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Monday, January 19, 2015

Renin - Angiotensin - Aldosterone System Explained

Renin, Angiotensin, Aldosterone, RAAS, nurse, ACE Inhibitors, ARBs


I'm not sure why, but it does seem that some systems are easier to understand than others. I've always struggled with the Renin - Angiotensin - Aldosterone System (RAAS). In this post I'll talk about the pathophysiology and pharmacology associated with this system.


Pathophysiology of RAAS 


  • There are three polypeptides: Angiotensin I, Angiotensin II, and Angiotensin III. Angiotensin I is a precursor to II. II has strong biologic activity, and III is formed by the degradation of II.
  • Angiotensinogen is catalyzed by renin to form angiotensin I. Angiotensin converting enzymes do just that and convert angiotensin I to angiotensin II.
  • Angiotensin II stimulates the release of aldosterone and causes vasoconstriction. Both actions increase blood pressure. Angiotensin II can indirectly cause vasoconstriction by acting on the sympathetic neurons to promote norepinephrine release, the adrenal medulla to promote epinephrine release, and the central nervous system to increase sympathetic outflow to blood vessels.
  • Aldosterone works on the distal tubules of the kidney to cause retention of sodium and excretion of potassium and hydrogen. Because it retains sodium, this retains water and causes an increase in blood volume, which causes blood pressure to rise. 

Pharmacology

  • ACE Inhibitors- Do just that, inhibit the formation of antiotensin converting enzymes, so angiotensin I (inactive) isn't converted to angiotensin II (active). It also increases levels of bradykinin through inhibition of kinase II. Note: ACE and Kinase II are the same thing but go by different names depending upon the substrate that action is taking place.
  • ARBs- Angiotensin II Receptor Blockers- The mechanism of action differs from ACE inhibitors in that ARBS block the ACTIONS of angiotensin II whereas ACE inhibitors block the PRODUCTION of angiotensin II. (Let that sink in.)

    ARBS block the access of angiotensin II to its receptors in blood vessels, the adrenals, and all other tissues. You cannot use these two drugs classes interchangeably, even though they have very similar effects. ACE inhibitors have more evidence to show their decrease in cardiovascular morbidity and mortality in comparison to ARBS. So ARBS are a second preference for patients who cannot tolerate an ACE inhibitor.
  • Aldosterone Antagonists- Can be broken down into two agents: Eplerenone and spironolactone. Eplerenone produces selective blockade of aldosterone receptors having little or no effect on receptors for other steriod hormones. Spironolactone also blocks receptors for aldosterone but it also binds with receptors for other steroid hormones. It has more side effects. Hyperkalemia is the major side effect with both of these drugs.



Based off of your interest in this post you might be interested in reading:

Fast Facts on HYPERkalemia

Quick Guide to HYPOkalemia






Let me know if you have any questions on this topic by leaving a comment below!


Xoxo,

Nightingale
 

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