Opoids Flashcards
nociception define
the detection of painful stimuli
where are pain receptors found?
The receptor for pain are free (naked) nerve endings in the skin, muscle and viscera
substance P
Neurotransmitters for nociceptors include substance P. Inhibition of the release of substance P is the basis of pain relief by opioids
A-delta fibers
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
C fibers
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
Lamina II (and III)?
Lamina II (and III) is Substantia Gelatinosa
Entry of A- delta and C fibers into the posterior horn. where do the cell bodies lie? where do the fibers ascend or descend?
Cell bodies lies in dorsal root ganglia (DRG)
Fibers ascend or descend in track of Lissauer
Pathway for slow chronic pain
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
name the A- delta fiber neurotransmitter
A- fiber; the neurotransmitter is glutamate
name the C fiber neurotransmitter.
what does it bind to?
C fibers; the neurotransmitter is substance P which binds to NK-1(neurokinin-1) receptor on the postsynaptic membrane
Pathway for fast sharp pain:
A-delta fibers terminates in Lamina I , cross to the contralateral, lateral spinothalamic tract and ascend to the brain
Neuraxial (intrathecal or Epidural ) placement of Hydrophilic Opioids: what drug is this?
Morphine, a hydorphilic opioid, crosses lipid membrane slowly
tell me about intrathecal (spinal) placement.morphine
onset?
ventilation?
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
Epidural Placement: morphine
tell me about onset
ventilation
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
Neuraxial (intrathecal or Epidural ) placement of Lipophilic Opioids : what drug is this?
fentanyl, alfentanil, sufentanil –rapidly diffuse through lipid membrane
Intrathecal (Spinal) Placement of fentanyl..
Rapid onset and short duration of analgesia
Early depression of ventilation due to systemic uptake
Late depression of ventilation does not occur
Epidural Placement of fentanyl…
Similar as intrathecal (spinal) placement
if you add one of the fentanyl to a spinal- what will the patient experience as a side effect
they will get an itchy nose
3mg epidural=?spinal
0.3 spinal
Spinal Analgesia
which receptor??
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
Supraspinal Analgesia
which receptor??
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”
Acupuncture releases what?
endorphins
descending neurons form?
The interneuron release
enkephalin inhibit release of what??
Dorsolateral tract modulates pain by??
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
Three types of opioids receptors, located in CNS, nerve terminals, GIT and ANS
mu
kappa
delta
Opioids interact with opioid receptors and mimic the action of endogenous opioids which are?
(enkephalins, endorphins and dynorphins) and activate brain analgesia system
mu 2 responsible for?
mu-2 are responsible for respiratory depression and addiction
Supraspinal and spinal analgesia is primarily by
mu-receptors
k
(Kappa)
all of it
Analgesia (Spinal & Supraspinal)
Dysphoria
Low abuse
Potential
Miosis
Diuresis
delta
all of it
Analgesia (Spinal & Supraspinal)
Respiratory depression
Physical dependence
Constipation (mild)
mu 2
all of it
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
mu 1
Analgesia (Supraspinal and spinal)
Euphoria
Low abuse potential
Miosis (PPP)
Bradycardia
Hypothermia
Urinary retention-C/I in BPH
Opioid Agonist
Morphine, fentanyl (sublimaze), codeine, heroin, methadone, meperidine (demerol), dextromehtophan, hydormorphone (Dilaudid) Sufentanil (sufenta), Remifnetanil ( Ultiva)
clinical use: cough suppression
(dexomethorphan),
diarrhea
loperamide, diphenoxylate
acute pulmonary edema
maintenance program for addicts
methadone
toxicity of opioid agonist
addition
respiratory depression
constipation
pinpoint pupil
if they have pinpoint pupils??
