These agents are simple nitric and nitrous acid esters of polyalcohols. Otherwise called, Nitro-vasodilators Nitroglycerin may be considered the prototype of the group. Important molecular donors of exogenous nitric oxide. Denitration of the organic nitrates to liberate nitric oxide. Relax smooth muscle (especially vascular smooth muscle, but also other types including oesophageal and biliary smooth muscle).

1. Ramagopalan S

2. • These agents are simple nitric and nitrous acid esters of
polyalcohols. Otherwise called, Nitro-vasodilators
• Nitroglycerin may be considered the prototype of the group.
• Important molecular donors of exogenous nitric oxide.
• Denitration of the organic nitrates to liberate nitric oxide.
• Relax smooth muscle (especially vascular smooth muscle, but
also other types including oesophageal and biliary smooth
muscle).

3. a. Short acting:
• Glyceryl trinitrate (GTN, Nitro-glycerine)
b. Long acting:
• Isosorbide dinitrate (short acting by sublingual route),
• Isosorbide mononitrate,
• Erythrityl tetranitrate,
• Pentaerythritol tetranitrate

4. Mechanism of action: Nitrates
nitrites
Nitrates
nitrites
NO
Guanylyl
Cyclase(GC)
Activated GC
GTP cGMP
PDE
GMP
Myosin-LCMyosin-LC-PO4
Ca2+
MLCK*
Myosin
light chains
(myosin-LC)
Actin
Contraction Relaxation
Ca2+
MLCK
Calmodulin
Smooth
muscle
Contraction is triggered by
influx of calcium through
transmembrane calcium
channels.
Calcium combines with
calmodulin to form a complex
that converts the enzyme
myosin light-chain kinase to
its active form (MLCK∗)
MLCK* phosphorylates the
myosin light chains, thereby
initiating the interaction of
myosin with actin.
Finally, contraction occurs.
Nitroglycerin can be denitrated
by glutathione S-transferase or
ALDH in smooth muscle
Nitric oxide combines with the
heme group of soluble
guanylyl cyclase, activating
that enzyme and increase
synthesis of cGMP
Therefore, Inhibits
phosphorylation of myosin light
chains, in turn preventing the
interaction of myosin with actin.
increase in cGMP increases
the rate of inactivation of
myosin light chain kinase.

5. Antianginal action of nitrates involves:
Vasodilation by relaxation of
vascular smooth muscle
Venous bed Arterial bed
↓ Venous blood return to
heart
↓ Peripheral resistance
↓ Afterload↓ Preload
Reduced cardiac oxygen
requirement
Relief from angina
↓ workload

6. Direct cardiac effect:
• Redistribution of coronary flow towards
ischaemic areas via collaterals
• Relief of coronary spasm.

7. But,
After more than a century of study, the
mechanism of action of
nitroglycerin is still not fully
understood…….
If any doubt?
Refer-
katzungs Basic & Clinical Pharmacology (or)
Goodman & Gilman’s – the pharmacological basis of thearapeutics