Hypertension is the most common cardiovascular disease determined by increase blood pressure (pressure exerted by blood against the wall of a blood vessel )in arteries. The onset of hypertension is defined as having a blood pressure of 140/90 mm Hg or greater . Hypertension is the major risk factor for coronary artery disease, heart failure, stroke and renal failure.

1. Antihypertensive drug

2. Anti-hypertensive agents
What are antihypertensive agents? Classify with suitable examples with structure.
Discuss in detail the calcium channel blockers.
10M
Classify antihypertensive agents. Discuss in detail the class of calcium channel
blockers.
10M
What are antihypertensive agents? Discuss with one example from each class, SARand
MOAofantihypertensiveagents.
10M
What are antihypertensive agents ? Classify them giving the structure and IUPAC of
at least one drug belonging to each class. Discuss in detail the calcium channel
blockers.
10M
Discuss in detail the irreversible AchE inhibitors. 4M
Write a note on rennin-angiotensin system. Discuss any oneACE inhibitor. 4M
Write a note on rennin-angiotensin system. Discuss any oneACE inhibitor. 4M
Explain chemistry of ACE inhibitors 3M
Write a short note on beta blockers. 3M
Write a structure, MOA and uses of Reserpine. 3M

3. Definition-Hypertension is the most common cardiovascular
disease determined by increase blood pressure (pressure exerted
by blood against the wall of a blood vessel )in arteries.
The onset of hypertension is defined as having a blood pressure of
140/90 mm Hg or greater .
Hypertension is the major risk factor for coronary artery disease,
heart failure, stroke and renal failure.
Normal blood pressure-
120/80 mmHg systolic/diastolic
Symptoms that may occur
include:
•Confusion
•Ear noise or buzzing
•Fatigue
•Headache
•Irregular heartbeat
•Nosebleed
•Vision changes
BP= CO X SVR
BP = Blood pressure
CO =Cardiac output
SVR=Systemic vascular resistance

4.  It is defined disorder to which both environmental and genetic factors contribute.
 Hypertension - An inc. in BP such that systolic is > 140 mm Hg & diastolic > 90 mm Hg on
2 or more occasions after initial screening
 Hypertension is classified into two group
 1) Essential or primary hypertension
 2) Secondary hypertension
 Primary hypertension is the most common from of hypertension but the etiology of this
form is not yet clear
 Secondary hypertension occurs due to definable causes like renal diseases, diseases of
adrenal gland, endocrine disorder, pregnancy etc.
 Different factors involved in etiology of hypertension are
 1) Neural 2) Humoral 3) Electrolyte 4) Vessel wall 5) Genetic
Category Systolic Blood
Pressure(mmHg)
Diastolic Blood
Pressure(mmHg)
Pre-hypertension 120-139 80
Hypertension – Stage 1 140-159 90-99
Hypertension – Stage 2 160-179 100-109
Hypertension – Stage 3 >180 >110

5. Classification
1- drugs affecting sympathetic tone.
 I – drugs that alter central sympathetic activity
 II- drugs that act as adrenergic neuron blockers.
 III- Sympathetic Ganglionic blocking drugs.
 IV- α adrenoceptor blocking agents.
 V- β adrenoceptor blocking agents.
2- vasodilators-
 I- direct vasodilator e.g. hydralazine, minoxidil
 II- Indirect Vasodilator
3- Agents acting on renin-angiotensin system
 A- renin Inhibitor
 B- Angiotensin antagonists e.g. saralasin
 C- Angiotensin converting enzyme inhibitor e.g captopril,enalapril
4- Diuretic
 I- Thiazides e.g Hydrochlorothiazide
 II – Loop diuretics e.g furosemide
 III – Potassium sapring diuretic e.g. sprinolacton
5- Calcium channel blockers

6.  I – drugs that alter central sympathetic activity e.g. methyldopa, clonidine.
 II- drugs that act as adrenergic neuron blockers. e.g. Guanethedine, reserpine

7. Reserpine
 Reserpine an alkaloid obtained from roots of Rauwolfia serpentina inhibits uptake of NE from synaptic
cleft into neuron
 Reserpine is natural alkaloid, the changes structure will cause changes in activity as
 1- 11-OCH3 group is not essential. Deserpidine is equally active
 2-Changes in substitution at 16,17,18 affects activity
 17 α OH group- inactive compound
 17 α CH3- decreased activity
 16- COOH - inactive
 18- ester group- essential for activity
 3- Unsaturation in C, D and E ring eliminated activity
 4- substitution as 10-CH3, 12OCH3, 12SCH3 lead to compounds with antipsychotic activity

8.  III- Sympathetic Ganglionic
blocking drugs.
 α adrenoceptor blocking
agents

9.  V- β adrenoceptor blocking agents Example :

11.  2- vasodilators-
• I- direct vasodilator e.g. hydralazine, minoxidil
 II- Indirect Vasodilator- e.g. Sodium nitroprusside.

