hypertension

1. ANTIHYPERTENSIVE DRUGS
Kumaraswamy. B
Dept. of Pharmaceutical Chemistry
Advanced Medicinal Chemistry
Acharya & BM Reddy College of Pharmacy
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2. CONTENTS
1. INTRODUCTION
2. TYPES OF HYPERTENSION
3. CLASSIFICATION
4. MECHANISM OF ACTION
5. STRUCTURE ACTIVITY RELATIONSHIP (SAR)
6. SYNTHESIS
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3. INTRODUCTION
Hypertension (high blood pressure) is when the pressure in
your blood vessels is too high (140/90 mmHg or higher).
CLASSIFICATION SYSTOLIC(mmHg)<1
30
DIASTOLIC(mmHg)<
85
Normal <120 <80
Prehypertension 120-139 80-89
Stage 1 Hypertension 140-159 90-98
Stage 2 Hypertension 160-179 100-109
Stage 3 Hypertension 180-209 110-119
Stage 4 Hypertension >210 >120
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4. SYMPTOMS OF HYPERTENSION
• severe headaches
• chest pain
• dizziness
• difficulty breathing
• nausea
• vomiting
• blurred vision or other vision changes
• anxiety
• confusion
• abnormal heart rhythm
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5. IDEAL CHARACTERISTICS OF ANTIHYPERTENSIVE
AGENTS
 It should have specific site of action.
 It should not alter the heart rate.
 It should not have interaction with other commonly used drugs.
 It should be stable in light and heat.
 It should not cause cardial, renal or cerebral damage.
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6. CLASSIFICATION OF ANTIHYPERTESIVE DRUGS
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7. COMPARISION OF ACE INHIBITORS AND ARBs
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8. MECHANISM OF ACTION
CLASS OF
DRUG
MECHANISM OF ACTION
Calcium channel
blockers
Blocks the calcium channels, thus prevents
vasoconstriction
Beta blockers Blocks the sympathetic activity of beta receptors
Diuretics By reducing the sodium reabsorption in the kidney leads
to significant decrease in the vascular space less blood
returns to heart cardiac output BP
Vasodilators Vasodilation will be facilitated, thus reduces blood
pressure
Alpha blockers Blocks the sympathetic activity of alpha receptors
Central alpha 2
agonist
Stimulate alpha 2 receptors decrease catecholamine
production Decrease in cardiac out put BP
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9. LOSARTAN
CHLOROTHIAZIDE
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10. METHYLDOPA
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11. SAR OF ACE INHIBITORS
1. Substitution on N-ring
 The N-ring must contain a carboxylic acid to mimic like the C-terminal of
ACE substrates.
 Large hydrophobic heterocyclic rings in the N-ring increase the potency
and alter the pharmacokinetics parameters.
2. Substitution on X
 If X is substituted by methyl group CH3 to mimic like the side chain of
alanine with decarboxylate series.
 If X is substituted by n-butyl amine it becomes orally active drugs.
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12. Substitution on Zn2+
Compound A, B and C serves as a Zn2+ binding groups.
 Among group A, B, C, group A sulphahydryl group shows superior binding
with Zn.
 Sulphahydryl containing drugs produce skin rash and taste disturbances in
majority of cases.
 Sulphahydryl containing compounds can form disulphides, which may
shorten duration of action.
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13.  Binding to Zn+2 through either carboxylate or phosphinate group mimics the
peptide hydrolysis in transition state.
 Esterification of carboxylate / phosphinate produce an orally bioavailabel
drug.
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14. SYNTHESIS OF METHYLDOPA
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