Lecture 3

Question 1

what are the neurons for pain called

Answer 1

nociceptors

Question 2

what is pain

Answer 2

the emotional experience of the nociceptors being activated

Question 3

the nociceptor neurons send the signal to the brain via

Answer 3

the spinal cord

Question 4

what is the thalamus

Answer 4

think about it as a filter for all of the neuron information
- filters all sensory information before sending it to the rest of the brain

Question 5

algesia is

Answer 5

pain

Question 6

what is hyperalgesia

Answer 6

means that there is more pain than usual

Question 7

what is allodynia

Answer 7

means you are now experiencing a sensation that is painful which is normally innocuous

Question 8

for pain there is an (pathways)

Answer 8

ascending and a descending pathway

Question 9

two ways to reduce pain

Answer 9

reduce the ascending pathway or augment the descending pathway

Question 10

what is the ascending pathway

Answer 10

the system of neuron signals (nociceptors) that send pain information to the brain

Question 11

what is the descending pathway

Answer 11

the system of neurons that attempt to inhibit the pain being experienced so that the affected area can keep functioning

Question 12

name for pain medicine

Answer 12

analgesics

Question 13

local anesthetics

Answer 13

drugs that stop all action potentials
- block voltage gated sodium channels of all neurons
- they are antagonists of the sodium channels and will block all neuron transmission

Question 14

what was the first local anesthetic

Answer 14

cocaine

Question 15

what are NSAIDs

Answer 15

non steroidal anti inflammatory drugs

Question 16

what do NSAIDs do

Answer 16

block the production of prostaglandins
- inflammation means redness, swelling, pain, fever which is all called by prostaglandins
- inhibiting this will reduce symptoms

Question 17

acetominophen

Answer 17

• unknown mechanism of action
• does not affect prostaglandin production

Question 18

opioids (origin)

Answer 18

○ Opiates are derived from poppy (morphine, heroin, opium)
§ Two molecules of morphine attached together becomes heroin (which is why its called a semi-synthetic)
§ Fentanyl is fully synthetic and is easier to produce
○ Opioids are drugs that activate the mu opioid receptor

Question 19

how do prostaglandins contribute to symptoms of inflammation on the ascending pathway

Answer 19

• Prostaglandins facilitate firing of peripheral nociceptors.
• Prostaglandins facilitate firing of central neurons in ascending pathway

Question 20

Process for prostaglandins (three steps)

Answer 20

• When there is an injury, an enzyme called cyclooxygenase 2 (COX2) is activated. COX2 makes a chemical called prostaglandin (PGE2).
• Prostaglandins cause swelling and increase blood flow. They bind to prostaglandin receptors on the sensory nerves (nociceptors). When prostaglandin binds to those receptors, they fire more often. This activates the ascending pathway.
• Non-steroidal anti-inflammatory drugs act as antagonists of COX2 – they prevent the enzyme from making prostaglandins. Therefore they block pain and reduce swelling and redness. They also reduce fever by preventing prostaglandin production in the brain.

Question 21

what are some common NSAIDs

Answer 21

ibuprofen, naproxen, aspirin, diclofenac (over 20 NSAIDs)

Question 22

benefits of NSAIDs

Answer 22

reduces pain, swelling, redness, fever
- used for rhematoid arthritis and reduces blood clotting (low dose aspirin)

Question 23

side effects of NSAIDs

Answer 23

stomach / gastrointestinal ulceration (prostaglandins protect the stomach and intestinal lining)
- can reduce kidney function if used in high doses
- can exacerbate asthma
- some people are allergic

Question 24

acetaminophen is not

Answer 24

a NSAID
- it reduces pain and fever
- but it does not reduce redness or swelling and is not an anti inflammatory

Question 25

what is a ligand

Answer 25

a molecule that sticks to a receptor

Question 26

opioids are agonists of which receptor

Answer 26

the mu opioid receptor

Question 27

endogenous ligands (agonists) for the mu receptor are

Answer 27

endorphins and enkephalin

Question 28

where are mu opioid receptors located (MORs)