12.  3- Agents acting on renin-angiotensin system
 A- renin Inhibitor
 B- Angiotensin antagonists e.g. saralasin
 C- Angiotensin converting enzyme inhibitor e.g captopril, enalapril

13. Diuretic-

15.  5- Calcium channel blocker

16. Prof. A. S. Dighe
calcium channel blockers

17. Introduction
 Calcium channel blockers also are known as slow channel blockers,
calcium entry blockers and calcium antagonist.
 Calcium channel mainly regulate transmitter release or muscle
contraction.
 they are first line antihypertensive drugs.
 the onset of antihypertensive action is quick.
 may also slow the heart rate, relieve chest pressure and control an
irregular heartbeat.
 The calcium antagonists selectively block the transmembrane Ca2+
influx into the excited heart muscle without affecting Na+
 They are structurally related to sodium channels and include L
(long lasting), T ( transient), N ( neuronal), p ( Purkingje cells, Q and
R types.
 The most effective calcium antagonist is verapamine.
 They clinically used in treatment of hypertension.

18.  Currently , 10 calcium channel blockers are available for
therapeutic uses.
 monotherapy with CCBs is effective in about 50% of the
hypertensive's, can also be used for treating angina.
 These compounds have diverse chemical structure and can
be grouped into one of four chemicals classifications, each of
which produces a different pharmacological profile.
 A- 1,4 dihyropyrimidines- ( 1,4 DHP) eg. nifidipine.
 B- Phenylalkyalmines – eg. Verapamil
 C- Benzothiazepines- eg. Deltiazem
 D- Diaminopropanol ethers- eg. Bepridil.

20. SAR of 1,4,DHP
1- A substituted phenyl ring at the C4 position show optimum activity
2- hetroaromatic rings such as pyridine, produce similar therapeutic effects but are not
used animal toxicity.
3- C4 substitution with a small nonplaner alkyl or cycloalkyl group decrease activity.
4-phenyl ring substitution (X) is important for size and position rather than for electronic
nature
5- compound with ortho or meta substitution posses optimum activity or para
substitution show a significant decrease in activity.
6- 1,4 DHP ring is essential for activity
7- substitution of N1 position or reduced pyridine ring system decrease activity.
8- Ester group at the C3 and C5 position optimize activity. Other replacement in electron
withdrawing groups show decrease activity.
9- All 1,4 DHP have C2 and C6 methyl group essential for activity.

21. Pharmacokinetic parameter-
 All calcium channel blockers have excellent oral absorption.
 All compound are highly plasma protein bound and eliminated as
inactive metabolites in the urine.
 well absorbed through GIT.
 first pass metabolism.
 highly bound to plasma proteins.
 metabolized in liver.
 Therapeutical Application-
 Calcium cannel blocker have been approved for the treatment of
Hypertension, angina pectoris and specific type of arrhythmias.
 Verapamil is the most versatile agents in that , it is indicated for all
three types of angina
 Nifidipine is used in the treatment of essential hypertension.
 Adverse effects-
 Hypotension, nasal Congestion, Chest pain, headache, rash, nausea,
abdominal pain, diarrhea, vomiting, weakness etc.

22. Prof. A. S. Dighe
ACE inhibitors

23.  Introduction-
 ACE Inhibitors are medications that belong in the class of medications known
as antihypertensive medications.
 ACE Inhibitors work on the Renin - Angiotensin - Aldosterone System
 Angiotension-converting Enzyme (ACE) is the enzyme responsible for
conversion of Angiotensin I to Angiotensin II in the pathway leading to
elevation of Blood pressure.
 The drugs that act as inhibitor of ACE are responsible for reducing
hypertension.
 Currently there are 11 ACE inhibitors approved for therapeutic uses in the US
 ACE inhibitors, widely used to treat hypertension and congestive heart failure.
 These compounds can be sub classified into three groups based on their
chemical composition.
 A- Sulfahydryl containing Inhibitors. ( Captopril )
 B- Dicarboxylate containing Inhibitors. (Enalapril )
 C- Phosphonate containing Inhibitors. (Fosinopril)
 All of these compounds effectively block the conversion of angiotensin I to
angiotensin II and have similar therapeutic and pharmacological effects.
 The compound different in potency and pharmacokinetic profile.

