QUESTIONS

1. When blood pressure drops, how is this perceived by one's body?
    
2. What are the three effects of angiotensin II that are helpful in the event of acute blood pressure drop?  Why are these same three things not so good in the long run?
    
3. What is the relationship between Angiotensin Converting Enzyme & Bradykinin?
    
4. How is GFR protected by Angiotensin II when blood pressure drops?
    
5. Is enalapril a potent ACE Inhibitor?
    
6. Is an ACE Inhibitor a good emergency heart failure drug?
    
7. What biotoxin are ACE inhibitors analogs of?
    
8. What are the main adverse effects to watch for with ACE Inhibitor use?
   
   
   
   
    

ANSWERS

1. There are two ways that a blood pressure drop is perceived by the body. The first way (which isn't relevant to the ACE inhibitor) is the mechanism that results in an increase in sympathetic tone.  There are baroreceptors located in the aortic arch & bifurcation of the carotid artery & when they feel bp drop, they send an message up the afferents of the vagus nerve & the glossopharyngeal nerves to the medulla oblongata.  The CNS then sends a message back down to speed things up.  (Recall the vagus is the "brake" & the phrenic is the "gas."  The baroreceptors and CNS are constantly communicating & stimulation to the heart is continuous.  It isn't like the baroreceptors are sleeping until BP drops & then they start firing.)
   
   OK, the second way  is relevant to the ACE inhibitor.  There are also baroreceptors in the macula densa of the distal renal tubule.  These preceive a drop in BP & send a message to the juxtaglomerular apparatus to release renin.
   
   
   
   
    
2. Angiotensinogen (produced by the liver) is floating around in the circulation.  It is converted by renin into angiotensin I.
   
   In the lung, Angiotensin Converting Enzyme converts angiotensin I to angiotensin II.
   
   Angiotensin II is a potent vasoconstrictor, stimulates aldosterone release, & stimulates release of antidiuretic hormone.  THESE ARE THE THREE THINGS THAT ANGIOTENSIN DOES TO HELP IN ACUTE BP DROP.
   
   By vasoconstricting, we are squirting more blood out of the venous system into the heart to increase preload.  This is acute so Starling's law will give us a stronger contraction to pump this greater volume of blood.  More blood to pump & a stronger contraction = more cardiac output. Good.But in the long term, it just means more afterload to pump against & that's extra hard for the heart. Bad. (Paul, is there more to add here?)
   
   Antidiuretic hormone conserves fluid so there will be more blood volume & less urine.  Aldosterone causes sodium retention so there will be more blood volume.  More blood volume brings up blood pressure. Good.  But causes volume overloading in the long run. Bad.  (Can you actually get K+ depletion in the long run & subsequent muscle weakness, too?)
   
   
   
   
    
3. Angiotensin Converting Enzyme breaks down bradykinin.  When bradykinin is around it facilitates prostaglandin E2 & I2 production & these guys are vasodilators.  It is not certain how much these prostaglandins are helping us when we use ACE inhibitors but it may be part of the big picture.
   
   
   
   
    
4. Angiotensin II has a greater constricting effect on the efferent arteriole than on the afferent arteriole.  This keeps blood in the glomerulus even though BP is low.  Remember, when you use an ACE inhibitor this is abolished & pre-renal azotemia can be unmasked/unleashed.  DO NOT GIVE ACE INHIBITORS TO A DEHYDRATED PATIENT.  If your heart failure patient is dehydrated (could be after a ton of lasix), let it rehydrate itself by drinking before starting ACE Inhibitor.  If the patient is not drinking, you can given maintenance fluids (but no more) until it is not dehydrated anymore.
   
   (Paul. when is an ACE Inhibitor totally contraindicated in a patient? Like I mean you can't use it on them ever.  If there is CRF present?  Even if you have CRF compensated?  Any CRF?  Mild CRF?  If you start to get azotemic after starting ACE inhibitor, can you just drop lasix back or should you actually stop the ACE inhibitor?  If you have to stop the ACE inhibitor does this mean you can't an ACE inhibitor at all?)
   
   
   
   
    
5. Trick Question. Enapril is not a very potent ACE inhibitor.  After it is activated by the liver into enalaprilat (how do you pronounce that? I can barely pronounce enalapril.) which is a very potent ACE Inhibitor.
   
   
   
   
    
6. ACE Inhibitors exert their most beneficial effects by decreasing aldosterone concentration & this takes 4-7 days to see.  BP only drops about 5 torr in the short term (not a big vasodilatory drop).  So no, they aren't very good for emergencies.  Hydralazine works in 30 min after oral dosing & drops BP 20-30 torr.  Might be a better choice but we usually fix pulm edema w/lasix anyway.
   
   
   
   
    
7. The biotoxin is Teprotide, from the venom of the South American Pit Viper.  (Recall, those of you who treat rattlesnake bites:  the usual cause of death is cardiovascular collapse.  This is because of the vasodilating properties of this type of toxin.)
   
   
   
   
    
8. Watch out for GI upset, hyperkalemia, systemic hypotension (in the first 48 hours), & renal dysfunction (discussed above.)