Pharm-angiotensins

Question 1

Potent renin inhibitor
Orally active
Low bioavailability
Half life?

Answer 1

Aliskiren

>24 hrs

Question 2

MOA:

Aliskiren

Answer 2

Suppression of plasma renin activity, thus decreasing levels of Ang I and II

Question 3

Uses:

Aliskiren

Answer 3

HTN, but not 1st line

Question 4

Contraindications:

Aliskiren

Answer 4

Pregnancy

Bilateral renal artery stenosis

Question 5

MOA:
ACEI
Consequences?

Answer 5

Inhibition of the conversion of Ang I to Ang II

• decrease in aldosterone
• renal retention of Na, but K increases

Question 6

What is “aldosterone escape”?

Answer 6

Due to ACEI, aldosterone levels decrease, but can then increase over time

Question 7

Beneficial effects of ACEI

Answer 7

• Lower BP by decreasing PVR
• Improve arterial compliance
• decrease afterload
• decrease preload through venodilation
• improve renal perfusion
• improve insulin sensitivity and glucose metabolism

Question 8

Examples of ACEI

Answer 8

-prils

Question 9

ACEI:

Prodrugs

Answer 9

Enalapril
Fosinopril
Ramipril

Question 10

ACEI:

Non prodrugs

Answer 10

Captopril

Lisinopril

Question 11

Clinical uses for ACEI

Answer 11

HTN 
HF
Acute MI
Chronic renal failure 
Reduce adverse cardiovascular events

Question 12

Contraindications:

ACEI

Answer 12

Pregnancy

Bilateral renal a. stenosis

Question 13

Adverse effects:

ACEI

Answer 13

Hyperkalemia
Hypotension
Renal function impairment 
Dry cough
Angioedema

Question 14

Drug interactions:

ACEI

Answer 14

NSAIDs

Question 15

MOA:

ARB

Answer 15

AT1 receptor blockers (NOT AT2)

Question 16

Examples:

ARB

Answer 16

-sartans

Question 17

Orally active ARB
Extensive first pass metabolism
Has an active metabolite with a longer half life than the parent compound

Answer 17

Losartan

Question 18

True or false:

ARBs cross the BBB

Answer 18

False

Question 19

Clinical uses:

ARB

Answer 19

Similar to ACEI for pts who can’t tolerate ACEI

Question 20

Contraindications:

ARB

Answer 20

Same as ACEI (so avoid combo)

Question 21

Adverse effects:

ARB

Answer 21

Similar to ACEI except no dry cough

Question 22

Examples of Kallikrein inhibitors

Answer 22

Aprotinin

Ecallantide

Question 23

MOA

Kallikrein inhibitors

Answer 23

Inhibit synthesis of kinins

Question 24

How do ACEI affect the kallikrein-kinin system?

Answer 24

They prolong the actions of bradykinin by inhibiting its degradation

Question 25

___ is a bradykinin B2 receptor antagonist that reduces vascular permeability

Answer 25

Icatibant

Question 26

Clinical uses: | Icatibant

Answer 26

Hereditary angioedema | ACEI associated angioedema

Question 27

ET-1 has a biphasic effect on blood vessels:

Answer 27

Transient vasodilation followed by prolonged vasoconstriction

Question 28

Under normal physiologic conditions, what effect does ET1 have on the heart?

Answer 28

Positive inotropic and chronotropic

Question 29

ET1 causes ___ of airway smooth muscle

Answer 29

Contraction(bronchoconstriction)

Question 30

MOA: | Endothelin receptor antagonists

Answer 30

Block ET receptors thus relax vascular smooth muscle

Question 31

Examples: | ET receptor antagonists

Answer 31

-entans

Question 32

1. Orally active, nonselective ETA/ETB receptor antagonists | 2. Selective ETA receptor blocker

Answer 32

1. Bosentan, macitentan | 2. Ambrisentan

Question 33

Clinical uses: | ET antagonists

Answer 33

Pathological and physiological pulmonary arterial BP control - vasoconstriction - also relaxation through PGI2 and NO

Question 34

Adverse effects of ETA receptor antagonists

Answer 34

``` Headache Flushing Peripheral edema Palpitations Elevated liver enzymes ```

Question 35

Contraindications: | ETA receptor antagonists

Answer 35

Pregnancy

Question 36

Examples of natriuretic peptides

Answer 36

Atrial and brain type ANP BNP

Question 37

___ is a recombinant of human BNP. It relaxes arteries and veins and promotes diuresis and natriuresis, leading to reduced cardiac workload. What else does it do?

Answer 37

Nesiritide Decrease remodeling Lower BP

Question 38

Clinical uses: | Nesiritide

Answer 38

Acute decompensated congestive HF, given IV

Question 39

___ is a neprolysin inhibitor

Answer 39

Sacubitril (prodrugs activated to LBQ657 by esterases)

Question 40

MOA: | Sacubitril

Answer 40

Inhibits neprilysin, which is responsible for the degradation of ANP and BNP -also increases Ang II levels which may counteract the effects listed above. SO it must be COMBINED with AT1 receptor blocker in treating chronic HF

Question 41

LCZ696 (entresto) =

Answer 41

Sacubitril + valsartan

Question 42

Clinical uses: | LCZ696

Answer 42

Chronic HF in pts with reduced EF (CHFrEF)

Question 43

MOA: | LCZ696

Answer 43

Enhance effects of ANP and BNP | Block Ang II

Question 44

Adverse effects: | LCZ696

Answer 44

Hypotension Hyperkalemia Renal impairment Angioedema (rare but severe)

Question 45

Contraindications: | LCZ696

Answer 45

Hx of angioedema | Use of ACEI, ARB, or aliskiren