HYPERTENSIVE AGENTS

Hypertension
High blood pressure; HBP; Blood
pressure - high
 Hypertension is the term used to describe
high blood pressure.
 Blood pressure is a measurement of the
force against the walls of your arteries as
the heart pumps blood through the body.
 Blood pressure readings are measured in
millimeters of mercury (mmHg) and usually
given as two numbers -- for example, 120
over 80 (written as 120/80 mmHg). One or
both of these numbers can be too high.
Causes, incidence, and risk
factors

 Many factors can affect blood

pressure, including:
 How much water and salt you have in
your body
 The condition of your kidneys,
nervous system, or blood vessels
 The levels of different body hormones
higher risk of high blood pressure
 Are African American
 Are obese
 Are often stressed or anxious
 Eat too much salt in your diet
 Have a family history of high blood
pressure
 Have diabetes
 Smoke
secondary hypertension
 Alcohol abuse
 Atherosclerosis
 Autoimmune disorders such as 
periarteritis nodosa
 Chronic kidney disease
 Coarctation of the aorta
 Cocaine use
 Diabetes 
Symptoms

 Most of the time, there are no symptoms.

Symptoms that may occur include:
 Confusion
 Ear noise or buzzing
 Fatigue
 Headache
 Irregular heartbeat
 Nosebleed
 Vision changes
CLASSIFICATION
 Alpha blockers
 Angiotensin-converting enzyme (ACE)
inhibitors
 Angiotensin receptor blockers (ARBs)
 Beta blockers
 Calcium channel blockers
 Central alpha agonists
 Diuretics
 Renin inhibitors, including aliskiren
 (Tekturna)
 Vasodilators
 Eat a heart-healthy diet, including potassium and
fiber, and drink plenty of water.
 Exercise regularly -- at least 30 minutes a day.
 If you smoke, quit -- find a program that will help you
stop.
 Limit how much alcohol you drink -- 1 drink a day for
women, 2 a day for men.
 Limit the amount of sodium (salt) you eat -- aim for
less than 1,500 mg per day.
 Reduce stress -- try to avoid things that cause stress
for you. You can also try meditation or yoga.
 Stay at a healthy body weight -- find a weight-loss
program to help you, if you need it.
ANGIOTENSIN RECEPTOR
ANTAGONIST

 LOSARTAN
 CANDESARTAN
 VALASARTAN
 A synthesis of [14C]-losartan has been described: The
bromination of 4'-methylbiphenyl-2-carbonitrile (I) with Br2
and silver trifluoroacetate in dichloromethane gives 3'-
bromo-4'-methylbiphenyl-2-carbonitrile (II), which is
treated first with trimethylstannyl azide in refluxing toluene,
and then with trityl chloride and triethylamine in hot
dichloromethane, yielding 5-(3'-bromo-4'-methylbiphenyl-2-
yl)-2-(triphenylmethyl)tetrazole (III). The bromination of
(III) with N-bromosuccinimide (NBS) in refluxing carbon
tetrachloride affords the corresponding bromomethyl
derivative (IV), which is then condensed with 2-butyl-5-
(tert-butyldimethylsilyloxymethyl)-4-chloro-1H-imidazole
(V) by means of NaH in DMF to give (VI). The deprotection
of (VI) with HCl in methanol yields the bromolosartan
derivative (VII), which is finally tritiated by debromination
with tritiated sodium borohydride and palladium acetate in
methanol-THF.
 An angiotensin II receptor antagonist
 drug used mainly to treat high blood
pressure (hypertension). Losartan
was the first angiotensin II receptor
antagonist to be marketed. 
LOSARTAN
 (2-butyl-4-chloro-
1-{[2'-(1H-
tetrazol-5-
yl)biphenyl-4-
yl]methyl}-1H-
imidazol-5-
yl)methanol
KINETICS
 Bioavailability 25–35%
 Metabolism Hepatic (CYP2C9, CYP3A4
)
 Half-life 1.5–2 hours
 Excretion Renal 13–25%, biliary 50–
60%
 Solubility
MOA
 Losartan is a selective,
competitive Angiotensin II receptor type
1 (AT1) receptor antagonist, reducing the
end organ responses to angiotensin II.
 Losartan administration results in a
decrease in total peripheral resistance
(afterload) and cardiac venous return
(preload)
 All of the physiological effects of
angiotensin II, including stimulation of
release of aldosterone, are antagonized in
the presence of losartan.
 Reduction in blood pressure occurs
independently of the status of
the renin-angiotensin system. As a
result of losartan dosing, plasma
renin activity increases due to
removal of the angiotensin II
feedback.
SAR
 Tetrazole ring is important for it’s
activity because it allows it’s binding
to angiotensin receptor
 Imidazole ring when substituted by
benzimidazole ring activity enhanses
QUERIES?
Presented By:
Adeel Hassan Kahoot
Ch.Yousaf Hassan
Ch.M.Ali Tasleem
A.S.Javaid Qureshi
Mr.Masood Manzoor
M.Arslan Jafferi