Agilosart-H 50/12.5 Agimexpharm treatment for hypertension (3 blisters x 10 tablets)

Losartan is a specific and selective antagonist on Angiotensin II receptor while hydrochlorothiazid is a thiazid diuretic. Both drugs have a powerful effect on blood pressure. The effectiveness of high blood pressure treatment is often higher when combining a small dose of thiazid diuretics such as hydrochlorothiazid with Angiotensin II receptor antagonist.

Moreover, due to diuretic effects, hydrochlorothiazid increases plasma renin activity, increases aldosteron secretion, reduces serum potassium and increases angiotensin II levels. Using Losartan will prevent all the physiological effects of Angiotensin II and through Aldosteron inhibitors may tend to reduce the loss of potassium associated with this diuretics.

losartan:

Losartan is the first substance of the new anti -hypertension drug group, which is a receptor antagonist (Type AT1) Angiotensin II.

angiotensin II, made up of angiotensin I in the reaction due to enzyme transferred angiotensin (ACE) catalyzed, is a strong vascular contract; It is the main hormone that activates the Renin-Anotensin system, and is an important component in the pathology of hypertension. Angiotensin II also stimulates the adrenal glands of Aldosteron.

Losartan and main metabolites have a clogging and aldosteron secretion of Angiotensin II by preventing Angiotensin II selective, not attached to the AT1 receptor contained in many tissues (for example, blood vessel muscles, adrenal glands).

Both Losartan and the main active metabolites do not show the local dominant effects in the AT1 receptor and have a much larger AT1 receptor (about 1,000 times) than the AT2 receptor. Losartan is a competitive, reversible inhibitor of AT1 receptor.

Metabolic substances have the activity of drugs 10 to 40 times stronger than Losartan, calculated by weight and is a non -competitive, reversible inhibitor of the AT1 receptor. Angiotensin II antagonists also have hemodynamic effects such as ACE inhibitors, but there is no unwanted effect of the common ACE inhibitors are dry cough.

hydrochlorothiazid:

hydrochlorothiazid is a drug in the group of thiazid diuretics that increases the secretion of sodium chloride and is accompanied by the mechanism of inhibiting the reabsorption of sodium and chlorine ions in the distance. The excretion of other electrolytes also increases, especially potassium and magnesi, and calcium decreases.

hydrochlorothiazid also reduces the activity of the carbon dioxide, so it increases the secretion of bicarbonate but this effect is common compared to the effect of Cl- excretion and does not significantly change the urine pH. Thiazid diuretics may also reduce the filtration rate of the glomerular. Thiazids have a moderate diuretic effect, because about 90% of sodium ions have been reabsorbed before arriving in the distance is the main position of the drug.

hydrochlorothiazid has the effect of lowering blood pressure, firstly due to a decrease in plasma volume and extracellular fluid related to sodium cards.

Then during the use of the drug, the effect of lowering blood pressure depends on the decrease in peripheral resistance, through the gradual adaptation of blood vessels from the reduction of Na+concentration. Therefore, the hypotension effect of hydrochlorothiazid is shown slowly after 1-2 weeks, while the diuretic effect occurs quickly and can be seen right after a few hours. Hydrochlorothiazid increases the effects of other antihypertensive drugs.

pharmacokinetics

losartan:

After drinking, Losartan absorbs well and initially metabolized through the liver thanks to the cytochrom P450 enzymes (CYP2C9 and CYP3A4). Losartan's biology is approximately 33%.

About 14% of the dose of losartan oral transformed into active metabolites, this substance is mostly antagonist Angiotensin II.

Losartan's waste time is about 2 hours, and of metabolites about 6-9 hours. The average peak concentration of Losartan reaches within 1 hour, and of the metabolites with activity within 3-4 hours.

Both Losartan and metabolites have a lot of activity that is linked to plasma proteins (> 98%), mainly albumin and they do not pass the bloodstream barrier.

Losartan's distribution volume is about 34 liters and of metabolites with an activity of about 12 liters. The total clearance of Losartan's plasma is about 600 ml/min and the metabolites are active as 50ml/min, their clearance in the kidney corresponds to about 75ml/min and 25ml/min.

Losartan eliminates 35% by urine and about 60% in feces.

In patients with mild to medium cirrhosis, the area under the curve (AUC) of Losartan and of the metabolitus has a higher activity, 5 times and 2 times more than in patients with normal liver. Losartan and E-3174 metabolites are not excluded when hemolysis.

hydrochlorothiazid:

After drinking, hydrochlorothiazid is relatively fast, about 65-75% of the dose, but this ratio may decrease in heart failure.

Food can reduce the absorption of the drug. Hydrochlorothiazid accumulated in red blood cells. 40 - 68% of the drug is associated with plasma protein. The drug excreted mainly through the kidneys, largely in the form of non -metabolic.

The sale time of hydrochlorothiazid is about 9.5 - 13 hours, but may last in the case of renal failure, so the dose should be adjusted. Hydrochlorothiazid passes through the placenta, distributed and reached high concentrations in the fetus.

Diuretelli effects appear after drinking 2 hours, reaching maximum after 4 hours and lasting about 12 hours.

Anti -hypertension effect is much slower than diuretic effects and can only achieve adequate effect after 2 weeks, even with the optimal dose between 12.5 - 25 mg/day. It is important to know that the anti -hypertension effect of hydrochlorothiazid is usually optimal at 12.5mg.

Modern clinical treatment and clinical trial guidelines emphasize the lowest and optimal use, which reduces the risk of harmful effects. The important issue is to wait enough time to assess the body's response to the hypotension effect of hydrochlorothiazid, because the effect on the peripheral resistance takes time to be clear.

hydrochlorothiazid may cause excessive potassium loss. This effect depends on the dose and can be reduced when low doses (12.5 mg/day), the best dose for hypertension treatment, while minimizing harmful reactions. Diuretics also often causes hypoglycemia.

Common, ADR> 1/100

Rare, ADR

Instructions on how to handle ADR:

Dose or medication reduction when there are unwanted effects.

Excessive treatment of hypotension: Put the patient on your back, if the severe hypotension is necessary to infusion of the physiological saline solution to increase the volume of fluid.