Adrenergic & Angiotensin Block in CHF

Question 1

Action of:
Hydralazine
Isosorbide

Answer 1

Both are vasodilators:

Hydralazine: arterial vasodilation

Isosorbide: venous vasodilation

Question 2

What structure produces:
Angiotensinogen
\_\_\_\_\_\_\_\_\_\_
Renin
ACE

Answer 2

Angiotensinogen: Liver
__________
Renin: Kidney Juxtaglomerular cells
ACE: lungs (but found w/in the circulation)

*note: Renin and ACE are enzymes

Question 3

Major side effect of hydralazine

Answer 3

drug induced SLE

Question 4

Major side effect of isosorbide

Answer 4

hypotension, headache, dizziness

Question 5

Major side effect of a combination of hydralazine and isosorbide

Answer 5

Headache

Question 6

What triggers the Juxtaglomerular cells to trigger renin release?

Answer 6

1. low blood pressure
2. sympathetic nerves
3. macula densa cells in distal convoluted tubules sensing low [Na+] and send prostaglandin to JG cells

Question 7

Briefly Describe how the RAAS system works

Answer 7

1. Renin produced by the JG cells will convert Angiotensinogen to Angiotensin I.
2. Angiotensin I is converted to Angiotensin II by the endothelial cells in blood vessels (ACE)
3. Angiotensin II affects smooth muscles, liver, kidneys, and

Question 8

How does Angiotensin II affect:

1. smooth muscles?
2. kidney?
3. Pituitary gland?
4. Adrenal gland?

Answer 8

1. vasoconstriction → ↑ resistance
2. hold on to more water → ↑ volume → ↑ stroke volume
3. secretes ADH and causes 1 + 2
4. secretes aldosterone and causes 2

Question 9

what structure secretes ADH? Aldosterone?

Answer 9

ADH? pituitary gland

Aldosterone? adrenal gland

Question 10

The bradykinogen system runs side by side with the angiotensinogen system. Describe it.
- why is it important to know?

Answer 10

1. Liver produces Bradykininogen
2. It is converted by KallikRENIN to Bradykinin
3. Bradykinin is converted by Kinase II (ACE) to inactive fragment

*if we use ACEI, then we have a drop in angiotensin II, but also an ↑ in bradykinin

Question 11

↑ Bradykinin has what effects?

Answer 11

1. potent pulmonary irritant
   
   • cough
2. large impact on LV remodeling
3. Potent vasodilator (↑ afterload reduction)

Question 12

What structures does Angiotensin II act on?

Answer 12

1. Vascular smooth muscle
2. CNS and Peripheral NS
3. Adrenal cortex
4. Direct kidney
5. Brain

Question 13

What are the CNS and Peripheral NS effects of Angiotensin II?

Answer 13

↑ sympathetic activity
→ ↑ Arteriolar constriction
→ ↑ CO

→→ ALL LEADING TO ↑↑ ARTERIAL BLOOD PRESSURE

Question 14

What are effects of Angiotensin II on the adrenal cortex?

Answer 14

↑ aldosterone secretion
□ →→ ↑ NA Resorption

→→ ALL LEADING TO ↑↑ ARTERIAL BLOOD PRESSURE

Question 15

What are effects of Angiotensin II on the brain?

Answer 15

↑ ADH (from pituitary gland)
Thirst
↑ Na + H2O retention

→→ ALL LEADING TO ↑↑ ARTERIAL BLOOD PRESSURE

Question 16

Effects of angiotensin II

Answer 16

↑ Arteriolar constriction
 ↑ CO
 ↑ NA Resorption
 ↑ Na + H2O retention
 ↑ H2O absorption
 ↑ H2O ingestion
	□ →→  ALL LEADING TO ↑↑ ARTERIAL BLOOD PRESSURE

Question 17

3 ACEI we need to know

Answer 17

*the prils

Captopril
Enlapril
Lisinopril

Question 18

Enlapril

Answer 18

Bid (twice a day)

Question 19

Lisinopril

Answer 19

once a day.

Question 20

Captopril

Answer 20

short half life: 3x a day

Question 21

Side effects of ACEI

- what can do use instead?

Answer 21

1. cough
2. hyperkalemia
3. angioedema
4. renal dysfunction
5. neutropenia
6. hypotension

• if these occur: can switch over to angiotension blocker (or even hydralazine/isosorbide - iffy)

Question 22

ACEI DDI

Answer 22

○ NSAIDS BAD!!!
	§ Inhibit renal protective prostaglandins
○ Lithium = salt
	§ Bump up lithium levels
	§ Narrow therapeutic index drug
	□ Seizure, coma, and death
○ K+ sparing diuretics
○ Loop diuretics
○ Salt substitutes

Question 23

ACEI contraindications

Answer 23

○ Pregnancy
○ Renal Failure
○ Bilateral renal artery stenosis
○ Angioedema
○ Hyperkalemia 
     >5, you should reconsider…

Question 24

Do ACEI and ARBs reduce morbidity and mortality?

Answer 24

ACE inhibitors and ARBs are recommended in patients with HFrEF and current or prior symptoms, UNLESS contraindicated, to reduce morbidity and mortality ~equal

• using the two together, does not “stack” the reduction in mortality

Question 25

Difference between ACEI and ARBs

Answer 25

ARBs: no cough (doesnt affect bradykinin), cheaper

- same side effects
MINUS COUGH!
- same DDI
- same precautions/contraindications

Question 26

Non-renin systems
what is it
- examples

Answer 26

can convert angiotensinogen directly to Angiotensin I □ t-p Factor
□ Catepsin G
□ Tonin

Question 27

non-ACE systems
what is it
- examples

Answer 27

Angiotensin I can be converted to angiotensin II by Non-ACE
□ Chymase
□ CAGE
□ Catepsin G