they need to be reversed
opioid mechanism of action
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)
Opioid Antagonist
Naloxone (Narcan), Naltrexone ( Trexate), Nalmefene
They are competitive antagonist of opioid receptor
opioid antagonist
side effects
increase sympathetic activity Reversal of Analgesia Excitement / Dysphoria Tachycardia Hypertension Dysrhythmias – V fib Pulmonary edema
Mixed Agonist/Antagonist
will they experience respiratory depression
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
if you meant to give a epidural but gave a spinal where do you stick now?
stick above the spot
When do we give stadol
give it in OB
Side Effects of opioids
9
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
Kids and versed, grandma and Ativan
– cns excitation
If someon has treatment for addiction
- possibly no nartocs- will come with a letter from their treatment center
Morphine: moa
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
Morphine: actions
Analgesia – pain relief without loss of consciousness
increase pain threshold
Alters brain’s pain perception “ I feel the pain but I don’t care”
morphine actions to respirations?
Causes respiratory depression by decreasing sensitivity to CO2
MCC of death due to opioid overdose
Euphoria
morphine cough action
Depression of cough reflex
morphine action of pupils
Pin point pupil (PPP)
increase parasympathetic stimulation by III nerve
Show no tolerance to the effect
morphine action gut
Emesis Stimulating CTZ GIT decrease motility , relieves diarrhea Constipation
morphine Actions
CVS
No major effect except for large doses
increase CO2 retention; increase CSF pressure ,therefore C/I in head injury
morphine action with histamine
Histamine release
Itching and vasodilatation
Bronchoconstriction, therefore C/I in asthma
morphine and hormones
Hormonal actions
morphine and labor
Labor: increase 2nd stage
Cross placenta increase resp depression and physical dependence in neonates
morphine uses?
Analgesia
Diarrhea
Cough relief
Acute pulmonary edema associated with LVH
morpine Pharmacokinetics
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)
morphine Adverse effects
Severe respiratory depression Vomiting Dysphoria Hypotension increase ICP Urinary retention
morphine Tolerance and physical dependence
Tolerance to analgesic, euphoric and sedative effect
metabolite of morphine
Morphine-6-Glucuronide
Greater duration of action
650 x analgesia then morphine
Low permeability to BBB
Meperidine MOA
Through mu and kappa receptor
meperidine side effects
Respiratory depression
decrease total peripheral resistance increase CO
increase CSF pressure
meperidine uses
post op shivering
employed in obstetrics
meperidine what id the duration? is it well absorbed?
Well absorbed orally
Shorter duration of action
meperidine Adverse effect
Tremors, twitching or convulsion with large dose
Hyperactive reflexes
Hypotension with large dose
Dry mouth and blur vision
Methadone receptor
Through mu receptor
methadone actions
respiratory depression< morphine
methadone Uses
Control heroin withdrawal symptoms
methadone Pharmacokinetics
Well absorbed orally
Shorter duration of action
methadone Adverse effect
Physical dependence like morphine
Cabg drug of choice?
sufentanil
Fentanyl
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
sufentanil is more potent than
fentanyl
Codeine (Moderate Agonist)
Converts to morphine leads to analgesia Much less analgesia than morphine Cough suppression Less euphoria Low potential of abuse Rarely produce dependence
Drugs that stimulate one receptor but block another are termed
agonist-antagonists
Pentazocine
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
Buprenorphine
Used in opioid detoxification
Act on mu receptor
Less severe side effects in high dose
Nalbuphine and butorphanol
Limited role as analgesic
Causes psychotic symptoms
Tramadol
Act on mu receptor
Moderate to severe pain relief
Less respiratory depression
Naloxone
Use to reverse respiratory depression of opioid over dose
Competitive antagonist of mu, delta, kappa receptors
Produces opioid withdrawal syndrome in abusers
mixed agonist/antagonist which receptors do they work on?
Mediate their effect by kappa and delta receptors
spinal analgesia act where?
After IV administration, opioid acts on periventricular and periaquaductal gray — spinal analgesia
what is suppressed in spinal analgesia?
Occurs when transmission of pain through substantia gelatinosa (L II) is suppressed
supra spinal acts where?
Opioids act on limbic system, hypothalamus and thalamus.
