Lecture - Pharmacology (ACE inhibitors, RAAS)

Question 1

Renin-Angiotensin-Aldosteron System (RAAS)

1. It works ____ with the autonomic nervous system to form what?
2. And also to stimulate the relase of what?
3. What are the two main physiological actions of these two things?

Answer 1

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Question 2

RAAS

Step 1:

1. Renin is released - what is it? What does it do?
2. Induced release from what cells? What three things will induce its release? (be specific)
3. What are these cells lining? What receptor do they have on their surface?
4. What do the macula densa cells sense?

Step 2:

1. What thing does this step involve?
2. There are 2 forms of this thing - what are the two forms called, were are they found, what do they do?
3. Which of these two forms can you readily hit with the drugs?

Okay, go read the summary slide on slide 8 carefully!

1. Where is angiotensinogen made? Where does it go to after that?
2. There are 2 types of angio2 receptors - what are they? What does each do when replicated?

Flowchart on slide 10

1. So when you have a drop in BP, what detects this?
2. Then what gets stimulated (like what does question 1 send a signal to?)
3. Where in this do beta blockers fit?
4. So renin is released - what will renin then do?
5. What will ACE do?
6. What does active angio2 do and where? (3 things!)
7. Where does the hornome released in question 6 act?
8. What are effects of the action of hornome in question 6?
9. In the end, what is the result?

Answer 2

Angiotensinogen stays in criculation after made in liver

Question 3

1. Angiotensin 1 - is it active or inactive?
2. What is AT1 formed by?
3. What sort of biological activity does AT1 have?
4. Angiotensin 2 - is it active or inactive?
5. Formed into what and by who?
6. What is this an agonist at? Which of these receptors is ‘patholoical’ and which one is ‘beneficial’?

Answer 3

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Question 4

Angiotensin 2 receptors

AT(1):

1. Mediates what?

AT(2):

1. So it’s considered beneficial but that was in brackets
2. Inhibits what?
3. Increases what? What does this compound do?
4. Anti-what 2 things?
5. Vasoconstriction or vasodilaiton?

Answer 4

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Question 5

Impact of Angiotensin II on AT(1) receptor:

Now, you need to know these effects off by heart without my list helping you. The lecturer told you all of them without forgetting anything so you need to be able to do that too. There are 5 effects of it - what are they?

In detail and with reference to the diagram - what is the action of angio2 on pre-synaptic AT(1) receptors? How does clonidine come into this?

On slide 15, there is one more effect of angio2 that isnt mentioned elsewhere, what is it?

Answer 5

Slide 15: thirst

Question 6

On te flow diagram of decreasd BP to increas BP - where do ACE inhbiitors fit?

Answer 6

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Question 7

ACE inhbiitors:

1. SO you know how the beta blockers are the ‘olol’s - what are the ACE inhibitors? Give me an exmple of an ACE inhibitor
2. So with these inhibitors, there in inhibition of _____ ACE activity
3. What three things will that lead to?
4. Tie the effects in with these things: afterload*, preload**, kinins, vasodilation x2
5. What does bradykinin do and how?
   * Afterload* = what is it? Whereabouts in the cardiac cycle does it refer to?*
   * Preload** = what is it? Whereabouts in the cardiac cycle does it refer to?*
   * -Actually, explain these two concepts using the CO = HR x SV*
   * -What vessels does each relate to?*

More actions of ACE inhibitors

1. By reducing angio2 effect in kidney and reducing aldosterone release from adrenal cortex, what does it promote? So you reduce what? How does this tie in with BP?
   - It also reduces the production of what? What does that lead to?
2. They also inhibit something else that is associated with chronic HTN, MI and HF

Question 8

ACE inhibitor pharmacokinetics - Carazipill

1. Respell the drug into the correct spelling and pronounse it outloud
2. What’s the route?
3. What is its oral abs like? Bioavailability?
4. What is cilazapril metabolised to? By what?
   - so what will affect the formation of this but not the clearance of it?
   - what will reduce clearance? So this results in what?
5. When are the cilazaprilat Peak plasma levels?
6. What’s the half life?

Answer 8

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Question 9

ACE inhibitors - therapeutic uses

1. What’s the main use?
   - what do ACE inhibitors reduce that is relevant here?
   - what’re the effects on the cardiovascular component? (there are 2)
   - what’re the effects on kidney? (there are 2) What can we assist this by?
2. Do ACE inhibitors work in pateitns that don’t have hyper-reninemic hypertension (aka pateints with low-to-normal circulating renin levels)?
3. What is the effectiveness of lowering BP in pateints w/o excess plasma renin activity due to?
4. Even if you dont have hyperreninemic hypertension, ACEIs means inhibition of angio2 and that will reduce ______/______ conseuqences of RAS activation
5. It’s also got a 2nd main disease that it is used for - what is it? What 4 things that reduced angio2 level produce are useful for this disease?
6. What’re the doses like?

Answer 9

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Question 10

ACE inhibitors: adverse effects

1. Bradykinin related ADRs include what 2 things? Why’s this?
2. There are 4 other adverse effects you should know - what are they?
3. You mentioned renal issues in quesion 2 - what should you do with the dose if one has renal impairment? Caution should be taken with concomitant use of what? ACE inhibitors - they induce or exacerbate the renal impairment in patients with what? (no effect in ____)
4. Go to slide 31 - what is the gist of it? This is to do with being careful with using ACEIs in people with renal issues
5. Read slide 33 and recite it to a wall about why you need to be careful with NSAIDs and bilateral renal artery stenosis

Answer 10

4. Basically, you want to reduce the angio2 so it doesnt constrct the afferent arteriole but you don’t want to drop GFR since there are renal issues going on. If you have angio2, you will first constrct efferent arterile and that will increase GFR since increase glomerular pressure. Then if you get much more angio2, you will constrict afferent and get hypoxic kidney. So you want to reduce the angio2 enough to not get hypoxic kidney but keep the angio2 still there so you can keep GFR up by keeping the glomerular pressure.

Question 11

Angiotensin receptor blockers

1. What circumstance are they used under?
2. “olol”s are B-blockers so what are these? Give 1 example pls
3. O_____ a_____ angio2 receptor ________
   - do they cause kinin accululation? From the previous knowlesge you have, what does accumulation of bradyikinin cause? (slide 34)
   - what about the cough?
4. What are the pathways of angio2 generation? So what does using ARBs do?
5. It is potent antagonsit selective for what receptor? So it blocks all effects of angio2 on that receptor
6. Just to drum it in, it will prevent the effects of angio2 - what are its effects?
7. ARBS show theoratical benefits over ACEIs - what are the 3?
8. What are the indications of ARBS aka what three things are they used for? Are they equally as effective as ACEIs?
9. What’re the side effects of ARBs?
10. Pharmacokinetics of ARBs
    - orally active but what?
    - how are ARBs mostly or in part eliminated? Metablised by what?
    - What’re the Losartan Peak plasma levels? What about the half life? What about the half life of its active metabolite?
    - what recudes the level of active metabolite?
    - decreased renal function can affect what?

Answer 11

1. If can’t take ACE inhibitors then take this
2. The ‘sartan drugs - Losartan
3. So if we inhbiti ACE then only affecting renal-angiotensin system stuff, if we block the receptor then we stop angio2 from any direction affecting reagrdless whether its ACE or chymase from heart etc