The Composite Management of Hypertension
D E S C R I P T I O N / M O D E O F A C T I O N
Losartan potassium, the first of a new class of antihypertensives, is an angiotensin II receptor (type AT1) antagonist. Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1[p-(o-1H-tetrazol-5-dylphenyl)benzyl]imidazole-5-methanol monopotassium salt. Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Both losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor. The active metabolite is 10 to 40 times more potent by weight than losartan.
Hydrochlorothiazide- INHIBITOR OF NA+ -CL– SYMPORT
The mechanism involves increased proximal reabsorption owing to volume depletion, as well as direct effects of thiazides to increase Ca2+ reabsorption in the DCT. In this regard, inhibition of the Na+ -Cl– symporter in the luminal membrane decreases intracellular Na+ levels, thereby increasing the basolateral exit of Ca2+ via enhanced Na+ -Ca2+exchange . Thiazide diuretics may cause a mild magnesuria by a poorly understood mechanism, and there is increasing awareness that long-term use of thiazide diuretics may cause magnesium deficiency, particularly in the elderly . Since inhibitors of Na+ -Cl– symport inhibit transport in the cortical diluting segment, thiazide diuretics attenuate the ability of the kidney to excrete a dilute urine during water diuresis.
Oral bioavailability- 70%, plasma half life- 2.5h, excreted by renal elimination.
C O M P O S I T I O N
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I N D I C AT I O N S
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D O S A G E
Lotace 50 – H : One tablet daily
S I D E E F F E C T S
Fetopathic potential – Not to be administered during pregnancy.
Angioedema is reported in few cases, Headache, dizziness, weakness, upper GI side effects are mild.
Hypokalemia, acute saline depletion, dilutional hyponetremia, hearing loss, hyperuricaemia,
P R E S E N TAT I O N & PACK
Lotace 50 – H: Blister pack of 10 x 10’s Tablets
