Pharm: Vasoactive Peptides

Question 1

What are the 4 major vasoactive peptides that have important roles for regulating hemodynamics?

Answer 1

Angiotensin
Kinins
Endothelins
Vasopressin

Question 2

Which angiotensin is most pharmacologically and pathologically active?

Answer 2

Angiotensin I

Question 3

Describe the general mechanism of action of vasoactive peptides?

Answer 3

Act on cell surface receptors (GPCRs) leading to production of second messengers or opening of ion channels

Question 4

Describe the steps that lead to the production of angiotensin III

Answer 4

Renin converts angiotensinogen to angiotensin I
ACE converts Angiotensin I to II (II is the active form)
II is degraded into III

Question 5

What is the major action of angiotensin II?

Answer 5

Profound vasoconstriction

Question 6

How many amino acids are found in angiotensinogen, angiotensin I, and angiotensin II?

Answer 6

Angiotensinogen: 14
Angiotensin I: 10
Angiotensin II: 8

Question 7

What molecules increase the production of angiotensinogen?

Answer 7

Corticosteroids
Estrogens
Thyroid Hormones
Angiotensin II

Question 8

What are the other names of angiotensin converting enzyme (ACE)?

Answer 8

Peptidyle dipeptidase

Kininase II

Question 9

Where is ACE primarily located in the body?

Answer 9

On the luminal structure of the endothelial cells throughout the vasculature

Question 10

What is the function of angiotensinase?

Answer 10

Breaks down angiotensin II and III into small fragments

Question 11

What is the effect of excessive production of angiotensin II?

Answer 11

Hypertension and disorders of hemodynamics

Question 12

Compare the potency of angiotensin II and norepinephrine

Answer 12

Angiotensin II is 40x more potent than NE

Question 13

What are the processes targeted by anti-angiotensin II drugs?

Answer 13

Block renin secretion/action
Inhibit ACE function
Block angiotensin receptors

Question 14

In addition to ACE inhibitors blocking Ang II production, what other peptides are inhibited?

Answer 14

Bradykinin metabolism is blocked by ACE inhibitors

Leads to hypotension

Question 15

What are the names of the orally active ACE inhibitors?

Answer 15

Captopril

Enalapril

Question 16

What are the angiotensin antagonist drugs?

Answer 16

Saralasin
Losartan
Valsartan

Question 17

Compare the clinical benefits of angiotensin receptor antagonists and ACE inhibitors

Answer 17

They are basically identical: decreased function of angiotensin II

Question 18

Do angiotensin receptor antagonists have any effect on the actions of ACE?

Answer 18

No

Question 19

What is the general effect of the kinins?

Answer 19

Vasodilation, hypotension

Question 20

What is the function of kallikrein?

Answer 20

Converts HMW kininogen to bradykinin, leading to vasodilation and hypotension

Question 21

How is kallikrein related to the coagulation cascade?

Answer 21

Plasma prekallikrein is also known as Fletcher factor, which promotes the intrinsic pathway of coagulation.
Factor XIIa also increases kallikrein production

Question 22

What vascular beds are affected by bradykinin?

Answer 22

Heart, liver, kidney, intestine, skeletal muscles, liver

Question 23

Compare the potency of kinins to histamine

Answer 23

Kinins are 10x more potent than histamine

Question 24

Describe the role of kinins in pain

Answer 24

Promote redness, local heat, swelling and pain

Pain is produced via nociceptive afferents in the skin and viscera

Question 25

What are the kinin receptors,?

Answer 25

B1 and B2 B1 are the main receptors that are responsible for the kinin biological effects B2 are targeted by drugs to block bradykinin

Question 26

What is the effect of ACE inhibitors on bradykinin levels?

Answer 26

Bradykinin levels are increased by ACE inhibitors due the inhibition of kininase II Leads to hypotension

Question 27

What is the mechanism of action of icatibant?

Answer 27

B2 receptor inhibitor | May be useful for hypotension and myocardial hypertrophy

Question 28

What is the general effect of vasopressin?

Answer 28

Increased BP via increased renal resorption of water

Question 29

What is desmopressin?

Answer 29

A vasopressin analogue drug | Used for diabetes insipidus, hemophilia and vWF disease (increases VIII), and dental procedures

Question 30

What are the major natriuretic peptides?

Answer 30

ABC: Atrial NP Brain NP C-type NP

Question 31

What is the effect of vasopeptide inhibitors (omapatrilat, sampatrilat, fasidotrilat)?

Answer 31

Enhanced vasodilation, reduced vasoconstriction and increased sodium excretion Mechanism: increased levels of natriuretic peptides and decreased formation of Ang II

Question 32

What is the general effect of endothelins?

Answer 32

Vasoconstriction

Question 33

What are the endothelin receptors?

Answer 33

ET-A and ET-B

Question 34

What is Bosentan?

Answer 34

A non-selective ET antagonist available orally and IV | Inhibits endothelin

Question 35

Describe the function of vasoactive intestinal peptide

Answer 35

VIP causes vasodilation and also functions as a neuromodulator

Question 36

What is the effect of substance P?

Answer 36

Vasodilation via release of NO

Question 37

What is the effect of neurotensin?

Answer 37

Vasodilation, hypotension, increased vascular permeability, hyperglycemia and inhibition of gastric motility

Question 38

What is the effect of calcitonin gene related peptide (CGRP)?

Answer 38

Hypotension and tachycardia

Question 39

In what situations are adrenomodulin levels increased?

Answer 39

Intense exercise Hypertension Renal failure Septic shock

Question 40

What is the effect of neuropeptide Y?

Answer 40

Vasoconstriction, mediates hypertensive responses

Question 41

What is the effect of urotensin?

Answer 41

Vasoconstriction of arterial beds | Increased in patients with end stage heart failure