Eprosartan is a competitive and reversible angiotensin II receptor antagonist with the anti-hypertensive property. Eprosartan blocks the binding of angiotensin II to the angiotensin (AT)1 receptor in vascular smooth muscle, thereby blocking the principal pressor action of angiotensin II on the renin-angiotensin system resulting in vascular dilatation. In addition, this agent blocks angiotensin II-induced stimulation of aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, the activity of the sympathetic nervous system, and smooth muscle cell growth. Furthermore, eprosartan inhibits sympathetic norepinephrine production, thereby further reducing blood pressure.
Mechanism of Action of Eprosartan
Eprosartan blocks 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. Eprosartan does not exhibit any partial agonist activity at the AT1 receptor. Its affinity for the AT1 receptor is 1,000 times greater than for the AT2 receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT1 receptor. Eprosartan has also been shown to bind to AT1receptors both presynaptically and synaptically. Its action on presynaptic AT1 receptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with the response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. a dry cough).
Angiotensin II (formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (kininase II)), a potent vasoconstrictor, is the principal pressor agent of the renin-angiotensin system. Angiotensin II also stimulates aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, the activity of the sympathetic nervous system, and smooth muscle cell growth. Eprosartan blocks 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. Eprosartan does not exhibit any partial agonist activity at the AT1 receptor. Its affinity for the AT1 receptor is 1,000 times greater than for the AT2 receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT1 receptor. Blockade of the AT1 receptor removes the negative feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II do not overcome the effect of eprosartan on blood pressure. Teveten does not inhibit kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin; whether this has clinical relevance is not known. It does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Indications of Eprosartan
- High Blood Pressure (Hypertension)
- Congestive Heart Failure
- Diabetic Nephropathies
- Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.
- Coronary artery disease in those intolerant of ACE inhibitors.
- Pediatric hypertension 6 to 16 years of age.
- Post-myocardial infarction.
- Heart attack
- Congestive heart failure,
- Systolic dysfunction,
- For the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).
Therapeutic Indications of Eprosartan
- Eprosartan is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensives such as diuretics and calcium channel blockers.
- Both angiotensin II receptor antagonists including eprosartan 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 eprosartan have been used in the management of congestive heart failure. While angiotensin II receptor antagonists appear to share the hemodynamic effects of ACE inhibitors, some experts 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 (e.g., because of intractable cough or angioedema).
Contra-Indications of Eprosartan
- Low amount of sodium in the blood
- The high amount of potassium in the blood
- Renal artery stenosis
- Abnormally low blood pressure
- Kidney disease with the reduction in kidney function
- Decreased blood volume
- Allergies to Eprosartan & ARB-Angiotensin Receptor Antagonist
Dosage of Eprosartan
Strengths: 400 mg; 600 mg
- Initial dose: 600 mg orally once a day as monotherapy assuming euvolemia
- Maintenance dose: 400 to 800 mg orally per day in 1 or 2 divided doses.
- Usual range: 400–800mg/day given as a single dose or in two divided doses. Moderate-to-severe renal impairment: max 600mg daily.
Side Effects of Eprosartan
The most common
- cold symptoms such as stuffy nose, sore throat, cough
- 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
- 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 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 Eprosartan
Eprosartan 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)
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- 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, )
- other beta-blockers (e.g., propranolol, metoprolol)
- fusidic acid
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- monoamine oxidase inhibitors (MAOIs; e.g., phenelzine, rasagiline, selegiline, )
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
Medical Problems of Eprosartan
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially
- Diabetic patients who are also taking or
- Asthma, history of—May increase the likelihood of having an allergic reaction.
- Congestive heart failure, severe—Use may lead to kidney problems.
- Diabetes or
- Electrolyte imbalances (e.g., high or low potassium, magnesium, or sodium in the body) or
- Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
- Glaucoma, secondary angle closure or
- Gout or
- Hypercalcemia (high calcium in the blood) or
- Kidney problems or
- Liver disease or
- Myopia, acute (changes in the eyeball causing vision problems) or
- Systemic lupus erythematosus (an autoimmune disorder)—Use with caution. May make these conditions worse.
Pregnancy & Lactation of Eprosartan
FDA Pregnancy Category D
The use of angiotensin II receptor blockers is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor blockers is contraindicated during the second and third trimester of pregnancy.Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Infants whose mothers have taken Eprosartan should be closely observed for hypotension
Because no information is available regarding the use of Teveten during breastfeeding, Teveten is not recommended and alternative treatments with better-established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.