2nd unit anti-anginal agents

Prepared by
G. Nikitha, M.Pharmacy
Assistant Professor
Department of Pharmaceutical Chemistry
Sree Dattha Institute Of Pharmacy
Hyderabad
2nd UNIT
ANTI-ANGINAL AGENTS
1
Subject: Medicinal Chemistry-II
Year: B.Pharmacy 3rd Year
Semister: 1st Semister

Contents
 Introduction.
 Symptoms
 Types of Angina Pectoris
 Classification
 Vasodilators
 Calcium Channel Blockers
 Mechanism of action .
 SAR.
 Structure , Synthesis.
 Adverse Drug Reactions , Uses.
 References
2

Introduction
3
 Angina Pectoris is a symptom of Ischemic heart disease occurs due to
imbalance between demand and supply of oxygen. It is characterized
severe pain in the middle of chest which spreads towards the left arm,
throat, jaws, and teeth and sometimes towards right arm.
 Angina is a manifestation of myocardial ischemic which may occur due
to any of the reason like heart valve disease, thickening of heart
muscles, coronary heart disease, hypertension, smoking etc.

Symptoms
4
 Sweating
 Weakness
 Discoloration of skin
 Shortness of breath
 Nausea, vomiting
 Indigestion etc.

Types of Angina Pectoris
5
 Stable/ Typical/common Angina: It is the classical form of angina
Pectoris where in the cause of pain is predictable. It occurs during
severe exercise, emotional stress, hence it is also termed exertional
angina.
 Unstable/ Uncommon Angina: It is new or sudden worsening
previous angina. Rare form of angina where in chest pain may occurs
even when the person is at rest. However the anginal attacks may be
more severe prolonged or occur with increased frequency. It required
immediate hospitalization. The cause might be the same as seen in
myocardial infraction where in a thrombus formed would associate
with the rupture plaque and block the myocardial blood flow.

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 Variant or Prinzimetal Angina: Characterized by pain at chest. It
occurs more commonly in women caused due to coronary vasospasm
and occurs during night.
 Micro vascular agents: It is a recently discovered type of angina. In
these patient experiences chest pain but there is no apparent coronary
artery blockage.

Classification
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 Agents are used to prevent the attack of angina by decreasing the
consumption of oxygen by heart known as Antianginal agents.

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1. Vasodilators:
a. Organic nitrates and nitrites/ short acting compounds:
Amylnitrile
Nitro glycerine

9
b. Long acting compounds:
Isosorbide dinitrate Pentaerythrial tetranitrate
Isosorbide mononitrate

10
c. Peripheral coronary vasodilators:
i. Potassium channel activators:
Nicorandil
Minoxidil
Diazoxide

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ii. Other Peripheral vasodilators:
Dipyridamole Papaverine

12
 2. Calcium Channel antagonist:
 a. Phenyl alkyl amine derivative:
bepridilVerapamil

13
b. Benzothiazepine derivaties:
Diltiazem

14
C. Dihydropyridine derivatives
Drugs R1 R2 R3 X
First Generation:
nefedipine -CH3 -CH3 CH3 2-NO2

15
Second Generation
Amlodipine -C2H5 CH3 2-Cl
Felodipine CH3 -C2H5 -CH3 -2,3-Cl
nicardipine CH3 -CH3 2-NO2
nimodipine CH3 -[CH2]2-O-CH3 -CH3
3-NO2

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3. β-blockers/ β-receptor antagonist:
Propranolol
nadalol
Atenolol

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4. Miscellaneous drugs:
Aspirin
Clopidogrel
Ticlopidine

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 Vasodilators are the agents used to treat various conditions like
hypertension, angina pectoris, and cardiac failure. They act by dilating
the blood vessels, increasing the blood flow to the constricted blood
vessels there by decreases the arterial and venous pressure, because of
this decrease in pressure the work done by myocardium decreases as a
result of which the oxygen demand by heart also decreases.
 Hence Vasodilators are effective in the treatment of angina as they
balance the oxygen demand by heart. Compounds included under
coronary vasodilators act by dilating the coronary vessels.

