| Class | ACE-inhibitor |
|---|---|
| Chemistry |
Imidazole analogues
|
| Routes of administration |
Oral, for all of them |
| Absorption |
Apart from irbesartan which has 60-80% oral bioavailability, the others are poorly available (20%-40%)
|
| Solubility |
pKa range is from 6.0 (candesartan) to 3.6 (valsartan)
|
| Distribution |
Small volumes of distribution, 0.14 L/kg for candesartan to 0.7 L/kg for irbesartan. The exception is telmisartan (7L/kg), as it is highly protein-bound (>99.5%) and distributed to the tissues.
|
| Metabolism |
All ARBs are incompletely dependent on hepatic metabolism (40% to 80%), except for telmisartan, which is 100% reliant on hepatic metabolism.
|
| Elimination |
20%-60% renally excreted unchanged, except for telmisartan (0%)
|
| Time course of action |
Most of these are long acting agents, eg. telmisartan (24 hrs half life). Shortest acting are losartan (2-6 hrs) and valsartan (6 hrs)
|
| Target receptor |
Angiotensin II receptor (AT1 receptor). These drugs bind to the receptor site but do not activate the actual receptor, making them blockers rather than agonists. Angiotensin II binds at the same binding site but also at a couple of other binding sites, which is what confers the activating effect. |
| Mechanism of action |
By interfering with the binding of Angiotensin-II and its receptor (by competitive inhibition), these drugs interrupt the effects of renin-angiotensin-aldosterone system activation, which are mainly mediated by Angiotensin II via the AT1 receptor. |
| Clinical effects |
Vasodilation (without reflex tachycardia), increased natriuresis, increased sensitivity to diuretics, decreased glomerular filtration. Positive effects of vascular and myocardial remodelling in CCF. No angioedema, unlike ACE-inhibitors. |
| Literature reference |
FDI PI booklet |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 9(p.2) from the second paper of 2008 |