UNIT 2 ANS Flashcards
What are the 4 classifications of receptors?
- ion channel
- GPCR
- enzyme linked receptor
- intracellular receptor
Describe the general architecture of the GPCR second messenger system.
1st messenger (extracellular signaling)
receptor (responds)
G protein (turns off/on an effector)
effector (activates/inhibits a 2nd messenger)
2nd messenger (primary intracellular signal)
enzymatic cascade
cellular response
What second messenger system is associated w/ alpha-1 receptor? What other receptors share the same pathway?
Gq –> phospholipase C –> IP3/DAG/Ca++
others:
- histamine 1
- muscarinic 1, 3, 5
- vasopressin 1
What second messenger is associated w/ alpha-2 receptor? What other receptors share a similar pathway?
G1 –> adenylate cyclase –> ATP to cAMP
others:
- muscarinic 2
- dopamine 2
What second messenger system is associated w/ beta1 & beta2 receptors? What other receptors share a similar pathway?
Gs –> adenylate cyclase –> ATP to cAMP
others:
- histamine 2
- vasopressin 2
- dopamine 1
describe the autonomic innervation of the heart
myocardium - B1 = increased contractility - M2 = decreased contractility conduction system - B1 = increased HR & conduction speed - M2 = decreased HR & depressed CV
SNS: cardiac accelerator fibers from T1-T4
PNS: vagus
describe the autonomic innervation of the vasculature
vasculature:
arteries a1>a2 –> vasoconstriction
veins a2>a1 –> vasoconstriction
specific vascular beds:
- myocardium B2 = vasodilation
- skeletal m B2 = vasodilation
- renal DA = vasodilation
- mesenteric DA = vasodilation
Describe the autonomic innervation of the bronchial tree
B2 = bronchodilation M3 = bronchoconstriction
B2 aren’t innervated, just respond to catecholamines in the systemic circulation or the airway (inhaled)
Describe the autonomic innervation of the kidney
renal tubules: a2 = diuresis via ADH inhibition
renin release: B1 = increased renin release
Describe the autonomic innervation of the eye
sphincter m (iris) = M = contraction (miosis)
radial muscle (iris) = a1 = contraction (mydiasis)
ciliary m =
B2 = relaxation (far vision)
M = contraction (near vision)
Describe the autonomic innervation of the GI tract
sphincters
a1 = contraction
M = relaxation
motility & tone
a1/a2/B1/B2 = decrease
M = increase
salivary glands
a2 = decrease
M = increase
gallbladder & ducts
B2 = relaxation
M = contraction
describe the autonomic innervation of the pancreas
islet (beta cells)
a2 = decrease insulin release
B2 = increase insulin release
describe the autonomic innervation of the liver
a1/B2 = increase serum glucose
describe the autonomic innervation of the uterus
a1 = contraction B2 = relaxation
describe the autonomic innervation of the bladder
trigone & sphincter
a1 = contraction
M = relaxation
destrusor m
B2 = relaxation
M = contraction
describe the autonomic innervation of the sweat glands
a1 = increase secretion M = increase secretion
list the steps of NE synthesis. What is the rate limiting step?
tyrosine
- -> DOPA (via tyrosine hydroxylase)
- -> dopamine (via DOPA decarboxylase)
- -> NE (via dopamine B-hydroxylase)
- -> Epi (via phenylethanolamine N-methyltransferase)
Tyrosine hydroxylase is the rate limiting step
All occurs in the adrenal medulla
What are the 3 ways in which NE can be removed from the synaptic cleft? Which is the most important?
- reuptake (80%)
- diffusion away
- reuptake by extraneural tissue
What enzymes metabolize NE & Epi? What is the final metabolic byproduct?
MAO
COMT
final byproduct = vanillylmandelic acid (VMA) aka 3-methoxy-4-hydroxymandelic acid
elevated VMA in urine aids in diagnosis of pheochromocytoma
list the three types of cholinergic receptors. Where are each of these found inside the body?
