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MHD/Pharm Block 4 > Pharm: Vasoactive Peptides > Flashcards

Pharm: Vasoactive Peptides Flashcards

1
Q

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

A

Angiotensin
Kinins
Endothelins
Vasopressin

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2
Q

Which angiotensin is most pharmacologically and pathologically active?

A

Angiotensin I

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3
Q

Describe the general mechanism of action of vasoactive peptides?

A

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

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4
Q

Describe the steps that lead to the production of angiotensin III

A

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

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5
Q

What is the major action of angiotensin II?

A

Profound vasoconstriction

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6
Q

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

A

Angiotensinogen: 14
Angiotensin I: 10
Angiotensin II: 8

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7
Q

What molecules increase the production of angiotensinogen?

A

Corticosteroids
Estrogens
Thyroid Hormones
Angiotensin II

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8
Q

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

A

Peptidyle dipeptidase

Kininase II

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9
Q

Where is ACE primarily located in the body?

A

On the luminal structure of the endothelial cells throughout the vasculature

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10
Q

What is the function of angiotensinase?

A

Breaks down angiotensin II and III into small fragments

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11
Q

What is the effect of excessive production of angiotensin II?

A

Hypertension and disorders of hemodynamics

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12
Q

Compare the potency of angiotensin II and norepinephrine

A

Angiotensin II is 40x more potent than NE

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13
Q

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

A

Block renin secretion/action
Inhibit ACE function
Block angiotensin receptors

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14
Q

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

A

Bradykinin metabolism is blocked by ACE inhibitors

Leads to hypotension

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15
Q

What are the names of the orally active ACE inhibitors?

A

Captopril

Enalapril

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16
Q

What are the angiotensin antagonist drugs?

A

Saralasin
Losartan
Valsartan

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17
Q

Compare the clinical benefits of angiotensin receptor antagonists and ACE inhibitors

A

They are basically identical: decreased function of angiotensin II

18
Q

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

A

No

19
Q

What is the general effect of the kinins?

A

Vasodilation, hypotension

20
Q

What is the function of kallikrein?

A

Converts HMW kininogen to bradykinin, leading to vasodilation and hypotension

21
Q

How is kallikrein related to the coagulation cascade?

A

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

22
Q

What vascular beds are affected by bradykinin?

A

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

23
Q

Compare the potency of kinins to histamine

A

Kinins are 10x more potent than histamine

24
Q

Describe the role of kinins in pain

A

Promote redness, local heat, swelling and pain

Pain is produced via nociceptive afferents in the skin and viscera

25
Q

What are the kinin receptors,?

A

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

26
Q

What is the effect of ACE inhibitors on bradykinin levels?

A

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

27
Q

What is the mechanism of action of icatibant?

A

B2 receptor inhibitor

May be useful for hypotension and myocardial hypertrophy

28
Q

What is the general effect of vasopressin?

A

Increased BP via increased renal resorption of water

29
Q

What is desmopressin?

A

A vasopressin analogue drug

Used for diabetes insipidus, hemophilia and vWF disease (increases VIII), and dental procedures

30
Q

What are the major natriuretic peptides?

A

ABC:
Atrial NP
Brain NP
C-type NP

31
Q

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

A

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

32
Q

What is the general effect of endothelins?

A

Vasoconstriction

33
Q

What are the endothelin receptors?

A

ET-A and ET-B

34
Q

What is Bosentan?

A

A non-selective ET antagonist available orally and IV

Inhibits endothelin

35
Q

Describe the function of vasoactive intestinal peptide

A

VIP causes vasodilation and also functions as a neuromodulator

36
Q

What is the effect of substance P?

A

Vasodilation via release of NO

37
Q

What is the effect of neurotensin?

A

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

38
Q

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

A

Hypotension and tachycardia

39
Q

In what situations are adrenomodulin levels increased?

A

Intense exercise
Hypertension
Renal failure
Septic shock

40
Q

What is the effect of neuropeptide Y?

A

Vasoconstriction, mediates hypertensive responses

41
Q

What is the effect of urotensin?

A

Vasoconstriction of arterial beds

Increased in patients with end stage heart failure

MHD/Pharm Block 4 (25 decks)

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