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PDA Block 2 > Renin-Angiotensin System Pharmacology > Flashcards

Renin-Angiotensin System Pharmacology Flashcards

1
Q

Renin-Angiotensin System

A 
Angiotensinogen 
***converted by renin***
Angtiotensin I
***Converted by ACE***
Angiotensin II
-Leads to: 
vasoconstriction
sympathetic activation
aldosterone secretion
***which all lead to blood pressure regulation
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2
Q

Juxtaglomerular Apparatus

A

Renin containing cells

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3
Q

Sympathetic Nerves

A

Afferent arteriole

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4
Q

Macula Densa

A

Specialized epithelial cell distal tubule

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5
Q

Intrarenal baroreceptor

A

Sense Stretch/renal perfusion pressure

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6
Q

What do the intrarenal baroreceptors signal when they sense low blood pressure

A

increased renin release so that more Na and water are held onto, which increases blood pressure

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7
Q

What happens when the macula densa senses a low Na load

A

they signla increased renin release

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8
Q

How does the sympathetic nervous system signal renin release

A

-increased renal sympathetic tone activated the B1 adrenergic receptors on JGCs this causes renin release

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9
Q

Exaplin how the macula densa is in involved in juxtaglomerular cell signaling to increase renin release

A
  • decreased Na transport to the apical macula densa
  • increases COX2 which produces PGs that activate adenylate cyclase in the juxtaglomerular cell and lead to increased cAMP which increases renin release
  • Increases Renin
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10
Q

Explain how the Increased Angiotensin II leads to decreased renin

A

Angiotensin II binds to and activates an AT1 receptor on the juxtaglomerular cell. This activates PLC which uses PK-C as a second messenger to inhibit renin release

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11
Q

Where n the body does Angiotensin II activate its receptor and what is the receptor

A

Angiotensin II activates AT1 receptors on renal vascular smooth muscle to reduce renal blood flow

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12
Q

How does Angiotensin II influence GFR

A

It slightly reduces it

-

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13
Q

What does Aldosterone do

A

It activates the expression of target genes responsible for N and K transport

In kidneys Aldosterone increases Na and water reabsorption and increases secretion of K and H into urine

it also causes fibrosis and hypertrophy in the heart

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14
Q

What three things does Angiotensin II lead to

A

when it binds to the AT1 receptor it leads to

  • vasoconstriction
  • cell growth
  • Aldosterone production
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15
Q

What does Angiotensin II do to the heart

A

hypertrophy of cardiac myocytes

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16
Q

How is Angiotensin II involved in hypertension

A

It leads to Na and water reabsorption which increases blood pressure. SO
If you inhibit production of Angiotensin II then you will have lower blood pressure

17
Q

Losartan

A

AT1 receptor blocker: Competitive angiotensin receptor antagonist. Selective for the AT1
receptor subtype.
*Doesn’t let Angiotensin II bind to its receptor and elicit its effects
-decreased aldosterone secretion
-decreased vasoconstrictio
-decreased sympathetic activation
-All of this leads to decreased blood pressure
-makes more Angiotensin II bind to the AT2 receptors which leads to vasodilation, antiproliferation and apoptosis

18
Q

Renin-Angiotensin System Inhibitors

A
  • drugs that inhibit RAS by different mechanisms
  • blood pressure lowering related to plasma renin activity
  • Vasodilation arterial (dominant) and venous circulations
  • decrease blood pressure with no change in heart rate
  • can cause hypotension or hyperkalemia
  • contraindicated in preganancy-fetal wasting
19
Q

What is a side effect that you have to be really careful about when someone is taking a RAS drug

A

K!!! they could get hyperkalemia

20
Q

How long does it take for a person taking Losartan to have effects on their blood pressure after administration of the first dose

A

6 weeks

21
Q

List the Angiotensin Converting Enzyme Inhibitors

A

Captopril
Enalapril
Lisinopril

22
Q

Captopril

A

ACE Inhibitor

23
Q

Enalapril

A

ACE Inhibitor

24
Q

Lisinopril

A

ACE Inhibitor

25
Q

What do ACE Inhibitors (Captopril, Enalapril, Lisinopril) do?

A
  • Blocks conversion of Angtiotensin I to Angiotensin II
  • so it decreases Angiotensin II and increases Angiotensin I
  • ACE also is responsible for inactivating bradykinin which increases NO and prostaglandins. SO an ACE inhibitor will increase bradykinin levels yay!
26
Q

Effect of an ACE inhibitor on bradykinin

A

increase bradykinin levels bc ACE can’t break it down to an inactive peptide

27
Q

ACE Inhbitor adverse effects

A

Cough

Angioedema

28
Q

Aliskiren

A 
renin inhibitor (direct renin inhibitor
-renin is responsible for turning angiotensinogen to angiotensin I so Aliskiren stops this. This decreases angiotensin I concentrations, and angiotensin II concentrations and aldosterone concentrations bc angiotensin II stimulates adlosterone release
29
Q

B adrenergic antagonists and renin

A
  • decrease heart rate
  • decrease renin release

-used in treatment of HTN

30
Q

Aldosterone antagonists

A

Spironolactone Eplerenone

31
Q

Spironolactone and Eplerenone

A

inhibit aldosterone

Competitive aldosterone antagonists at mineralocorticoid receptor

PDA Block 2 (13 decks)

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