Vasoactive Peptide Pharmacology Flashcards
Where in the cell do vasoactive peptides typically act?
Cell surface receptors (largely GPCRs to affect production of second messengers or open ion channels)
Angiotensin
What enzyme catalyzes its creation from angiotensinogen?
Renin
How many AAs in angiotensin I?
10
Decapeptide
Which angiotensin is most active?
Angiotensin II
What enzyme catalyzes conversion of angiotensin I to angiotensin II?
ACE
Angiotensin Converting Enzyme
What enzyme converts angiotensin II to angiotensin III?
Aminopeptidase
What enzymes degrades angiotensin?
Angiotensinases
How many AAs in angiotensin II?
8
Octapeptide
ACE is also known as…?
Kininase II
Peptidyl dipeptidase
List the pharmacologic actions of angiotensin II
- Vasoconstriction
- Aldosterone production from adrenal cortex
- lucocorticoid biosynthesis
- Mitogenic agent for vascular and cardiovascular muscle cells
What are the two general mechanisms by which we inhibit angiotensin?
- ACE inhibitors
- Angiotensin receptor blockers
ACE inhibitors inhibit the conversion of…?
Angiotensin I to Angiotensin II
ACE inhibitors inhibit the degradation of…?
Bradykinin
List two ACE Inhibitors
Captopril
Enalapril
List the Angiotensin Receptor Antagonists
Losartan
Valsartan
Plasma prekallikrein is activated by what to become plasma kallikrein?
Factor 12a (Hageman Factor)
Trypsin
Kallikrein
What does plasma kallikrein catalyze?
Conversion of HMW kininogen to bradykinin
What does tissue kallikrein catalyze?
Conversion of LMW kininogen to Kallidin (Lysylbradykinin)
What is the function of kininases I and II?
Degrade bradykinin and kallidin into inactive fragments
An excess of kallikrein will lead to….
Excess bradykinin production, leading to hypotension
What is the predominant peptide in hypotensive shock?
Bradykinin
What drug would you never give to a septic patient? Why?
ACE Inhibitor
They would inhibit kininase II (ACE), preventing the degradation of bradykinin and exacerbating the problem of hypotension in septic shock
What are the various physiological actions of kinins?
- Vasodilation
- Stimulate NO release (active NOS2)
- Prostaglandin release
- Potent algesics (cause pain)
- Promote water and solutions’ movement into the EC space, causing edema
How are kinins involved in pain?
They are algesics (they cause pain).
They promote redness, local heat, swelling, and pain
What are the two bradykinin receptors and their primary functions?
B1 - mediating biological actions of bradykinin
B2 - drugs that block the action of bradykinin target B2 receptor
Why is kininase II important in bradykinin regulation?
Kininase II (ACE) degrades bradykinin into inactive products.
Icatibant
MOA
B2 receptor inhibitor
Icatibant
Indications
Angio-neurotic edema (edema of an unknown immunologic nature)
What drug can be used to block the algesic effects of kinins?
Aspirin
Vasopressin (ADH)
General role in hemostasis
Long term control of blood pressure through kidney and increased H2O reabsorption
Desmopressin
Indications
- Used in pediatrics.
- Analog of ADH that is used in blood banking, mild hemophilia, and vWF deficiency.
- Mild surgical/dental procedures
Desmopressin
MOA
Increases Factor 8 activity
Vasopeptide Inhibitor Drugs
Physiological effects
Increase natriuretic peptide levels and decrease formation of angiotensin II.
Vasodilation
Increased sodium excretion
Vasopeptide Inhibitors
List 3
Omapatrilat
Sampartilat
Fasidotrilat
Endothelins
What effect do they have on vascular tone?
Vasoconstrictors
What drug is a non-selective antagonist of endothelins?
Bosentan
Bosentan
MOA
Antagonist of Endothelin
Bosentan
Indication
Pulmonary artery hypertension
VIP causes vaso…..?
Vasodilation
Substance P causes vaso….? How?
Vasodilation by stimulating the release of NO
Neurotensin
Causes vasodilation, hyperglycemia
Adrenomodulin levels are increased during…
Exercise
Hypertension
Renal failure
Septic shock
