201 pain

Question 1

what the types of pain

Answer 1

-acute
-chronic
-nociceptive: related to tissue damage
-nociplastic: no clear evidence of threat
-neuropathic: unrelated to nociception
(caused by thalamic stroke, peripheral nerve damage, spinal damage or infection)
*fast pain: adelta fibre
slow pain: non-myelated C (smaller) (αβ)

Question 2

what stimulates nociceptors

Answer 2

-high mechanical stimulation
-thermals stimulation
-low pH
-chemicals (bradykinin, histamine)

Question 3

what is the ascending pain pathway

Answer 3

-sensory input from first order afferent neuron enters spinal cord via dorsal dorm
-synapses with second order neuron
-travel to thalamus
-synapses with third order neuron in thalamus
-third order neuron extends to primary somatosensory cortex

Question 4

what is the difference between allodynia and hyperalgesia

Answer 4

-allodynia: pain to non-noxious stimulus
-hyperalgesia: increased pain to noxious stimulus
*caused by sensitization:
peripheral : increased sensitivity of nociceptors
central: increased transmission in spinal cord
(caused by NMDA glutamate receptors and neurokinin receptors)

Question 5

what is the descending pain pathway

Answer 5

-PAG receives input from different brain areas (hypothalamus, cortex, amygdala)
-neurones descend through medulla to spinal cord
-neurones from locus coeruleus
-can inhibit ascending pain pathway

Question 6

what are the different types of analgesics

Answer 6

-NSAID, aspirin, paracetamol: inhibit COX (prostaglandin) - sensitize opening of other channels-reduce nociception
-opioid: activate descending pathway, inhibit transmission in dorsal horn, inhibit excitation in periphery

Question 7

how do opioids work

Answer 7

-opioid receptors (κ.μ.δ)- GPCRs, inhibit adenylyl cyclase
-close ca channels (inhibit)
-open K channels (hyperpolarization)
-block neurotransmitter release
-activate descending pathway, inhibit ascending pathway
eg. methadone, morphine, fentanyl (strong)
codeine, buprenorphine

Question 8

what are the effects of opioids in different areas

Answer 8

• cerebral hemisphere- sedation, mood
  -amygdala- emotional behaviour (euphoria)
  -dorsal horn of spinal cord- supress release of SP and CGRP (analgesia)
  -respiratory center- respiratory depression
  -GI tract- constipation
  -cough center of medulla- depression of cough reflex
  -chemoreceptor trigger zone- nausea

Question 9

what is an issue with opioids?

Answer 9

-tolerance- higher doses are required to achieve therapeutic effect (desensitization of opioid receptor)

Question 10

what are some non-opioid options?

Answer 10

• TCA: inhibit noradrenaline reuptake
  -anti-seizure eg. pregablin, gabapentin (ca channel blocker)
  -canabinoid receptor agonists (neuropathic pain)
  -glutamate receptor blockers (ketamine)

Question 11

what are the common pediatric analgesic formulations?

Answer 11

-suspensions
-solutons (ethanol-not recomended)
-suppositories: melt at body temperature (useful for nausea)
-orodispersable tablets: dissolve in mouth
(made through direct compression- use of superdisitegrants)
-parenteral (IV)- severe
-buccal
-transdermal (fentanyl patch)
-intranasal

Question 12

what is lyophilization?

Answer 12

-oral lyophilisates produced by lyophilization
Stage:
1. freezing (liquid nitrogen is used)- (-30C)
2. vacuum application (bring pressure down below triple point)
3. sublimation (vapour removed)
4. secondary drying (residual moisture removed by raising temp to 50-60)

Question 13

what are the issues of protein/peptide drugs

Answer 13

-stability on storage
-in vivo delivery (hydrolysis of peptide bond, high MW hindering absorption)
-rapidly eliminated from the blood (renal excretion, opsonization, generation of neutralizing antibodies, proteolyisis)

Question 14

what are the benefits of attaching a polymer on protein drugs

Answer 14

-higher MW reduces glomerular flitration
-polymer shields protein from proteases slowing down hydrolysis
-opsonization is reduced
longer half-life

Question 15

what are the ideal properties of polymer required for hiding dugs?

Answer 15

-non-toxic
-lacks immunogenicity
-water soluble
-mobile and highly hydrated
-easy to attach to proteins
-cleared from the body after metabolism

Question 16

what is PEGylation?

