| Indication |
For the treatment of hypertension. |
| Pharmacodynamics |
Olmesartan, a specific angiotensin II type 1 antagonist, is used
alone or with other antihypertensive agents to treat hypertension.
Unlike the angiotensin receptor antagonist losartan, olmesartan does not
have an active metabolite or possess uricosuric effects. 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. |
| Mechanism of action |
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 AT1 receptor in vascular smooth muscle. Its action is,
therefore, independent of the pathways for angiotensin II synthesis.
Olmesartan has more than a 12,500-fold greater affinity for the AT1 receptor than for the AT2 receptor. |
| Absorption |
Bioavailability is about 26%. Food does not affect the bioavailability of olmesartan. |
| Volume of distribution |
|
| Protein binding |
Highly bound to plasma proteins (99%) and does not penetrate red blood cells. |
| Metabolism |
Olmesartan is rapidly and completely bioactivated by ester
hydrolysis to olmesartan during absorption from the gastrointestinal
tract. There is virtually no further metabolism of olmesartan. |
| Route of elimination |
Not Available |
| Half life |
Approximately 13 hours |
| Clearance |
- Total plasma cl=1.3 L/h
- Renal cl=0.6 L/h
|
| Toxicity |
Symptoms of overdose include dehydration (dry mouth, excessive
thirst, muscle pain or cramps, nausea and vomiting, weakness),
dizziness, low blood pressure, and slow or irregular heartbeat. |
