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67 Cards in this Set

  • Front
  • Back
Many autocoids act through the production of which gas?
What are NO three main functions?
1. neurotransmitter in PNS and CNS
2. mediates vasodilation (= endothelium-derived relaxing factor, EDRF)
3. in lg quantities it can kill or inhibit growth of microorganisms, tumor cells, or lymphocytes
Which two nitric oxide synthase (NOS) isoforms are constitutively expressed?
endothelial NOS (eNOS)
neuronal NOS (nNOS)
What activates eNOS and nNOS?
calcium/calmodulin binding
(from ACh, serotonin, Histamine, bradykinin...) to make small amounts of NO
Which NOS isoform is expressed only after stimulation of cells with cytokines, microbes, or microbial products?
inducible NOS (iNOS)
What happens once it iNOS is expressed?
it is constitutively active and makes large amounts of NO
Where is iNOS made?
variety of cell types-
cells of immune system,
vascular sm mm cells
pancreatic islet cells,
How is NO transported?
it's not, its a gas-- it diffuses through membranes to act on surrounding cells
What is the t1/2 of NO?
short- a few seconds
How is NO inactivated?
interaction with O2 --> converted to nitrite or nitrate
What happens when NO binds Fe in heme group?
activates guanylate cyclase --> inc cGMP --> activates cGMP dependent protein kinase --> relaxes sm mm --> vasodilation
What is the reaction catalyzed by NOS?
L-arginine + NADPH + O2 --> L-citrulline + NADP + NO
What may be involved in processes ranging from excitotoxic cell death to memory?
Ca entry through NMDA receptors --> activates nNOS --> glutamate inc
Which NOS is involved with NonAdrenergic NonCholinergic (NANC) in GI, urogenital, and vascular systems?
What do children get when they have deficient nNOS myenteric nerves at the pylorus?
pyloric stenosis
What may account for some forms of erectile dysfunction?
NO (via nNOS)
What are three actions of eNO
1. vasodilator
2. prevents platelet adherence and aggregation and neutrophil aggregation
3. prevents sm mm proliferation
Which NO is part of an adaptive response during inflammation and injury?
iNO- it kills foreign bodies through formation of damaging radicals and peroxynitrite ions
When would inhibition of NOS be beneficial?
When large amounts of NO are causing damage during septic shock
Are thre any isoform specific inhibitors of NOS?
When is inhaled NO used to produce selective pulmonary vasodilation and improved oxygenation?
persistent pulmonary hypertension of newborn
What are prostaglandins?
eicosanoids derived from arachidonic acid
Where are prostaglandins stored?
they're not stored- synthesized in response to stimuli and released in bursts into extracellular space
Where do prostaglandins act?
through specific G protein linked cell surface receptors; act locally
Mechanism of prostaglandin synthesis?
membrane phospholipids --> (phospholipase A2) --> arachidonic acid --> (cyclooxygenase) --> PGG2 --> prostaglandins
Where do NSAIDS work?
inhibit cyclooxygenase
analogue of PGE2
used for abortion
analogue of 15-methyl-PGF2a
used for postpartum hemorrhage
analogue of PGE1
used for erectile dysfunction
alprostadil (Caverject)
analogue of PGE2a derivative
used for gastric ulcers/abortion
analogue of PGE2a derivative
used for abortion
analogue of prostacyclin
used for Raynaud's disease
infused to keep ductus arteriosus in neonate awaiting surgery
PGE1 (alprostadil)
What is used when there is delayed closure of ductus arteriosus?
Even though several prostaglandins are potential vasodilators, why are they rarely used?
Name four effects of prostaglandins on female reproductive system?
1. contraction of uterine sm mm
2. used with anti-progestins to prematurely terminate preg
3. used to induce cervical ripening to aid labor
4. responsible for menstrual cramps (--> use NSAIDS)
Does VIP vasoconstrict or vasodilate?
potent vasodilator
Where is VIP expressed?
enteric nervous system
How does VIP act?
through G protein linked receptors
Name three roles of VIP?
circadian rhythms
growth factor
Where is VIP often co-localized with NOS?
in PNS neurons- may help with neurotransmission
relate VIP to pancreatic D cell tumors?
overexpressed in these tumors --> pancreatic cholera --> watery diarrhea, hypokalemia, acidosis
How is a pancreatic D cell tumor managed?
surgically or with the drug streptozocin
What is the rate limiting step in the development of an erection?
ability to achieve sm mm relaxation --> allowing increased blood flow into corporal sinusoids
What is the mechanism of action of all drugs available for treatment of erectile dysfunction?
relaxation of sm mm of corpora cavernosa through increases in cyclic nucelotids cAMP or cGMP; some also have uses as vasodilators
What are three main routes of administration of drugs used to tx erectile dysfunciton?
intracavernous injection
transurethral suppositories
oral administration
cGMP phophodiesterase inhibitor
inc cGMP
sildenafil = Viagra
oral and injected
alpha1/alpha2 antagonist
inc cAMP
urethral suppository and injection
inc cAMP
cAMP phosphodiesterase inhibitor
inc cAMP
parasympathetic neurotransmitter and al/a2 antagonist
inc cAMP
not yet FDA approved
VIP and
Name two newer drugs of the same class as viagra?
tadalafil (cialis)
vardenafil (levitra)
all pt's taking nitrate drugs --> systemic vasodilation and visual impairment
What causes the visual impairment in pt's on nitrates who take viagra?
inhibition of cGMP phosphodiesterase type 6 found in the retina
What is t1/2 of bradykinin?
short - about 15 sec
Name five roles of bradykinin?
1. produces pain
2. marked vasodilation (10x that of HA)
3. inc vascular permeability (--> hypotension)
4. induces prostaglandin E's (through activation of phospholipase A2)
5. stimulates production of HA and serotonin
What bradykinin receptor is upregulated during inflammation and may be important in the inflammatory response?
Which bradykinin receptor is constitutively expressed and activation leads to release of NO and consequent vasodilation, hypotension, permeability and pain?
Kininase II is identical to which molecule?
What does ACE have to do with bradykinin?
some of the effects of ACE-inhibitors are due to enhanced effects of bradykinin
Work through the steps of prekallikrein all the way to inactive fragments
prekallikrein ->(HFa or trypsin)-> kallikrein

kininogen ->(kallikrein)-> bradykinin ->(kininase I and II)-> inactive fragments
This neuropeptide found in the CNS, PNS, and ENS is a potent arteriolar relaxant
substance P
What is substance P made from and what receptors does it act on?
made from preprotachykinin
acts through tachykinin receptors
What may substance P be involved in ?
How is calcitonin gene related peptide (CGRP) made?
by alternative splicing of the calcitonin gene
Where is CGRP expressed
CV system and Urogenital system
What does CGRP have in common with substance P?
it may also be involved in migraines