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Prof. Ravisankar
Vignan Pharmacy college
Valdlamudi
Guntur Dist.
Andhra Pradesh
India.
banuman35@gmail.com
00919059994000
HYPERTENSION
It is defined as a physiologic condition where there is
an increase in the arterial blood pressure above
normal.
•Normal B.P is 120/80 mm Hg.
•An individual is hypertensive when
B.P is >140/90 mm Hg.
Hypotension may be defined as a physiologic state where there is a
HYPERTENSION IS DEVIDED IN TO 2 TYPES:
1.PRIMARY HYPERTENSION OR ESSENTIAL HYPERTENSION
1.SECONDARY HYPERTENSION OR MALIGNANT HYPERTENSION.
In PRIMARY OR ESSENTIAL HYPERTENSION In majority of casses where etiology
Is unknown cause and is known as primary hypertension.
The following factors may contribute to elevate of B.P
•Dietary intake of more sodium and less potassium.
In some cases primary hypertension may be herediatary.
Advancement of age.
Decreased vascular synthesis of Nitric oxide (No)( is useful in vasodialatation)
In SECONDARY HYPERTENSION where etiology can be identified.
Secondary hypertension is due to
Renal disease (kidney disorders ( Chronic glomerular nephritis.)
Adrenal disease (endocrine disorders)
Pheochromocytoma (tumour on adrenal medulla) which secretes excessive
catechol amines like adrenaline and nor adrenaline)
Hyper aldosteronism.
Muscular disorders:
Contraction (narrowing)of aorta.
Renal artery stenosis(narrowing of artery )
Toxemia of pregnancy (presence of toxins in the blood stream)
Encephalitis(inflammation of the briain)
Increased intra cranial pressure.
Thyrotoxicosis(toxic condition caused by over activity of thyroid gland)
oral contraceptives.
CAUSES OF HYPERTENSION
Classification
(category of
Hypertension)
Systolic Blood
Pressure
(mmHg)
Diastolic
Blood
Pressure
(mmHg)
Normal (B.P) 120 and 80
Prehypertension 121-139 or 81-89
Stage 1 (mild)
hypertension
140-159 or 90-99
Stage 2
hypertension
(moderate)
160-179 or 100-109
6
Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206–1252.
Stage III (severe) 180-209 110-119.
Stage iV (very >210 >120.
severe)
On etiological basis hypertension is divided into two
types
1.Primary hypertension
A definite cause is not known in primary
hypertension.
Following factors may contribute to elevation of B.P.
•Dietary intake of more sodium and less potassium.
•Decrease in vascular synthesis of nitric oxide
responsible for vasodilation.
•In some cases it may be heriditary.
2.Secondary Hypertension
In some cases Hypertension may be secondary to
other diseases like
a.Endocrine disorders
•Pheochromocytoma
•Hyperaldosteronism
b.Chronic glomerular nephritis
c.Muscular disorders
•Contraction of aorta
•Renal artery stenosis
Stenotic renal arteryStenotic renal artery
Classification of antihypertensive agents
10
Hypertension = Disease of the blood vessels
Vascular biology altered
Treat the vasculature
Therapeutic options
Beta
Blockers
ACE ARB Diuretics CCB Others
Adapted from Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director
The Renin-Angiotensin Cascade and the 3 Available Approaches to
Pharmacologic Inhibition of Production or Action of Angiotensin II. Direct
renin inhibitors (DRI), angiotensin-converting enzyme inhibitors (ACEI),
and angiotensin (AT) type 1 receptor blockers (ARB).
Drugs interacting with Renin-Angiotensin system
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Depending on chemical classification
ACE inhibitors
Sulphydryl
E.g:Captopril
Dicarboxylate
E.g:Enalapril
,Lisinopril
Phosphate
E.g:Fosinopril
CAPTOPRIL
ENALAPRIL
FOSINOPRIL
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Structure activity relationship[SAR]
R Groups that bind
to Zn+2
ion
CH C
R
1
(N
O
Ring)
Essential for
stabilisation
Methyl group
resembles side
chain of
alanine
Enhances the
potency of the
compound
Sulfhydryl
group leads to
shorter
duration of
action
n-butylamine in
dicarboxylate
containing
componds orally
active.
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Mechanism of action
They inhibit ACE which is involved in the conversion of AngI
to Ang II.
