CALCIUM CHANNEL BLOCKER - AMLODIPINE

1. PRESENTATION ON -
Calcium Channel Blocker -AMLODIPINE
Department of Chemistry and Chemical Sciences
SUBMITTED TO - Dr. Shiwani Berry.
COURSE CODE - CCS 506.
COURSE NAME – Organic Chemistry
Specialization V.
SUBMITTED BY – Kanupriya.
M.Sc. 4th sem.
CUHP19CCS11.

2. CONTENT
• Introduction to Calcium Channel Blockers(CCB’s) and
their uses.
• Classification of CCB’s.
• Introduction to Amlodipine.
• Method of synthesis and mode of action of Amlodipine.
• Side effects of Amlodipine.

3. Calcium Channel Blocker-
AMLODIPINE.
1960 Godfrained coined the term CALCIUM ANTAGONIST

4. What are calcium channel blockers- CCB’s are a
type of medication that people take to increase the flow of blood and oxygen to heart.
Doctors may prescribe a calcium channel blocker to treat high bp or a variety of heart
conditions.
• CCB’S are common medications
that have a low risk of
complications.
• AMERICAN HEART ASSOCIATION
recommended calcium channel
blockers as a first-line
pharmacological treatment for
high blood pressure in most
people.

5. Why lowering of high blood pressure is
important-
• Lowering of high
blood pressure helps
to prevent strokes,
heart attacks and
kidney problems.
Cardioselective
CCB's
Non- Cardioselective
CCB's

6. Role of Calcium ions in Human
Body -
• Calcium is necessary for muscle contractions to occur throughout the
body. This mineral enters muscle cells through various ion
channels(L,N,T,P and R), which are tiny pores on the surface of the
cell. This process is essential for normal body functioning.
• CCB’s reduce the amount of calcium that can enter muscle cells in the
heart and blood vessel walls via L-type calcium-channels.
• This lowers the pressure in the blood vessels and on the heart.

7. Uses of calcium channel blockers- Doctors
commonly use calcium channel blockers to treat high blood pressure. These drugs also have a
range of other possible uses, such as for :-
• Chest pain, or angina
• Coronary heart disease.
• An irregular heart beat ,or arrhythmia.
• Migraine
• Scientists are currently exploring other
potential uses for calcium channel
blockers e.g, by reducing high bp, they
believe that calcium channel blockers
may be able to lower the risk of
Alzheimer’s disease.

8. CLASSIFICATION OF CCB’s -

9. 1) DIHYDROPYRIDINE
• Dihydropyridines CCB’s are derived from the
molecule dihydropyridine. All “pines” are non-
cardioselective drugs.
• These target a specific type of calcium channel(L-
TYPE) in the body. They causes blood vessels to
widen, thus lowering blood pressure.
• They are mostly used to reduce total peripheral
resistance and arterial pressure.
• Sometimes they are used to treat angina.
• They are easily identified by their suffix
“dipine”.e.g., Amlodipine, felodipine, nifedipine.

10. 2) NON – DIHYDROPYRIDINE- These widen
blood vessels in the same way as dihydropyridines. However, these act on heart that
can help to control a rapid heart rate. These are divided into two classes-
-Phenylalkylamine.
-Benzothiazepine.
Benzothiazepine
• It belongs to the molecule
benzothiazepine.
• These drugs are intermediate
class between dihydropyridine
and phenylalkylamines. These
have both cardiac depressor and
vasodilator action.
• Example- Diltiazem.
PHENYLALKYLAMINE
• This class of CCB’s mainly affect
the cells of the heart.
• They have minimum vasodilator
effects compared with
dihydropyridine. It reduces chest
pain as it relaxes blood vessels
and reduces the amount of
oxygen that the heart requires.
• Example – Verapamil etc.

14. AMLODIPINE
• Amlodipine is a dihydropyridine calcium channel blocker medication used to treat high blood
pressure and coronary artery disease. While not typically recommended in heart failure, amlodipine may be
used if other medications are not sufficient for treating high blood pressure or heart-related chest pain .It is taken
by mouth and has an effect that lasts for at least a day.
• Calcium channel blockers, including amlodipine, may provide greater protection against stroke than other
classes of blood pressure-lowering medications. It inhibits the movement of calcium ions into vascular smooth
muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth
muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood
pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries.
• Amlodipine is a long acting and slow acting drug.
• The plasma of life of Amlodipine -35 to 48 hours and peak action is seen after 6 to 9 hours.
• Amlodipine keeps the B.P. at lower side even after 24 hours and this is why it has to be given once a
day.
• It is always compared with nifedipine- the problem with nifedipine was that it was short acting and immediate
acting drug. The heart rate increases with nifedipine and B.P. reduces very fast and it causes chest pain.

15. Method For AMLODPINE
Synthesis
1. Ethyl-4-chloroacetate reacts with 3-
azidoethanol in presence of sodium hydride
to give ethyl 4-(2-azidoethoxy)-3-
oxobutanoate.
2. Ethyl 4-(2-azidoethoxy)-3-oxobutanoate then
reacts with 2-chlorobenzaldehyde and
methyl-3-aminocrotonate to give 3-ethyl-5-
methyl-2-[(-azidoethoxy)methyl]-4-(2-
chlorophenyl)-1,4-dihydro-6-methyl-3,5-
pyridinecarboxylate.
3. On reduction of the above formed
compound, amlodipine is formed.

16. Mechanism Of Action Of
Amlodipine
• AMLODIPINE(a smooth muscle relaxant) is used to treat both angina and
hypertension. Angina is related to smooth muscles of heart and
hypertension to the peripheral blood vessels.
• Amlodipine blocks the entry of calcium ions into vascular smooth
muscles and cardiac muscles at the time of depolarization.
• Amlodipine can bind with dihydropyridine and non dihydropyridine
receptor sites present on the cell membrane.
• There is a stronger effect of this drug on vascular smooth muscles than
on cardiac muscles which helps in reducing the peripheral vascular
resistance (in case of hypertension) which helps in lowering the blood
pressure.
• In cardiac muscles by dilating the arterioles the after load of the heart
reduces which reduces the oxygen demand and by dilation of the
coronary the blood supply to the heart increases. So the demand is
reducing by arteriolar dilation and the blood supply is increasing by
coronary vasodilation and that’s why demand and supply equations are
positively affected. Demand is reducing and supply is increasing, so
patient gets benefited in the case of Angina.

17. Amlodipine works by relaxing blood vessels so blood can flow more easily. Amlodipine
is also used to prevent certain types of chest pain(angina). It may help to increase
your ability to exercise and decrease the frequency of angina attacks.
Amlodipine Dilates coronary artery leading
to increase in the blood supply to the heart.
Heart
Peripheral Arteries
Amlodipine brings peripheral
vasodilation and thus reduces B.P.
In hypertension In Angina

18. RESULTS OF AMLODIPINE
ACTION

19. Side effects of Amlodipine-
• Swelling.
• Dizziness.
• Nausea.
• Lightheadedness.
• Rapid heartbeat.