L6 angina practice essay

Angina is one of the key symptoms of IHD or ischaemic heart disease. Angina occurs due to reduced
coronary blood flow which impairs the ability to washout accumulated adenosine which is a product
of ATP metabolism.

There are 3 types of angina – stable angina, unstable angina and prinzmetal’s variant. Stable angina
occurs due to the presence of a large atheroma or plaque which is a fixed obstruction the blood
vessel but allow for sufficient blood flow to occur. This means that there isn’t accumulation of
metabolites at rest so there isn’t chest pain. When an individual with stable angina performs
exercise, it is then that they feel angina as the vessel would not be wide enough to allow sufficient
blood flow therefore resulting in accumulation of metabolites and resulting in chest pain. Unstable
angina is when the atheroma forms cracks or fissures which exposes the lipid rich core that also
contains calcium deposits. When this core is exposed to the blood it activate circulating platelets in
the blood which can lead to formation of a thrombus that can eventually occlude the coronary
artery. Prinzmetal’s variant produces angina spontaneously due to coronary spasms, it is possible
that there is no involvement of an atheroma at all in this case.

In the event of an acute angina attack, sublingual nitroglycerin proves rapid relief by venodilation
which has a negative inotropic effect. We can administer prophylactic drugs for the different types of
angina. Stable angina is treated using nitrates, beta blockers, calcium channel blockers and
ivabradine. Unstable angina is treated using aspirin as secondary prevention and for the variant type
we either administer nothing or nitroglycerin (GTN).

At rest the coronary supply equates coronary demand, but when the individual is doing exercise and
coronary supply is not meeting demand it is an issue of insufficient coronary dilation. However
because of the atheroma, which is a fixed structure, we cannot treat angina by coronary. So we have
to look at other mechanisms of treatment. Starting with long acting nitrates, such as isosorbide
dinitrate which reduce preload by venodilation. Nitrates are slow acting produce a long lasting effect
and they act on capacitance veins but nitrates are functionally selective so initially they act on
resistance arterioles but then the sympathetic reflex causes constriction of arterioles and surmounts
the activity of the nitrates on the arterioles. When they dilate capacitance veins it reduces preload
and reduces the ionotropic state of the left ventricle. However tolerance to nitrates can be
developed relatively fast which means that intermittent dosing regime has to be implemented. The
mechanism of action of nitrates is as follows. Nitrates enter the blood stream and become de-
ntirated, which produces NO or nitric oxide. Nitric oxide diffuses into smooth muscle which triggers a
cascade of events involving cGMP. This cascade eventually results in smooth muscle relaxation. In a
bit more detail NO and nesiritide diffuse through the endothelial layer into the smooth muscle
cytosol and act on guanylyl cyclase to activate it. Activated guanylyl cyclase converts GTP to cGMP
which then activates protein kinase G, eventually this leads to venous smooth muscle relaxation.

Calcium channel blockers are also used in the prophylaxis of stable angina. Verapamil produces
selective afterload reduction. Verapamil blocks all L type calcium channels, which results in blocking
of calcium entry into cells via the slow inward current. The blockage of calcium entry into vascular
smooth muscle cells, and ventricular muscle cells results in decreased cell contraction. In the vessels
this means there is vasodilation and in the heart this means there is negative inotropy.

Beta blockers are also used in the prophylaxis of stable angina. There are B non selective and B1
selective adrenoreceptor antagonists which have negative ionotropic and chronotropic effects
meaning that there is reduced heart rate and reduced energy consumption of the cardiac cells.
Catecholamine binds to B1 adrenoreceptors and triggers a cascade of events that results in
contraction of the cell. When catecholamine binds to B1 adrenoreceptors which is coupled with
adenylyl cyclase. It triggers adenylyl cyclase to convert ATP to cAMP. cAMP then converts kinase from
inactive to active form which triggers a phosphorylation cascade ultimately leading to contraction of
heart muscle. If we use beta blockers, it prevents the catecholamine from binding to the receptor
and producing the contraction in the cell. Administration of beta blockers in asthmatic patients
should be done carefully as it can cause bronchospasm, so B1 selective blocker should be
administered.