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Aadarsh Richhariya

ANTI-ANGINAL DRUGS

ANGINA PECTORIS

Angina pectoris, commonly referred to as angina, is a medical condition characterized by chest

pain or discomfort. It occurs when there is a temporary restriction in the blood supply to the
heart muscle, resulting in an inadequate oxygen supply to the heart. Angina is often described
as a squeezing, tightness, pressure, or pain in the chest, although it can sometimes radiate to
the arms, neck, jaw, shoulders, or back. Understanding the classification of angina is essential
for proper diagnosis and treatment. Angina is classified into several types:

1. Stable Angina (Angina Pectoris):

 Definition: Stable angina is the most common form of angina. It occurs predictably during
physical activity or emotional stress when the heart requires more oxygen but is unable to
receive an adequate blood supply due to narrowed coronary arteries.

 Characteristics: Chest pain or discomfort that is typically triggered by exertion and relieved
with rest or nitroglycerin. The pain follows a predictable pattern and has a consistent duration.

2. Unstable Angina:

 Definition: Unstable angina is a more severe and unpredictable form of angina. It often occurs
at rest, with increasing frequency, or with less exertion. Unstable angina is considered a
medical emergency as it can progress to a heart attack (myocardial infarction).

 Characteristics: Chest pain or discomfort that is more intense, lasts longer, and may not
respond to rest or nitroglycerin. It may be accompanied by other symptoms like nausea,
shortness of breath, and cold sweats.

3. Variant Angina (Prinzmetal's Angina):

 Definition: Variant angina is a rare form of angina caused by coronary artery spasm, which
leads to a temporary narrowing of the arteries and reduced blood flow to the heart.

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 Characteristics: Chest pain or discomfort that often occurs at rest, during sleep, or with
minimal exertion. It is caused by coronary artery spasms and tends to be more severe but
generally responds well to medications that relax the blood vessels.

CLASSIFICATION OF ANTI-ANGINAL DRUGS

1. Nitrates

Nitro-glycerine (Glyceryl trinitrate), isosorbide dinitrate, isosorbide mononitrate, Erythritol

tetranitrate

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2. Beta-Blockers

Metoprolol, Propranolol, Atenolol etc.

3. Calcium channel blockers:

Phenyl alkylamine – Verapamil

Benzothiazepines – Diltiazem

Dihydropyridines – Nifedipine, Nimodipine, Amlodipine, Nicardipine, Felodipine

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4. Potassium Channel Opener: Nicorandil

5. Miscellaneous: Aspirin, Ivabradine, Dypyridamole, Ranolazine, Bepridil etc.

NITRATES (VASODILATOR)

Mode of action: These types of drugs are rapidly denitrated enzymatically in the smooth cells
to release the reactive free radical nitric oxide (NO), which activates cytostolic guanyl cyclase
and increases the cyclic guanosine mono phosphate (cGMP) that causes dephosphorylation of
myosin light chain kinase (MLCK) through cGMP dependent protein kinase. The reduction in
phosphorylated MLCK interferes with myosin and fails to cause contraction. Relaxation also
occurs due to reduced Ca2+ entry.

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Synthesis of Nitroglycerin

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Synthesis of Isosorbide dinitrate

CALCIUM CHANNEL BLOCKERS

Calcium channel blockers (CCBs), also known as calcium antagonists or calcium ion channel
blockers, are a class of medications commonly used in cardiology and cardiovascular
medicine. They are used to treat a variety of cardiovascular conditions, including hypertension
(high blood pressure), angina pectoris (chest pain), and certain arrhythmias (irregular heart
rhythms). CCBs work by interfering with the movement of calcium ions across cell
membranes, particularly in cardiac and smooth muscle cells, leading to various therapeutic
effects.

Chemistry: Chemically, calcium channel blockers are a diverse group of compounds, and they
can be categorized into two main classes:

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1. Dihydropyridines (DHPs): These CCBs typically have a dihydropyridine ring as a core

structure. Examples include nifedipine, amlodipine, and felodipine.

2. Non-Dihydropyridines (Non-DHPs): Non-DHP CCBs have different chemical structures

and include verapamil and diltiazem.

Mode of action

The mode of action of calcium channel blockers revolves around their interference with
calcium channel receptors on cell membranes. These medications effectively block the release
of calcium ions, thereby disrupting the formation of calcium-calmodulin complexes. This
disruption leads to a notable reduction in the activation of myosin light chain phosphorylation,
a crucial step in muscle contraction regulation, particularly in cardiac and smooth muscle cells.
By inhibiting this process, calcium channel blockers significantly diminish muscle contraction,
which yields various therapeutic benefits, including the lowering of blood pressure and relief
from conditions like angina.

SAR of Ca+ channel blockers

Basic Structures of Dihydropyridine

1. Substitution on C1

• 1, 4-Dihydro pyridine ring is essential for activity. Substitution at N or oxidation or

reduction of the ring reduces or abolishes the activity.

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2. Substitution on C2 and C6

Generally small alkyl group like -CH3 attached on this position for the optimum activity, but
there is one exception in case of Amlodipine where large alkyl group attached on C6 position.

3. Substitution on C3 and C5

Both carbon atoms attached with ester group for the maximum activity. R2 and R3 substituted
with large alkyl group which result in the lipophilic characteristics of the drug leads to increase
distribution in the body. If R2 and R3 substituted with electron withdrawing group EWG such
as cl-, Br-, No2—groups result in agnostic activity.

Eg. Felodipine

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4. Substitution on C4

A phenyl substitution at the 4th position is optimum for the activity. Substitution at para or
unsubstituted phenyl ring reduces the activity. Substitution at Ortho and Meta position of
phenyl ring with EWG groups results in optimum activity

Eg. Amlodipine, Nifedipine

 When the ester at C3 and C5 are nonidentical, the C4 become chiral and stereo selectivity
is observed. S-enantiomers found to be more effective than R-enantiomers.
Eg. S-enantiomer of amlodipine (S-Amlodipine) is more potent than Amlodipine