Ramipril, Hydrochlorothiazide

Indications

Ramipril, Hydrochlorothiazide is used for: RAMIPRIL
For the management of mild to severe hypertension. May be used to reduce cardiovascular mortality following myocardial infarction in hemodynamically stable individuals who develop clinical signs of congestive heart failure within a few days following myocardial infarction. To reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events. May be used to slow the progression of renal disease in individuals with hypertension, diabetes mellitus and microalubinuria or overt nephropathy
HYDROCHLOROTHIAZIDE
For the treatment of high blood pressure and management of edema

Adult Dose

Child Dose

Renal Dose

Administration

Contra Indications

Precautions

Pregnancy-Lactation

Interactions

Adverse Effects

Side effects of Ramipril, Hydrochlorothiazide :

Mechanism of Action

RAMIPRIL
There are two isoforms of ace: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ace has two functionally active domains, n and c, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The c-domain is predominantly involved in blood pressure regulation while the n-domain plays a role in hematopoietic stem cell differentiation and proliferation. Ace inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the c-domain. Ramiprilat, the principle active metabolite of ramipril, competes with ati for binding to ace and inhibits and enzymatic proteolysis of ati to atii. Decreasing atii levels in the body decreases blood pressure by inhibiting the pressor effects of atii as described in the pharmacology section above. Ramipril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by atii on the release of renin and/or stimulation of reflex mechanisms via baroreceptors
HYDROCHLOROTHIAZIDE
Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (slc12a3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium atpases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium atpase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron