UNIT 2 ANS Flashcards

1
Q

What are the 4 classifications of receptors?

A
  1. ion channel
  2. GPCR
  3. enzyme linked receptor
  4. intracellular receptor
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2
Q

Describe the general architecture of the GPCR second messenger system.

A

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

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3
Q

What second messenger system is associated w/ alpha-1 receptor? What other receptors share the same pathway?

A

Gq –> phospholipase C –> IP3/DAG/Ca++

others:
- histamine 1
- muscarinic 1, 3, 5
- vasopressin 1

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4
Q

What second messenger is associated w/ alpha-2 receptor? What other receptors share a similar pathway?

A

Ex of 2nd messenger: adenylate cyclase –> ATP to cAMP

others:
- muscarinic 2
- dopamine 2

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5
Q

What second messenger system is associated w/ beta1 & beta2 receptors? What other receptors share a similar pathway?

A

Gs –> adenylate cyclase –> ATP to cAMP

others:
- histamine 2
- vasopressin 2
- dopamine 1

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6
Q

describe the autonomic innervation of the heart

A
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

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7
Q

describe the autonomic innervation of the vasculature

A

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
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8
Q

Describe the autonomic innervation of the bronchial tree

A
B2 = bronchodilation
M3 = bronchoconstriction

B2 aren’t innervated, just respond to catecholamines in the systemic circulation or the airway (inhaled)

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9
Q

Describe the autonomic innervation of the kidney

A

renal tubules: a2 = diuresis via ADH inhibition

renin release: B1 = increased renin release

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10
Q

Describe the autonomic innervation of the eye

A

sphincter m (iris) = M = contraction (miosis)

radial muscle (iris) = a1 = contraction (mydiasis)

ciliary m =
B2 = relaxation (far vision)
M = contraction (near vision)

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11
Q

Describe the autonomic innervation of the GI tract

A

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

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12
Q

describe the autonomic innervation of the pancreas

A

islet (beta cells)
alpha 2 = decrease insulin release

Beta 2 = increase insulin release

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13
Q

describe the autonomic innervation of the liver

A

a1/B2 = increase serum glucose

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14
Q

describe the autonomic innervation of the uterus

A
a1 = contraction
B2 = relaxation
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15
Q

describe the autonomic innervation of the bladder

A

trigone & sphincter
a1 = contraction
M = relaxation

destrusor m
B2 = relaxation
M = contraction

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16
Q

describe the autonomic innervation of the sweat glands

A
a1 & M = increase secretion
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17
Q

list the steps of NE synthesis. What is the rate limiting step?

A

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

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18
Q

What are the 3 ways in which NE can be removed from the synaptic cleft?

A
  1. reuptake (80%)
  2. diffusion away
  3. reuptake by extraneural tissue
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19
Q

What enzymes metabolize NE & Epi? What is the final metabolic byproduct?

A

MAO & COMT

final byproduct = vanillylmandelic acid (VMA) aka 3-methoxy-4-hydroxymandelic acid

elevated VMA in urine aids in diagnosis of pheochromocytoma

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20
Q

list the three types of cholinergic receptors. Where are each of these found inside the body?

A

Nicotinic M type (muscle)
- NMJ

Nicotinic N type

  • preganglionic fibers at autonomic ganglia (SNS & PNS)
  • CNS

Muscarinic

  • postganglionic PNS fibers at effector organs
  • CNS
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21
Q

Describe the synthesis, release, and metabolism of acetylcholine

A

choline diffuses into cholinergic neuron while the mitochondria produces AcetylCoA

Acetyl CoA + Choline = Ach (via the enzyme ChAT)

released into synaptic cleft onto mAChR or nAChR

converted to choline + acetate

  • choline reuptake
  • acetate into vasculature
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22
Q

list the 5 components of the autonomic reflex arc

A
  1. sensor
  2. afferent pathway
  3. control center
  4. efferent pathway
  5. effector
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23
Q

compare and contrast the architecture of the SNS & PNS efferent pathways

A

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
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24
Q

What is the origin of the efferent SNS pathways?

