The Cardiovascular section of the 2023 CICM Primary Syllabus Pharmacopeia asks the exam candidate to have a "Level 3" knowledge of these drugs, and makes a distinction between them and the angiotensin receptor blockers, but does not single out any specific agents.
| Class | ACE-inhibitor |
|---|---|
| Chemistry |
All are L-proline derivatives with different active groups (sulfhydryl group in captopril, phosphoryl group in fosinopril, and dicarboxylate (-COOH) group for enalapril, lisinopril perindopril quinapril and ramipril)
|
| Routes of administration |
Oral, except for enalaprilat |
| Absorption |
Range from 28% oral bioavailability (ramipril) to 75% (capropril)
|
| Solubility |
pKa ranges from 9.8 (captopril) to 2.5 (lisinopril)
|
| Distribution |
VOD ranges from 0.1L/kg (ramipril) to 3.6-7.8 L/kg (quinapril)
|
| Metabolism |
All ACE-inhibitors undergo some (usually extensive) hepatic metabolism, except lisinopril. Many (perindopril, ramipril, quinapril, fosinopril) are administered as a prodrug.
|
| Elimination |
Only lisinopril is excreted renally as 100% unchanged drug; the others undergo extensive metabolism, of which ramipril perindopril and quinapril are especially dependent on the liver, and capto/enala/fosinopril are partially handled by both systems
|
| Time course of action |
Effects are maximal very shortly (15min) following oral administration for most agents, but the effect of many is short-lived (~ 2 hrs for captopril and quinapril). Long acting ones are enalapril, lisinopril, fosinopril and ramipril (10-17 hrs)
|
| Target receptor |
ACE enzyme |
| Mechanism of action |
By interfering with a zinc moiety on the ACE enzyme, this drug nterrupts the conversion of Angiotensin-I into Angiotensin-II, thereby interrupting 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. Also, dry irritating cough and a chance of random angioedema. |
| Literature reference |
FDI PI booklet |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 9(p.2) from the second paper of 2008. |