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?

 

List:

·      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

Aldosterone

·  ↑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:

 

Pharmacology

Problems under GA

Β1-adrenoceptor antagonists

β1 -> ↓Renin release etc.

Bradycardia

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

 

 

 

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