A

SNS efferent pathway: 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

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25
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
26
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
27
describe the hemodynamic management of the patient with pheochromocytoma
MUST ALPHA BLOCK BEFORE BETA BLOCK!!!! if you dont: - B2 block inhibits skeletal m vasodilation & increases SVR - B1 block decreases inotropy & **can precipitate CHF** in the setting of increased SVR a-antagonists: - nonselective: phenoxybenzamine & phentolamine - a1 selective: doxazosin & prazosin
28
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 lysis - hyperosmolarity - succinylcholine
29
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
30
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 ```
31
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
32
describe the anatomy & physiology of the oculocardiac reflex
KNOW THIS **five (V) afferent & dime (X) efferent 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
33
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**
34
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)
35
A pt presents for removal of a glomus tumor. What are your primary concerns when planning your anesthetic?
(glomangiomas) originate from neural crest cells. Tend 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 increases **risk of VAE**
36
what are the anesthetic considerations for multiple system atrophy?
(previously known as Shy-Drager syndrome) **Autonomic dysfunction, and also causes degneration of the locus coeruleus** intermediolateral column of the SC (where cell bodies for SNS efferent fibers live), & peripheral autonomic nerves - autonomic dysfunction causes orthostatic hypotension - Premature death, cerebral hypoperfusion, urinary retention - **treat with volume & direct acting sympathomimetics** - exaggerated hypertensive response to ephedrine & possibly ketamine
37
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
38
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.
39
list 4 clinical indications for isoproterenol
1. chemical pacemaker for bradycardia unresponsive to atropine 2. heart transplant 3. bronchoconstriction 4. cor pulmonale
40
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
41
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) ```
42
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
43
list 6 drugs that are selective for the B1 receptor
``` atenolol acebutolol betaxolol bisoprolol esmolol metoprolol ```
44
list 6 nonselective B blockers
``` coreg labetalol nadolol pindolol propranolol timolol ```
45
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)**
46
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
47
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
48
list 3 alpha antagonists. What is the MOA for each?
reduce BP by causing vasodilation (decreased SVR) **phenoxybenzamine: nonselective, noncompetitive binding, long acting- you can’t reverse it** phentolamine: nonselective, competitive binding, short acting prazosin: selective alpha1 antagonist
49
In which cranial nerves are parasympathetic nervous system preganglionic fibers found?
There’s a total of 4 pairs: 3,7,9,10
50
What drugs cause apoptosis?
Anything that has GABA agonist or NMDA antagonist Like ketamine, propofol, nitrous oxide
51
Beta 1
Increases renin release
52
CAMP in vessels cause _________
Dilation While cAMP in the heart = constriction
53
What turns off caMP?
PDE3
54
Alpha 2
Decreases insulin, sedation in the locus coerulus, and decrease pain in dorsal horn
55
Cushing’s triad
Hypertension, bradycardia, irregular respirations
56
Signal transduction steps
RECAP: **1st messenger, G protein, Effector, 2nd messenger** 1st messenger example is Epi and glutamate
57
Exogenous NE metabolized
MAO and COMT and by liver and kidneys
58
What is the primary area for relay of afferent chemoreceptor and baroreceptor information from the vagus and glossopharyngeal nerves?
Located within the medulla, the **nucleus tractus solitarius** is the main area responsible for relaying afferent chemoreceptor and baroreceptor information from the vagus and glossopharyngeal nerves.
59
What is referred to as the thoracolumbar nervous system?
The efferent SNS is also known as the thoracolumbar nervous system. It starts in the intermediolateral gray column of T1-12 and the first three lumbar segments (L1-3) of the spinal cord.
60
The fusion of the inferior cervical and first thoracic sympathetic nervous system ganglia is called the
Fusion of the inferior cervical and first thoracic SNS ganglia is called the **stellate ganglion**. It provides sympathetic innervation to the head, neck, upper extremities, heart, and lungs.
61
The parasympathetic innervation of the gastrointestinal tract is primarily via which nerve?
The vagus nerve provides the primary parasympathetic innervation to the gastrointestinal tract. It is comprised of both efferent and afferent fibers.
62
What is the predominant pathway for inactivation of the endogenous catecholamines?
Reuptake is the main pathway for inactivation of the endogenous catecholamines, while metabolism by the liver and kidneys is the main pathway for catecholamines rendered eXogenously.
63
Which of the following would be caused by beta-2 receptor stimulation? (select two) A. vasodilation B. bronchodilation C. increased cardiac contractility D. increased heart rate
A. vasodilation B. bronchodilation
64
Which BB has membrane stabilizing properties?
Propranolol KNOW THIS MATCHING CHART
65
Where is renin produced?
Kidney!! Liver produces Angiotension
66
KNOW THIS
67
Which muscarinic receptors signal through Gq and PLC?
M1 and M3
68
Inhibitory responses at postsynaptic membranes are produced
Potassium and chloride
69
Primary excitatory neurotransmitter in the brain?
Glutamate
70
Increased platelet aggregation is mediated by:
Alpha 2 agonist
71
Adenylate cyclase is inhibited by stimulation of the:
- alpha-2 receptor - muscarinic-2 receptor
72
Type N nicotinic cholinergic receptors are located at the:
The three locations where N nicotinic cholinergic receptors are found are: Parasympathetic ganglia Neuromuscular junction Sympathetic ganglia
73
Nicotinic cholinergic receptors are found in the:
Adrenal medulla
74
Parasympathetic fibers emerge with spinal nerves from which spinal segments?
S2-S4
75
Nonshivering thermogenesis in the neonate is modulate by:
NE
76
enzyme dopamine beta-hydroxylase is abundant in:
Adrenal medulla and sympathetic nerve endings
77
Norepinephrine can inhibit its own release by agonizing the:
presynaptic alpha-2 receptor
78
Which sign or symptom is MOST likely in multiple system atrophy (formerly Shy-Drager syndrome)?
Difficulty maintaining blood pressure when standing
79
Which agents possess intrinsic sympathomimetic activity?
Carvedilol, labetolol, Pindolol
80
Calcium channel blockers improve ischemic myocardium by:
- decrease preload -decrease afterload - increase diastolic perfusion