2.5 - Anti-hypertensives - ACE-Is, ARBs, & direct renin inhibitors

Question 1

What are the effects of angiotensin II on the body?

Answer 1

1. Stimulating norepinephrine release to trigger epinephrine release to make SNS constrict PVS, increase HR, contractility, etc.
2. Pit gland is stimulated to release ADH to retain water in collecting duct
3. Adrenal gland cortex on kidney releases aldosterone to reabsorb Na+, Cl-, (leads to water reabsorption) at collecting duct
4. Direct effect to vasoconstrict arteriols, increasing PVR (peripheral vascular resistance)

Question 2

Where does ACE effect the renin-angiotensin cascade?

Answer 2

• ACE = angiotensin converting enzyme.
• It acts in two ways:
  
  • ONE: It converts Ang-1 to Ang-2.
  • TWO: It breaks down bradykinin, which is a vasodilator.
• By blocking ACE, we both prevent vasoconstriction via Ang-2’s multiple effects. We also are directly promoting vasodilation by allowing more bradykinin. The overall effect is vasodilation.

Question 3

What are Ace Inhibitors used to treat?

What are the concerns about ACE Inhibitors?

What is the black box warning?

What are potential effects on K? Why?

Answer 3

• ACE-I’s are used to treat hypertension and stabilise CKD (stabilizing renal function and reducing proteinuria)
  
  • Benefits are that there is no reflex sympathetic response and no major effect on HR or CO
• Negative effects of ACE inhibitors naturally follow from the blocking of Angiotensin-2 and the incresaing bradykinin.
• ACE inhibitors can cause severe hypotension, in particular when combined with diuretics.
• Bradykinin increase can lead to angioedema (rare but possibly fatal) and a cough (not harmful).
• Black box warning: NOT FOR USE IN PREGNANCY, can cause fetal hypotension and renal damage
• Orange: Risk of hyperkalemia. Careful when using with K+ supplements or potassium sparing diuretics

Question 4

• What are Losartan and Valsartan used for? What class are they?
• How are they different than ACE-I’s?
• When are they prescribed, in contrast to ACE-I’s?
• What are concerns?

Answer 4

• Losartan and valsartan are ARBs (Angiotensin Receptor Blockers)
• Same benefit for CHF, CKD
• They differ in effect from ACE-I in that they do not prevent breakdown of bradykinin since Ang-2 production is not stopped. They are used when a patient can’t tolerate an ACI-I.
• Contraindicated in pregnancy.

Question 5

How does a direct renin inhibitor work? What is the medication name?

Black box warning?

Answer 5

Question 6

Physiologic mechanisms that can be pharmacologically targeted to treat blood pressure include all of the following EXCEPT

• Decreasing circulating blood volume
• Decreasing vascular tone
• Increasing peripheral vascular resistance
• Decreasing cardiac output

Answer 6

• Increasing peripheral vascular resistance

Question 7

Review Key Points of Anti-hypertensives

Question 8

Since alpha-1 antagonists cause reflex retention of Na and water, how can you attenuate this?

Answer 8

Add a diuretic

Question 9

Which of the following prescriptive choices is not advisable?

• Using an alpha one antagonist in an elderly man with BPH
• Using a calcium channel blocker in a patient with angina
• Using a beta-blocker in a patient with labile type I diabetes

Answer 9

Using a beta-blocker in a patient with labile type I diabetes

Question 10

What is the difference between vasodilators that dilate the aterioles, and those that dilate both arterioles and veins?

Answer 10

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