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All of the following are examples of second messengers except:
a. Calcium
b. inositol triphosphate
c. cyclic adenosine monophosphate
d. glutamate
d. glutamate
Glutamate is the FIRST messenger for the NMDA receptor
Stimulation of which receptors activates phospholipase C (select 2):
a. Beta 1
b. M-2
c. Alpha 1
d. Vasopressin 1
C & D
alpha 1
vasopressin 1
Voltage gated Na+ channels in neurons are an example of what type of cellular communication?
ion-channels open or close to allows ions down a concentration gradient
What is an enzyme-linked receptor?
the receptor is also an enzyme
signal binging actiate the catalytic domain
ex. insulin receptor in skeletal muscle linked to tyrosine kinase
What is the first messenger?
the ligand that binds to a G-protein coupled receptor
can be a neurotransmitter, hormone, or drug
How does the G-protein coupled receptor activate the effector?
alpha dissociates from beta and gamma
After an effector activates the second messenger, what is the next step?
2nd messenger starts an enzymatic cascade to lead to a cellular response
The intracellular response to the 2nd messenger is _________________ _________________.
tissue specific
What are some examples of effectors that can be activated by a G-protein coupled receptor?
adenylate cyclase
phospholipase C
GABA
M2
How many second messengers are there and what are they?
FIVE
1. cAMP
2. cGMP
3. IP3
4. DAG
5. Ca++
Beta 1 stimulation in the SNS causes .....
increased contractility, increased HR, and increased conduction speed
Which alpha receptor is predominantly stimulated in the SNS in the arteries?
alpha 1
Which alpha receptors is predominantly stimulated in the SNS in the veins?
alpha 2
Which receptor causes vasodilation by SNS stimulation in the myocardium and skeletal muscle?
beta 2
Which receptor causes vasodilation by SNS stimulation in the renal and mesenteric vascular beds?
dopamine
Stimulation of the M2 receptors by the PNS causes.....
decreased contractility
decreased HR
decreased conduction speed
Which receptor in the bronchial tree cauess bronchoconstriction by PNS stimulation?
M3
Which receptor in the kidneys, when stimulated by the SNS, causes diuresis via ADH inhibition? Where in the kidneys are they located?
alpha 2
renal tubules
Which receptor in the kidneys, when stimulated by the SNS causes increased renin release?
Beta 1
Stimulation of the alpha 2 receptor reduces (select two):
a. sympathetic tone
b. platelet aggregation
c. serum glucose
d. shivering
A & D
a. sympathetic tone
d. shivering
Which enzyme metabolizes cAMP?
a. protein kinase A
b. adenylate cyclase
c. phospholipase C
d. phosphodiesterase III
d. phosphodiesterase III
Select the true statements regrding norepinephrine synthesis and release (select 2).
a. Norepinephrine in the synaptic cleft inhibits its release
b. Norepinephrine is converted to epinephrine in sympathetic post-ganglion nerves
c. Tyrosine hyroxylase catalyzes the rate limiting step in norepinephrine synthesis.
d. The adrenal medulla releases 80% norepinephrine and 20% epinephrine.
A & C
a. Norepinephrine in the synaptic cleft inhibits its release
c. Tyrosine hydroxylase catalyzes the rate limiting step in norepinephrine synthesis
What is the PRIMARY mechanism for termination of action of norepinephrine in the synaptic cleft
a. catechol-O-methyltransferase
b. reuptake
c. diffusion
d. monoamine oxidase
b. reuptake
What is the end product of norepinephrine metabolism?
a. tyrosine
b. vanillylmandelic acid
c. metanephrine
d. normetanephrine
b. vanillylmandelic acid
What are the 3 areas for the mechanism of action of alpha-2 receptors?
1. presynaptic
2. postsynaptic
3. nonsynaptic (platelets)
Why does rapid infusion of Precedex cause a transient increase in hypertension?
postsynaptic alpha 2 receptors in arterial and venous circultions cause vasoconstriction and HTN
the CNS effect of vasodilation lags slightly behind
How does Milrinone increase intracellular Ca and cardiac contractility?
PDE 3 inhibition-->increased cAMP
How does PDE 3 inhibition impact vascular smooth muscle?
cAMP inhibits MLCK causing vasodilation and decreased SVR
What is the primary neurotransmitter in the SNS?
Norepinephrine
What is the rate-limiting factor in the production of norepinephrine?
tyrosine hydroxylase
The adrenal medulla releases _______ epinephrine and ______norepinephrine.
