2021B02 Briefly outline the mechanisms by which ACE inhibitors and angiotensin receptor blockers produce a) their therapeutic effects b) potential adverse effects.

 

List:

     RAAS flowchart

     Hormone effects

     Drug effects

 

RAAS flow chart:

 

Hormone effects:

Summary

      Whole body response to hypotension and hypovolaemia

      Vasoconstriction -> ↑SVR / afterload

      ↑Fluid and sodium retention -> ↑ECF volume -> ↑preload -> ↑CO

      ↑Blood pressure

AT2

      AGTR1 receptor agonist

      Systemic vasoconstriction

      Renal efferent > afferent arteriolar vasoconstriction

      ↑Na+/H2O reabsorption from proximal tubule

      ↑Release of aldosterone and ADH

      ↑Thirst

Aldosterone

      Mineralocorticoid receptor agonist

      ↑ENaC activity -> ↑ECF [Na+] (distal nephron, colon, sweat gland)

      ↑Release of ADH release (indirect via ↑[Na+])

Bradykinin

      Bradykinin receptor agonist

      ↑Release of vasoactive factors (prostanoids, nitric oxide)

      Vasodilation, capillary leak, diuresis

 

Drug effects:

MoA

      ACEi: prevent formation of AT2 and breakdown of bradykinin

      ARB: competitive antagonist at AGTR

Therapeutic

      ↓Preload, ↓afterload -> ↓LV wall stress -> ↓remodelling -> ↓progression of heart failure

      ↓Risk of AMI

      ↓Risk of diabetic nephropathy

      ↓Blood pressure

Adverse

      Vasodilation + hypovolaemia -> peri-op refractory hypotension

      ↓Aldosterone -> hyperkalaemia (important if renal impairment)

      Renal vasoconstriction -> dysfunction (especially peri-op, thiazide, NSAID)

      Bradykinin -> angioedema, cough (ACEi only)

 

 

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