20
These are further sub-divided into Three categories, namely
a. Organic nitrates and nitrites/ short acting compounds
b. Long acting compounds
c. Peripheral coronary vasodilators

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a. Organic nitrates and nitrites
 These esters formed due to the reactions between organic alcohols with
nitric acid are known as organic nitrates. Chemically they are
considered as nitrate esters. All the compound included under the
reaction of isoamyl alcohol with nitrous acid.
 Organic nitrates and nitrites are successful in relaxing angina pain
because of their ability to release nitric oxide which is primarily
responsible for producing vasodilating activity.
 These drugs cannot be used in the pure and concentrate forms for the
treatment of angina because of their explosive nature so diluted
preparation are recommended.
The drugs which comes under short acting compounds : Amylnitrile, Nitro
glycerine

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General Mechanism of action:

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 Organic nitrates converts into nitrites in the body and release nitric
oxide which is responsible for the direct and non specific relaxation of
vascular smooth muscle.
 Organic nitrites provide reactive free radical nitric oxide through
enzymatic denitration. They released nitric oxide activates the cytosolic
guanyl cyclase enzyme that causes an increase in the production of
cyclic GMP. Cyclic GMP causes dephosphorylated interaction and
myosin light chain kinase enzyme that is essential for the activation of
myosin pigment. As MLCK is dephosphorylated interaction between
action and myosin does not occur which ultimately results in relaxation
of smooth muscles.

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SAR:
 Presence of an ester group makes the compound effective in relieving
angina pain because the ester group binding Lipophilic will easily
penetrate the lipodial barriers and thus effectively reduce the angina
attacks presence of this ester group renders the compounds volatile.
 Therapeutic activity of the compound decreases in the presence of
moisture due to the ester bond hydrolysis.
 Compounds with high partition coefficient are known to be more
potent than compounds with low values.

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Common Adverse Drug Reactions:
 Weakness
 Dizziness
 Palpitation
 Facial flushing
 Decrease in blood pressure
 Continuation use of drug may leads to drug dependence.
 Sudden deaths
Common Uses:
 Use in the treatment of angina pectoris, congestive heart failure,
myocardial infarction, left ventricular fibrillation, interventional cardiac
procedures, prophylaxis of pain in bile duct, prophylaxis of cyanide
poisoning, to provide relief from esophageal spasm.

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 Amyl Nitrite
Structure:
IUPAC: Pentyl nitrite/ 2-Methyl butyl nitrite
Properties:
 Amyl nitrite is a clear yellow liquid, Penetrating fragrant, somewhat
fruity odor, Pungent, aromatic taste, Very slightly soluble in water,
miscible with alcohol, acetone, chloroform.
Molecular formula: C5H11NO2

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Pharmacokinetics:
 Oral route of administration is low, so it is administered through nasal
route, metabolized by the liver to form inorganic nitrites, which are
much less potent vasodilators than the parent drug. One-third of the
inhaled dose is excreted in urine.
Adverse Drug Reactions:
 headache, dizziness,
 flushing of the face, lightheadedness or fainting,
 involuntary urination or defecation,
 low blood pressure,
 nausea, vomiting,
 shortness of breath, cold sweat,
 pale skin, rapid heart rate,
 restlessness, weakness, or slowed breathing

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Therapeutic Uses:
 Amyl nitrite is employed medically to treat heart diseases as well
as angina.
 Amyl nitrite is sometimes used as an antidote for cyanide poisoning.

