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)

 

 

Feedback welcome at ketaminenightmares@gmail.com