24. Classification
 classified into three groups based on their chemical
composition.
 A- Sulfahydryl containing Inhibitors. ( Captopril )
 B- Dicarboxylate containing Inhibitors. (Enalapril )
 C- Phosphonate containing Inhibitors. (Fosinopril )

25. SAR
1- the N ring must contain a carboxylic acid
2- large hydrophobic heterocyclic rings ( i.e. N ring ) increase potency and alter
pharmacokinetic parameter.
3- the zinc binding group can be either sulfahydryl (A) , a carboxylic acid (B) or a
Phosphoric acid (C)
4- the sulfahydryl group show superior binding to zinc
5- sulfahydryl containing compounds produce high incidence of skin rash and taste
disturbance.
6- sulfahydryl containing compounds can form dimer and disulfides, which may
short duration of action.
7- esterification of the carboxylate or phospinate produce an orally bioavilable
prodrug.
8- X is usually methyl to optimum activity
9- optimum activity occurs when stereochemistry of inhibitor

26. Mechanism of Action for ACE Inhibitors
 ACE Inhibitors work in the lungs to inhibit Angiotensin
Converting Enzyme from turning Angiotensin I into
Angiotensin II.
 These medications inhibits kinase II, another name for
Angiotensin Converting Enzyme.
 Blood Pressure is decreased due to a decrease in blood
volume, peripheral resistance, and cardiac load.
 ACE Inhibitors, inhibit vasoconstriction and release of
aldosterone which inhibits the retention of sodium and
water.

27. Physiochemical Properties
 Captopril and Fosinopril are acidic drug.
 All other ACE inhibitors are amphoteric.
 The carboxylic acid attached to the N- ring is a common
structural feature in all ACE inhibitors.
 It has pka in range 2.5 to 3.5
 Therapeutically application-
 The ACE inhibitors have been approved for the treatment of
Hypertension, heart failure.
 Reduction of risk heart attack
 Diabetic nephrology

28.  ADR-
 Hypotension, hyperkalemia, cough, rash, taste disturbances,
headache, fatigue, nausea, vomiting, diarrhea, acute renal
failure, proteinuria.

29. Prof Amol S. Dighe
Beta Blocker

30. Q.
 Explain chemistry of Beta blocker.
 short note on Beta blockers

31.  beta blockers are also know as B adrenergic blocking agents
 Usually, beta blockers are categorized in a few different ways.
 Some are "cardio selective" (meaning they are more likely to
affect the heart and blood vessels rather than other parts of
the body),
 some have "intrinsic sympathomimetic activity" ( slightly
stimulate beta receptors while also blocking them), and
 some are alpha blockers as well as beta blockers.
 Β1,β2 and β3 receptors.
 ] β1-adrenergic receptors are located mainly in the heart and in
the kidneys.
 β2-adrenergic receptors are located mainly in the lungs,
gastrointestinal tract, liver, uterus, vascular smooth muscle, and
skeletal muscle.
 β3-adrenergic receptors are located in fat cells

32.  The B adrenergic blocking agents:
 The B adrenergic drugs reduce cardiac activity by decreasing
B- adrenergic receptor stimulation.
 These drugs usually reduce myocardial oxygen demand and
improve exercise tolerance in patients with angina.
 These drugs reduce blood pressure by their action on heart
and reduction in cardiac output.
 B blockers are used for hypertension, cardiac arrhythmia,
angina and myocardial infraction.
 Since B1 antagonists do not block B2 receptors, they can be
safely used in case of asthma patients.
 Some important B adrenergic blocking drugs are-

33.  Propranolol- it is water soluble compound. The chemical
structure is
It is used as antiarrthmic drug and is useful for angina
pectoris, hypertension etc.

34. SAR

35.  β-blocker it's essential for the compound to contain
an aromatic ring
 The X part of the side chain can either be directly linked to the
aromatic ring or linked through a -OCH2- group.
 When X is -CH2CH2-, -CH=CH-, -SCH2- or -NCH2- there is little or
no activity.
 The R group can only be a secondary substitution and
branched is the optimal choice.
 Alkyl (CH3) substituent's on the α, β or γ carbon (if X = OCH2)
lower beta blockade, especially at the α carbon.
 Large para-substituents usually decrease activity but large
ortho-groups retain some activity.
 For the highest cardio selectivity, the substituent should be as
following: para > meta > ortho.
 Polysubstitution on carbon 2 and 6 makes the compound
inactive but when the substitution is on carbon 3 and 5 there's
some activity.

36.  Mechanism of Action :
 Inhibition of cardiac B1 and B2 adrenoceptors reduces the contractility of
the myocardium
 Decreasing heart rate
 Decreasing Blood pressure.
 Blocking sympathetic outflow from the CNS and suppressing renin release
 Therapeutic Application:
 Beta blockers, also written β-blockers, are a class of medications that are
predominately used to manage abnormal heart rhythms, and to protect the
heart from a second heart attack (myocardial infarction) after a first heart
attack (secondary prevention).
 They are also widely used to treat high blood pressure (hypertension),
although they are no longer the first choice for initial treatment of most
patients
 Effective treatment for hypertension, especially when used in conjugation
with a diuretic.
 Adverse effects:
 Common adverse effects for the BBs include decreased exercise tolerance,
cold hands, depression, sleep disturbance.