•Which is a potent vasoconstrictor.
Adverse effects
•Dry cough
•Dysgysia
•Skin rashes
•Foetal toxicity
Uses
First choice in treatment of Hypertension.
In left ventricular failure
In diabetic nephropathy
In myocardial infarction
•Benazepril (Lotensin®)
•Captopril (Capoten®)
•Fosinopril (Monopril®)
•Lisinopril
(Prinivil®,Zestril®)
•Enalapril (Vasotec®)
•Quinapril (Accupril®)
•Ramipril (Altace®)
•Trandolapril (Mavik®)
ACE inhibitors
Angiotencin receptor Antagonists
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
CH2
N
NH
X
Acidic group
STRUCTURE ACTIVITY RELATIONSHIP[SAR]
Essential for
activity to
mimic Asp1
carboxylate of
Ang-II
Substituted
with
ketones,cooH
forms
Ionic,dipole-
dipole helps
drug to
interact with
AT1
Require to mimic
the His side
chain of
Angiotensin-II
Mechanism of action
They act by blocking the Angiotensin I which regulates the
effects of angiotensin on B.P,heart and sodium and water
balance.
Adverse effects
Hyperkalaemia
Angioedema
Foetal toxicity
Gidisturbances
Uses
In treatment of hypertension as an alternative to
ACE Inhibitors.
 Valsartan (Diovan®)
 Telmisartin (Micardis®)
 Candesartan (Atacand®)
 Losartin (Cozaar®)
Irbesartin (Avapro®)
Angiotensin receptor blockers
Diuretics
•
28
Diuretics ("water pills") increase the
kidneys' excretion of salt (sodium) and
water, decreasing the volume of fluid in
the bloodstream and the pressure in the
arteries. Diuretics are the oldest and
most studied antihypertensive agents.
Thiazide
chlorthalidone, hydrochlorothiazide (HCTZ),
indapamide, metolazone
Loop
bumetanide, furosemide, torsemide
Potassium-sparing
amiloride, triamterene
Aldosterone antagonists
eplerenone, spironolactone
CLASSIFICATION
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Thiazide Diuretics
Dose in morning to avoid nocturnal diuresis
More effective antihypertensives than loop diuretics .
Chlorthalidone 1.5 to 2 times as potent as HCTZ
Adverse effects
• hypokalemia
• hypomagnesemia
• hypercalcemia
• sexual dysfunction
lithium toxicity with
Concurrent adminstration.
3131
Loop Diuretics
Dose in AM or afternoon to avoid nocturnal diuresis
Higher doses may be needed for patients with
severely decreased glomerular filtration rate or heart
failure
Furosemide
Adverse effects:
hypokalemia,
hypomagnesemia,
 hypocalcemia
32
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Mechanism of Action
inhibit Na+ and Cl- transporter in distal convoluted
tubules
increased Na+ and Cl- excretion
weak inhibitors of carbonic anhydrase, increased
HCO3- excretion
increased K+/Mg2+
excretion
decrease Ca2+ excretion
Potassium-sparing Diuretics
 Dose in AM or afternoon to avoid nocturnal diuresis
 Generally reserved for diuretic-induced hypokalemia
patients
 Weak diuretics, generally used in combination with
thiazide diuretics to minimize hypokalemia
Adverse effects:
may cause hyperkalemia especially in combination with an
ACE inhibitor, angiotensin-receptor blocker or potassium
supplements
avoid in patients with diabetes
35
Aldosterone antagonists
Dose in AM or afternoon to avoid nocturnal diuresis
Adverse effects:
may cause hyperkalemia especially in combination with ACE
inhibitor, angiotensin-receptor blocker or potassium
supplements
Gynecomastia: up to 10% of patients taking
spironolactone
36
Calcium channel blockers
Depending upon their chemical structure
Benzothiazepines
Eg:Diltiazem
Diphenylalkylamines
Eg:Verapamil
1,4-dihydropyridines
Eg:Nifedipine
Diaminopropanol ether
Eg:Bepridil
Verapamil Diltiazem
NifedipineNifedipine
N
H
CH3
R
COOR''
R'
OOC
N1 substitution
reduses the activity
Presence of non
polar alkyl or
cyclo alkyl
reduces the
activity
Ester group for
optimum
activity,-NO2
may decreases
the activity
Methyl group is
present except in
amlodipine
SAR of 1,4-dihydropyridines
Potency is high
when compared to
others
Electron with
drawing groups
decreases the
activity
DRUGS Mode of
action
Adverse
Drug
reactions
Uses
Diltiazem Acts by
inhibiting
Voltage
sensitive
Calcium
channels in
myocardium
and vascular
smooth muscles.
