(Mode of Action of Drugs)
PharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamics
Chapter
1.4
Chapter
4.3 Antianginal Agents
Angina pectoris is a symptom of ischaemic
heart disease. It develops as a result of an
imbalance between the oxygen supply and
oxygen demand of the myocardium. There
is a paroxysmal chest pain which occurs
when coronary blood flow is inadequate to
supply required amount of oxygen to
myocardium. There is a characteristic radi-
ating pain in distribution in left arm, chest,
jaw and neck region. This pain is mainly
brought about by exertion/excitement when
oxygen demand of heart increases and myo-
cardial perfusion is decreased. Decrease in
myocardial perfusion is due to deposition
of atherosclerotic plaques in blood vessels.
These plaques are due to accumulation of
cholesterol and other lipid compounds
which develop as patches on inner side of
tunica intima of blood vessels i.e. subinti-
mal layer.
The drugs used in the treatment of an-
gina pectoris are classified as in table 4.3.1.
GLYCERYL TRINITRATE
Glyceryl trinitrate (GTN) releases nitrite
ion (NO 2 – ) which is further metabolised to
NO by enzymatic step involving reaction
with tissue sulphydryl (–SH) groups in
vascular smooth muscles.
NO released by GTN activates soluble,
cytosolic form of guanylyl cyclase in vascular
smooth muscles by interacting with haem
group in the enzyme. This converts GTP to
cGMP. cGMP dephosphorylates myosin light
chain kinase and prevent myosin interaction
with actin leading to relaxation.Pharmacodynamics
Action is almost exclusively on smooth
muscle cells.
Effect on vascular smooth muscles:
Both large arteries and veins relax in re-
sponse to GTN. But in small doses, marked
venorelaxation is seen leading to reduced
preload. This causes decrease in stroke
volume which is compensated with reflex
tachycardia.
Arterioles relax less than venules because
GTN evokes reflexes by baroreceptors which
respond to decreased arterial pressure
leading to reflex sympathetic discharge
causing tachycardia and increased cardiac
contractility.