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Dose:
 Liquid for inhalation:
0.3 ml (0.85-103%) crushable glass ampule
 Acute Relief of Angina:
0.3 ml by inhalation of crushed ampule, may repeat q3-5min
Wave crushed ampule under nose multiple times for 2-6 nasal
inhalations
 Cyanide Poisoning:
0.3 ml ampoule crushed and contents poured onto a gauze and placed in
front of patient's mouth or endotracheal tube, if patient intubated, to
inhale over 15-30 sec; repeat q Min until IV sodium nitrite available
Each ampul lasts ~3 min; separate administration by at least 30 sec to
allow patient to adequate oxygenate

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 Nitro glycerine
Structure:
IUPAC: 1,2,3-Propanetriol trinitrate
Properties:
 Pale-yellow, oily liquid, Sweet, burning taste, poor solubility in water,
Sparingly sol in petroleum ether, liquid petrolatum, glycerol, Miscible
with glacial acetic acid, nitrobenzene, pyridine, ethylene
bromide, dichloroethylene, ethyl acetate.
Molecular formula: C3H5N3O9

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Mechanism of Action:
 Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase
(mtALDH) to nitric oxide (NO), an active substance which then
activates the enzyme guanylate cyclase.
 The activation of this enzyme is followed by the synthesis of cyclic
guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein
kinase-dependent phosphorylation events in smooth muscles.
 This process eventually leads to the dephosphorylation of the myosin
light chain of smooth muscles, causing relaxation and increased blood
flow in veins, arteries and cardiac tissue.
 The above processes lead to decreased work of the heart decreased
blood pressure, relief of anginal symptoms, and increased blood flow to
the myocardium.
 One in vitro study using mouse aorta suggests that nitric oxide (an
activated metabolite of nitroglycerin) targets the natriuretic peptide
receptors.

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Pharmacokinetics:
 Oral, sublingual, transdermal route of administration.
 Nitroglycerin is metabolized to nitrite, 1,2-glyceryl dinitrate, and 1,3
glyceryl dinitrate.
 Nitrite is then metabolized to nitric oxide or S-nitrosothiol.
 The 1,2-and 1,3-dinitroglycerols are less potent in strength than
nitroglycerin, but they have longer half-lives, explaining some
prolonged effects of nitrates.
 Both dinitrates are subsequently metabolized to mononitrates that are
not active on the blood vessels, and to glycerol and carbon dioxide in
the final step of metabolism.
 Metabolism is the main route by which nitroglycerin is eliminated from
the body.

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 headache, weakness, dizziness, lightheadedness,
 nausea, and
 Flushing as your body adjusts to this medication.
 mild burning or tingling with the tablet in your mouth, and
 Flushing (warmth, redness, or tingly feeling under your skin).
Therapeutic Uses:
 Nitroglycerin is used for the treatment of angina, acute myocardial
infarction, severe hypertension, and acute coronary artery spasms.
Dose:
2.5-6.5 mg PO q6-8hr.

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b. Long acting compounds
The drugs which comes under Long acting compounds
Isosorbide dinitrate,
Pentaerythritol tetranitrate,
Isosorbide mononitrate

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 Pentaerythrial tetranitrate
Structure:
IUPAC: 2,2-Bis[(nitrooxy)methyl]propane-1,3-diol dinitrate
Properties:
 White crystalline solid, mild odor, Soluble in acetone, sparingly soluble
in alcohol, ether, Very soluble in acetone, Soluble in benzene, pyrene,
Soluble in toluene; slightly soluble in methanol.

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Pharmacokinetics
 Oral route of administration, extensively metabolized in the liver
 Metabolites: pentaerythritol trinitrate, pentaerythritol dinitrate,
pentaerythritol mononitrate, & pentaerythritol (inactive), eliminated
through urine.
 skin irritation
 head ache
 dry mouth
 blurred vision
 Elder patient requires the caution in receiving nitrates,
 Renal failures
 Liver problem

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Therapeutic Uses:
 It is used medically as a vasodilator in the treatment of heart
conditions. These drugs work by releasing the signaling gas nitric
oxide in the body.
 It is used exploser, in the preparation of bombs.
Dose:
 Angina Pectoris (Treatment and Prevention)
10-20 mg orally four times daily, may increase to 40 mg orally four
times daily.
 Erythrityl Tetranitrate (Cardilate)
10 mg orally/SL as needed to no more than 100 mg/day