oConstipation
oDizziness
oOedema
oIn
arrythmias
oIn Angina
Verapamil oFlushing
oOedema
•In Angina
In Arrythmias
Nifedipine oTachycardia In Angina
•Idradipine (DynaCirc®)
•Nicardipine (Cardene®)
•Nisoldipine (Sular®)
•Felodipine (Plendil®)
•Amlodipine (Norvasc®)
Calcium channel blockers
Centrally acting sympatholytics
Mechanism of action
Methyldopa is an α2 adrenergic receptor agonist acts centrally by
decreasing the sympathetic outflow which inturn lowers B.P.
Methyldopa
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Adverse effects
Sedation and drowsyness
Constipation
Gynacomastia
Sexual impotense
Uses
Treat of Hypertension in combination
With diuretics.
clonidine
Mode of action:
Its acts by stimulating α2-adrenergic receptros and
thereby reducing sympathetic outflow and
noradrenaline release
In moderate to severe
hypertension
For withdrawl therapy
of alcohol opioids
To diagnose
pheochromocytoma
Sedation and drowsiness
Dryness of mouth and
nase
Constipation
Bradycardia
Adverse drug reaction uses
PrazosinPrazosin phentolamine
Adrenergic receptor antagonist
Drugs Mode of
action
Adverse
drug
reaction
Uses
prazosin
It acts by
selective
blocking of
α-1 receptors
in the
peripheral
blood vessels
leading to
vasodilation
First dose
effect:
Postural
hypotension
and syncope
Drowsines
s
Headache
Nasal
congestion
In the
treatment of
moderate to
serve
hypertension
in
combinaton
with a β-
blocker and a
diuretic
Adrenergic receptor antagonists
α-blockers
Drugs Mode of
action
Adverse
drug
reaction
Uses
Phentolamine
It blocks
both α1 and
α2-
receptors
leading to
vasodilation
and increase
in
noradrenali
ne release
Hypotensio
n
Tachycardia
Increase in
gastric acid
secretion
Pheochrom
ocytoma
PROPANOLOL ATENOLOL
LABETOLOL
β-adrenergic Blockers
PROPRANOLOL
Drugs Mode of
action
Adverse
drug
effects
Uses
Propanolol Inhibits
sympathetic
activity by
blocking β1
and β2
receptors
•Fatigue
•Bradycardi
a
•Hypoglyce
mia
•In angina
•In
myocardial
infarction
•In
arrythmias
β-adrenergic Blockers
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Drug Mode of
action
Adverse drug
reactions
Uses
Atenolol Inhibit
Sympathetic
activity by
selective
blockage of
β1 receptors.
•Fatigue
•Bradycardia
In angina
In
arrythmia
s
Drug Mode of
action
Adverse
effects
Uses
•Carvedilol
•Labetalol
They block
β and α1
receptor
there by
inhibit
sympathetic
activity.
•Dry mouth
•Gidisturbances
•Sexual
dysfunction
•Cavedilol-
CHF
•Labetalol-
Emergencies
MINOXIDIL HYDRALAZINE
Direct vasodilators
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Drug Mode of
action
Adverse
effects
Uses
Minoxidil It opens the
potassium
channels
and causes
hyperpolari
zation.
•Tachycardia
•Fluid
retension
•Hypertricho
sis
•In
treatment
of
Baldness
Direct Vasodilators
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
Drug Mode of
action
Adverse
effects
Uses
Hydralazine Direct
relaxation of
vascular
smooth
muscles by
stimulating
cGMP
•Flushing
•Tachycardia
•Fluid
retension
Emergencies
Say No to Smoking, Excessive Drinking (smoking
16% CHF)
Shake That Salt Habit
Control Your Pressure
Good Reasons to Exercise
blood pressure checked every time they visit their
doctor.
Being obese or overweight.
yoga asanas.
Have the dash diet.
