Treatment of Angina Flashcards
What factors are responsible for pain in angina pectoris?
Chemicla factors that cause pain in skeletal muscle (potassium, hydrogen, adenosine)
Which treatments reduce symptoms and which prolong survival?
Reduce chest pain symptoms - BB, nitrates, CCBs, nicorandil, ivabradine
Prolong survival - BB, aspitin, statins, ACEI’s, ARBs)
Where is window for coronary flow in left ventricle?
What shrinks this window?
Bottom between two systoles of ventricles (diastolic phase), top between two systoles in arota (diastolic phase)
Where aortic pressure > ventricular pressure
Shrinked by:
- Shortened diastole (e.g. increased HR)
- Increased ventricular end diastolic pressure (e.g. progressive decline in ventricular emptying, aortic valve stenosis)
- Reduced diastolic arterial pressure (mitral/aortic valve incompetence, HF)
What are the issues with coronary blood flow?
- Myocardium cannot function anaerobically (anaerobic glycolysis increases lactic acid production)
- Arterioles close mechanically during systole
- Decreased diastolic filling period during exercise
- Increased oxygen demand and increased metabolic demand during exercise
Work output of heart increases 6-9x during strenuous exercise
Uses 70-80% coronary blood flow oxygen at rest - increased demand needs increased flow
Autoregulation of arteriolar radius
Matches tissue demand to blood flow by altering flow at arteriolar level
Metbolic control - muscle cell produces byproducts (e.g. adenosine) which trigger vascular smooth muscle cells to relax (potentially via an intermediate produced by endothelial cells)
What are coronary ischaemia and infarction caused by and what do they cause?
Coronary ischaemia usually the result of atherosclerosis and causes angina
Sudden ischaemia usually caused by thrombosis and may result in MI
Coronary spasms sometimes cause angina - variant angina
Cellular calcium overload results from ischaemia - may cause cell death and dysrhythmias
What is stable angina?
Fixed stenosis/demand ischaemia
- predictable chest pain on exertion
- caused by fixed narrowing of coronary arteries
- treated by decreasing workload of heart and therefore decreasing oxygen requirement
- also use drugs to prolong survival (aspirin, statins, ACE-I’s)
What is unstable angina?
Thrombus/supply ischaemia
- occurs at rest and with less exertion than stable angina
- associated with thrombus around a ruptured atheromatous plaque but without complete occlusion of vessel (similar to MI)
What is variant (prinzmetal) angina?
vasospasm/supply ischaemia
- uncommon
- caused by coronary artery spasm
- not completely understood but sometimes associated with atherosclerosis
How do antianginal drugs work generally?
Mainly work by decreasing the metabolic demand of the heart
Nitrates, nicorandil and CCBs are vasodilators - decrease preload/afterload
BB and ivabradine slow down the heart - decrease metabolic demand of the muscle
Preload - venous pressure and venous return to heart (end diastolic pressure/volume, EDP or EDV)
Afterload - aortic/pulmonary artery pressure
BB action in angina
Propylaxis and treatment - first line in stable and unstable angina
Decrese cardiac oxygen consumption by slowing heart
Also have antidysrhythmic action - reduce death after MI
CCB action in angina
Inhibits calcium entry upon muscle depolarisation - in heart and smooth muscle
Dihydropyridines - amlodipine
Rate-limiting - verapamil/diltiazem
Vasodilator effect mainly on resistance vessels - reduces after-load, also dilate coronary vessels (important in variant angina)
Verapamil and diltiazem can reduce and impair AV conduction and myocardial contractility
SAN depolarisation - ion movement in the 3 different phases?
Phase 1 - Gradual drift increase in resting membrane potential due to increased sodium as ‘funny’ F-type sodium channels open and decreased potassium as potassium channels slowly close - pacemaker potential
Transient (T) calcium channels help with the final push
Phase 2 - moderately rapid depolarisation due to calcium entry via slow (L) channels
Phase 3 - rapid re-polarisation as elevated internal calcium stimulates opening of potassium channels and an increase in gK+
Clinical uses of CCBs
Amlodipine safe in patients with HF, used instead of a BB in prinzmetal angina or alongside BB in most anginas
Diltiazem/verapamil - used but CI in HF, bradycardia, AV block or in presence of BB
Also…
- Antidysrhythmics (verapamil) - slows ventricular rate in rapid AF, prevents recurrence of supraventricular tachycardia (SVT), no efect on ventricular arrhythmias
- HTN - mainly amlodipine/lercanidipine
How do organic nitrates work?
- Powerful vasodilators
- Work by being metabolised to NO and relax smooth muscle (particularly vascular smooth muscle)
- Acts on veins to decrease cardiac preload (higher concentrations can affect arteries therefore decrease afterload)
- Decreased cardiac workload is helped by dilation of collateral coronary vessels. This improves the disrubution of coronary blood flow towards ischaemic areas. Dilation of constricted coronary vessels is particularly beneficial in variant angina.
