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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