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Pharm 2024 > PPT 6- ANS & Sympathetic transmission > Flashcards

PPT 6- ANS & Sympathetic transmission Flashcards

Exam 2

1
Q

What is the afferent pathway, and what information is sent?

A

going towards CNS
a) special sensory receptors - 5 senses, except touch
b) somatic sensory receptors - skin, skeletal muscle, pressure, pain
c) visceral sensory receptors - internal organs

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2
Q

What is the efferent pathway, and what information is sent?

A

going away from CNS
a) somatic nervous system - conscious control
b) autonomic nervous system - smooth muscle, cardiac muscle, glands. (parasympathetic and sympathetic NS)
c) enteric nervous system

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3
Q

What is the somatic nervous system?

A

part of the peripheral nervous system that controls voluntary movement

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3
Q

Where are neuron cell bodies for the somatic system located?

A

in the CNS

has axons that leave the CNS, but cell bodies are in the CNS

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4
Q

Where are neuron cell bodies of the autonomic system located?

A

outside the CNS (ganglia)

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5
Q

What are the subdivisions of the autonomic nervous system?

A

sympathetic, parasympathetic, and enteric

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6
Q

What is the enteric system?

A

primitive system, gut feeling

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7
Q

What is the nerve that is important for regulating cardiac function?

A

vagus nerve (CN X)

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7
Q

Chain ganglion are present in which NS? parasympathetic or sympathetic?

A

sympathetic

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7
Q

Where do sympathetic axons leave the CNS?

A

Thoracolumbar region

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8
Q

What are sympathomimetic drugs?

A

Mimic the effects of NE binding to receptors

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8
Q

Sympathetic NS postganglionic fibers release which neurotransmitter?

A

NE, skeletal muscles and sweat glands release ACh

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8
Q

For sympathetic NS, preganglionic fibers are ________, while postganglionic fibers are _________.

A

preganglionic= short
postganglionic= long

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8
Q

For parasympathetic NS, preganglionic fibers are ________, while postganglionic fibers are __________

A

Preganglionic= long
postganglionic= short

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9
Q

Where do parasympathetic axons leave the CNS?

A

Craniosacral regions.

Most from brainstem, bladder and genitals from sacral

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10
Q

Sympathetic NS preganglionic fibers release which neurotransmitter?

A

ACh

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11
Q

Which drugs are direct acting sympathomimetics?

A

Epinephrine, isoproterenol, albuterol

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12
Q

Which drugs are indirect acting sympathomimetics?

A

ephedrine and amphetamines

don’t bind directly to receptor, but block the reuptake of NE or reverse the NET, leaving NE in the synapse longer

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13
Q

What effects are seen from sympathomimetics?

A

Vasoconstriction
Increased inotropic and chronotropic effects
Decrease bronchiole tone
Decreased uterine muscle tone

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14
Q

What are sympatholytics?

A

drugs that inhibit the sympathetic nervous system

alpha/beta blockers

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15
Q

What effects are seen from sympatholytics?

A

vasodilation, decreased BP
decreased chronotropy (heart rate)

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16
Q

Which muscarinic receptors are excitatory?

A

M1, M3, M5

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17
Q

Which muscarinic receptors are inhibitory?

A

M2, M4

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18
Q

What neurotransmitter(s) acts on cholinergic receptors?

A

ACh

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19
Q

What neurotransmitter(s) acts on adrenergic receptors?

A

epinephrine and norepinephrine

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20
Q

How many types of alpha receptors are there?

A

2

alpha 1
alpha 2

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21
Q

How many types of beta receptors are there?

A

3

beta1, heart
beta2, lungs
beta3, fat tissue

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21
Q

How many types of dopamine receptors are there?

A

5

D1-5

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22
Q

Which alpha receptors are stimulatory and what does it activate?

A

alpha 1, activates Gq protein, activates phospholipase C which activates secondary messengers IP3 and DAG

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23
Q

which alpha receptors are inhibitory and what does it inhibit?

