201 pain Flashcards
what the types of pain
-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)
what stimulates nociceptors
-high mechanical stimulation
-thermals stimulation
-low pH
-chemicals (bradykinin, histamine)
what is the ascending pain pathway
-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
what is the difference between allodynia and hyperalgesia
-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)
what is the descending pain pathway
-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
what are the different types of analgesics
-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
how do opioids work
-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
what are the effects of opioids in different areas
- 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
what is an issue with opioids?
-tolerance- higher doses are required to achieve therapeutic effect (desensitization of opioid receptor)
what are some non-opioid options?
- TCA: inhibit noradrenaline reuptake
-anti-seizure eg. pregablin, gabapentin (ca channel blocker)
-canabinoid receptor agonists (neuropathic pain)
-glutamate receptor blockers (ketamine)
what are the common pediatric analgesic formulations?
-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
what is lyophilization?
-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)
what are the issues of protein/peptide drugs
-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)
what are the benefits of attaching a polymer on protein drugs
-higher MW reduces glomerular flitration
-polymer shields protein from proteases slowing down hydrolysis
-opsonization is reduced
longer half-life
what are the ideal properties of polymer required for hiding dugs?
-non-toxic
-lacks immunogenicity
-water soluble
-mobile and highly hydrated
-easy to attach to proteins
-cleared from the body after metabolism
what is PEGylation?
-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
what are examples of drugs that are pegylated
-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
what is the classification of pain
-duration (acute, chronic)
-cause (cancer, non-cancer, surgery, cardiac)
-mechanism (nociceptive, nociplastic, neuropathic)
how do you treat the different types of pain
-nociceptive: paracetamol, NSAIDS, opioids, anti-spasmodic
-neuropathic: TCA, SNRI, pregablin, carbamezapine
-nociplastic: exercise, sleep, stress reduction, pregablin
what is the pathophysiology of chronic pain
what factors affect chronic pain
how do you manage chronic pain
-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
what are the side-effects of opioids
-hyperalgesia (more sensitive, loss of opioid efficacy, stop opioid for 3 months)
-addiction
-respiratory depression
-dependency
-immuni-suppresion
what is NNT and NNH
-number needed to treat: the lower the better
-number needed to harm: the higher the better
what are the symptoms and treatment of fibromyalgia
-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)
how do you treat neuropathic pain
-1st- TCA
-2nd- gabapentin
-pregabalin if gabapentin not tolerated
-duloxetine
-combine TCA+ gabapentin/pregabalin/duloxetine