80% epi, 20% norepi
Norepinephrine stimulation of alpha 2 in the synaptic cleft causes.......
inhibition of its own release
Norepinephrine augments its own release by stimulating _____________.
Beta 2
Norepinephrine release from the presynaptic neuron into the synaptic cleft is dependent on ____________.
Ca++
Reuptake is responsible for how much of norepinephrine's removal from the synaptic cleft?
80%
Norepinephrine's reuptake into the nerve terminal can be blocked by _______________________ and ________________________.
tricyclic antidepressants and cocaine
Norepinephrine that is diffused away from the synaptic cleft is metabolized by ________________________.
MAO and COMT in the liver and kidneys
Increased vanillylmandelic acid in the urine indicates......
pheochromocytoma
Preganglionic nerve fibers in the SNS are
a. unmyelinated C fibers
b. myelinated C fibers
c. myelinated B fibers
d. unmyelinated B fibers
c. myelinated B fibers
Sympathetic nerves that directly innervate the adrenal medulla are:
a. C fibers that release acetylcholine
b. C fibers that release norepinephrine
c. B fibers that release norepinephrine
d. B fibers that release acetylcholine
d. B fibers that release acetylcholine
Stimulation of which receptor causes a transcellular potassium shift?
a. alpha 1
b. alpha 2
c. beta 1
d. beta 2
d. beta 2
Which surgical procedures are most likely to activate the baroreceptor reflex (select 2):
a. C section
b. mediastinoscopy
c. carotid endarterectomy
d. strabismus repair
B & C
b. mediastinoscopy
c. carotid endarterectomy
What drugs are MOST likely to impair the intergrity of the baroreceptor reflex (select 3):
a. norepinephrine
b. labetolol
c. hydralazine
d. Sevoflurane
e. propofol
f. thiopental
B, D, E
b. labetolol
d. Sevoflurane
e. propofol
These drugs can lower both HR and BP, inhibiting the baroreceptor reflex from compensating.
Activation of the Bezold-Jarish reflex manifests as (select 3):
a. coronary atery vasoconstriction
b. bradycardia
c. tachycardia
d. coronary artery vasodilation
e. hypotension
f. hypertension
B, D, E
b. bradycardia
d. coronary artery vasodilation
e. hypotension
occurs with profound hypovolemia, heart is trying to acheive more time to fill
Risk factors that contribute to the manifestation of the oculocardiac reflex include all of the following EXCEPT:
a. hypercarbia
b. retrobulbar block
c. old age
d. strabismus surgery
c. old age
Identify the BEST agents to augment the HR in patients with a heart transplant (select 2):
a. isoproterenol
b. atropine
c. epinephrine
d. phenyleprhine
A & C
a. isoproterenol
c. epinephrine
Have to use DIRECT-agents
What is the primary neurotransmitter in the PNS?
acetylcholine
How is acetylcholine removed from the synaptic cleft?
acetylcholinesterase hydrolyzes ACh into choline and acetate
choline is recycled and acetate is diffused away
How and where is acetylcholine created?
Choline acetyltransferase (ChAT) joins choline and acetyl CoA to make acetylcholine in the cytoplasm of the nerve terminal
Where does Acetyl CoA come from?
mitochondria of the nerve cell body
How is acetylcholine released into the synpatic cleft?
ACh is packaged into vesicles after production. Ca++ influx into the nerve releases the packages of ACh into the synaptic cleft
How does magnesium cause muscle weakness and prolongation of neuromuscular blockers?
magnesium is an antagonist of Ca++ in the nerve terminal, decreasing Ca++ influx into the nerve ending to release ACh
What are the 3 control centers of autonomic reflexes?
hypothalamus, brainstem, and spinal cord
What is a ganglion?
site where a preganglionic nerve and postganglionic nerve synpase
Cholinergic PNS postganglionic fibers release _______________.
ACh
Adrenergic SNS postganglionic fibers release _______________.
norepinephrine
What division of the ANS has short preganglionic fibers and long postganglionic fibers?
SNS
What division of the ANS has long preganglionic fibers and short postganglionic fibers?
PNS
What is the origin of the SNS division of the ANS?
known as the thoracolumbar division
T1-L3
What are the origins of the PNS division of the ANS?
known as the craniosacral division
CN 3, 7, 9, 10 (occulomotor, facial, glossopharyngeal, vagus)
S2-S4
Where are the ganglia located in the SNS?
near the spinal cord
Where are the ganglia located in the PNS?
near or inside the effector organ
What part of the SNS does NOT have postglanglionic fibers?
adrenal medulla
Chromaffin cells release epi and norepi directly into the bloodstream
What is the difference between the gray and white rami?