A

alpha 2, inhibits adenylyl cyclase; leads to decreased cAMP

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24
Q

Where is the ganglia located in the sympathetic NS?

A

Close to the spinal cord

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25
Q

Where is the ganglia located in the parasympathetic NS?

A

In the visceral effector organs

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26
Q

The enteric NS is mainly under _____ control

A

parasympathetic
Sympathetic input mainly inhibitory

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27
Q

Many neurons in the enteric NS are mostly _____

A

non-adrenergic, non-cholinergic (NANC)

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28
Q

What are the effectors of the ANS vs somatic?

A

ANS - cardiac muscle, smooth muscle, and glands (not skeletal)
Somatic - skeletal muscle

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29
Q

Axons of the ANS are a ___-neuron chain

A

2
- The preganglionic (first) neuron has a lightly myelinated axon
- The ganglionic (second) neuron extends to an effector organ

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30
Q

In the skeletal muscle, there are ____ ganglion

A

no

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31
Q

In the ANS, the preganglionic fibers release ____, while postganglionic fibers release ____

A

ACh
NE or ACh

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32
Q

Parasympathetic NS mostly releases what neurotransmitter?

A

ACh

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33
Q

The sympathetic NS mostly releases what neurotransmitter?

A

NE, some ACh (sweat glands)

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34
Q

Sympathetic drugs that mimic the sympathetic nervous system are called _____

A

Sympathomimetics

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35
Q

Albuterol directly acts on what?

A

beta receptors in lungs

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36
Q

Sympathomimetics are taken up by ____

A

NET (NE transporter)

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37
Q

Ionotropic is ____ chronotropic is ____

A

Force, rate

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38
Q

Propranolol

A

Beta selective sympatholytic

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38
Q

Phentolamine

A

Alpha selective sympatholytic

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39
Q

Labetolol

A

Mixed selective sympatholytic

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40
Q

Are Beta receptors inhibitory or stimulatory?

A

All beta receptors are stimulatory - stimulates adenylate cyclase, increasing cAMP

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41
Q

What are the types of cholinergic receptors?

A

Muscarinic and nicotinic

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42
Q

What type of receptors are muscarinic receptors?

A

GPCRs

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43
Q

What type of receptors are nicotinic receptors?

A

Ion channels

44
Q

What are the adrenergic receptors? What do they respond to?

A

Alpha, beta, dopamine
NE

45
Q

What are the 2 nicotinic receptor subtypes in the PNS? Where are they located?

A

Neuronal (occurs at ganglion)
Muscular (occurs skeletal muscle endplates)

46
Q

Where are dopamine receptors located?

A

mostly in brain, some in smooth muscle, CV, and kidneys

47
Q

What is the GPCR that alpha 1 activates? Effector?

A

Gq/G11 - activates phospholipase C

48
Q

What is the GPCR that alpha 2 activates? Effector?

A

Gi - inhibits adenylate cyclase

49
Q

What is the GPCR that beta activates? Effector?

A

Gs - stimulates adenylate cyclase

50
Q

Where are alpha 1 receptors primarily found?

A

in the smooth muscle cell that surrounds the blood vasculature

51
Q

How does IP3 work to increase BP?

A
  • IP3 opens Ca++ channels from sarcoplasmic reticulum → releasing Ca++ into cell
  • Ca++ in smooth muscle cell activates enzymes MLCK → MLCK phosphorylates myosin → contraction of smooth muscle cell → increased BP
52
Q

How does DAG work to increase BP?

A

DAG activates protein kinase C (PKC) → Ca++ sensitization → inhibits MLCP (removes phosphate from myosin) → more active myosin → contraction → increase BP

53
Q

How does the activation of beta receptors work in the heart?

