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Pharm Block 2 > 9 - Renin-Angiotensin, Vasoactive Peptides > Flashcards

9 - Renin-Angiotensin, Vasoactive Peptides Flashcards

1
Q

What is the main function of the renin-angiotensin system?

A

Conservation of salt and water.

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2
Q

What are the components of the renin-angiotensin system?

A

Renin cleaves angiotensinogen to give you AngI, a decapeptide.

Then ACE (angiotensin converting enzyme) converts AngI to AngII, an 8 amino acid peptide.

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3
Q

How can you prevent angiotensinogen from being turned into angiotensin I?

A

By blocking renin.

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4
Q

What are the components of the juxtaglomerular apparatus?

A

juxtaglomerular apparatus is made of renin containing cells - specialized cells at the end of the afferent arteriole that secrete renin.

Sympathetic nerves innervate cells along the afferent arteriole.

Macula densa cells in the distal tubule that sense salt delivery.

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5
Q

What are the mechanisms that sense the need for renin release?

A

Intrarenal baroreceptors sense stretch/renal perfusion pressure.

Decreased pressure increases renin release.

Increased pressure in preglomerular vessels (increased volume) decreases renin release.

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6
Q

What is a second mechanism of renin release (besides the intrarenal baroreceptors)?

A

Macula densa senses the sodium load.

Decrease salt intake causes increased renin release.

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7
Q

What is the third mechanism of renin release (besides macula densa and intrarenal baroreceptors)?

A

Sympathetic nervous system: B1 adrenergic receptor mediated.

Sympathetic nerve stimulation increases renin release.

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8
Q

What is the mechanism that causes an increase in renin release?

A

Decreased salt transport at the apical macula densa results in an increase in COX-2.

When COX-2 is up, juxtaglomerular cells release prostaglandin E2 causing an increase in cAMP and an increase in renin release.

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9
Q

What is the mechanism that causes a decrease in renin release?

A

Increased angiotensin II activates AT1 receptors, resulting in a decrease in renin. (negative feedback).

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10
Q

Angiotensin II works on what type of receptors? What is the one that is currently targeted by drugs?

A

AT-1: responsible for the primary actions of ANGII (only drugs we have are for this receptor).

AT-2

AT-4

Mas and PRR (prorenin)

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11
Q

What effect does angiotensin II have on AT1 receptors?

A 
Vasocontriction
Vascular proliferation
Aldosterone secretion
Cardiac myocyte proliferation
Increased sympathetic tone

If it spills over, ANGII can also activate AT2 receptors and cause those effects.

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12
Q

What effect does angiotensin II have on AT2 receptors?

A

Vasodilation
Antiproliferation
Apoptosis (not bad though)

Put some of the breaks on what AT1 is doing.

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13
Q

What is the signaling cascade associated with AT1 receptors?

A

AT-1 activates PLC to cleave PIP2 into IP3 and DAG.

IP3 causes an increase in calcium and DAG causes an increase in PK-C that goes on to phosphorylate proteins.

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14
Q

What does angiotensin II cause?

A

Aldosterone secretion
Vasoconstriction
Sympathetic activation

All help to regulate blood pressure.

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15
Q

Angiotensin II have a major effect on _____, and can cause ______ when it’s inappropriately elevated.

A

Blood pressure.

ANGII can lead to HTN when it’s inappropriately elevated.

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16
Q

When there’s an increase in angiotensin II, arterioles _______ and BP _______ until it returns to normal.

A

Vasocontrict.

Increases.

17
Q

What effect does ANGII have on tubular reabsorption?

A

AngII acts on the adrenal cortex to increase aldosterone.

Aldosterone causes an increase in Na and H2O reabsorption and an increase in K+ and H+ secretion.

18
Q

What are the actions of aldosterone?

A

Expression of Na and K epithelial transport genes: activates Na/K ATPase to bring sodium in and cause some K secretion.

Kidney principal and intercalated cells in the collecting duct.

Heart: causes fibrosis and hypertrophy

19
Q

What effect does angiotensin have on sympathetic neurons?

A

It binds to AT1 on the presynaptic neuron and causes norepi release.

