Mednotes

ACE inhibitors & ARBs

3 min read

Overview

Ace inhibitors and ARBs are drugs which block the Renin-aldestrone-angiotensin system from namely causing vasoconstriction and sodium retention. They are prescribed to reduce hypertension.

Uses

MOA and context

ACEs and ARBS have different mechanisms of action but both work to reduce hypertension through blocking the RAAS from vasocontriction and sodium retention. There are some other factors in play like fibrosis and remodeling but this isnt as frontline i think.

ACE inhibitors

These drugs inhibit ACE (angiotensin converting enzyme). This means that less Ang II will be produced from Ang I

Therefore:

  • Decreases levels of Ang II released
    • Reduces vasocontriction reducing systemic vascular resistance (reduced afterload)
    • Increases venous vasodilation (reduced preload)
  • Increases levels of bradykinin by stopping ACE from breaking it down -> can lead to dry cough
  • reduces aldosterone production
    • promote Na+ excretion and water excretion reducing plasma volume
    • inhibit cardiac and vascular remodeling and fibrosis associated with CVD

ARBs

These work to block the action of Ang II on the Angiotensin II Type I receptor (AT1R), which is responsible for most of the unwanted results we see from the RAAS system. The specific block of this receptor means that the AT2R can still be activated which leads to some positive effects like reduction of fibrosis, nitric oxide production leading to vasodilation and reduction in cell proliferation and apoptosis.

You would often prescribe these in the case that the patient cannot tolerate ACE-Is

Therefore:

  • a lot of the same effects of ACE-Is have minus kinin accumulation and AT2R block
    • may channel Ang II to AT2Rs to get increased positive effects
  • additionally blocks Ang II no matter how its formed
  • In theory is more beneficial than ACEs

Shared reduction in negative outcomes from Ang II

Both of these drug classes will mean that there will be less vasocontriction and less aldosterone.

Generations and subgroups

finish

Examples

ACE inhibitors covered in lectures or in personal formulary list.

ARBs (‘sartans)

ACE inhibitors covered in lectures or in personal formulary list.

RAAS (context) ! move to renal section

This is to give context on the associated drug system:
The Renin-Aldosterone-Angiotensin-System is involved in body regulation of water and salts.

The system is started with the release of renin from the kidney from juxtaglomerular cells in response to sympathetic stimulation, low blood pressure in kidneys, and low Na+ in distal tubule. These kick off the RAAS.

We then see a number of interactions occuring

  1. Renin cleaves angiotensinogen produced by the liver to form angiotensin I

  2. Angiotensin I is cleaved by ACE (Angiotensin converting enzyme) to form Angiotensin II a far more potent version. ACEs are often bound ot endothelial walls. The angiotensin II is can then bind to Angiotensin receptors I or II (AtI or AtII)

Angiotensin receptor 1 (AT1R) has a lot of potentially pathological effects such as Na+ reabsorption, vasoconstriction, and aldosterone release and in general is profibrotic, apoptotic, cell proliferative which are all bad things.
Angiotensin receptor 2 (AT2R) leads to positive effects, such as antiproliferative, antifibrosis, and vasodilation

  1. Angiotensin receptors generally directly and indirectly lead to:
  • Na+ and fluid retention
  • increase in BP (vasoconstriction and fluid retention)
  • Aldosterone secretion

The RAAS can be modified at each of its points

- Reducing renin release (beta blockers and renin inhibitors)
- Reducing Ang II production (ACE inhibitors)
- Inhibiting At1 receptors (ARB inhibitors)
- Decreasing aldosterone mediated effects (Mineralcorticoid receptor inhibitor)

And these are all the ways the drugs will be covered.

(ACE also cleaves bradykinin to deactivate it so dry cough can occur in patients under ACE inhibitors)

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