Tips to stop the silent killer
Salt
Dietary approaches to stop hypertension
"The way drugs are being used to control high blood
pressure today is much more effective than in the past,"
Saunders said. "Doctors are using ACE inhibitors,
Calcium channel blockers, Beta-blockers, Angiotensin-
receptor blockers (ARBs), Alpha-blockers and low-dose
diuretics in ways that don't cause the sexual
complications and other side effects of older therapies.
Also, these new drugs only need to be taken once a day,
instead of two or three times a day. This is a lot easier for
patients." .
We need to make sure that we eat eight servings of fruits
and vegetables a day, and get more exercise. We need to
get ourselves and our children away from the television
sets and the computers, and start them exercising early in
their lives."
CONCLUSION
The treatment of hypertension has become one of the greatest challenges for
medical professionals today. It is estimated that by 2025 some 1.56 billion people
will have hypertension
The first direct renin inhibitor, aliskiren, thus constitutes an important milestone
in the history of RAS blockade.
When Aliskiren bound to the (pro)renin receptor, Aliskiren binds to the S3bp
binding pocket of renin, essential for its activity.Binding to this pocket prevents
the conversion of angiotensinogen to angiotensin I.
The use of the direct rennin inhibitor, aliskiren, combined with the angiotensin
receptor blocker, valsartan. “Dual renin system blockade” gave enhanced blood
pressure lowering in patients with mild to moderate hypertension.
Aliskiren produces dose-dependent blood pressure (BP) reduction and 24-h BP
control up to a dose of approximately 300 mg once daily. Its antihypertensive
potency is approximately equivalent to that of angiotensin receptor blockers,
angiotensin-converting enzyme inhibitors, and diuretics.
Clinical trials are currently underway assessing the effects of aliskiren combined
with an angiotensin receptor blocker on intermediate markers of end organ
damage, and long-term end point trials are planned. The results of these studies
will ultimately determine the place of renin inhibition and aliskiren in the
treatment of hypertension and related cardiovascular disorders.
Aliskirin latest antihypertensive agnet.
REFERENCES
Wilson and Gisvolds Text book of Organic Medicinal And
Pharmaceutical chemistry
Principles of Medicinal chemistry Dr.S.S.Kadam
Dr.K.R..Mahadik
Dr.K.G.Bothara
Text book of Medicinal chemistry vol-1 K.Ilango
P.Valentine
Principles of Medicinal chemistry by William foeye
Advanced practical Medicinal chemistry by Ashutoshkar
Profiles in drug synthesis vol-1 Dr.v.N.GOGTE
The organic chemistry of drug synthesis vol-3 DANIEL
LEDNISER,LESTER .A.MITSCHER
Medicinal chemistry D.SRIRAM,P.YOGEESWARI
Essentials of Medicinal chemistry II Edition –
ANDREJUS KAROLKOVAS
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.

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ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.

  • 1. Prof. Ravisankar Vignan Pharmacy college Valdlamudi Guntur Dist. Andhra Pradesh India. banuman35@gmail.com 00919059994000
  • 2. HYPERTENSION It is defined as a physiologic condition where there is an increase in the arterial blood pressure above normal. •Normal B.P is 120/80 mm Hg. •An individual is hypertensive when B.P is >140/90 mm Hg.
  • 3. Hypotension may be defined as a physiologic state where there is a HYPERTENSION IS DEVIDED IN TO 2 TYPES: 1.PRIMARY HYPERTENSION OR ESSENTIAL HYPERTENSION 1.SECONDARY HYPERTENSION OR MALIGNANT HYPERTENSION.
  • 4. In PRIMARY OR ESSENTIAL HYPERTENSION In majority of casses where etiology Is unknown cause and is known as primary hypertension. The following factors may contribute to elevate of B.P •Dietary intake of more sodium and less potassium. In some cases primary hypertension may be herediatary. Advancement of age. Decreased vascular synthesis of Nitric oxide (No)( is useful in vasodialatation) In SECONDARY HYPERTENSION where etiology can be identified. Secondary hypertension is due to Renal disease (kidney disorders ( Chronic glomerular nephritis.) Adrenal disease (endocrine disorders) Pheochromocytoma (tumour on adrenal medulla) which secretes excessive catechol amines like adrenaline and nor adrenaline) Hyper aldosteronism. Muscular disorders: Contraction (narrowing)of aorta. Renal artery stenosis(narrowing of artery ) Toxemia of pregnancy (presence of toxins in the blood stream) Encephalitis(inflammation of the briain) Increased intra cranial pressure. Thyrotoxicosis(toxic condition caused by over activity of thyroid gland) oral contraceptives.
