Lecture 3: RAAS- Antihypertensives

Question 1

Which commonly used drugs have been associated with the induction of HTN?

Answer 1

Oral contraceptives

Question 2

Angiotensin II formed from RAAS is a potent _________.

Answer 2

Angiotensin II formed from RAAS is a potent vasoconstrictor.

Question 3

Angiotensin II acts to increase what 2 things?

Answer 3

1) Total peripheral resistance
2) Extracellular fluid volume

Question 4

What 3 things are stimulated by angiotensin II?

Answer 4

1. Stimulates thirst
2. Aldosterone secretion (causes retention of Na⁺)
3. ADH secretion (retention of H₂O)

Question 5

What is the MOA of Captopril?

Answer 5

• Competitive inhibitor of ACE
• Prevents conversion of angiotensin I —> angiotensin II
• Increases plasma renin and decreases aldosterone secretion = lower BP

Question 6

Why is enalapril significant?

Answer 6

Is a prodrug, w/ active form being enalaprilat

Question 7

What are ACE inhibitors used for clinically?

Answer 7

• HTN, can combo w/ thiazide or loop diuretic
• Acute HTN (urgency/emergency)
• HF w/ reduced ejection fraction
• Diabetic nephropathy

Question 8

What are the adverse effects associated w/ ACE inhibitors?

Which AE is the reason most people stop taking the drug and what is a potentially deadly AE?

Answer 8

• Cough = #1 reason people stop taking
• Hypotension, HA, drowsiness
• Angioedema = can be fatal
• Loss of/altered taste

Question 9

ACE inhibitor drugs have what suffix?

Answer 9

-pril

Question 10

What is the MOA of the -sartans?

Answer 10

- Competitive nonpeptide angiotensin II receptor antagonist

• Blocks the vasocontrictor and aldosterone-secreting effects

Question 11

What is the clinical application of the -sartans (i.e., losartan)?

Answer 11

• Diabetic nephropathy w/ ↑ Scr and proteinuria
• HTN, alone or in combo
• Heart failure if intolerant of ACE inhibitors

Question 12

What is the big advantage of the -sartans for HTN and other clinical applications?

Answer 12

Doesn’t produce as much of a cough as the ACE inhibitors so is better tolerated

Question 13

What is the significance of Valsartan and Candesartan?

Answer 13

• Valsartan = is NOT a prodrug requring activation
• Candesartan = has irreversible binding of the angiotensin II receptor

Question 14

Which drug is often used in people w/ heart failure that are intolerant to ACE inhibitors (i.e., too much cough)?

Answer 14

Losartan

Question 15

Which drug used for the tx of HTN is a direct renin inhibitor?

Answer 15

Aliskiren

Question 16

What are the effects of Aliskiren?

Answer 16

Direct renin inhibitor –> blocks conversion of angiotensinogen to angiotensin I

Question 17

What is the clinical application of Aliskiren?

How often is it used?

Answer 17

• Tx of HTN, alone or in combo w/ others
• New, expensive, no obvious benefits, some evidence of increased risk of AE’s

Question 18

What are some of the AE’s associated w/ Aliskiren?

Answer 18

• Skin rash
• Diarrhea
• >300% increase in creatine phosphokinase (1%)
• Hyperkalemia, especially if combined or pt has renal dysf. or DM

Question 19

You should NOT use a β-blocker, like propranolol, in patients with what 2 disorders?

Answer 19

1) Asthma
2) Diabetes

Question 20

Which drugs work well in combo when treating an African American for HTN?

Answer 20

• Diuretics and Ca²⁺ channel blockers
• β-blockers, ACE inhibitors and ARBS work well when added to diuretic, but NOT as monotherapy

Question 21

Which HTN drugs should not be given to sexually active girls?

Answer 21

• ACE inhibitors
• ARBs

Question 22

Which drug used for HTN is contraindicated throughout pregnancy?

Answer 22

ACE inhibitors

Question 23

What is the effect of drugs that interfer with Angiotensin II on pts with bilateral renal stenosis and pts with diabetes?

Answer 23

• Can precipitate renal failure in pts w/ bilateral renal stenosis
• Can help preserve renal function in diabetics

Question 24

What type of HTN is associated with unilateral renal artery stenosis?

Answer 24

Angiotensin II-dependent HTN