1
Q

nociception define

A

the detection of painful stimuli

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2
Q

where are pain receptors found?

A

The receptor for pain are free (naked) nerve endings in the skin, muscle and viscera

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3
Q

substance P

A

Neurotransmitters for nociceptors include substance P. Inhibition of the release of substance P is the basis of pain relief by opioids

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4
Q

A-delta fibers

A

Fast sharp pain is carried by A-delta fibers. It has a rapid onset and offset and is well localized
A-delta fibers are thicker and myelinated
Myelinated
Transmit fast/sharp pain
Well localize , can point to pain

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5
Q

C fibers

A

Slow chronic pain is carried by C fibers. It is characterized as aching, burning or throbbing that is poorly localized.
C fibers are thinner and unmyelinated
Unmyelinated
Transmit slow/chronic pain
Diffuse , burning ,aching , throbbing sensation

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6
Q

Lamina II (and III)?

A

Lamina II (and III) is Substantia Gelatinosa

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7
Q

Entry of A- delta and C fibers into the posterior horn. where do the cell bodies lie? where do the fibers ascend or descend?

A

Cell bodies lies in dorsal root ganglia (DRG)

Fibers ascend or descend in track of Lissauer

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8
Q

Pathway for slow chronic pain

A

C fibers terminates in Lamina II and Lamina III (Substantia Gelatinosa ).
Interneuron transmit C fibers impulses to Lamina V from Lamina II and III.
Neurons leaving Lamina V cross immediately to the contralateral, lateral spinothalamic tract and ascend to brain

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9
Q

name the A- delta fiber neurotransmitter

A

A-  fiber; the neurotransmitter is glutamate

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10
Q

name the C fiber neurotransmitter.

what does it bind to?

A

C fibers; the neurotransmitter is substance P which binds to NK-1(neurokinin-1) receptor on the postsynaptic membrane

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11
Q

Pathway for fast sharp pain:

A

A-delta fibers terminates in Lamina I , cross to the contralateral, lateral spinothalamic tract and ascend to the brain

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12
Q

Neuraxial (intrathecal or Epidural ) placement of Hydrophilic Opioids: what drug is this?

A

Morphine, a hydorphilic opioid, crosses lipid membrane slowly

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13
Q

tell me about intrathecal (spinal) placement.morphine

onset?
ventilation?

A

Slow onset and long duration of analgesia
No early depression of ventilation
Late depression of ventilation occur due to rostral (towards head) spread of CSF

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14
Q

Epidural Placement: morphine

tell me about onset
ventilation

A

Slow onset and long duration of analgesia
Early depression of ventilation (within 2 hrs) due to increase systemic uptake
Late depression of ventilation occur due to rostral spread

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15
Q

Neuraxial (intrathecal or Epidural ) placement of Lipophilic Opioids : what drug is this?

A

fentanyl, alfentanil, sufentanil –rapidly diffuse through lipid membrane

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16
Q

Intrathecal (Spinal) Placement of fentanyl..

A

Rapid onset and short duration of analgesia
Early depression of ventilation due to systemic uptake
Late depression of ventilation does not occur

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17
Q

Epidural Placement of fentanyl…

A

Similar as intrathecal (spinal) placement

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18
Q

if you add one of the fentanyl to a spinal- what will the patient experience as a side effect

A

they will get an itchy nose

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19
Q

3mg epidural=?spinal

A

0.3 spinal

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20
Q

Spinal Analgesia

which receptor??

A

Occurs when transmission of pain through substantia gelatinosa (L II) is suppressed
mu-2 is the dominant receptor
After IV administration, opioid acts on periventricular and periaquaductal gray — spinal analgesia

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21
Q

Supraspinal Analgesia

which receptor??

A

Opioids act on limbic system, hypothalamus and thalamus.
mu-1 is the dominant receptor
After IV administration of opioids
“ I feel pain but I don’t care”

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22
Q

Acupuncture releases what?

A

endorphins

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23
Q

descending neurons form?

The interneuron release

enkephalin inhibit release of what??

Dorsolateral tract modulates pain by??

A

periventricular and periaqueductal gray terminates on interneuron in substantia geletinosa (Enkephalin neurons)

enkephalin

Enkephalin inhibit release of substance P-spinal analgesia

by hyperpolarizing second order neurons

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24
Q

Three types of opioids receptors, located in CNS, nerve terminals, GIT and ANS

A

mu
kappa
delta

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25
Q

Opioids interact with opioid receptors and mimic the action of endogenous opioids which are?

