LosartanName : Danny Liew Teck Yee

ObjectiveTo learn what is Losartan

To describe the mechanism of action of Losartan

To state the adverse effects of Losartan

ContentsIntroductionAppearanceMechanism of actionPharmacokineticIndicationDosage and administrationContraindicationPrecautionPregnancy classAdverse effectsDrug Interaction

IntroductionLosartan – the first Angiotensin II

receptor developed in 1986

Tradename : Cozaar

Manufacturer: Merck Sharp and Dohme Limited United Kingdom

• http://faculty.babson.edu/gbhardwaj/Losartan%20Case%20History%20-%20EODD.pdf

• http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

Introduction

AppearancePowder form – A white to off-white powder,

freely soluble in water; slightly soluble in acetonitrile; soluble in isopropyl alcohol

http://www.excitienps.com/losartan-powder-534363.html

AppearanceFilm-coated tablets form-1. 50 mg – white color with mark 952 in

teardrop shape2. 100mg – white color with mark 960 in

teardrop shape

http://www.mims.com/Malaysia/drug/info/Cozaar/?q=losartan&type=brief

IntroductionChemical name: 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol mono potassium salt

Empirical formula: C22H23ClN6OStructural formula:

http://structures.wishartlab.com/molecules/DB00678/image.png

Mechanism of Action

http://www.drugbank.ca/drugs/DB00678

Mechanism of ActionLosartan competitively inhibit the binding of Angiotensin II to AT1 in many tissues

Result : It decreased vascular resistance and blood pressure. 

• http://www.drugbank.ca/drugs/DB00678• www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

PharmacokineticsAbsorption : Bioavailability is 33%

Distribution : Volume of distribution of Losartan is 34 L, 99.7% bound to albumin

Biotransformation : About 14% of orally administered Losartan convert to active metabolite

Elimination : about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite.• http://www.drugbank.ca/drugs/DB00678

http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

IndicationHypertension

Hypertensive patients with left ventricular hypertrophy except Black African patient

Nephropathy in Type 2 Diabetic Patients

• Drug fact and comparison 2010, page 782• http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf• British National Formulary 56 September 2008, page 105-106

Dose and AdministrationHypertension- 50mg once daily, and may

increases to 100mg once dailyHypertensive patients with left ventricular

hypertrophy- 50 mg once per daily, may co-administration with 12.5 mg of hydrochlorothiazide

Neuropathy in Type 2 diabetes mellitus - starting dose is 50mg once per day, and may increases to 100mg once per day based on blood pressure response.

• Drug fact and comparison 2010, page 782• British National Formulary 56 September 2008, page 105-106• http://www.mims.com/Malaysia/drug/info/Cozaar/?q=losartan&type=brief • http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

ContraindicationPatients who hypersensitive to Losartan

Pregnant women

• http://www.mims.com/Malaysia/drug/info/Cozaar/?q=losartan&type=brief

• http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

CautionHepatic impairments - Data showing plasma

concentration of Losartan increased in cirrhotic patients

Renal impairments – Some patients reported reversible renal failure

Lactation – Unknown if it excreted to human milk. A research shown losartan excreted in rat milk.

• http://www.mims.com/Malaysia/drug/info/Cozaar/?q=losartan&type=brief http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

Pregnancy ClassClass D in 2nd and 3rd trimesters

There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk

• Drug fact and comparison 2010, page 782- 783

• http://www.mims.com/Malaysia/drug/info/Cozaar/?q=losartan&type=brief

Adverse EffectsDizziness

Hypotension

Hyperkalaemia

Angioedema

• http://www.drugs.com/food-interactions/losartan.html• British National Formulary 56 September 2008, page 105-

106

Drug Interaction

Losartan

Potassium

sparing

diuretics or

potassium

supplements

Hyperkalae

mia• http://www.merck.com/product/usa/

pi_circulars/c/cozaar/cozaar_pi.pdf• http://www.drugs.com/food-

interactions/losartan.html

Drug Interaction

Losartan

Lithium

Lithium

toxicity

http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

Drug interaction

Losartan

NSAIDS

Decreases of

effect of

Losartan

• http://www.drugs.com/drug-interactions/losartan.htmll

• http://www.merck.com/product/usa/pi_circulars/c/cozaar/cozaar_pi.pdf

References1. British National Formulary 56 September 2008, page 105-

1062. Drug Facts and Comparisons 2010, page 782-7833. Martindale Edition 36, page 1326-13274. http://www.drugs.com/drug-interactions/losartan.html5. http://www.mims.com/Malaysia/drug/info/Cozaar/?

q=losartan&type=brief6. http://www.drugbank.ca/drugs/DB006787. http://faculty.babson.edu/gbhardwaj/Losartan%20Case

%20History%20-%20EODD.pdf8. http://www.excitienps.com/losartan-powder-534363.html9. http://www.merck.com/product/usa/pi_circulars/c/cozaar/

cozaar_pi.pdf