Pharmacology of Vasoactive Peptides Flashcards
What are the 2 functions of angiotensin converting enzyme (ACE)?
- Converts ATI to ATII
2. Kininase II activity to metabolize bradykinin
What is ACE also known as?
Kininase II
What are 2 drugs that are known as ACE Inhibitors?
Captopril
Enalapril
What is that action of bradykinin?
Vasodilation
What is the action of atrial natriuretic peptide?
Lowers blood pressure by stimulating Na excretion, antagonized the effects of aldosterone
What is the action of kallikreins?
They promote coagulation process via intrinsic system AND exert control to lower blood pressure via generation of kinins (like bradykinin)
What is the action of endothelins?
Potent vasoconstrictors
What is the function of vasoactive intestinal peptide (VIP)?
VIP is present in the central and peripheral nerves where it functions as a neuromodulator. VIP produces marked vasodilation.
What is the function of substance P?
Substance P induces vasodilation by stimulating the release of nitric oxide.
What is the function of calcitonin gene-related peptide (CGRP)?
CGRP is present in large amounts in the thyroid gland. CGRP is also found in the CNS and GI tract with substance P. Intravenous administration of CGRP can cause hypotension and tachycardia.
What is the effect of desmopressin on endothelial cells?
Desmopressin increase the factor VIII and vWF activity of patients with mild hemophilia and von Willebrand disease. It is effective in the control of bleeding in mild surgical process.
What is the effect of aprotonin on the actions of kallikrein?
Kallkrein inhibitor that leads to the blockage of bradykinin generation
Which of the following enzymes is responsible for the generation of Angiotensin II? A. Renin B. Kininase-I C. Kininase-II D. Plasmin E. Kallikrein
C. Kininase-II
An elderly diabetic patient was treated with an ACE inhibitor for hypertension. During hospitalization he developed sepsis and sustained a severe drop in blood pressure. What is the likely cause for this condition? A. Inhibition of renin B. Excessive generation of angiotensin C. Excessive generation of bradykinin D. Inhibition of plasmin E. Inhibition of kallikrein
C. Excessive generation of bradykinin
What is the general MOA of vasoactive peptides?
These peptides all act on cell surface receptors. Most act via G protein-coupled receptors and cause the production of second messengers, some may open ion channels.
What converts ATII to ATIII?
Aminopeptidase
What converts angiotensinogen to ATI?
Renin
What converts ATI to ATII?
ACE
What is the only active AT?
ATII
What is the action of ATII?
Produces profound vasoconstriction
Angiotensinase
A group of peptidases which hydrolyze angiotensin II and angiotensin III into smaller fragments.
What is the function of ACE inhibitors?
Controls hypertension.
ACE inhibitors not only block the conversion of angiotensin I to angiotensin II but also inhibits the degradation of other vasopeptides such as bradykinin
What are angiotensin receptor antagonists?
Antagonize the action of angiotensin II
What are some angiotensin receptor antagonists?
Losartan
Valsartan
What is the action of plasma kallikrein?
Conversion of HMW kininogen to bradykinin
What is plasma kallikrein also known as?
Fletcher Factor
What is plasma prekallikrein activated by?
XIIa (Hageman factor)
What is a cause of hypotension in DIC patients?
Many of the patients with consumption coagulapathy (DIC) develop hypotension due to increased kallikrein production.
Do the angiotensin antagonists have any effect on the actions on ACE?
No
Can these angiotensin antagonists be given to a hypertensive patient with sepsis?
Yes
What is the role of kinins in inflammation and pain?
Kinins promote redness, local heat, swelling and pain. Kinins are potent algesic agents.
How can hypotension occur as a result of ACE inhibitors?
Angiotensin converting enzyme inhibitors such as captopril therefore can inhibit the generation of angiotensin II simultaneously bradykinin levels may increase resulting in hypotension.
Are there specific kinin antagonist drugs?
No
What is ictibant?
Ictibant is a second generation B2 kinin receptor inhibitor which has undergone limited clinical trials in pain and inflammation.
What is the action of vasopressin?
It plays an important role in the long term control of blood pressure through its action on the kidney to increase water resorption. It has short term vasoconstrictor actions.
What is the action of these drugs: omapatrilat, sampartilat and fasidotrilat?
These drugs enhance vasodilation, reduce vasoconstriction and increase sodium excretion via inhibition of metaloproteases
What is a non-selective antagonist of endothelin receptors?
Bosentan
What is the action of neurotensin?
In peripheral circulation it causes vasodilation, hypotension, vascular permeability, hyperglycemia and inhibition of gastric motility.
What is the action of adrenomodulin?
It is widely distributed and circulates in blood and mediates hypothyroid responses. Circulating adrenomodulin levels are increased during intensive exercise, patients with hypertension, renal failure and septic shock.
What is the action of neuropeptide Y?
Besides a CNS effect it produces vasoconstriction and mediates hypertensive responses.
What is the action of urotensin?
It is a potent vasoconstrictor primarily acting on arterial beds. It is one of the most potent vasoconstrictors.
Captopril and Enalapril MOA and Indication
ACE Inhibitors
Hypertension
Losartan and Valsartan MOA and Indication
Angiotensin receptor inhibitor
Hypertension
What is ROA of Captopril and Enalapril and Losartan and Valsartan?
Oral
Icatibant MOA and ROA
Bradykinin receptor inhibitor
Oral
Icatibant Indication
Inflammatory responses
Aprotonin MOA and ROA
Kallikrein inhibitor
IV
Aprotonin Indication
Inflammation
Desmopressin (DDAVP) MOA and ROA
Vasopressin analogue
IV
Desmopressin Indication
Bleeding
Bosentan MOA and ROA
Endothelin receptor inhibitor
Oral
Bosentan Indication
Pulmonary hypertension