Norepi binds to the post-synaptic alpha-1 receptor to activate the sympathetic nervous system.

AngII can also bind to post-synaptic AT1 receptor to cause smooth muscle contraction (vasocontriction).

20
Q

What can cause HTN?

A

When there’s inappropriate levels of ANGII for the salt and water status of your body.

AT-1 and aldosterone then cause you to hold onto too much water and salt.

21
Q

What are the three main effects that occur when AngII binds to the AT1 receptor?

A

Vasoconstriction: increased vascular resistance and increased BP

Cell growth: LVH vascular remodeling

Aldosterone production: increased sodium/water retention, increased BP.

22
Q

What detrimental effects does AngII via the AT-1 receptors have on organs?

A 
Stroke
Hypertension
Heart failure 
MI 
Renal failure
23
Q

How does a B-adrenergic antagonist impact renin release?

A

B-adrenergic antagonists decrease adenylate cyclase and decrease intracellular cAMP levels in juxtaglomerular cells.

This causes a decrease in renin release.

24
Q

What are the general effects of renin-angiotensin system inhibitors?

A

BP lowering related to plasma renin activity.

Vasodilation that’s arterial dominant

Decrease in BP with no change in HR

25
Q

What adverse side effects are associated with renin-angiotension system inhibitors? When are these contraindicated?

A

Can cause hypotension of hyperkalemia.

Blocking the Na/K ATPase prevents K from being secreted.

Contraindicated in pregnancy because renin is important for fetal development. Can cause fetal wasting.

26
Q

What are the three ways that you can inhibit the renin-angiotensin system?

A

Inhibit renin
Inhibit ACE
Inhibit angiotensin receptor blockers (ARB).

27
Q

What drug is an AT-1 receptor blocker (ARB)? What effects does this drug have?

A

Losartan.

Prevents AngII from binding it’s AT1 receptor, resulting in:

  • decreased aldosterone secretion
  • decreased vasoconstriction
  • decreased sympathetic activation

All of these work to decrease BP.

28
Q

What happens to the AngII levels in the body when giving angiotensin receptor blockers (ARBs) like losartan?

A

Angiotensin II levels in the body will increase when you give the AT1 receptor blocker.

This increased AngII can act on AT2 receptors and cause:

  • vasodilation
  • antiproliferation
  • apoptosis (good though).
29
Q

How long does it take for losartan to have its maximal effect? What needs to be monitored?

A

6 weeks

Blood draws needed to make sure pt isn’t becoming hyperkalemic.

30
Q

What three drugs are ACE inhibitors?

A

Captopril
Enalapril
Lisinopril

31
Q

How do ACE inhibitors work?

A

That prevent AngI from being cleaved into AngII.

ALSO blocks the kinase that degrades bradykinin, resulting in increased bradykinin levels. (some positive effects via NO and PG release)

32
Q

What are adverse effects of ACE inhibitors?

A

Persistent cough

Angioedema: life-threatening

33
Q

What drug inhibits renin directly? How does it do this?

A

Aliskiren

Blocks enzymatic pocket and doesn’t allow renin to have it’s activity.

Results in decrease in AngI and AngII and therefore a decrease in BP with no change in HR.

34
Q

What effect do B-adrenergic receptor antagonists have on the heart and the kidneys? What are these used to treat?

A

Cardiac: decrease HR via B1 receptor
Renal: decrease renin release via B1 receptor

Used to treat HTN; BP lowering releases to plasma renin activity.

35
Q

What drug is a B1B2 antagonist used to treat HTN? What drug is a B1 antagonist used to treat HTN?

A

B1B2 antagonist: propranolol

B1 antagonist: metoprolol

36
Q

What effects do aldosterone antagonists have? What are two examples of drugs that do this?

A

Spironolactone and eplerenone

These are diuretics that increase salt and water excretion.

37
Q

What are the effects of entresto?

A

Inhibits enzyme called neprilysin and allows you to increase natriuretic peptides.

Good to combat heart failure.

Also blocks AT1 receptor which blocks AngII.

Pharm Block 2 (12 decks)

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