  • 6. Classification (category of Hypertension) Systolic Blood Pressure (mmHg) Diastolic Blood Pressure (mmHg) Normal (B.P) 120 and 80 Prehypertension 121-139 or 81-89 Stage 1 (mild) hypertension 140-159 or 90-99 Stage 2 hypertension (moderate) 160-179 or 100-109 6 Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206–1252. Stage III (severe) 180-209 110-119. Stage iV (very >210 >120. severe)
  • 7. On etiological basis hypertension is divided into two types 1.Primary hypertension A definite cause is not known in primary hypertension. Following factors may contribute to elevation of B.P. •Dietary intake of more sodium and less potassium. •Decrease in vascular synthesis of nitric oxide responsible for vasodilation. •In some cases it may be heriditary.
  • 8. 2.Secondary Hypertension In some cases Hypertension may be secondary to other diseases like a.Endocrine disorders •Pheochromocytoma •Hyperaldosteronism b.Chronic glomerular nephritis c.Muscular disorders •Contraction of aorta •Renal artery stenosis
  • 10. Classification of antihypertensive agents 10 Hypertension = Disease of the blood vessels Vascular biology altered Treat the vasculature Therapeutic options Beta Blockers ACE ARB Diuretics CCB Others Adapted from Vascular Biology Working Group, University of Florida College of Medicine, Carl Pepine, MD, Director
  • 11. The Renin-Angiotensin Cascade and the 3 Available Approaches to Pharmacologic Inhibition of Production or Action of Angiotensin II. Direct renin inhibitors (DRI), angiotensin-converting enzyme inhibitors (ACEI), and angiotensin (AT) type 1 receptor blockers (ARB). Drugs interacting with Renin-Angiotensin system
  • 13. Depending on chemical classification ACE inhibitors Sulphydryl E.g:Captopril Dicarboxylate E.g:Enalapril ,Lisinopril Phosphate E.g:Fosinopril
  • 17. Structure activity relationship[SAR] R Groups that bind to Zn+2 ion CH C R 1 (N O Ring) Essential for stabilisation Methyl group resembles side chain of alanine Enhances the potency of the compound Sulfhydryl group leads to shorter duration of action n-butylamine in dicarboxylate containing componds orally active.
  • 19. Mechanism of action They inhibit ACE which is involved in the conversion of AngI to Ang II. •Which is a potent vasoconstrictor. Adverse effects •Dry cough •Dysgysia •Skin rashes •Foetal toxicity
  • 20. Uses First choice in treatment of Hypertension. In left ventricular failure In diabetic nephropathy In myocardial infarction
  • 21. •Benazepril (Lotensin®) •Captopril (Capoten®) •Fosinopril (Monopril®) •Lisinopril (Prinivil®,Zestril®) •Enalapril (Vasotec®) •Quinapril (Accupril®) •Ramipril (Altace®) •Trandolapril (Mavik®) ACE inhibitors
  • 24. CH2 N NH X Acidic group STRUCTURE ACTIVITY RELATIONSHIP[SAR] Essential for activity to mimic Asp1 carboxylate of Ang-II Substituted with ketones,cooH forms Ionic,dipole- dipole helps drug to interact with AT1 Require to mimic the His side chain of Angiotensin-II
  • 25. Mechanism of action They act by blocking the Angiotensin I which regulates the effects of angiotensin on B.P,heart and sodium and water balance. Adverse effects Hyperkalaemia Angioedema Foetal toxicity Gidisturbances
  • 26. Uses In treatment of hypertension as an alternative to ACE Inhibitors.
  • 27.  Valsartan (Diovan®)  Telmisartin (Micardis®)  Candesartan (Atacand®)  Losartin (Cozaar®) Irbesartin (Avapro®) Angiotensin receptor blockers
  • 28. Diuretics • 28 Diuretics ("water pills") increase the kidneys' excretion of salt (sodium) and water, decreasing the volume of fluid in the bloodstream and the pressure in the arteries. Diuretics are the oldest and most studied antihypertensive agents.