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 Isosorbide dinitrate
Structure:
IUPAC: 3,7-dihydro-2,6- dioxynitrate -D-glucitol
Properties:
 Hard colorless crystals, odorless, soluble in water, freely soluble in
organic solvent such as acetone, alcohol, ether.
Molecular Formula: C6H8N2O8

40
Synthesis:
Step-I: D-glucose undergoes hydrogenation with platinum as catalyst to
yield D-sorbital

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Step-II: D-sorbital upon treating with sulphuric
acid loses one molecule of water to yield
Isosorbide

42
Step-III: Isosorbide on nitration yields Isosorbide
dinitrate

43
Mechanism of Action:
 Isosorbide dinitrate is converted to the active nitric oxide to activate
guanylate cyclase.
 This activation increases levels of cyclic guanosine 3',5'-
monophosphate (cGMP).
 cGMP activates protein kinases and causes a series of phosphorylation
reactions which leads to dephosphorylation of myosin light chains of
smooth muscle fibers.
 Finally there is a release of calcium ions which causes smooth muscle
relaxation and vasodilation.

44
Pharmacokinetics:
 Oral route of administration, metabolized in the liver, eliminated
through urine
 Headache
 dizziness
 lightheadedness
 Fast, slow, pounding, or uneven heart rate;
 worsening angina pain;
 blurred vision or dry mouth;
 Nausea, vomiting, sweating, pale skin, feeling like you might pass out;
or. Blue-colored skin, tiredness, and feeling short of breath.
 Flushing may occur as your body adjusts to this medication.

45
Therapeutic Uses:
 Isosorbide dinitrate is used to prevent chest pain (angina) in patients
with a certain heart condition (coronary artery disease).
This medication belongs to a class of drugs known as nitrates. It works
by relaxing and widening blood vessels so blood can flow more easily
to the heart.
Dose:
 5 to 20mg orally 2 to 3 times a day- Intermediate release
 40 to 60 mg/day orally

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c. Peripheral coronary vasodilators
These are further sub-divided into two categories, namely
i. Potassium channel activators:
 Nicorandil
 Minoxidil
 Diazoxide
ii. Other Peripheral vasodilators:
 Dipyridamole
 Papaverine

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 Dipyridamole
Structure:
IUPAC: 2,2',2'',2'''-{[4,8-Di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-
2,6-dinitro}tetraethanol
Properties:
 Bright yellow color, almond and methanol flavor

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Pharmacokinetics:
 Oral, i.v route of administration, metabolized in the liver
(glucuronidation), eliminated through urine
 dizziness,
 stomach upset,
 diarrhea,
 vomiting,
 Headache, and.
 Flushing (warmth, redness, or tingly feeling under your skin),
particularly at first as your body adjusts to the medication.

49
Therapeutic Uses:
 Dipyridamole is used to dilate blood vessels in people with peripheral
arterial disease and coronary artery disease.
 Dipyridamole has been shown to lower pulmonary hypertension
without significant drop of systemic blood pressure
 It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9)
in vitro and results in reduction of hsCRP in patients.
 It inhibits proliferation of smooth muscle cells in vivo and modestly
increases unassisted patency of synthetic arteriovenous hemodialysis
grafts.
 It increases the release of tissue plasminogen activator from brain
microvascular endothelial cells.

50
 It results in an increase of 13-hydroxyoctadecadienoic acid and
decrease of 12-hydroxyeicosatetraenoic acid in the subendothelial
matrix and reduced thrombogenicity of the subendothelial matrix.
 Pretreatment it reduced reperfusion injury in volunteers.
 It has been shown to increase myocardial perfusion and left ventricular
function in patients with ischemic cardiomyopathy.
 It results in a reduction of the number of thrombin and PECAM-
1 receptors on platelets in stroke patients.
Dose:
 The recommended dose is 75-100 mg four times daily as an adjunct to
the usual warfarin therapy. Please note that aspirin is not to be
administered concomitantly with coumarin anticoagulants.