Nicotinic M type (muscle)
- NMJ
Nicotinic N type
- preganglionic fibers at autonomic ganglia (SNS & PNS)
- CNS
Muscarinic
- postganglionic PNS fibers at effector organs
- CNS
Describe the synthesis, release, and metabolism of acetylcholine
choline diffuses into cholinergic neuron; mitochondria produces AcetylCoA
Acetyl CoA + Choline
–> Ach (via ChAT)
released into synaptic cleft onto mAChR or nAChR
converted to choline + acetate
- choline reuptake
- acetate into vasculature
list the 5 components of the autonomic reflex arc
- sensor
- afferent pathway
- control center
- efferent pathway
- effector
compare and contrast the architecture of the SNS & PNS efferent pathways
both have pre & post ganglionic nerve fibers
PNS
- preganglionic: long, myelinated, B fiber, releases ACh
- postganglionic: short, unmyelinated, C-fiber, releases ACh
SNS
- preganglionic: short, myelinated, B-fiber, releases ACh
- postganglionic: long, unmyelinated, C-fiber, releases NE normally
- releases ACh at sweat glands, piloerector m, and some vessels
What is the origin of the efferent SNS pathways?
thoracolumber T1-L3
- cell bodies from the intermediolateral region of the SC & axons exit via the ventral nerve roots
preganglionic fibers usually synapse w/ postganglionic fibers in the 22 paired sympathetic ganglia
What is the origin of the efferent PNS pathways?
craniosacral CN 3, 7, 9, 10 & S2-S4
- preganglionic synapse w/ postganglionic near or in each effector organ
describe the innervation of the adrenal medulla. How is it different that then typical SNS efferent architecture?
there are no postganglionic fibers
pregang release ACh onto the chromaffin cells & the chromaffin cells release Epi & NE into the systemic circulation at a 80/20 ratio
describe the hemodynamic management of the patient with pheochromocytoma
MUST a BLOCK BEFORE B BLOCK!!!!
if you dont:
- B2 block inhibits skeletal m vasodilation & increases SVR
- B1 block decreases inotropy & can precipitate CHF in the setting of incresed SVR
a-antagonists:
- nonselective: phenoxybenzamine & phentolamine
- a1 selective: doxazosin & prazosin
What is the transcellular K+ shift & what causes it to occur?
describes a number of processes that alter serum K+ by shifting it in or out of cells
shift into cells = hypokalemia
- alkalosis
- B2 agonists
- theophylline
- insulin
shift out of cells = hyperkalemia
- acidsois
- cell ysis
- hyperosmolarity
- succinylcholine
describe the anatomy & physiology of the baroreceptor reflex
regulates short term blood pressure control
- high BP, reflex = decreased HR, contractility, & SVR
- low BP, reflex = increased HR, contractility, and SVR
sensors in the carotid bodies & the aortic arch –> medulla (efferent)
afferent is via SNS/PNS
describe the anatomy & physiology of the bainbridge reflex.
increases HR when venous return is too high. This is beneficial in minimizing venous congestion & promoting forward flow
sensor = SA node, RV, pulmonary veins afferent = vagus control = vasomotor center of medulla efferent = vagus effects = SA node
describe the anatomy & physiology of the Bezold-Jarisch reflex
decreases HR when venous return is too low. this gives an empty heart adequate time to fill
sensor = cardiac mechanoreceptors & chemoreceptors afferent = vagus control = medulla efferent = vagus effector = SA node & AV node
tx = restore preload & increase HR
describe the anatomy & physiology of the oculocardiac reflex
five (V) & dime (X) reflex
sensor = pressure to the eye or globe afferent = long & short ciliary n. --> ciliary ganglion --> V1 of CN V --> Gasserian ganglion control = medulla efferent = vagus effector = SA node & AV node (decreased HR & conduction velocity)
tx = remove stimulus, 100% FiO2, atropine/glyco
What is the primary determinant of CO in the pt w/ a heart transplant? What is the consequence of this?
severed from autonomic influence, so HR is determined by intrinsic SA rate. Often have resting tachycardia 100-120
CO is dependent on preload in these patients, they are very sensitive to hypovolemia
What drugs can be used to augment HR in the patient w/ a heart transplant?
no autonomic input from the cardiac accelerator fibers (T1-T4) or the vagus nerve. Thus, good to use: those that directly stimulate the SA node:
- epi
- isoproterenol
- glucagon
those that indirectly stimulate SA cannot be used (atropine, glyco, ephedrine)
A pt presents for removal of a glomus tumor. What are your primary concerns when planning your anesthetic?