Answer 16

-PEG is a synthetic linear polymer
-water soluble, biocompatible, well-tolerated and FDA approved
-slows clearance, opsonization, proteolysis
*PEGylation near active site of dug can reduce efficacy

Question 17

what are examples of drugs that are pegylated

Answer 17

-certolizumab pegol (TNF-α inhibitor) -RA treatment
-filgrastim
-pegloticase- used to treat gout (pegylated recombinant uricase)
-nanoparticles (carriers of drugs and vaccines) can also be pegylated

Question 18

what is the classification of pain

Answer 18

-duration (acute, chronic)
-cause (cancer, non-cancer, surgery, cardiac)
-mechanism (nociceptive, nociplastic, neuropathic)

Question 19

how do you treat the different types of pain

Answer 19

-nociceptive: paracetamol, NSAIDS, opioids, anti-spasmodic
-neuropathic: TCA, SNRI, pregablin, carbamezapine
-nociplastic: exercise, sleep, stress reduction, pregablin

Question 20

what is the pathophysiology of chronic pain
what factors affect chronic pain
how do you manage chronic pain

Answer 20

-peripheral sensitization due to repeated stimulation leading to increased sensitivity
-central sensitization: persistent transmission of signals from peripheral nervous system, reduction in GABA
*risk factors: surgery, chronic opioid use, pain syndromes, anxiety
-Factors: Biological (sex, age, magnitude of injury, genetics)
phycological (depression, anxiety, coping skills, catastrophizing)
Social (relationships, having fun)
-Management: amitriptyline, citalopram, fluoxetine, sertaline

Question 21

what are the side-effects of opioids

Answer 21

-hyperalgesia (more sensitive, loss of opioid efficacy, stop opioid for 3 months)
-addiction
-respiratory depression
-dependency
-immuni-suppresion

Question 22

what is NNT and NNH

Answer 22

-number needed to treat: the lower the better
-number needed to harm: the higher the better

Question 23

what are the symptoms and treatment of fibromyalgia

Answer 23

-widespread pain and tenderness
-non-refreshing sleep
-brain fog
-mood changes
-hyperalgesia
Treatment: aerobic and strengthening exercise
cognitive behavior therapy
hydrotherapy (improve pain)
sleep, diet, weight loss, relaxation techniques
pharmacological: pregablin (pain, sleep), duloxetine
(mood, pain)

Question 24

how do you treat neuropathic pain

Answer 24

-1st- TCA
-2nd- gabapentin
-pregabalin if gabapentin not tolerated
-duloxetine
-combine TCA+ gabapentin/pregabalin/duloxetine

Question 25

what are the differences between morphine and codeine

Answer 25

-codeine is a pro-drug, morphine is active analgesic
- morphine bind to μ-receptors better than codeine
- morphine binds to k receptors while codeine doesn’t
-codeine has less side effects
- codeine has a methoxy group while morphine has hydroxyl
-codeine is more hydrophobic

Question 26

what are the differences between fentanyl and morphine

Answer 26

-fentanyl is more potent (analgesic and anesthetic, lipophilic, synthetic, opioid agonist, bind to μ receptors)
-fentanyl is more hydrophobic (more Os), it passes through skin and mucus membranes more easily
-morphine remains at the administration site for longer, it is more hydrophilic, sterically bulky and better ability of hydrogen bonding

Question 27

what are the characteristics and synthetic processes of ibuprofen and paracetamol

Answer 27

-paracetamol:
not anti-inflammatory, hepatotoxicity in overdose
synthesized acetylation of 4-aminophenol
-ibuprofen: synthesized from isobutylbenzene

Question 28

what is the WHO analgesic ladder

Answer 28

-step 1: non-opioid: paracetamol, NSAID
-step 2: weak opioids (codeine, dihydrocodeine, tramadol)
-step 3: strong opioid (morphine)

Question 29

what are the side-effects of opioids and how do we manage them

Answer 29

-nausea:
if GI tract or vomiting center: cyclizine
if CTZ: haloperidol
if delayed gastric emptying: metoclopramide
-constipation: laxatives
stimulant: senna, bisacodyl
osmotic: macrogols

Question 30

what do you give if patient doesn’t respond to opioids

Answer 30

-bone pain: add NSAID or/and radiotherapy
-nerve pain: add adjuvants (anticonvulsants/ antidepressants)