Vasoactive Peptide Pharmacology

Question 1

Where in the cell do vasoactive peptides typically act?

Answer 1

Cell surface receptors (largely GPCRs to affect production of second messengers or open ion channels)

Question 2

Angiotensin

What enzyme catalyzes its creation from angiotensinogen?

Answer 2

Renin

Question 3

How many AAs in angiotensin I?

Answer 3

10

Decapeptide

Question 4

Which angiotensin is most active?

Answer 4

Angiotensin II

Question 5

What enzyme catalyzes conversion of angiotensin I to angiotensin II?

Answer 5

ACE

Angiotensin Converting Enzyme

Question 6

What enzyme converts angiotensin II to angiotensin III?

Answer 6

Aminopeptidase

Question 7

What enzymes degrades angiotensin?

Answer 7

Angiotensinases

Question 8

How many AAs in angiotensin II?

Answer 8

8

Octapeptide

Question 9

ACE is also known as…?

Answer 9

Kininase II

Peptidyl dipeptidase

Question 10

List the pharmacologic actions of angiotensin II

Answer 10

• Vasoconstriction
• Aldosterone production from adrenal cortex
• lucocorticoid biosynthesis
• Mitogenic agent for vascular and cardiovascular muscle cells

Question 11

What are the two general mechanisms by which we inhibit angiotensin?

Answer 11

• ACE inhibitors

- Angiotensin receptor blockers

Question 12

ACE inhibitors inhibit the conversion of…?

Answer 12

Angiotensin I to Angiotensin II

Question 13

ACE inhibitors inhibit the degradation of…?

Answer 13

Bradykinin

Question 14

List two ACE Inhibitors

Answer 14

Captopril

Enalapril

Question 15

List the Angiotensin Receptor Antagonists

Answer 15

Losartan

Valsartan

Question 16

Plasma prekallikrein is activated by what to become plasma kallikrein?

Answer 16

Factor 12a (Hageman Factor)
Trypsin
Kallikrein

Question 17

What does plasma kallikrein catalyze?

Answer 17

Conversion of HMW kininogen to bradykinin

Question 18

What does tissue kallikrein catalyze?

Answer 18

Conversion of LMW kininogen to Kallidin (Lysylbradykinin)

Question 19

What is the function of kininases I and II?

Answer 19

Degrade bradykinin and kallidin into inactive fragments

Question 20

An excess of kallikrein will lead to….

Answer 20

Excess bradykinin production, leading to hypotension

Question 21

What is the predominant peptide in hypotensive shock?

Answer 21

Bradykinin

Question 22

What drug would you never give to a septic patient? Why?

Answer 22

ACE Inhibitor
They would inhibit kininase II (ACE), preventing the degradation of bradykinin and exacerbating the problem of hypotension in septic shock

Question 23

What are the various physiological actions of kinins?

Answer 23

• Vasodilation
• Stimulate NO release (active NOS2)
• Prostaglandin release
• Potent algesics (cause pain)
• Promote water and solutions’ movement into the EC space, causing edema

Question 24

How are kinins involved in pain?

Answer 24

They are algesics (they cause pain).

They promote redness, local heat, swelling, and pain

Question 25

What are the two bradykinin receptors and their primary functions?

Answer 25

B1 - mediating biological actions of bradykinin | B2 - drugs that block the action of bradykinin target B2 receptor

Question 26

Why is kininase II important in bradykinin regulation?

Answer 26

Kininase II (ACE) degrades bradykinin into inactive products.

Question 27

Icatibant | MOA

Answer 27

B2 receptor inhibitor

Question 28

Icatibant | Indications

Answer 28

Angio-neurotic edema (edema of an unknown immunologic nature)

Question 29

What drug can be used to block the algesic effects of kinins?

Answer 29

Aspirin

Question 30

Vasopressin (ADH) | General role in hemostasis

Answer 30

Long term control of blood pressure through kidney and increased H2O reabsorption

Question 31

Desmopressin | Indications

Answer 31

- Used in pediatrics. - Analog of ADH that is used in blood banking, mild hemophilia, and vWF deficiency. - Mild surgical/dental procedures

Question 32

Desmopressin | MOA

Answer 32

Increases Factor 8 activity

Question 33

Vasopeptide Inhibitor Drugs | Physiological effects

Answer 33

Increase natriuretic peptide levels and decrease formation of angiotensin II. Vasodilation Increased sodium excretion

Question 34

Vasopeptide Inhibitors | List 3

Answer 34

Omapatrilat Sampartilat Fasidotrilat

Question 35

Endothelins | What effect do they have on vascular tone?

Answer 35

Vasoconstrictors

Question 36

What drug is a non-selective antagonist of endothelins?

Answer 36

Bosentan

Question 37

Bosentan | MOA

Answer 37

Antagonist of Endothelin

Question 38

Bosentan | Indication

Answer 38

Pulmonary artery hypertension

Question 39

VIP causes vaso.....?

Answer 39

Vasodilation

Question 40

Substance P causes vaso....? How?

Answer 40

Vasodilation by stimulating the release of NO

Question 41

Neurotensin

Answer 41

Causes vasodilation, hyperglycemia

Question 42

Adrenomodulin levels are increased during...

Answer 42

Exercise Hypertension Renal failure Septic shock