(glomangiomas) originate from neural crest cells. Tent to grow in the neuroendocrine tissues that lay in close proximity to the carotid artery, aorta, CN IX, and middle ear. Usually not malignant
- can release vasoactive substances that lead to HTN/hypotension (NE, 5-HT, histamine, bradykinin)
- octreotide can be used to treat carcinoid-like s/sx
- CN dysfunction (IX, X, XII) can cause swallowing impairment, aspiration of gastric contents, and a/w obstruction
- surgical dissection of glomulus tumor that has invaded the IJ vein increass risk of VAE
what are the anesthetic considerations for multiple system atrophy?
(previously known as Shy-Drager syndrome)
causes degneration of the locus coeruleus, intermediolateral column of the SC (where cell bodies for SNS efferent fibers live), & peripheral autonomic nerves
- autonomic dysfunction (orthostatic hypotension)
- tx hypotension w/ volume & direct acting sympathomimetics
- exaggerated hypertensive response to ephedrine & possibly ketamine
Compare & contrast low, intermediate, and high dose epi
low (0.01-0.03mcg/kg/min)
- nonselective B effects predominate –> increased CO w/ reduction in SVR & possibly a slight reduction in BP w/ widened pulse pressure)
intermediate (0.03-0.15mcg/kg/min)
- mixed B & a effects
high (>0.15mcg/kg/min)
- a effects prevail –> HTN, risk for SVT
describe the cardiovascular effects of isoproterenol
synthetic catecholamine that stimulates B1 & B2 receptors
- increases HR, contractility, & myocardial O2 consumption
- decreases SVR, which reduces DBP, which may reduce CPP
- causes severe dysrhythmias & tachycardia
- vasodilates nonessential vascular beds (i.e. muscle & skin). This precludes its use in septic shock.
list 4 clinical indications for isoproterenol
- chemical pacemaker for bradycardia unresponsive to atropine
- heart transplant
- bronchoconstriction
- cor pulmonale
in what situations should ephedrine not be used to treat hypotension?
- when neuronal catecholamine stores are depleted (sepsis) or absent (heart transplant)
- risk of hypertensive crisis in pts on MAO inhibitors
- conditions where increased HR or contractility is detrimental to hemodynamics
How does vasopressin increase BP
V1 = intense vasoconstriction V2 = increases intravascular volume by stimulating the synthesis & insertion of aquaporins into the walls of the collecting ducts (increases water reabsorption & lowers serum osmolarity)
What is the best treatment for vasoplegic syndrome
aka refractory hypotension. Key = hypotension doesn’t respond to conventional therapies such as adrenergic agonists, hydration, and reducing depth of anesthesia
- vasopressin is the best tx (0.5-1U IV bolus, 0.03U/min)
- incidence is increased by ACEI or ARBs
- methylene blue is the next best choice
list 6 drugs that are selective for the B1 receptor
atenolol acebutolol betaxolol bisoprolol esmolol metoprolol
list 6 nonselective B blockers
coreg labetalol nadolol pindolol propranolol timolol
what is the primary site of metabolism of the commonly used beta blockers? what are two exceptions?
most depend on the liver as their primary site of metabolism
2 exceptions: esmolol (by RBC esterases) & atenolol (by kidneys)
which beta blockers have LA properties? What is another name for this?
propanolol
acebutolol
another name = membrane stabilizers
effect = reduction in the rate of the rise of the cardiac AP
what is intrinsic sympathomimetic activity? Which drugs exert this effect?
BB that exert a partial agonist effect, while simultaneous blocking other agonsts that have a higher affinity for the B receptor
labetalol
pindolol
list 3 alpha antagonists. What is the MOA for each?
reduce BP by causing vasodilation (decreased SVR)
phenoxybenzamine: nonselective, noncompetitive binding, long acting
phentolamine: nonselective, competitive binding, short acting
prazosin: selective alpha1 antagonist