A

(enkephalins, endorphins and dynorphins) and activate brain analgesia system

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26
Q

mu 2 responsible for?

A

mu-2 are responsible for respiratory depression and addiction

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27
Q

Supraspinal and spinal analgesia is primarily by

A

mu-receptors

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28
Q

k
(Kappa)

all of it

A

Analgesia (Spinal & Supraspinal)

Dysphoria

Low abuse
Potential

Miosis
Diuresis

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29
Q

delta

all of it

A

Analgesia (Spinal & Supraspinal)

Respiratory depression

Physical dependence

Constipation (mild)

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30
Q

mu 2

all of it

A

Analgesia (Spinal)

Respiratory depression(decrease sensitivity of resp. center to CO2)

Addiction

Constipation (marked) decrease motility and tone of GI muscles
increase CSF pressure (cerebral edema) C/I in head injury

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31
Q

mu 1

A

Analgesia (Supraspinal and spinal)

Euphoria

Low abuse potential

Miosis (PPP)

Bradycardia

Hypothermia
Urinary retention-C/I in BPH

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32
Q

Opioid Agonist

A
Morphine, 
fentanyl (sublimaze), 
codeine, 
heroin, 
methadone, 
meperidine (demerol), dextromehtophan, hydormorphone (Dilaudid) Sufentanil (sufenta), Remifnetanil ( Ultiva)
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33
Q

clinical use: cough suppression

A

(dexomethorphan),

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34
Q

diarrhea

A

loperamide, diphenoxylate

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35
Q

acute pulmonary edema

maintenance program for addicts

A

methadone

36
Q

toxicity of opioid agonist

A

addition
respiratory depression
constipation
pinpoint pupil

37
Q

if they have pinpoint pupils??

A

they need to be reversed

38
Q

opioid mechanism of action

A

Modulate (decrease intensity) synaptic transmission by opening K+ channels and closing Ca++ channels lead to decrease synaptic transmission and decrease release of neurotransmitters (Ach, NE, glutamate, substance P)

39
Q

Opioid Antagonist

A

Naloxone (Narcan), Naltrexone ( Trexate), Nalmefene

They are competitive antagonist of opioid receptor

40
Q

opioid antagonist

side effects

A
increase sympathetic activity
Reversal of Analgesia
Excitement / Dysphoria
Tachycardia
Hypertension
Dysrhythmias – V fib
Pulmonary edema
41
Q

Mixed Agonist/Antagonist

will they experience respiratory depression

A

Nalorphine (Nalline) ,Dezocine(Dalgan), Buprenorphine ( Buprenex), Nulbuphine (nubain) , Butorphanol (Stadol), Pentazocine (Talwin)
They have mixed agonist and antagonist activity – stimulate one receptor but block another
Sever respiratory depression is unlikely

42
Q

if you meant to give a epidural but gave a spinal where do you stick now?

A

stick above the spot

43
Q

When do we give stadol

A

give it in OB

44
Q

Side Effects of opioids

9

A
Pruritus
Due to histamine release
Urinary retention
Inhibit sacral (parasympathetic) nerve 
Bladder relaxation leads to  retention
Respiratory depression 
Monitor pulse ox
Give Supplemental O2
Prophylactic naloxone
Sedation
CNS excitation
Viral reactivation herpes- fentanyl- shows back up on their lips a few days lateral

Sustained erection
Constipation
Addiction

45
Q

Kids and versed, grandma and Ativan

A

– cns excitation

46
Q

If someon has treatment for addiction

A
  • possibly no nartocs- will come with a letter from their treatment center
47
Q

Morphine: moa

A

Derived from poppy
Acts on opioid receptors
Hyperpolarizes the nerve cells
Inhibition of nerve firing
Inhibits release of NT that carry pain sensation
Acts on k receptors in Lamina I and II (spinal analgesia)
Acts on mu-1 receptors (supraspinal analgesia)
Decreases release of substance P

48
Q

Morphine: actions

A

Analgesia – pain relief without loss of consciousness
increase pain threshold
Alters brain’s pain perception “ I feel the pain but I don’t care”

49
Q

morphine actions to respirations?