A

NE activates beta receptors - G stimulatory → stimulates adenylyl cyclase → increases cAMP → activates PK-A → more ICF Ca++ (from ECF and from sarcoplasmic reticulum) → contraction

54
Q

How does the activation of beta 2 receptors work in the peripheral muscle?

A

NE binds to B2 in periphery → Increases cAMP → inhibit MLCK → no active myosin → relaxation - allows peripheral vessels to dilate

55
Q

Describe the negative feedback loop of NE and beta 1

A

NE in the synapse for a prolonged period will inhibit further NE release by binding to alpha 2 on the cell that released it - keeps heart from working too hard

56
Q

What are the primary sympathetic receptors?

A

Alpha and beta

57
Q

What are the primary parasympathetic receptors?

A

Cholinergic receptors

58
Q

_____ causes dilation of skeletal blood vessels, whereas ____ causes constriction of the blood vessels in the abdominopelvic cavity

A

ACh, NE

59
Q

Skeletal muscle blood vessels are innervated by

A

ACh postganglionic fibers of the sympathetic division - dilation

60
Q

Describe how the autonomic feedback loop works to lower an increase in MAP

A

Baroreceptors sense increased pressure on arteries → notifies CNS vasomotor center → activate PANS → ACh release → decrease HR and CO→ MAP back to normal

61
Q

Describe how the autonomic feedback loop works to raise a decrease in MAP

A

Decrease in MAP → baroreceptors sense this → notifies CNS vasomotor center → activates SNS → NE binds to alpha and beta 1 receptors → increases MAP
- beta 1 receptors in heart (increase HR and CO)
Increases contractile force
- alpha receptors in peripheral vasculature (increasing blood return to heart)
Increases venous tone

62
Q

Describe how the hormonal feedback loop responds to a decrease in MAP in the RAA system

A

MAP too low → kidney senses in tubules (juxtaglomerular apparatus) → releases renin → activates angiotensin cascade (can restrict blood flow directly or go to adrenal cortex) → increases aldosterone production → take up more water in blood volume, produce less urine → increased venous return → increased SV → increased CO → increased MAP

63
Q

What is a heteroreceptor?

A

A receptor on the neuron that responds to something that the neuron isn’t releasing (releases epi and receptor for ACh, slows down the release of epi)

64
Q

What is an autoreceptor?

A

A receptor that responds to the same neurotransmitter that is being released (epi and epi)
Can be inhibitory (negative feedback) or excitatory (positive feedback)

65
Q

What are the mechanisms for presynaptic regulation feedback control?

A

Herteroreceptors and autoreceptors - receptors on the cell releasing neurotransmitters

66
Q

Compare the SNS vs PANS of the SA node and which receptors are present

A

SNS: accelerates SA node - B1 and B2
PANS: decelerates the SA node - M2

67
Q

Compare the SNS vs PANS of the heart contractility and which receptors are present

A

SNS: increases heart contractility - B1 and B2
PANS: decreases heart contractility - M2

68
Q

Compare the SNS vs PANS of bronchiolar smooth muscle and which receptors are present

A

SNS: relaxes bronchiolar smooth muscle - B2
PANS: contracts bronchiolar smooth muscle - M3

69
Q

Compare the SNS vs PANS of the blood vessels and which receptors are present

A

SNS:
- alpha: vasoconstriction of smooth blood vessels → dominant effect
- beta and cholinergic - vasodilation of arterioles in skeletal muscles

PANS: vasodilation of GI tract, genitalia, and salivary glands; little effect on total peripheral resistance - M3

70
Q

At rest, skeletal muscles take up ___% of circulating blood flow

A

20%

71
Q

During physical activity or sympathetic stimulation, skeletal muscles take up to ___% of circulating blood flow

A

80&

72
Q

Differentiate between cholinomimetics, parasympatholytics, sympathomimetics, and sympatholytics

A

Cholinomimetics (Parasympathomimetics) - mimic the effects of ACh
Parasympatholytics (Antimuscarinics) - Block effect of PANS
Sympathomimetics - Mimic effect of PANS
Sympatholytics (α-blockers, β-blockers) - Block SNS

73
Q

The ____ is the gap between the neuron and the cell

A

synapse

74
Q

List three types of synapses

A
  • Neurons and other neurons
  • Neurons and muscle - somatic NS
  • Neurons and effector organs (heart, kidneys, lungs)
75
Q

The synapse is the target for many drugs, including

A

Sleep modulators, general anesthetics - CNS
CV - PNS

76
Q

What is the role of the neuron?

