ACE Inhibitors

Question 1

3 mechanisms of ACE inhibitors

Answer 1

Inhibits ACE
Changes concentrations of other vasoactive peptides
Increase bradykinin levels

Question 2

Angiotensin II antagonists

Answer 2

Inhibits ang II type I receptors

Question 3

Type I angiotensin receptor locations

Answer 3

Kidney
Heart
Vascular smooth muscle
Brain
Adrenal glands
Adipocytes
Placenta

Question 4

Type II angiotensin receptor locations

Answer 4

Heart
Adrenal glands
CNS
Kidney

Question 5

Effects of ang II on cardiac myocytes

Answer 5

Hypertrophy
Apoptosis
Impaired relaxation
Increased oxygen consumption

Question 6

Effects of ang II on fibroblasts

Answer 6

Hyperplasia
Collagen synthesis
Fibrosis

Question 7

Effects of ang II on peripheral arteries

Answer 7

Vasoconstriction
Hypertrophy
Decreased compliance
Endothelial dysfunction

Question 8

Effects of ang II on coronary arteries

Answer 8

Vasoconstriction
Endothelial dysfunction
Atherosclerosis
Thrombosis

Question 9

Most common ACEi

Answer 9

Cilazapril (0.5–5 mg od)

Question 10

Most common ang II antagonist

Answer 10

Candesartan (4–32 mg od)

Question 11

ACEi pharmacokinetics

Answer 11

Prodrugs that are hydrolysed in the liver
Variable half lives
Renally excreted

Question 12

AIIA pharmacokinetics

Answer 12

Half lives variable

Variable excretion –still take care with renal impairment

Question 13

Candesartan and losartan excretion

Answer 13

60% renal

40% bile

Question 14

Why doesn’t the heart rate increase with ACEi therapy?

Answer 14

Decreased sympathetic activity means HR is maintained while decreasing BP via vasodilation and natriuresis/diuresis (aldosterone inhibition)

Question 15

ACEi indications

Answer 15

Hypertension (monotherapy and in combo with diuretic)

Congestive cardiac failure, especially HFrEF (in combo with diuretic, beta-blocker, and/or aldosterone antagonist)

Question 16

AIIA indications

Answer 16

For ACEi intolerant patients (HT and HF)

Question 17

Common treatment regimen for HT

Answer 17

Diuretic + ACEi + vasodilator

Question 18

Common treatment regimen for HF

Answer 18

Diuretic + ACEi/AIIA + B-blocker + spironolactone

Question 19

Side effects of ACEis

Answer 19

Dry cough (due to bradykinin/substance P inhibition irritating lung receptors)
Hyperkalemia
Hypotension
Angioedema

Question 20

Contraindications of ACEis and AIIAs

Answer 20

Pregnancy (causes poor fetal renal growth and oligohydramnios)
Bilateral renal artery stenosis (afferent arteriole blockage = efferent arteriole pressure must increase to maintain GFR therefore ang II absolutely necessary)

Question 21

Sides effects of AIIAs

Answer 21

Dry cough (much less than ACEis)
Hyperkalemia
Hypotension
Angioedema (less than ACEis)

Question 22

Cautions with use of ACEis and AIIAs

Answer 22

Hyperkalemia
Renal impairment
Volume deplete/diuresed patients (can exacerbate this)

Question 23

Ang II and diabetes

Answer 23

Reduced incidence of developing new diabetes on ACEis or AIIAs
Ang II increases oxidative stress and inflammation, increases SNS, impairs insulin signalling, impairs pancreatic function and reduces insulin sensitivity

Question 24

Can you use ACEis and AIIAs together?

Answer 24

Maybe more effective RAAS inhibition, but more adverse effects. Currently contraindicated by MHRA and FDA.

Question 25

Renin inhibitors

Answer 25

Not available in NZ Decreased BP When used in combo, synergistic decreased BP and increased adverse effects

Question 26

Entresto

Answer 26

Combo drug of valsartan (AIIA) and sacubitril (vasopeptidase inhibitor) Now licensed in NZ for HF resistant to other therapies Might increase hypotension and needs to be monitored

Question 27

Vasopeptidase inhibitors

Answer 27

Decrease vascular tone, decrease Na+ retention, decrease neurohormonal activation, decrease cardiac hypertrophy and decrease cardiac fibrosis