Answer 28

located in brain areas that control pain sensation and emotional response to pain - thalamus and descending pain pathway

Question 29

when the MORs on a neuron are bound by an agonist

Answer 29

then the result is less firing of that neuron - opioids are depressants - the descending pathway is engaged by morphine - depressants will also cause sleepiness and reduced consciousness

Question 30

naloxone is an

Answer 30

antagonist of the MOR - naloxone and other MOR antagonists are antidotes for opioid overdose

Question 31

oxycodone is a

Answer 31

prescribed opioid that can be formulated as a slow release medicine

Question 32

oxycodone story

Answer 32

- Physicians were told by Purdue that oxycodone was not addictive because it was slow-release. This was a lie. - Like other opioids, oxycodone is addictive. It is also abused by crushing the pill, snorting or injecting intravenously. - In 2012, regulations to reduce access to oxycodone were put in place, and the pill was made harder to crush and solubilize. - became cheaper to buy heroin than oxy

Question 33

fentanyl is a

Answer 33

synthetic opioid that is 100 times more potent than morphine. it can be found in other street drugs and is the primary cause of overdose

Question 34

what is codeine

Answer 34

- tylenol 3 (acetominophen and codeine) - codeine is converted to morphine in the liber - morphine is the active drug - some people are fast metabolizers and some are slow due to differences in genetics - it is not a pain reliever but the body converts it into morphine - 0.1x as potent as morphine

Question 35

what is morphine

Answer 35

- active ingredient in the poppy plant - source for many other semi synthetic opioids

Question 36

how much more potent is oxycodone and hydrocodone than morphine

Answer 36

1.5x

Question 37

how much more potent is hydromorphone (diluiad) than morphine

Answer 37

5x

Question 38

how much more potent is diamorphine than morphine

Answer 38

10x

Question 39

what does potency mean

Answer 39

how much of a drug you need to get the desired effect

Question 40

what does affinity mean

Answer 40

refers to the goodness of fit between the drug and the receptor (how hard is it to pull it off)

Question 41

what does selectivity mean

Answer 41

refers to the range of receptors a given drug prefers

Question 42

t/f drugs that have a high potency are usually selective for just one type of receptor

Answer 42

true

Question 43

t/f drugs with high potency have a better affinity for the receptor than drugs with a low potency

Answer 43

true

Question 44

what is receptor desensitization

Answer 44

when an agonist binds to a receptor it causes the receptor to internalize into the neuron and stop the signal - this is a feature of all G Protein coupled receptors - even if morphine is still circulating, the receptors get internalized so the morphine stops working

Question 45

opioids work

Answer 45

for a few hours, but then the effects begin to fade

Question 46

what is the reason for the gap between doses of opioids

Answer 46

- The drug is still in the body, but the receptors that mediate the feeling of pain have been desensitized to the drug - They don’t give you more drugs because other receptors, like receptors for breathing, but they are still affected

Question 47

why are opioids addictive

Answer 47

- they inhibit the neurons that usually inhibit dopamine

Question 48

methadone treatment

Answer 48

- Nothing that is effective at addressing the addiction ○ Instead replace the opioid with something else to help them survive the withdrawal symptoms § It treats the symptoms of withdrawal but does not give them the same high - Methadone is also an opioid. It also activates mu opioid receptors. - It is given in tapered doses to lessen withdrawal from heroin. However, methadone withdrawal is as aversive as heroin withdrawal. - Methadone is not effective to reduce heroin use relapse rates unless it is accompanied by other interventions like counseling.

Question 49

Buprenorphine Treatment

Answer 49

- Buprenorphine is also an opioid. It also activates mu opioid receptors but it is a partial agonist. - It is given in tapered doses to lessen withdrawal from heroin. Because it is a partial agonist it doesn’t fully activate the mu receptor. It is less rewarding and causes less withdrawal than methadone. - Buprenorphine is not effective to reduce heroin use relapse rates unless it is accompanied by other interventions like counseling.