Pharm: Vasoactive Peptides Flashcards
What are the 4 major vasoactive peptides that have important roles for regulating hemodynamics?
Angiotensin
Kinins
Endothelins
Vasopressin
Which angiotensin is most pharmacologically and pathologically active?
Angiotensin I
Describe the general mechanism of action of vasoactive peptides?
Act on cell surface receptors (GPCRs) leading to production of second messengers or opening of ion channels
Describe the steps that lead to the production of angiotensin III
Renin converts angiotensinogen to angiotensin I
ACE converts Angiotensin I to II (II is the active form)
II is degraded into III
What is the major action of angiotensin II?
Profound vasoconstriction
How many amino acids are found in angiotensinogen, angiotensin I, and angiotensin II?
Angiotensinogen: 14
Angiotensin I: 10
Angiotensin II: 8
What molecules increase the production of angiotensinogen?
Corticosteroids
Estrogens
Thyroid Hormones
Angiotensin II
What are the other names of angiotensin converting enzyme (ACE)?
Peptidyle dipeptidase
Kininase II
Where is ACE primarily located in the body?
On the luminal structure of the endothelial cells throughout the vasculature
What is the function of angiotensinase?
Breaks down angiotensin II and III into small fragments
What is the effect of excessive production of angiotensin II?
Hypertension and disorders of hemodynamics
Compare the potency of angiotensin II and norepinephrine
Angiotensin II is 40x more potent than NE
What are the processes targeted by anti-angiotensin II drugs?
Block renin secretion/action
Inhibit ACE function
Block angiotensin receptors
In addition to ACE inhibitors blocking Ang II production, what other peptides are inhibited?
Bradykinin metabolism is blocked by ACE inhibitors
Leads to hypotension
What are the names of the orally active ACE inhibitors?
Captopril
Enalapril
What are the angiotensin antagonist drugs?
Saralasin
Losartan
Valsartan
Compare the clinical benefits of angiotensin receptor antagonists and ACE inhibitors
They are basically identical: decreased function of angiotensin II
Do angiotensin receptor antagonists have any effect on the actions of ACE?
No
What is the general effect of the kinins?
Vasodilation, hypotension
What is the function of kallikrein?
Converts HMW kininogen to bradykinin, leading to vasodilation and hypotension
How is kallikrein related to the coagulation cascade?
Plasma prekallikrein is also known as Fletcher factor, which promotes the intrinsic pathway of coagulation.
Factor XIIa also increases kallikrein production
What vascular beds are affected by bradykinin?
Heart, liver, kidney, intestine, skeletal muscles, liver
Compare the potency of kinins to histamine
Kinins are 10x more potent than histamine
Describe the role of kinins in pain
Promote redness, local heat, swelling and pain
Pain is produced via nociceptive afferents in the skin and viscera
What are the kinin receptors,?
B1 and B2
B1 are the main receptors that are responsible for the kinin biological effects
B2 are targeted by drugs to block bradykinin
What is the effect of ACE inhibitors on bradykinin levels?
Bradykinin levels are increased by ACE inhibitors due the inhibition of kininase II
Leads to hypotension
What is the mechanism of action of icatibant?
B2 receptor inhibitor
May be useful for hypotension and myocardial hypertrophy
What is the general effect of vasopressin?
Increased BP via increased renal resorption of water
What is desmopressin?
A vasopressin analogue drug
Used for diabetes insipidus, hemophilia and vWF disease (increases VIII), and dental procedures
What are the major natriuretic peptides?
ABC:
Atrial NP
Brain NP
C-type NP
What is the effect of vasopeptide inhibitors (omapatrilat, sampatrilat, fasidotrilat)?
Enhanced vasodilation, reduced vasoconstriction and increased sodium excretion
Mechanism: increased levels of natriuretic peptides and decreased formation of Ang II
What is the general effect of endothelins?
Vasoconstriction
What are the endothelin receptors?
ET-A and ET-B
What is Bosentan?
A non-selective ET antagonist available orally and IV
Inhibits endothelin
Describe the function of vasoactive intestinal peptide
VIP causes vasodilation and also functions as a neuromodulator
What is the effect of substance P?
Vasodilation via release of NO
What is the effect of neurotensin?
Vasodilation, hypotension, increased vascular permeability, hyperglycemia and inhibition of gastric motility
What is the effect of calcitonin gene related peptide (CGRP)?
Hypotension and tachycardia
In what situations are adrenomodulin levels increased?
Intense exercise
Hypertension
Renal failure
Septic shock
What is the effect of neuropeptide Y?
Vasoconstriction, mediates hypertensive responses
What is the effect of urotensin?
Vasoconstriction of arterial beds
Increased in patients with end stage heart failure