White rami are myelinated
What are the 3 paths preganglionic fibers can take in the spinal cord?
1. synapse with postganglionic fiber at the same spinal level
2. ascend or descend spinal levels before synapsing with postganglionic fiber and exiting the spinal cord
3. they can bypass the sympathetic chain entirely and synapse in a collateral ganglion
What are examples of collateral ganglions?
superior cervical
middle cervical
stellate
celiac
superior mesenteric
inferior mesenteric
What does the stellate ganglion innervate?
upper extremity, some of head and neck
In what circumstances would the stellate ganglion be purposefully blocked?
upper extremity sympathetic dystrophy, complex regional pain syndrome, to increase blood flow to an extremity
When is the stellate ganglion most commonly blocked?
unintentionally via a brachial nerve plexus block
What is the consequence of blocking the stellate ganglion?
Horner's syndrome: vasodilation, ptosis, anhidrosis, enopthalmos, miosis
What are the two parts of the adrenal medulla and what are their purposes?
1. medulla-->secretes catecholamines
2. cortex-->secretes glucocorticoids, mineralocorticoids, and androgens
At rest, the adrenal medulla secretes how much epi and norepi?
epi 0.2 mcg/kg/min
norepi 0.05 mcg/kg/min
Do catecholamines prefer to stay in the bloodstream or synaptic cleft?
stay 5-10x longer in the bloodstream
Pheochromoctomas release mainly which catecholamine?
norepinephrine
Symptoms of a pheochromocytoma
SNS activation leads to HA, diaphoresis, tachycardia
What is the gold standard for diagnosing a pheochromocytoma?
VMA in urine
What is the most important thing to remember with drug administration for the patient with a pheochromocytoma?
BLOCK alpha before beta for the love of all that is holy
What are the non-selective alpha blockers?
Phentolamine and phenoxybenzamine
What are the alpha 1 selective blockers?
doxasozin and prazosin
What happens if you block beta before alpha with a pheochromocytoma?
inhibition of skeletal muscle vasodilation, increased SVR, decreased inotropy can precipitate CHF
What should you prepare for once the pheochromocytoma is out?
hypotension and hypoglycemia
What does SNS stimulation cause increased insulin output?
Cells have to have insulin to utilize glucose
What drugs cause an intracellular shift in K+?
Beta 2 agonists, insulin, methylxanthines
How do volatile anesthetics impact the baroreceptor reflex?
dose-dependent decrease
Iso impacts the reflex the least
How do vasodilators impact the baroreceptor reflex?
preserve it
How do beta blockers impact the baroreceptor reflex?
prevent increased HR in setting of low BP
When is the Bezold-Jarisch reflex activated?
when the heart is empty from decreased preload or myocardial ischemia, decreased HR and BP
What is the purpose of the Bezold-Jarisch reflex?
give the heart more time to fill
What sensor activates the Bezold-Jarisch reflex?
the left ventricle
What is the Bezold-Jarisch triad?
bradycardia
hypotension
coronary vasodilation
When is the Bainbridge reflex activated?
when the heart is full from too much preload, tachycardia
What is the purpose of the Bainbridge reflex?
minimize venous congestion and promote forward flow
What are the sensors of the Bainbridge reflex?
SA node
RV
pulmonary veins
What is the body's response to the Bainbridge reflex?
tachycardia
decreased ADH release to decrease water retention
increased ANP release to cause diuresis
What stimlulates the oculocardiac reflex?
traction to extraocular muscles
strabismus surgery
pressure on globe or conjunctiva
ocular trauma
pressure on orbital tissue after enucleation
retrobulbar block
True or False. A retrobulbar block can prevent the oculocardiac reflex.
TRUE. It can cause OR prevent it.
Describe the afferent nerve stimulation process leading to the oculocardiac reflex.
Long and short ciliary nerve--> ciliary ganglion--> ophthalmic V1 branch of trigeminal nerve--> Gasserion ganglion-->M2 receptor on SA and AV nodes
How does the oculocardiac reflex present?
bradycardia
hypotension
junctional rhythm
AV block
asystole
What factors can worsen the severity of the oculocardiac reflex?
hypoxemia
hypercarbia
light anesthesia
True or False. The oculocardiac reflex fatigues with subsequent stimulation.
True