Opioids

Question 1

___ present on trigeminal nerve endings send signals on A-delta and C fibers to ___ ganglion which project to trigeminal nuclei located in the ___. The signal is then sent to the ___ which projects to the cerebral cortex and limbic system, both of which perceive pain.

Answer 1

Nociceptors; trigeminal; brainstem; thalamus

Question 2

What area does not have great spatial resolution?

Answer 2

trigeminal nuclei in the brainstem

Question 3

T/F. Orofacial pain follows a different basic pathway from other pain pathways throughout the body.

Answer 3

False, Orofacial pain follows THE SAME basic pathway from other pain pathways throughout the body.

Question 4

What are the three divisions of the trigeminal nerve?

Answer 4

opthalmic (V1), maxillary (V2), mandibular (V3)

Question 5

T/F. Nociceptors (pain receptors) are distributed throughout the skin, oral mucosa, and tooth pulp.

Answer 5

True.

Question 6

Describe an A-delta fiber.

Answer 6

faster, myelinated axons response first to noxious mechanical stimuli. Produce initial sensation of sharp pain

Question 7

Describe a C fiber.

Answer 7

slower, unmyelinated axons respond to thermal, mechanical and chemical assaults. Dull, aching, or burning pain.

Question 8

T/F. There are 5x more C fibers than A-delta fibers.

Answer 8

True.

Question 9

Nociceptors are ___ sensors. Different nociceptors respond to various noxious stimuli such as ___, ___, mechanical ___, or ___. Their activation leads to local ___ which in turn initiates action potentials.

Answer 9

molecular; heat; cold; perburbations; protons; depolarization

Question 10

Nociceptors express many ___ channels that are modulated by ___ to produce ___. If depolarization is great enough to reach activation ___ or voltage gated sodium channels then an action potential can be initiated.

Answer 10

ion; acid; depolarization; threshold

Question 11

T/F. Nociceptive pain and inflammation are unrelated.

Answer 11

False, they go hand-in-hand

Question 12

___ damage leads to the release of inflammatory ___ from neurons and resident ___ cells that interact with receptors and facilitate the transmission of ___ signals through the nervous system.

Answer 12

Tissue; mediators; immune; pain

Question 13

List some mediators released following tissue damage.

Answer 13

prostaglandins, substance P, tumor necrosis factor-alpha, interleukin-16 and -6

Question 14

What leads to sensitization of the pain response?

Answer 14

tissue injury

Question 15

Define hyperalgesia and allodynia.

Answer 15

hyperalgesia: heightened sense of pain to noxious stimuli
allodynia: pain resulting from normally painless stimuli

Question 16

___ act to inhibit the CNS and in the periphery, ___ ___ inhibit signaling to the CNS and non-steroidal and steroidal anti-inflammatories inhibit at the ___.

Answer 16

Opioids; local anesthetics; periphery

Question 17

What are the four families of endogenous opioids?

Answer 17

1. pro-opimelanocortin peptides: beta-endorphin
2. pro-enkephalin peptides: met-enkephalin and leu-enkephalin
3. Prodynorphin peptides: Dyn-A, Dyn-B and alpha-neo-endorphin
4. Endomorphins: endomorphin-1 and endomorphin-2

Question 18

What are the 3 important opioid receptors involved in responses to pain?

Answer 18

mu
kappa
delta

Question 19

What do mu, kappa, and delta have in common?

Answer 19

They are all GPCR
They are widely distributed in the CNS
They activate G-alpha-i

Question 20

POMC is made in the ___ and ___ as a ___ amino acid peptide that is processed into _-___, which is the natural agonist of the ___-opioid receptor.

Answer 20

pituitary; hypothalamus; 31; B-endorphin; mu

Question 21

What is the pentapeptide sequence for met-enkephalin? Where is it derived from? Where is it found?

Answer 21

tyr-gly-gly-phe-met

derived from pro-enkephalin precursor (5 copies)

adrenal medulla and throughout the CNS

Question 22

What is the pentapeptide sequence for leu-enkephalin? Where is it derived from? Where is it found?

Answer 22

tyr-gly-gly-phe-leu

derived from pro-enkephalin and pro-dynophin

through the CNS

Question 23

Met-enkephalin and leu-enkephalin are natural agonist against the ___ opioid receptor.

Answer 23

delta

Question 24

What does the precursor pro-dynophin form? How many peptides make up each product? where are they found? What are they an agonist against?

Answer 24

dynorphin-A (13 aa)
dynorphin-B (13 aa)
alpha/beta neo-endorphin (10 aa - alpha / 9 aa - beta)

Found throughout the CNS

Agonists of kappa opioid receptor

Question 25

What happens when an opioid activates it GPCR?

Answer 25

1. it activates G-alpha-i and dissociates GbetaGgamma 2. Gi inhibits AC activity 3. cAMP levels decrease and there is a reduction in PKA 4. reduction of Ca2+ entry from voltage sensitive Ca2+ channels

Question 26

Activation of the opioid receptor leads to activation of a particular type of ___ channel via ___. This will ___ the cell and make it more difficult to transmit nerve impulses.

