Pharm of vasoactive peptides Flashcards
What are the 5 vasoactive peptides?
1) angiotensin (I, II, III)
2) kinins (bradykinin)
3) endothelins
4) vasopressin
5) ANP
True or false: all vasoactive peptides act on cell surface receptors
TRUE (mostly via GPCRs)
True or false: angiotensin II is the only active form of AT that produces profound vasoconstriction
true
What enzyme converts angtiotensinogen to angtiotensin I
renin
What enzyme converts angiotensin I to angiotensin II?
ACE
angiotensin converting enzyme
Which drugs are known to produce an increase in angiotensin?
corticosteroids
estrogens
thyroid hormones
angiotensin II
AT I is a decapeptide while ATII is a ____________
octapeptide
What are 2 other names for ACE?
peptidyl dipeptidase
kininase II
Where is ACE found?
widely distributed in the vasculature on the luminal structure of the endothelial cells
What enzyme hydrolyzes ATII to ATIII?
angiotensinase
What is the danger of too much ATII production?
hypertension
True or false: ATII promotes the release of epi and nor epi from adrenal medulla
true
What 3 parts of angiotensin pathway are targeted by drugs?
1) renin secretion
2) converstion of ATI to ATII
3) block AT receptors
In addition of blocking the conversion of ATI to ATII, what else do ACE inhibitors do?
inhibit degradation of bradykinins (as well as substance P and enkephalin)
Why do you see hypotensive effects after treatment with ACE inhibitors/
because ACE inhibitors inhibit the degradation of bradykinins
What are the orally active ACE inhibitors?
captopril
enalapril
What is the chemistry behind angiotensin receptor blockers?
substitution of sarcosine for phenylalanine in position 8 of ATII
What class does saralasin belong to?
peptide ARBs
angiotensin receptor blockers
What are the nonapeptide ARBs?
losartan
valsartan
What enzymes produce kinins?
kallikreins (kininogenases)
True or false: kinins can be generated by insect bites
true
What enzyme converts plasma prekallikrein to plasma kallikrein?
trypsin kallikrein hageman factor (factor XIIa)
kallikrein converts __________ to __________
kininogen to bradykinin
Where are kallikreins made?
liver
Where are kallikreins present?
plasma kideny pancreas GI tract sweat glands salivary glands
What is Fletcher factor?
plasmatic prekallikrein
promotes coag process via intrinsic system
Why do DIC patients develop hypotension?
increased kallikrein production
What are kininogens?
substrates for kallikreins
What 2 varieties of kininogens are there?
low molecular weight
high molecular weight
plasma kallilkrein cleaves ________ to generate bradykinin
HMW kininogen (high molec weight)
What are the 3 kinds of kinins?
1) bradykinin
2) lysyl bradykinin
3) meth-lysylbradykinin
Bradykinin is released by ________ __________
plasma kallikrein
lysyl bradykinin is released by __________ ________
glandular kallikrein
meth-lysylbradykinin is released by _______
pepsin
Where in the body are the 3 kinins found
plasma
urine
True or false: kinins stimulate the release of NO
true
What are the 2 types of kinin receptors?
B1 = predominant receptors B2 = targeted by drugs
What is another name for kininase II?
ACE (can also inactivate bradykinin)
What does icatibant target?
second generation B2 receptor inhibitor (treat hypotension)
How do ACE inhibitors affect bradykinin?
augment its effects by blocking the degradation of it
How does aspirin affect the kallikrein kinin system?
blocks the algesic effects of prostaglandins
What are the effects of vasopressin
increased blood pressure (short term vasoconstrictor actions)
What is the clinically used analogue of vasopressin?
desmopressin
What is the effect of desmopressin?
increases factor 8 activity and von willebrand factor
What do the drugs omapatrilat, sampartilat, and fasidotrilat do?
enhance vasodilation, reduce vasoconstriction, and increase sodium excretion (via increasing levels of natriuretic peptides)
What do the endothelins do?
vasoCONSTRICT
What are the 2 receptors for endothelin actions?
ETa and ETb
What is Bosentan?
a non selective antagonist of endothelin (treats pulm hypertension)
What is VIP?
vasodilator made in nervous system
What is substance P?
vasodilator (releases NO by upregulating iNOS)
What is neurotensin
vasodilator
Where is calcitonin gene related peptide found?
thyroid gland, CNS, GI
What is adrenomodulin?
increases in exercise, hypertension, renal failure, septic shock
vasodilator
What is neuropeptide Y?
vasoconstrictor
What is urotensin?
vasoconstrictor (increases with end stage heart failure)
When patients are treated with ACE inhibitors for hypertension, why might they go into shock?
excessive generation of bradykinin