  • 29. Thiazide chlorthalidone, hydrochlorothiazide (HCTZ), indapamide, metolazone Loop bumetanide, furosemide, torsemide Potassium-sparing amiloride, triamterene Aldosterone antagonists eplerenone, spironolactone CLASSIFICATION
  • 31. Thiazide Diuretics Dose in morning to avoid nocturnal diuresis More effective antihypertensives than loop diuretics . Chlorthalidone 1.5 to 2 times as potent as HCTZ Adverse effects • hypokalemia • hypomagnesemia • hypercalcemia • sexual dysfunction lithium toxicity with Concurrent adminstration. 3131
  • 32. Loop Diuretics Dose in AM or afternoon to avoid nocturnal diuresis Higher doses may be needed for patients with severely decreased glomerular filtration rate or heart failure Furosemide Adverse effects: hypokalemia, hypomagnesemia,  hypocalcemia 32
  • 34. Mechanism of Action inhibit Na+ and Cl- transporter in distal convoluted tubules increased Na+ and Cl- excretion weak inhibitors of carbonic anhydrase, increased HCO3- excretion increased K+/Mg2+ excretion decrease Ca2+ excretion
  • 35. Potassium-sparing Diuretics  Dose in AM or afternoon to avoid nocturnal diuresis  Generally reserved for diuretic-induced hypokalemia patients  Weak diuretics, generally used in combination with thiazide diuretics to minimize hypokalemia Adverse effects: may cause hyperkalemia especially in combination with an ACE inhibitor, angiotensin-receptor blocker or potassium supplements avoid in patients with diabetes 35
  • 36. Aldosterone antagonists Dose in AM or afternoon to avoid nocturnal diuresis Adverse effects: may cause hyperkalemia especially in combination with ACE inhibitor, angiotensin-receptor blocker or potassium supplements Gynecomastia: up to 10% of patients taking spironolactone 36
  • 37. Calcium channel blockers Depending upon their chemical structure Benzothiazepines Eg:Diltiazem Diphenylalkylamines Eg:Verapamil 1,4-dihydropyridines Eg:Nifedipine Diaminopropanol ether Eg:Bepridil
  • 39. N H CH3 R COOR'' R' OOC N1 substitution reduses the activity Presence of non polar alkyl or cyclo alkyl reduces the activity Ester group for optimum activity,-NO2 may decreases the activity Methyl group is present except in amlodipine SAR of 1,4-dihydropyridines Potency is high when compared to others Electron with drawing groups decreases the activity
  • 40. DRUGS Mode of action Adverse Drug reactions Uses Diltiazem Acts by inhibiting Voltage sensitive Calcium channels in myocardium and vascular smooth muscles. oConstipation oDizziness oOedema oIn arrythmias oIn Angina Verapamil oFlushing oOedema •In Angina In Arrythmias Nifedipine oTachycardia In Angina
  • 41. •Idradipine (DynaCirc®) •Nicardipine (Cardene®) •Nisoldipine (Sular®) •Felodipine (Plendil®) •Amlodipine (Norvasc®) Calcium channel blockers
  • 42. Centrally acting sympatholytics Mechanism of action Methyldopa is an α2 adrenergic receptor agonist acts centrally by decreasing the sympathetic outflow which inturn lowers B.P. Methyldopa
  • 44. Adverse effects Sedation and drowsyness Constipation Gynacomastia Sexual impotense Uses Treat of Hypertension in combination With diuretics.