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 These drug include a heterogeneous class of compound which act by
preventing the entry of ca+2 ions the cells which are required for the
contraction of muscles.
 The drugs act on the ca+2 ions cause blockage of ca+2 channels.
 The ultimate effect of these drugs would be relaxation of muscular
system or decreases in muscular activity and negative inotropic,
chronotropic effects on heart.

53
These are further sub-divided into Three categories, namely
a. Phenyl alkyl amine derivative
b. Benzothiazepine derivaties
c. Dihydropyridine derivatives

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General Mechanism of action:
 ca+2 channels blockers act by inhibiting the voltage sensitive calcium
channel and there by prevent the entry of extracellular calcium into the
myocardial and vascular smooth muscle cells.
 This leads to decrease in availability of intracellular calcium and
consequent decrease in calcium dependant coupling of action and
myosin filaments in the muscle leading to relaxation of the muscle
Therapeutic uses:
 Used in the treatment of hypertension, Angina, Cardiac arrhythmias,
Hypertrophic cardiomyopathy.

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a. Phenyl alkyl amine derivative
The drugs which comes under Phenyl alkyl amine derivative
1. Verapamil
2. Bepridil

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 Verapamil:
Structure:
IUPAC: 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxy phenyl) ethyl]
(methyl) amino}-2-(propan-2-yl)pentanenitrile
Properties:
 It is viscous pale yellow oil having a boiling point of 246OC insoluble
in water, sparingly soluble in Hexane, soluble in benzene and ether,
freely soluble in the acetone, alcohol, ethyl acetate and chloroform. It is
available as Verapamil Hcl which is a white crystalline powder soluble
in water, methanol.
molecular formula: C27H38N2O4

57
Pharmacokinetics:
 Verapamil is well absorbed on oral administration but its bioavailability
is less due to extensive first pass hepatic metabolism. The onset of
action is quick. It is highly bound to plasma proteins. The plasma half-
life is about 5-6 hours. The metabolite of Verapamil is also active. It is
primarily excreted in urine.
 Constipation, headache, dizziness, hypotension, bradycardia.
 Congestive heart failure, nausea, tiredness, flushing, shortness of breath
 Skin itching, rapid weight gain, stomach pain, sweating, liver problems.

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Therapeutic Uses:
 Used in the treatment of hypertension, angina, arrhythmia. It helps to
prevent the stroke, heart attacks and kidney problems, prevent chest
pain.
Dose:
 40-80 mg t.i.d orally.

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 Bepridil hydrochloride
Structure:
IUPAC:N-benzyl-N-[3-(2-methylpropoxy)-2- (pyrrolidin-1-yl) propyl]
aniline
Molecular Formula: C24H37ClN2O2

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Properties:
 White or half white crystalline powder with bitter taste, slightly soluble
in water, soluble in acetone, very slightly soluble in chloroform,
alcohol.
Pharmacokinetics:
 Oral route of administration, metabolized in liver by cytochrome
enzyme, undergoes renal elimination.
 fatigue or tiredness,
 nausea, upset stomach, diarrhea, constipation, dyspepsia, dry mouth
 Headache, nervousness, dizziness, trouble sleeping (insomnia), or
tremor (shaking), drowsiness.
 Flu syndrome, palpitation, Dyspnea, respiratory infection
 Abdominal pain, Tremors, insomnia, nervousness.

61
Therapeutic Uses:
 It is a ca+2 channel blockers used to prevent hypertension, angina.
Dose:
 The usual starting dose of Vascor is 200 mg once daily.

