Olmesartan is a synthetic imidazole derivative and angiotensin II receptor antagonist with antihypertensive activity. Olmesartan selectively binds to the angiotensin type 1 (AT1) receptor subtype in vascular smooth muscle and adrenal gland, thereby competing with angiotensin II for binding to the AT1 receptor. This prevents angiotensin II-induced vasoconstriction and interferes with angiotensin II-mediated aldosterone secretion, thereby decreasing aldosterone production and preventing aldosterone-stimulated sodium retention and potassium excretion.
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.
Mechanism of Action of 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.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. An AT receptor is found also in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Olmesartan has more than a 12,500-fold greater affinity for the AT receptor than for the AT receptor. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is a mechanism of many drugs used to treat hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because olmesartan medoxomil does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II levels do not overcome the effect of olmesartan on blood pressure.
Indications of Olmesartan
- High Blood Pressure
- Diabetic Kidney Disease
- Diabetic Nephropathies
- Heart Failure,
- Migraine Prevention
- Treatment of uncomplicated hypertension,
- Isolated systolic hypertension and left ventricular hypertrophy.
- Delay or progression of diabetic nephropathy.
- Second line agent in the treatment of congestive heart failure,
- Systolic dysfunction,
- Myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors
- Risk of stroke in patients with hypertension and left ventricular hypertrophy.
- Diabetic nephropathy with an elevated serum creatinine and proteinuria
- May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay the progression of diabetic nephropathy.
Therapeutic Indications of Olmesartan
- Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents
- Benicar is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
- These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs.
- Both angiotensin II receptor antagonists including olmesartan and ACE inhibitors have been shown to slow the rate of progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy, and use of a drug from either class is recommended in such patients
- Angiotensin II receptor antagonists including olmesartan have been used with equivocal results in the management of congestive heart failure.
- While angiotensin II receptor antagonists appear to share the hemodynamic effects of ACE inhibitors, some clinicians state that in the absence of data documenting comparable long-term cardiovascular and/or renal benefits, angiotensin II receptor antagonists should be reserved principally for patients in whom ACE inhibitors are indicated but who are unable to tolerate the drugs
- The antihypertensive effects of Benicar in the pediatric population were evaluated in a randomized, double-blind study involving 302 hypertensive patients aged 6 to 16 years. The study population consisted of an all black cohort of 112 patients and a mixed racial cohort of 190 patients, including 38 blacks.
Contra-Indications of Olmesartan
- The high amount of potassium in the blood
- Renal artery stenosis
- Abnormally low blood pressure
- Liver problems
- Blockage of a bile duct
- Kidney disease with a reduction in kidney function
- Decreased Blood Volume
- Second and third trimester of pregnancy
- Biliary obstructive disorders.
- Severe hepatic impairment.
- Hypersensitivity to the active substance or to any of the excipients
- Decreased blood volume
- Severe vomiting, diarrhea, treatment with high doses of water tablets (diuretics) or if you are on a low salt diet
- Increased levels of potassium in your blood
- Problems with your adrenal glands.
Dosage of Olmesartan
Strengths : 5mg ,20mg , 40mg
- 20 mg orally once a day; may increase the dose to 40 mg in two weeks if further blood pressure reduction is needed.
- Maximum dose: 40 mg orally once a day
6 to 16 years
- 20 to less than 35 kg: 10 mg orally once a day; may increase the dose to 20 mg in two weeks if further blood pressure reduction is needed
- 35 kg or more: 20 mg orally once a day; may increase dose to 40 mg in two weeks if further blood pressure reduction is needed
Side Effects of Olmesartan
The more common
- A dry cough
- Dizziness and light-headedness due to low blood pressure
- Fatigue, especially in the early stages
- Mouth dryness in the early stages
- The most common (a burning feeling in the chest, behind the breastbone or gullet)
- Abdominal or stomach pain
- cold or flu symptoms such as stuffy nose, sneezing, sore throat, fever;
- Nausea, vomiting,
- painful or swollen gums
- numbness or heavy feeling in the jaw
- dull, aching pain in the hip, groin, or thigh
- stomach pain,
- a headache,
- reversible hair loss or thinning, and
- chills or fever
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- excessive sweating
- sudden drowsiness or need to sleep
- coughing up blood
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
- decreased amount of urine
- change in vision
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- cold and clammy skin
- fast and shallow breathing
- swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
- fast or abnormal heart rate or palpitations
- loss of appetite
- lower back, side, or stomach pain
- mental depression
- muscle pain or cramps
- Swelling of your feet or ankles
- Shortness of breath
- Nausea, fever, dark urine, loss of appetite
Drug Interactions of Olmesartan
Olmesartan may interact with following drugs, supplements, & may change the efficacy of drugs
- alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
- “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., clonazepam, diazepam, lorazepam)
- beta-blockers (e.g., atenolol, metoprolol, propranolol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, )
- asthma medications (e.g., theophylline)
- nonsteroidal anti-inflammatory medications (NSAIDs; e.g., indomethacin, naproxen)
- oral diabetes medications (e.g., metformin, pioglitazone)
- monoamine oxidase (MAO) inhibitors (e.g., phenelzine, selegiline, )
- heparin and low-molecular-weight heparins
- medications that increase the level of potassium in the blood (e.g., spironolactone,)
- non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
FDA Pregnancy Category D.
There is evidence of risk to the unborn baby based on studies in humans or adverse reaction data, but this medication may only be given to a pregnant woman if her healthcare provider believes that its benefits to the pregnant woman outweigh any possible risks to her unborn baby.
Tell your doctor if you are breastfeeding or plan to breastfeed.It is not known if olmesartan is excreted in human breast milk or if it will harm your nursing baby.