  • 45. clonidine Mode of action: Its acts by stimulating α2-adrenergic receptros and thereby reducing sympathetic outflow and noradrenaline release
  • 46. In moderate to severe hypertension For withdrawl therapy of alcohol opioids To diagnose pheochromocytoma Sedation and drowsiness Dryness of mouth and nase Constipation Bradycardia Adverse drug reaction uses
  • 48. Drugs Mode of action Adverse drug reaction Uses prazosin It acts by selective blocking of α-1 receptors in the peripheral blood vessels leading to vasodilation First dose effect: Postural hypotension and syncope Drowsines s Headache Nasal congestion In the treatment of moderate to serve hypertension in combinaton with a β- blocker and a diuretic Adrenergic receptor antagonists α-blockers
  • 49. Drugs Mode of action Adverse drug reaction Uses Phentolamine It blocks both α1 and α2- receptors leading to vasodilation and increase in noradrenali ne release Hypotensio n Tachycardia Increase in gastric acid secretion Pheochrom ocytoma
  • 52. Drugs Mode of action Adverse drug effects Uses Propanolol Inhibits sympathetic activity by blocking β1 and β2 receptors •Fatigue •Bradycardi a •Hypoglyce mia •In angina •In myocardial infarction •In arrythmias β-adrenergic Blockers
  • 54. Drug Mode of action Adverse drug reactions Uses Atenolol Inhibit Sympathetic activity by selective blockage of β1 receptors. •Fatigue •Bradycardia In angina In arrythmia s
  • 55. Drug Mode of action Adverse effects Uses •Carvedilol •Labetalol They block β and α1 receptor there by inhibit sympathetic activity. •Dry mouth •Gidisturbances •Sexual dysfunction •Cavedilol- CHF •Labetalol- Emergencies
  • 58. Drug Mode of action Adverse effects Uses Minoxidil It opens the potassium channels and causes hyperpolari zation. •Tachycardia •Fluid retension •Hypertricho sis •In treatment of Baldness Direct Vasodilators
  • 60. Drug Mode of action Adverse effects Uses Hydralazine Direct relaxation of vascular smooth muscles by stimulating cGMP •Flushing •Tachycardia •Fluid retension Emergencies
  • 61. Say No to Smoking, Excessive Drinking (smoking 16% CHF) Shake That Salt Habit Control Your Pressure Good Reasons to Exercise blood pressure checked every time they visit their doctor. Being obese or overweight. yoga asanas. Have the dash diet. Tips to stop the silent killer Salt
  • 62. Dietary approaches to stop hypertension
  • 63. "The way drugs are being used to control high blood pressure today is much more effective than in the past," Saunders said. "Doctors are using ACE inhibitors, Calcium channel blockers, Beta-blockers, Angiotensin- receptor blockers (ARBs), Alpha-blockers and low-dose diuretics in ways that don't cause the sexual complications and other side effects of older therapies. Also, these new drugs only need to be taken once a day, instead of two or three times a day. This is a lot easier for patients." . We need to make sure that we eat eight servings of fruits and vegetables a day, and get more exercise. We need to get ourselves and our children away from the television sets and the computers, and start them exercising early in their lives." CONCLUSION
  • 64. The treatment of hypertension has become one of the greatest challenges for medical professionals today. It is estimated that by 2025 some 1.56 billion people will have hypertension The first direct renin inhibitor, aliskiren, thus constitutes an important milestone in the history of RAS blockade. When Aliskiren bound to the (pro)renin receptor, Aliskiren binds to the S3bp binding pocket of renin, essential for its activity.Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I. The use of the direct rennin inhibitor, aliskiren, combined with the angiotensin receptor blocker, valsartan. “Dual renin system blockade” gave enhanced blood pressure lowering in patients with mild to moderate hypertension. Aliskiren produces dose-dependent blood pressure (BP) reduction and 24-h BP control up to a dose of approximately 300 mg once daily. Its antihypertensive potency is approximately equivalent to that of angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics. Clinical trials are currently underway assessing the effects of aliskiren combined with an angiotensin receptor blocker on intermediate markers of end organ damage, and long-term end point trials are planned. The results of these studies will ultimately determine the place of renin inhibition and aliskiren in the treatment of hypertension and related cardiovascular disorders.
  • 66. REFERENCES Wilson and Gisvolds Text book of Organic Medicinal And Pharmaceutical chemistry Principles of Medicinal chemistry Dr.S.S.Kadam Dr.K.R..Mahadik Dr.K.G.Bothara Text book of Medicinal chemistry vol-1 K.Ilango P.Valentine
  • 67. Principles of Medicinal chemistry by William foeye Advanced practical Medicinal chemistry by Ashutoshkar Profiles in drug synthesis vol-1 Dr.v.N.GOGTE The organic chemistry of drug synthesis vol-3 DANIEL LEDNISER,LESTER .A.MITSCHER Medicinal chemistry D.SRIRAM,P.YOGEESWARI Essentials of Medicinal chemistry II Edition – ANDREJUS KAROLKOVAS