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b. Benzothiazepine derivatives
The drugs which comes under Benzothiazepine derivatives
Diltiazem

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 Diltiazem hydrochloride
Structure:
IUPAC:5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-1,5-
benzothiazepin-3-yl acetate
Properties:
 White crystalline powder, freely soluble in water, methanol, methylene
chloride, slightly soluble in ethanol, odorless, bitter taste, insoluble in
benzene.
Molecular formula: C22H27ClN2O4S

64
Pharmacokinetics:
 Oral, I.V roué of administration, it is subject to extensive first-pass
metabolism, which explains its relatively low absolute oral
bioavailability. It undergoes metabolism primarily mediated by
CYP3A4, due to its extensive metabolism, only 2% to 4% of the
unchanged drug can be detected in the urine.
 Dizziness, lightheadedness, weakness, nausea,
 Flushing, constipation, and headache may occur.
 Hypotension, nausea, GI disturbances, hepatitis, dermatitis, allergic
reactions
 Tinnitus, Thrombocytopenia, not recommended for pregnant women,
breast feeding women.

65
Therapeutic Uses:
 Diltiazem is used to prevent chest pain (angina).
 It may help to increase your ability to exercise and decrease how often
you may get angina attacks.
 Diltiazem is called a calcium channel blocker. It works by
relaxing blood vessels in the body and heart and lowers the heart rate.
Blood can flow more easily and your heart works less hard to pump
blood.
Dose:
 30-60 mg b.i.d, orally.

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c. Dihydropyridine derivatives
The drugs which comes under Dihydropyridine derivatives
First Generation
1. Nefedipine
Second Generation
1. Amlodipine
2. Felodipine
3. Nicardipine
4. Nimodipine

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 Nifedipine
Structure:
IUPAC: 3,5-dimethyl,2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine
-3,5-dicarboxylate

68
Properties:
 Yellow crystalline odorless powder, soluble in acetone, chloroform,
ethyl acetate, methanol, methylene chloride.
Pharmacokinetics:
 It is well absorbed on oral administration. The onset of action is quick
but the duration of action is short. It is highly bound to plasma proteins.
It is primarily excreted in urine.
 Dizziness, headache, drowsiness, nausea
 Tachycardia, cough, shortness of breathing, Heart failure, hypotension
 Flushing, oedema, feeling tired.

69
Therapeutic Uses:
 It is used in the treatment of hypertension. However nifedipine is not
recommended for the long term treatment of hypertension.
 It is used in the treatment of some peripheral vascular diseases like
Raynaud’s syndrome.
 It is used as an alternative tocolytic agent.
 It can also be used in angina.
Dose:
 10-20 mg t.i.d, orally.

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 Amlodipine
Structure:
IUPAC:3-ethyl-5methyl-2-(2-aminoethoxymethyl)-4-(2-chloroPhenyl)-6-
methyl-1,4-dihydropyridine-3,5-dicarboxylate
Molecular formula: C20H25ClN2O5

71
Properties:
 White powder, slightly soluble in water, soluble in methanol, ethanol,
propanol.
Pharmacokinetics:
 Oral roué of administration, it undergoes metabolism primarily
mediated by CYP3A4, it is excreted via kidneys.
 Nausea, headache, dizziness, depression,
 Flushing, oedema, palpitations, dyspepsia, dyspnoea, mood changes,
pancreatitis,
 Visual disturbances, rashes, hepatitis.

72
Therapeutic Uses:
 Used as antihypertensive agent can be used alone or in combination
with other drugs like ACE inhibitor, adrenergic blockers or diuretics to
treat hypertension. It is also used as anti anginal drug.
 Used in the treatment of diabetic kidney disease, chest pain, heart
failure, silent heart attack.
Dose:
 2.5-10 mg OD Daily.