A

Sends AP from neuron cell body to the telodendria (endpoints) capped with synaptic boutons (where neurotransmitters are stored)

77
Q

info is coming into neuron through the _____

A

Dendrites

78
Q

Action potentials are generated in the ________

A

axon hillock

79
Q

What are the types of synapses?

A

Chemical - neurotransmitters
Electrical - Gap junctions

80
Q

After nurotransmitters are released, they are either

A

Broken down by enzymes and/or taken up into presynaptic cell

81
Q

What are En Passant Synapses?

A
  • Axon has swellings that can release neurotransmitters in some neurons
  • Additional synapses between cells
  • One neuron can effect multiple different effectors
82
Q

Describe the main stages of synaptic transmission

A
83
Q

What are the 4 possibilities of neurotransmitter fate?

A

All decrease neurotransmitter in synapse
1. Diffuses away from synapse
2. Degraded by enzymes
3. Uptake into pre-synaptic cell
4. Uptake into surrounding cells

84
Q

What are the 6 Neurotransmitter Classes?

A
  1. Esters
  2. Monoamines
  3. Amino Acids
  4. Purines
  5. Peptides
  6. Inorganic gases
85
Q

Give an example of an ester neurotransmitter

A

Acetylcholine (ACh)

86
Q

Give an example of a monoamine neurotransmitter

A

NE, Serotonin, Dopamine

87
Q

Give an example of an amino acid neurotransmitter

A

Glutamate, GABA, glycine

88
Q

Give an example of a purine neurotransmitter

A

Adenosine, ATP

89
Q

Give an example of a peptide neurotransmitter

A

Substance P, Endorphins - mediate pain and analgesia

90
Q

Give an example of a inorganic gas neurotransmitter

A

Nitric oxide (NO)

91
Q

NO is different than other neurotransmitters because it is not ______

A

stored - made as needed by nitric oxide synthase

92
Q

Compare the speed of nicotinic vs muscarinic receptors

A

Nicotinic - Ion Channel - FAST (NMJ)
Muscarinic - GPCRs - slower

93
Q

Monamines are released by

A

Adrenergic Fibers

94
Q

All human emotions can be boiled down to which 3 neurotransmitters?

A

NE, dopamine, and serotonin
Lovheim Cube of Emotion
If deficient in any of these in CNS, can’t fell full range of emotions

95
Q

How do SSRIs work to treat depression?

A

Prevent re-uptake of serotonin, allows serotonin to stay in synapse longer

96
Q

What is the most important excitatory neurotransmitter in brain?

A

Glutamate

97
Q

What are the inhibitory neurotransmitters in brain?

A

Glycine and GABA

98
Q

Differentiate between excitatory and inhibitory neurotransmitters

A
  • Excitatory neurotransmitters cause depolarizations (e.g., glutamate)
  • Inhibitory neurotransmitters cause hyperpolarizations (e.g., GABA and glycine)
99
Q

What happens at a cholinergic synapse?

A
  1. Starts from an AP coming from the axon hillock in the neuron → travels down the axon to terminal bouton → terminal bouton becomes depolarized
  2. Ca influx into terminal and binds to vesicles that bind to the surface of the cell, destabilizes storage vesicles → release of ACh into the synaptic cleft (exocytosis)
  3. ACh binds to receptors, opening Na channels and depolarizing post-synaptic cell → increase in Ca++
  4. ACh broken down by AChE
100
Q

Describe the formation and transport of ACh

A
  1. ACh made in the cytoplasm of the cell that is releasing it
  2. Transported into vesicles
101
Q

What is the name of the enzyme that creates ACh? Where is it found?

