A-24. Drugs used for hypertension III: Drugs acting on the RAAS

Question 1

What is the MOA of ACE inhibitors?

Answer 1

Inhibit the conversion of Angiotensin-I to Angiotensin-II

Question 2

Which ACEi drug has a SH group?

Answer 2

Captopril

Question 3

Which ACEi drug has a dicarboxyl group?

Answer 3

Lisinopril

Question 4

What are the ACEi drugs that fall under the category of Lisinopril? (5)

Answer 4

1. )Enalapril
2. )Perindopril
3. )Benazepril
4. )Quinapril
5. )Ramipril

Question 5

Which ACEi drug has a phosphate group?

Answer 5

Fosinopril

Question 6

Which Angiotensin II effects are inhibited by ACE-I drugs?

Answer 6

1. ) Direct activation of vascular smooth muscle via AT1 receptors
2. ) Increased central and peripheral sympathetic responses
3. ) Preserving GFR via efferent arteriole constriction
4. )Direct increase of NaHCO3 resorption in PCT; aldosterone-mediated Na/water resorption in collecting duct
5. ) Also increased ADH secretion, cardiac remodeling, and vascular SM proliferation

Inhibiting these leads to decreased hypertension, decreased afterload, decreased Na/water retention meaning decreased preload

Question 7

Indications of ACEi (4)

Answer 7

1. ) Hypertension
   - first line agent, no sympathetic compensation; safe in IHD
2. ) Chronic CHF
   - all stages of heart failure, decreases mortality
   - decreases remodeling and afterload by reducing vasoconstriction
3. )Acute MI
   - decreases morbidity and mortality via decreased blood pressure, remodeling, and increased LV function
4. )Diabetic Nephropathy
   - efferent arteriolar dilation
   - decreased remodeling, diminished late consequences of diabetes, and hyperkalemia (reduces insulin resistance)

Question 8

Kinetics of ACEi? Which two drugs are different?

Answer 8

Most are prodrugs transformed by liver esterases to active metabolites with exception of capto-/lisinopril

Question 9

Which ACEi do you have to take an hour before meals for better absorption

Answer 9

Captopril

Question 10

Where are most ACEi excreted? Which two are different?

Answer 10

Mostly excreted in kidney.

Except fosinopril and spirapril which are excreted via the kidney and liver

Question 11

Side effects of ACEi?

Answer 11

• Dry cough due to bradykinin inhibition (which causes further therapeutic BP decrease)
• Hypotension
• Hyperkalemia via aldosterone inhibition
• Angioedema via vasodilation

Question 12

Contraindications and interaction of ACE-i

Answer 12

1. ) Pregnancy
2. )Bilateral reanl stenosis- Angiotensin II effect is need to keep glomerular filtrationrate, need vasocontriction of efferant arteriole to increase pressure

NSAID interaction- COX inhibition leads to decreased PGs, afferent arteriolar constriction leading to decreased GFR which is enhanced by ACEi

Question 13

What drug names are the Angiotensin II-receptor antagonist (Angiotensin Receptor Blockers-ARBs)

Answer 13

Losartan, Candesartan, Valsartan, Eprosartan, Irbesartan, Telmisartan

Question 14

Mode of action of ARBs

Answer 14

Inhibition of AT1 receptor, so doesn’t inhibit bradykinin so no cough at expense of effectiveness

Question 15

Indication and contraindication of ARBs

Answer 15

Same as ACE-I

Question 16

Which ARB lowers cholesterol and improves lipid profile? Which other feature does it have? Half life?

Answer 16

Losartan

• No CNS entry
• 2 hour half life

Question 17

Which ARB improves cognitive dysfunction because it doesn’t inhibit AT2R

Answer 17

Candesartan

Question 18

Which ARB has best bioavailability and long DOA

Answer 18

Irbesartan

Question 19

Which ARB has longest duration of action?

Answer 19

Telmisartan

Question 20

Renin inhibitor name and function

Answer 20

Aliskiren, inhibits renin conversion of angiotensinogen to AT-1.
Used in hypertension with decreased renal function and hyperkalemia