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 Felodipine
Structure:
IUPAC:3-ethyl5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate
Molecular formula: C18H19Cl2NO4

74
Properties:
 White or yellow crystalline powder, practically insoluble in water,
freely soluble in acetone, ethanol, methanol, methylene chloride.
Pharmacokinetics:
 Oral route of administration, hepatic metabolism primarily via
cytochrome P450 3A4. Six metabolites with no appreciable
vasodilatory effects have been identified. Although higher
concentrations of the metabolites are present in the plasma due to
decreased urinary excretion, these are inactive. Animal studies have
demonstrated that felodipine crosses the blood-brain barrier and the
placenta.
 Head ache, dizziness, drowsiness, nervousness
 Weakness, nausea, difficulty in breathing, sneezing
 Constipation, diarrhea, stomach pain,
 Joint pain, redness, skin rashes, redness of skin, muscle cramps,
 Irregular heartbeat, chest pain, sweating
 Swelling of hands, legs, face

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Therapeutic Uses:
 Used to treat hypertension, angina pectoris.
 It will prevent the stroke, heart attacks, and kidney problems.
 It is known as ca+2 channel blockers by blocking calcium this
medication relaxes and widens blood vessels so blood can flow more
easily.
Dose:
 2.5–10 mg once daily.

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 Nicardipine
Structure:
IUPAC:3-{2-[benzyl(methyl) amino]ethyl} 5-methyl 2,6 dimethyl -4-(3-
nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

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Properties:
 White crystalline powder, soluble in water
Pharmacokinetics:
 Oral, I.V route of administration, it is metabolized extensively by the
liver, eliminated through kidneys.
 Headache, dizziness or lightheadedness, numbness
 upset stomach, constipation, dry mouth
 excessive tiredness, flushing
 fast heartbeat, muscle cramps
 heartburn, increased sweating
 It may cause damage to brain, heart, blood vessels, kidney and other
body parts
 Loss of vision

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Therapeutic Uses:
 Nicardipine is used to treat high blood pressure and to control angina
(chest pain).
 Nicardipine is in a class of medications called calcium channel
blockers.
 It lowers blood pressure by relaxing the blood vessels so the heart does
not have to pump as hard.
 It controls chest pain by increasing the supply of blood and oxygen to
the heart.
Dose:
 20-40 mg q8h oral route.
 0.5- 2 mg/hr I.V route.

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 Nimodipine:
Structure:
IUPAC: 3-(2-methoxyethyl) 5-propan-2-yl2,6-dimethyl-4-(3-
nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

80
Properties:
 Yellow crystalline powder, soluble in ethyl acetate, sparingly soluble in
ethanol, insoluble in water.
Pharmacokinetics:
 Oral, I.V route of administration. Hepatic metabolism via CYP 3A4.
Nimodipine is eliminated through urine, and feces.
 Flushing, headache nausea, dizziness
 Palpitation, constipation, vomiting
 Sweating, unusually fast or slow heartbeats
 Fainting, low blood pressure (hypotension).
 Thrombocytopenia, decrease platelet count
 Sweating, muscle pain, liver disease.

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Therapeutic Uses:
 Used to decrease problems due to certain type of bleeding in the brain.
 Used in the treatment of high blood pressure.
 It is not regularly used to treat the head injury, used to prevent the
seizures in women.
Dose:
 The oral dose is 60 mg (two 30 mg capsules) every 4 hours for 21
consecutive days, preferably not less than one hour before or two hours
after meals.

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Reference books
 Text book of Medicinal chemistry volume-1-3rd edition by V.Alagarasamy.
 Text book of Medicinal chemistry volume-2-3rd edition by V.Alagarasamy.
 Medicinal chemistry by Rama Rao Nadendla.
 Essentials of Medicinal chemistry 2nd edition by Andrejus Korol Kovas.
 Faye’s Principles of Medicinal Chemistry- 7th edition by Thoms L.Lemke,
Victoria F.Roche, S. Willam Zito.
 Medicinal Chemistry- 4th edition by Ashutosh Kar.
 Medicinal and Pharmaceutical Chemistry by Harkishan Singh, V.K Kapoor.
 Wilson and Gisvolid’s Textbook of Organic Medicinal and Pharmaceutical
chemistry-12th edition by John M. Beale, John. H. Block.

2nd unit anti-anginal agents

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