•Hypertension in 1995 by FDA with the brand name

•Hypertension
is a chronic disease characterized by rise in blood pressure (systolic
pressure) or arterial pressure.

 

•Primary
or Secondary

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•Primary
hypertension:

•about
90-95% of hypertension.  Also known as essential/ idiopathic hypertension
defined as hypertension with no known explanation. 

•Caused
due to overconsumption of Na+ or under consumption of K+

•Secondary
hypertension:

•Due
to a specific medical/ genetic conditions such as chronic kidney disease,
narrowing of arteries or endocrine disorders.

 

•Affects
40% of worlds population ages 25+

•Leading
cause of death and disabilities.

•According
to Canadian Health Measures Survey 1 in 5 Canadian adults are affected.

•Obesity
rates are rising in Canada, recent reports show 85% of Canadians do not meet
their weekly recommended physical activities.

•Lastly,
Funding for Hypertensive drugs have decreased both federally and by
pharmaceutical companies. 

 

•The
Angiotensin 2receptors were the first target for developing compounds that
could inhibit the renin angiotensin pathway .

•They
are also called as Angiotensin 2 receptor Antagonist and are the analouges of
Aangiotensin II.

     Tarrgets
Angiotensin II receptors.

•Two
types:  AT1 and AT2

•AT1
found in heart, brain, liver, kidney and adrenal glands.

•Main
function is to regulate blood pressure, fluids and electrolytes.

 

•Losartan
was a first angiotensin-receptor blocker (ARB) designed to treat hypertension.

•Its
a prodrug.

    It is uricosuric.

•Work
to lower blood pressure by competing with angiotensin II for its binding on AT1
by antagonizing the renin-angiotensin-aldosterone system..

• It
was first approved  in 1995 by FDA with the brand name of COZAAR.

•(Merck
sharp and Dhome corporation)

 

•Losartan
is well absorbed and undergoes substantial first-pass metabolism.

•Systemic
bioavailability of losartan is around 33%.

•Peak
concentration of losartan is achieved in 1 hour and its active compound in
3-4hours.

•Losartan’s
active metabolite, E-3174 is 10-40x more potent than losartan.

•Losartan
is metabolized to E-3174 (5-carboxylic acid derivative) primarily by cytochrome
P450.

•Following
oral administration 35% recovered in urine ,60% in feces.

•Following
IV administration 45% in urine ,50% in feces.

 

OBJECT. 

•Losartan
reduce the arterial pressure in normotensive rats.

METHOD

•Losartan
was infused for 10 days in two groups of rat.

•HNa
and Nna.

RESULT.

•plasma
renin activity was supressed  in Hna rats compared with

•Nna
rats.


Arterial pressure in Nna rats reduced


Arterial pressure in Hna rats was unaffected.

 

OBJECT.

•The
aim of this study was to establish an optimized fast and safe protocol for the
pharmacological screening of losartan.

METHOD.

•Rabbits
were divided into 7 group.

•they
were give same dose of anesthesia.

•drug
was infused at different infusion rate.

RESULT.

•The
continuous infusion of losartan at the dose of 1microgm/min for 20 min,
represent rapid and safe pharmacologic screening for losartan.

•Ie.

Other infusion rates did not produce the results that were necessary.

FETAL TOXICITY.

•Incomplete
ossification of skull bone, feed intolerance.

HEPATIC INJURY

ACUTE  TOXICITY

•cardiac
arrhythmia in excess doses.

NOT CARCINOGENIC.

 

OPEN LABEL. RANDOMIZED ,2 PERIOD
CROSSOVER STUDY TO EVALUATE BIO EQUIVALENCE  AFTER ADMINSTRATION OF
LOSARTAN 50mg VS COZAAR 50 mg

INVITRO Study,

       
Dissolution of drugs in different medium.

       
water, 0.1 NaCl and phosphate buffer,

INVIVO Study .

       
Randomized crossover study in 60 adult healthy male.

RESULTS

      
Similarity in both formulation > 50% in all medium.

      
losartan was bioequivalent to Cozaar tablet in the term of rate extent of
absorption

      
well tolerated.

 

 

 

•THE
EFFICACY AND SAFETY OF LOSARTAN IN DOUBLE BLIND CONTROLLED CLINICAL TRIAL 
WITH HYDROCHLOROTHIAZIDE.

METHOD.

•3700
Patient with uncomplicated mild to moderate hypertension.

•Half
was given a placebo.

RESULT.

•Losartan
alone or in combination with hydrochlorothiazide was effective

•well
tolerated with incidence similar to that of placebo.

•only
adverse effect was found more was dizziness.

 

 

Efficacy and
Safety of Amlodipine Plus Losartan Versus Amlodipine and Losartan monotherapy
in Patients With Essential Hypertension.

METHOD.

•440 patient was taken divided into 3 group.

•first group give losartan ,second amlodipine

•third group was given a combination of both.

RESULTS.

•Group taking amlodipine proved to be more effected
than

•losartan monotherapy.

•combination of both was more effective than
increased dose of either drug.

AN INDIAN POST MARKETING SURVEILLANCE.

•Efficacy
and Safety of Losartan-amlodipine combination

ABSTRACT.

•Conducted
by 109 doctors at 708 patients.

•patient
receive different doses of combination therapy.

•Therapy
was monitored for 20 days

RESULTS

•Reduction
in SBP WAS 19.90%.

•Reduction
in DBP was 17.70%.

ADVERSE EFFECT.

•Edema
of feet, palpitation. Muscular weakness , headache, insomnia

 

               

              

             

             
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