Azilsartan is an Angiotensin 2 Receptor Blocker. The mechanism of action of azilsartan is as an Angiotensin 2 Type 1 Receptor Antagonist. The physiologic effect of azilsartan is by means of Decreased Blood Pressure.
Azilsartan medoxomil is an angiotensin II receptor antagonist indicated for the treatment of mild to moderate essential hypertension. Azilsartan medoxomil is a prodrug of Azilsartan. Azilsartan medoxomil has so far been shown to be superior to olmesartan and valsartan in lowering blood pressure.
Mechanism of Action of Azilsartan
Azilsartan is an Angiotensin 2 Receptor Blocker. The mechanism of action of azilsartan is as an Angiotensin 2 Type 1 Receptor Antagonist. Azilsartan medoxomil decreases the pressor effect of angiotensin II. In response, angiotensin I, angiotensin II, and renin are increased while aldosterone is decreased. Azilsartan medoxomil blocks the angiotensin II type 1 receptor preventing angiotensin II from binding and causing vasoconstriction. Azilsartan’s ability to remain tightly bound to AT1 receptors for very long periods after drug washout is among its most unusual features. Azilsartan is an angiotensin II receptor blocker (ARB) used in the therapy of hypertension. It is associated with a low rate of transient serum aminotransferase elevations but has yet to be linked to instances of acute liver injury.
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Azilsartan medoxomil is a newly approved angiotensin receptor blocker (ARB) reported to lower 24 hr blood pressure more effectively than maximally recommended doses of older ARBs. Although azilsartan is considered to be an unusually potent angiotensin II type 1 (AT1) receptor antagonist, little is known about the potential pleiotropic effects of this molecule. /The purpose of this study was to investigate/ pleiotropic features of azilsartan in cell-based assay systems independent of its effects on blood pressure. In cultured 3T3-L1 preadipocytes, azilsartan enhanced adipogenesis and exerted greater effects than valsartan on the expression of genes encoding peroxisome proliferator-activated receptor a (PPARa), PPARd, leptin, adipsin, and adiponectin. The effects of azilsartan on adipocyte differentiation and gene expression were observed at concentrations of azilsartan that did not classically stimulate PPAR activity in cell-based transactivation assays. Azilsartan also potently inhibited vascular cell proliferation in the absence of exogenously supplemented angiotensin II. In aortic endothelial cells, azilsartan inhibited cell proliferation at concentrations as low as 1 umol/L, whereas valsartan showed little or no antiproliferative effects at concentrations below 10 umol/L. Antiproliferative effects of azilsartan were also observed in cells lacking AT1 receptors. In addition, azilsartan, but not valsartan, blocked angiotensin II-induced activation of mitogen-activated protein kinase in vascular smooth muscle cells 4-8 hr after washout of a drug from the incubation media. These findings suggest that azilsartan can function as a pleiotropic ARB with potentially beneficial effects on cellular mechanisms of cardiometabolic disease through actions that could involve more than just blockade of AT1 receptors and/or reduction in blood pressure.
Indications of Azilsartan
- High Blood Pressure
- Migraine Prevention
- Heart Failure
- Alport Syndrome
- Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.
- Isolated systolic hypertension,
- Left ventricular hypertrophy
- Diabetic Nephropathies
- 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
Therapeutic Indications
- Azilsartan is an angiotensin II receptor blocker (ARB) 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.
- Azilsartan may be used alone or in combination with other antihypertensive agents.
- Both angiotensin II receptor antagonists /eg, azilsartan/ 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.
Contra-Indications of Azilsartan
- Kidney problems
- Heart problems
- Recent excessive vomiting or diarrhea
- A condition called primary hyperaldosteronism.
- The high amount of potassium in the blood
- Renal artery stenosis
- Abnormally low blood pressure
- Liver problems
- Mild to moderate kidney impairment
- Pregnancy
- Decreased blood volume
Side Effects of Azilsartan
The most common
- A dry cough
- Depression
- 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
- Constipation
- High blood pressure
- 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
- fever.
Common
- 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
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- hallucinations
- a headache
- irritability
- lightheadedness
- 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
- Depression
Drug Interactions of Azilsartan
Azilsartan 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)
- angiotensin receptor blockers ; (ARBs; e.g., candesartan, irbesartan, losartan)
- antacids
- “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)
- carbamazepine
- cimetidine
- clopidogrel
- cyclosporine
- dasatinib
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- duloxetine
- asthma medications (e.g., theophylline)
- diltiazem
- medications for abnormal heart rhythms (e.g., disopyramide)
- nitroglycerin
- nonsteroidal anti-inflammatory medications (NSAIDs; e.g., indomethacin, naproxen)
- oral diabetes medications (e.g., metformin, pioglitazone)
- pentoxifylline
- monoamine oxidase (MAO) inhibitors (e.g., phenelzine, selegiline, )
- other beta-blockers (e.g., propranolol, metoprolol)
- oxtriphylline
- verapamil
- fusidic acid
- haloperidol
- imatinib
- imipramine
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- metronidazole
- monoamine oxidase inhibitors (MAOIs; e.g., phenelzine, rasagiline, selegiline, )
- pentoxifylline
- phenytoin
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- quetiapine
- rituximab
- sertraline
- simvastatin
- tetracycline
- theophylline
- tocilizumab
- warfarin
Some products that may interact with this drug include aliskiren, lithium, drugs that may increase the level of potassium in the blood (such as ACE inhibitors including benazepril/lisinopril, birth control pills containing drospirenone).
Pregnancy & Lactation of Azilsartan
FDA Pregnancy category D
Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started
Lactation
Because no information is available regarding the use of azilsartan medoxomil during breastfeeding, Edarbi is not recommended and alternative treatments with better-established safety profiles during breast-feeding are preferable, especially while breastfeeding a newborn or preterm infant.
Fertility
No data are available on the effect of azilsartan medoxomil on human fertility. Nonclinical studies demonstrated that azilsartan did not appear to affect male or female fertility in the rate.
References
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