ARB, ACE-I & Renin-I Pharmacology Flashcards
Angiotensinogen is converted to what substance by what enzyme?
It is converted to Angiotensin 1 by Renin
Where is Renin produced?
Kidneys
Agiontensin 1 is converted to Angiotensin 2 by what enzyme?
Angiotensin Converting Enzyme
Angiotensin 2 has what effects?
Vasoconstriction, Aldosterone secretion, Sympathetic activation
What cells in the kidney contain Renin?
Juxtaglomerular Apparatus
Where does Renin cleave Angiotensin?
Between Leucines on C end of peptide
Where does ACE cleave Angiotensin 1 to make Angiotensin 2?
Between the Phe and His on the C side of the peptide
What does the macula densa sense as plasma passes?
NaCl concentration of plasma
Renin is activated in what larger physiologic condition?
This is sensed by what portion of the kidney?
Low sodium conditions
Macula Densa
What other portions of the Kidney can cause Renin release?
Intrarenal Baroreceptor in Pre-glomerular vessels
Activation of what adrenergic receptors cause increased Renin release?
B1 Adrenergic receptors on Juxtaglomerular cells
What is the mechanism to recognize enough Renin has been released?
AT1 receptor on Juxtaglomerular cell activated by Angiotensin 2
What receptor mediates the majority of response from Angiotensin 2?
AT1
What effects does activation of AT1 receptor have? (5 items)
Vasoconstriction Vascular proliferation Aldosterone secretion Cardiac myocyte proliferation Increased sympathetic tone
What effects does activation of AT2 receptor have? (3 items)
Vasodilation
Antiproliferation
Apoptosis
What is the second messenger process of the AT1 receptor?
AT1 activation (G-protein coupled) –> PIP2 –> IP3 + DAG –> IP3 activates Ca2+ & DAG activates PKC
Where is the AT1 receptor located in the Adrenergic synapse? What effect does it have?
The AT1 receptor is pre-synaptic & post-synaptic. Its activation by ANG2 results in increased release of NE which activates postsynaptic alpha1 receptors. ANG2 also activates post-synaptic AT1 receptors which have a director vasoconstrictor effect.
What is Aldosterone’s effect on the kidney?
Reabsorption of Na and Water in intercalated cells of collecting duct
What are the broad effects of RAAS Inhibitors? (4 items)
Blood pressure lowering related to plasma renin activity
Decrease blood pressure with no change in heart rate
Can cause hypotension
Can cause fetal wasting in pregnancy
RAAS inhibition can occur in three locations in the RAAS pathway. What are they?
Direct inhibition of Renin release
Inhibition of ACE conversion from Ang1 to Ang2
Blockade of Angiotensin receptor
What is the hallmark AT1 receptor blocker medication?
Losartan
What type of inhibition does Losartan produce on AT1 receptors? What ramifications does this have?
Competitive inhibition
Increased Angiotensin 2 production can overcome the Losartan inhibition of AT1
What is the mechanism of action of Losartan?
What effects does this produce? (3 items)
Angiotensin 2 receptor (AT1) competitive inhibition
- Decreased aldosterone secretion
- Decreased vasoconstriction
- Decreased sympathetic activation
Does Losartan and other ARBs work immediately? If not, how long do they take to create maximal effect?
No, 4 weeks
What adjunct medication is frequently used to increase BP lowering effect?
Diuretics
What are the hallmark ACE inhibitors for this course? (3 items)
Captopril
Enalapril
Lisinopril
ACE inhibitors prevent production of what substance from what substance?
They prevent production of Ang2 from Ang1
What diagnostic would you check to decide if and ARB or ACE-inhibitor is indicated instead of another HTN medication?
Draw plasma Angiotensin 2 levels to check for inappropriate elevation.
How do black individuals’ response to ACE-I and HCTZ compared to non-black individuals?
The percentage of blacks who are responders to ACE-I is significantly less while the percentage who respond to an HCTZ type diuretic was slightly increased. Percentage for combination was about the same.
What is the effect of ACE-I on CHF mortality?
40% reduction after 6 months
What effect did ACE-I (Captopril) have after acute MI? (2 items)
Reduction in mortality AND Reduction in LV dysfunction
How do ACE-I compare with other vasodilator therapy in CHF therapy?
Overall reduction in mortality
What is the most common adverse effect of ACE-I?
Cough
What are the #2-5 common adverse effects of ACE-I? (4 items)
- Rash
- Taste Disturbance
- Angioedema
- Proteinuria
Why would an ACE-I exacerbate renal dysfunction/failure?
If the failure is a result of poor perfusion from the Renal artery, ACE-I will prevent compensation to improve perfusion.
What is the hallmark Renin inhibitor for this course?
Aliskiren
What is the mechanism of action of Aliskiren?
Aliskiren occupies the binding site for Angiotensinogen on Renin preventing conversion/production of Angiotensin 1.
Does Aliskiren increase/decrease/not change systolic, diastolic and HR?
Decreases both systolic and diastolic
Doesn’t change HR
On what cells in the kidney are Spironolactone and Eplerenone active?
Principal cells and Intercalated cells
What effect does Spironolactone and Eplerenone have?
Inhibition of the renal and extra renal actions of aldosterone (including Na and Water retention)