A

Choline acetyltransferase (ChAT) - found inside the neuron

102
Q

What is the name of the enzyme that breaks down ACh? Where is it found?

A

Aceytlcholinesterase (AChE) - found in the synapse
Breaks down ACh into Acetic acid and choline

103
Q

What are the transport molecules for ACh?

A

CHT – choline transporter into neuron - co-transporter with Na via facilitated diffusion
VAT – transports ACh into vesicle

104
Q

What are the components of the anchoring/docking portion of the cholinergic transmission?

A

SNARE Complex - Syntaxin and SNAP-25 - anchor vesicles near release site
VAMP - vesicular associated membrane protein, a part of the synaptic membrane

105
Q

What is the Ca++ sensor in the anchoring/docking portion of the cholinergic transmission?

A

Synaptotagmin - Binds to calcium during efflux → facilitates rapid exocytosis

106
Q

What are the 4 steps of cholinergic transmission?

A

Transport, anchoring/docking, priming, and fusion

107
Q

The priming portion of cholinergic transmission is

A
  • ATP dependent
  • Supports rapid exocytosis
108
Q

The fusion portion of the cholinergic transmission is

A

Calcium-induced (synaptotagmin)
- Fusion of membrane (fast)
- Fusion pore

109
Q

What are the 5 cholinergic Inhibitors?

A
  1. Hemicholiniums – CHT
    • Block choline transport (not therapeutic drug, experimental research)
  2. Vesamicol – VAT
    • Block acetylcholine transporter (research)
  3. Calcium channel blockers – Voltage gated calcium channels
    • Decreasing HR and BP
    • High levels of calcium channel blockers can inhibit neuron transmission
  4. Botulinum toxin – vesicle release fusion proteins
    • Proteins blocked by botox - paralyzes muscle b/c ACh can’t come out, no contraction
    • Treatment for wrinkles and excessive sweating
  5. Sarin (nerve gas) – AChE inhibitor
    • Blocks breakdown of ACh all over body all at once → OD of ACh → death if not treated with atropine
110
Q

In Myasthenia Gravis, we want to ____ ACh

A

Block - by targeting AChE

111
Q

In Myasthenia Gravis, there is creation of antibodies against

A

ACh receptors

112
Q

Tyrosine is the precursor to

A

L-dopa, dopamine, NE, epinephrine

113
Q

NE isn’t broken down in the synapse, but taken back up into the ___ by the transporter ____

A

Presynaptic neuron, NET

114
Q

The enzyme that breaks down monoamines is

A

Monoamine oxidase

115
Q

How do MAOIs treat depression? What is the catch?

A

MAOIs prevent the breakdown of NE and dopamine
Dangerous because can lead to high levels of neurotransmitters and a lot of drug interactions

116
Q

What are the 7 targets for drug action?

A
  1. Synthesis of Neurotransmitter
  2. Storage of Neurotransmitter
  3. Vesicle Secretion
  4. Vesicle Cycling and Endocytosis
  5. Reuptake of Neurotransmitter
  6. Biotransformation of Neurotransmitter
    • MAOIs
  7. Neurotransmitter Receptor - Multiple
117
Q

Differentiate between the 2 vesicle fusion hypotheses: when releasing neurotransmitters, why does the neuron end plate not get larger?

A
  • Clathirin coated pit recycling - clathirin embedded in membranes reform vesicles that go back up into the neuron - recycling of vesicles - so that vesicles can be reloaded
  • “Kiss-and-run” - vesicle touches membrane, opens up, and then goes back to being closed and returns to the neuron

Pharm 2024 (13 decks)

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