DESCRIPTION
Olmesartan -Olmesartan is an antihypertensive agent, which belongs to the class of medications called angiotensin II receptor blockers. It is indicated for the treatment of high blood pressure and is marketed under the name Olmetec®. The FDA label includes a black-box warning of injury and death to the fetus, so women of child-bearing age need to be warned and take the necessary precautions. Olmesartan is also contraindicated in diabetes mellitus patients taking aliskiren.Hydrochlorthiazise-A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.
CATEGORIES
Olmesartan -Angiotensin II Type 1 Receptor Blockers. Hydrochlorthiazise-Antihypertensive Agents, Diuretics,Sodium Chloride Symporter Inhibitors.
CHEMICAL FORMULA
Olmesartan -C24H26N6O3.Hydrochlorthiazise- C7H8ClN3O4S2.
COMPOSITION
Olmesartan 40 mg + Hydrochlorthiazise 12.5 mg
INDICATION
Olmesartan -For the treatment of hypertension. Hydrochlorthiazise-For the treatment of high blood pressure and management of edema.
PHARMACODYNAMICS
Olmesartan -Olmesartan is a specific angiotensin II type 1 (AT1) receptor antagonist, which blocks the blood pressure increasing effects of angiotensin II via the renin-angiotensin-aldosterone system (RAAS). During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: AT1 and AT2. AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure. Hydrochlorthiazise-Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the
MECHANISM
is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
MECHANISM
Olmesartan -Olmesartan is an ARB that selectively inhibits the binding of angiotensin II to AT1, which is found in many tissues such as vascular smooth muscle and the adrenal glands. This effectively inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in a decrease in vascular resistance and blood pressure. Olmesartan is selective for AT1 and has a 12,500 times greater affinity for AT1 than the AT2 receptor. Also unlike the well-known ARB losartan, olmesartan does not have an active metabolite or possess uricosuric effects.Hydrochlorthiazise-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.
ABSORPTION
Olmesartan -Bioavailability is about 26%. Food does not affect the bioavailability of olmesartan.Hydrochlorthiazise-50-60%.
VOLUME DISTRIBUTION
Olmesartan -The volume of distribution is 17 L and olmesartan poorly crosses the blood brain barrier.
METABOLISM
Olmesartan -Olmesartan is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. There is virtually no further metabolism of olmesart. Hydrochlorthiazise-Hydrochlorothiazide is not metabolized.
ELIMINATION
Olmesartan -Olmesartan is elminated unchanged in the urine (35% to 50%) and the remainder in the feces. Hydrochlorthiazise-Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
HALF LIFE
Olmesartan -The half life is approximately 13 hours.Hydrochlorthiazise-5.6 and 14.8 hours.
TOXICITY
Olmesartan -The main symptoms of overdose include low blood pressure and fast heartbeat. Hydrochlorthiazise-The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
FOOD INTERACTIONS
Olmesartan -Food does not affect the bioavailability of olmesartan.Hydrochlorthiazise-Avoid alcohol. Avoid excess salt/sodium unless otherwise instructed by your physician. Avoid natural licorice. Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication. Increase potassium intake; add a banana or orange juice; unless instructed otherwise. Take with food.
SIDE EFFECTS
Olmesartan -Feeling dizzy. Rise slowly over a few minutes when sitting or lying down. Be careful climbing. Cough. Loose stools (diarrhea). High potassium level. Signs include feeling weak, lightheaded, dizzy, feel like passing out, or have numbness or tingling. Kidney function that gets worse.