Products
Most sartans are commercially available as tablets or film-coated tablets. Losartan was the first agent approved in many countries in 1994 (Cosaar, USA: 1995, Cozaar). Sartans are often combined with hydrochlorothiazide fix. The name of the drug group is derived from the suffix -sartan of the active ingredients. The drugs are also called angiotensin II receptor antagonists.
Structure and properties
Typical structural elements of sartans include a biphenyl, heterocycles such as a tetrazole and imidazole, and a carboxylic acid. Some agents exist as prodrugs, such as losartan and candesartancilexetil. Losartan, the first prodrug, was developed at DuPont in the 1980s. The drug target is the angiotensin II receptor type 1, the so-called AT1 receptor. It is a GPCR with 7 transmembrane helices.
Effects
Sartans (ATC C09CA) interfere with the renin-angiotensin-aldosterone system. The effects are due to selective antagonism at the AT1 receptor. This abolishes the effects of angiotensin II at this receptor on various organs (vascular smooth muscle, adrenal glands, kidneys, heart). Sartans:
- Lower blood pressure
- Act vasodilator
- Inhibit the proliferation of smooth muscle cells (antihypertrophic)
- Reduce aldosterone secretion
- Are slightly diuretic
- Promote the excretion of sodium and the reabsorption of potassium
Indications
Indications for use include:
- Essential hypertension (high blood pressure).
- Hypertension with left ventricular hypertrophy to reduce the risk of stroke.
- Chronic heart failure
- Renal disease, diabetic nephropathy
Not all agents are approved for the same indications.
Active ingredients
- Azilsartan (Edarbi)
- Fimasartan (not commercially available in many countries).
- Losartan (Cosaar, generic).
- Valsartan (Diovan, generic)
- Irbesartan (Aprovel, generic)
- Candesartan (Atacand, Blopress, generic).
- Eprosartan (Teveten, generics)
- Olmesartan (Votum, Olmetec, generic).
- Telmisartan (Micardis, generics)
Dosage
According to the professional information. The drugs are usually taken once a day.
Contraindications
- Hypersensitivity
- Hereditary angioedema
- Angioedema on ACE inhibitors or sartans in patient history.
- Severe hepatic dysfunction
- Pregnancy, lactation
- Combination with aliskiren in patients with diabetes mellitus or impaired renal function.
- Children: see in the package leaflet
For full precautions, see the drug label.
Interactions
Some sartans are substrates of CYP450 isozymes. Combination with potassium supplements or drugs that increase potassium levels may result in hyperkalemia. Other antihypertensive drugs may cause further lowering of blood pressure. Other interactions are possible with lithium, NSAIDs, ACE inhibitors, and aliskiren (contraindicated) (selection). Dual inhibition of the RAAS is not recommended.
Adverse effects
Possible adverse effects include low blood pressure, headache, hyperkalemia, gastrointestinal discomfort, muscle pain, dizziness, and fatigue. Unlike ACE inhibitors, sartans do not inhibit angiotensin converting enzyme (ACE) and therefore have no effect on bradykinin breakdown. Bradykinin-mediated side effects such as irritable cough therefore occur only rarely.
