventing opening of voltage-gated L-type calcium channels.
-Bind to the a1 subunit of the cardiac L-type calcium channels but at different sites!
The main effects on cardiac and vascular smooth muscle, inhibiting calcium entry which is caused by depolarisation in these tissues, which CCB is relatively cardio-selective?
Verapamil
The main effects on cardiac and vascular smooth muscle, inhibiting calcium entry which is caused by depolarisation in these tissues, which CCB is relatively smooth muscle selective?
Nifedipine
The main effects on cardiac and vascular smooth muscle, inhibiting calcium entry which is caused by depolarisation in these tissues, which CCB is intermediate?
Diltiazem
How do CCB have a cardiac action?
-Antidysrhythmic effect because of impaired atrioventricular conduction - slow action potential from AV to ventricle
-Reduced contractility - HR/contraction
-Negative inotropic and chronotropic effect (little effect on cardiac output, due to reduction in peripheral resistance
What CCB is contraindicated in heart failure?
Verapamil
How does a CCB (nifedipine) work on vascualar smooth muscle?
-Arteriolar dilation - reduce BP/reduce afterload
-Coronary vasodilation - used in pts with variant angina (spasm) - increase in blood flow to cardiomyocytes