Answer 26

potassium; GbetaGgamma; hyperpolarization

Question 27

what effect will reduction of Ca2+ and hyperpolarization produce at the synapse?

Answer 27

They can inhibit synaptic transmission if located pre- or post-synaptically. Pre-synaptically, opioids will inhibit synaptic tranmission by reducing transmitter release. Post-synaptically, hyperpolarization will diminish generation of an action potential.

Question 28

Which opioid receptor has more adverse effects, such as respiratory depression and constipation?

Answer 28

mu receptors

Question 29

Of the three forms of mu receptors, which are the most important?

Answer 29

mu-1 and -2

Question 30

T/F. Majority of the mu receptors are located pre-synaptically and most analgesic drugs act on mu receptors.

Answer 30

True.

Question 31

Where are mu receptors found through out the body?

Answer 31

periaqueductal gray region, superficial dorsal horn of the spinal cord, nucleus accumbens, amygdala, cerebral cortex and GI tract

Question 32

Where is inhibition to the ascending pathway of pain most efficient?

Answer 32

1. inhibit excitatory neurotransmitter release | 2. inhibit transmission of impulse

Question 33

In the descending pathway, opioids ___ GABA release and therefore GABA cannot activate the ___ channel and produce hyperpolarization. Therefore, Opioids inhibit the inhibitor, helping to activate the pathway that produces CNS mediated inhibition of pain.

Answer 33

inhibit; Cl-

Question 34

What do all opioid analgesics produce?

Answer 34

``` analgesia respiratory depression constipation GI spasm physical dependence ```

Question 35

Morphine is a ___ agonist to the mu receptor and a ___ agonist to the kappa receptor.

Answer 35

strong; weak

Question 36

T/F. When morphine is not active it is toxic. This is preferred so that it doesn't get into the brain.

Answer 36

True, when it is activated by glucuronidation in the liver and brain it will become active and be more analgesic

Question 37

T/F. Morphine causes analgesia with sedation.

Answer 37

False, without sedation

Question 38

T/F. Morphine is more effective against sharp pains than dull aches.

Answer 38

False, it is more effective against dull aches than sharp pain

Question 39

What is the most serious acute adverse effect of the opioids?

Answer 39

respiratory depression

Question 40

What is a stage in which an organism no longer responds to a given dosage of drug and requires a higher dose to achieve the same effect?

Answer 40

Tolerance, it can manifest first as shortened to diminished analgesia

Question 41

The rate of tolerance development is a function of ___ and frequency of ___. It is generally seen after ___ days of treatment and its ___ effects remain even if tolerance has developed.

Answer 41

dose; administration; 5-7; toxic

Question 42

___ is the need for a drug even if the pain is gone. It has physical and psychological components.

Answer 42

Dependence

Question 43

Morphine is metabolized by ___ very quickly in the liver and brain into ___ (primary product) and ___ (secondary product).

Answer 43

UGT2B7; Morphine-3-glucuronide; morphine-6-glucuronide

Question 44

T/F. Morphine-3-glucuronide is usable.

Answer 44

False, it is not used. it cannot cross the BBB and therefore is excreted

Question 45

What can cross the blood-brain barrier? Which is a better agonist for the mu receptor?

Answer 45

Morphine and M-6-G M-6-G

Question 46

T/F. Morphine can be given orally?

Answer 46

False, it is not metabolized orally, therefore must be injected

Question 47

Why is codeine more effective orally? Is it more effective than morphine if administered intramuscularly? Does it bind to the mu receptor better than morphine?

Answer 47

it has a substitution at the 3 position that renders it more effective orally No, morphine is more effective intramuscularly No, it binds poorly to the mu receptor

Question 48

What is codeine initially metabolized into?

Answer 48

morphine (5%) and codeine-6-glucuronide (80% - crosses the BBB)

Question 49

What dose of codeine is an oral dose to be given daily with minimum side effects and little dependence?

Answer 49

30-60mg

Question 50

T/F. Pain (dental) with an inflammatory component should not be treated without an anti-inflammatory drug.

Answer 50

True.

Question 51

What other opioids are methylated at the 3' position and can be taken orally?

Answer 51

1. dihydrocodeine 2. oxycodone (percocet) 3. hydrocodone (vicodin)

Question 52

Which form of hydrocodone or oxycontin has the potential for abuse?

Answer 52

controlled release form because there is more drug per pill

Question 53

What are 3 mu opioid receptor antagonists used to treat opioid toxicity/overdose?

Answer 53

naloxone (injected and works rapidly) naltrexone (effective orally and long lasting) nalmefene (active orally and last longer than naltrexone)

Question 54

Explain mixed agonists-antagonist

Answer 54

since activation of all the opioid receptors produce analgesia, it is possible to produce drugs that act on kappa and delta receptors that don't cause major adverse effects (respiratory depression) or produce dependence.

Question 55

Which opioids are readily used in dentistry?

Answer 55

oral administration: codeine, hydrocodone, oxycodone, pentazocine