A

Causes respiratory depression by decreasing sensitivity to CO2
MCC of death due to opioid overdose

Euphoria

50
Q

morphine cough action

A

Depression of cough reflex

51
Q

morphine action of pupils

A

Pin point pupil (PPP)
increase parasympathetic stimulation by III nerve
Show no tolerance to the effect

52
Q

morphine action gut

A
Emesis
Stimulating CTZ
GIT
decrease motility , relieves diarrhea
Constipation
53
Q

morphine Actions

CVS

A

No major effect except for large doses

increase CO2 retention; increase CSF pressure ,therefore C/I in head injury

54
Q

morphine action with histamine

A

Histamine release
Itching and vasodilatation
Bronchoconstriction, therefore C/I in asthma

55
Q

morphine and hormones

A

Hormonal actions

56
Q

morphine and labor

A

Labor: increase 2nd stage

Cross placenta increase resp depression and physical dependence in neonates

57
Q

morphine uses?

A

Analgesia
Diarrhea
Cough relief
Acute pulmonary edema associated with LVH

58
Q

morpine Pharmacokinetics

A

Significant first-pass metabolism, therefore use parenterally
Rapid distribution , cross placental barrier
Conjugated in liver to active metabolite
Excreted in urine
Prolong duration when given in epidural space (less lipid soluble)

59
Q

morphine Adverse effects

A
Severe respiratory depression 
Vomiting 
Dysphoria
Hypotension
increase ICP
Urinary retention
60
Q

morphine Tolerance and physical dependence

A

Tolerance to analgesic, euphoric and sedative effect

61
Q

metabolite of morphine

A

Morphine-6-Glucuronide
Greater duration of action
650 x analgesia then morphine
Low permeability to BBB

62
Q

Meperidine MOA

A

Through mu and kappa receptor

63
Q

meperidine side effects

A

Respiratory depression
decrease total peripheral resistance increase CO
increase CSF pressure

64
Q

meperidine uses

A

post op shivering

employed in obstetrics

65
Q

meperidine what id the duration? is it well absorbed?

A

Well absorbed orally

Shorter duration of action

66
Q

meperidine Adverse effect

A

Tremors, twitching or convulsion with large dose
Hyperactive reflexes
Hypotension with large dose
Dry mouth and blur vision

67
Q

Methadone receptor

A

Through mu receptor

68
Q

methadone actions

A

respiratory depression< morphine

69
Q

methadone Uses

A

Control heroin withdrawal symptoms

70
Q

methadone Pharmacokinetics

A

Well absorbed orally

Shorter duration of action

71
Q

methadone Adverse effect

A

Physical dependence like morphine

72
Q

Cabg drug of choice?

A

sufentanil

73
Q

Fentanyl

A
100 x analgesic potency than morphine
Highly lipophilic
Rapid onset and short duration of action
I/V , epidural , spinal
Epidural in post operative analgesia and during labor
Transdermal patch for cancer pain
A/E:  hypotension
Use during cardiac surgery
Metabolized by P450
Urinary excretion
Adverse effect
Hypotension
74
Q

sufentanil is more potent than

A

fentanyl

75
Q

Codeine (Moderate Agonist)

A
Converts to morphine leads to analgesia
Much less analgesia than morphine
Cough suppression
Less euphoria
Low potential of abuse
Rarely produce dependence
76
Q

Drugs that stimulate one receptor but block another are termed

A

agonist-antagonists

77
Q

Pentazocine

A
Agonist on k receptor and weak antagonist on mu and delta receptors
Moderate analgesia
Less euphoria
Respiratory depression in high doses
decrease GIT activity
High dose causes
Hypertension
increase work of heart
Tolerance and dependence
78
Q

Buprenorphine

A

Used in opioid detoxification
Act on mu receptor
Less severe side effects in high dose

79
Q

Nalbuphine and butorphanol

A

Limited role as analgesic

Causes psychotic symptoms

80
Q

Tramadol

A

Act on mu receptor
Moderate to severe pain relief
Less respiratory depression

81
Q

Naloxone

A

Use to reverse respiratory depression of opioid over dose
Competitive antagonist of mu, delta, kappa receptors
Produces opioid withdrawal syndrome in abusers

82
Q

mixed agonist/antagonist which receptors do they work on?

A

Mediate their effect by kappa and delta receptors

83
Q

spinal analgesia act where?

A

After IV administration, opioid acts on periventricular and periaquaductal gray — spinal analgesia

84
Q

what is suppressed in spinal analgesia?

A

Occurs when transmission of pain through substantia gelatinosa (L II) is suppressed

85
Q

supra spinal acts where?

A

Opioids act on limbic system, hypothalamus and thalamus.