2012B05 Discuss the pharmacology of drugs that inhibit the activity of the renin-angiotensin system.
What particular problems can occur in the anaesthetized patient taking these drugs?



·      RAAS flowchart

·      Hormone effects

·      Drug effects and problems


RAAS flow chart:


Hormone effects:

Angiotensin 2

·  Constrict efferent > afferent arterioles

·  Hence ↓GFR with preserved GFP

·  ↑Na/H2O reabsorption from PT (via Na+/H+ exchange) (AGTR1)

·  ↑release of aldosterone

·  ↑release of ADH


·  ↑Na+ reabsorption from principal cells of connecting tubule and collecting duct (MR)

·  Indirectly causes H2O reabsorption via ↑ECF osmolality hence ↑ADH

·  ↑Na+ reabsorption from colon, sweat


Drug effects:



Problems under GA

Β1-adrenoceptor antagonists

β1 -> ↓Renin release etc.


AV conduction delay

ACE inhibitors

-Active: perindopril

-Prodrug: enalapril, ramipril

-Not metabolized: lisinopril

↓Angiotensin 2 etc

↓Inactivation of bradykinin and natriuretic peptides

Refractory hypotension

Increased risk renal impairment

Angiotensin receptor blocker

-e.g. irbesartan

↓Angiotensin 2 etc

(effect similar to ACEi)

As for ACEi

Mineralocorticoid receptor antagonists

-e.g. spironolactone

↓Aldosterone effect

Diuresis -> ↓hypovolaemia

Increased risk hyperkalaemia




Feedback welcome at ketaminenightmares@gmail.com