ACE Inhibitors and ARBs

Question 1

What stimulates renin release from the juxtaglomerular cell?

Answer 1

decreased sodium delivery at the macula densa, decreased renal blood flow, sympathetic activation (beta-1 receptors)

Question 2

What are the key effects of angiotensin II?

Answer 2

vasoconstricts, enhances SNS activity centrally and peripherally, increases aldosterone, causes fluid retention, promotes growth, inhibits renin production (quick feedback)

Question 3

What are the key effects of bradykinin?

Answer 3

vasodilation, natriuresis

Question 4

What are the actions of ACE?

Answer 4

cleave Ang I to Ang II (acitvating); cleave bradykinin (inactivating)

Question 5

Which ACE inhibitor has a sulfhydryl group at the zinc ligand site?

Answer 5

captopril

Question 6

What is the general route of elimination for ACE inhibitors?

Answer 6

renal

Question 7

Give an example of a carboxyl-containing ACEI.

Answer 7

lisinopril

Question 8

Which ACEI has the shortest half-life?

Answer 8

captopril

Question 9

Clinical indications for ACE inhibitors

Answer 9

HTN, CHF, chronic diabetic nephropathy, ischemic heart disease

Question 10

What is the MOA of ACE inhibitors?

Answer 10

blocks the conversion of Ang I to Ang II and the degradation of bradykinin, decreasing SVR

Question 11

How does ACEI lowering of SVR affect heart rate?

Answer 11

ACE inhibitors do not increase HR

Question 12

How does plasma renin activity correlate with ACEI efficacy in treating HTN?

Answer 12

more effective in treating patients with normal to high renin

Question 13

How do ACEIs help in treating CHF?

Answer 13

reduce afterload and systolic wall stress, increase CO w/o increasing HR, increase renal plasma flow-natriuresis

Question 14

How do ACEIs help in treating diabetic nephropathy?

Answer 14

decrease glomerular capillary pressure, decrease proteinuria, anti-proliferative

Question 15

Adverse effects of captopril

Answer 15

skin rash, neutropenia

Question 16

Class-specific adverse effects of ACEIs

Answer 16

fetal anomalies, hypotension, hyperkalemia, cough, renal failure, angioedema

Question 17

What is the mechanism of ACEI-induced renal failure?

Answer 17

perfusion (afferent areteriolar) pressure decreases in the setting of renal artery stenosis, e.g.; Ang II would maintain glomerular filtration by efferent arteriolar vasoconstriction, but it is blocked

Question 18

ACEI drug interactions

Answer 18

K-sparing diuretics, K supplements, NSAIDs (interfere w/ anti-hypertensive effects), antacids (decrease bioavailability), capsaicin (cough)

Question 19

What is an important difference between ACEIs and ARBs?

Answer 19

ACEIs increase bradykinin, ARBs may not affect to same degree (benefits vs. side effects of this)

Question 20

Which ARB has an active metabolite?

Answer 20

losartan

Question 21

adverse effects of ARBs

Answer 21

hypotension, hyperkalemia, GI, hepatotoxicity

Question 22

What is the half-life of losartan?

Answer 22

2 h (prodrug), 9 h (metabolite)

Question 23

Give an example of a renin inhibitor

Answer 23

aliskiren

Question 24

Pharmocokinetics of aliskiren

Answer 24

low bioavailability, long half-life (44 h)

Question 25

Important result from aliskiren study

Answer 25

increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren + ACEI or ARB

Question 26

ARBs and ACEIs may reduce new onset of this disease

Answer 26

diabetes