Opioids and other analgesics Flashcards
Difference between nociceptive and neuropathic pain
nociceptive - tissue
neuropathic - nerve
Analgesics used
- anti-epileptivs (gabapentin, pregablin)
- Antideprrsants (SNRI, TCA)
- NSAIDS
- Opiods
What are nociceptors
nerve endings that detect damaging mechanical, thermal, or chemcial stimuli
what is nociception?
NS processing of informtion from nociepetors
Excitatory neurotransmitters / where are they released or where do they travel to?
Glutamate and aspartame
release and travel through spinal cord to thalamus and other brain structures / cortical strutures
inhibitory neurtrasmittors / where do they travel
GABA and glycine
from cortical structures, down the descending pathways to dorsal ganglion root and spinal cord
what are some abnormal pain responses? think of the curve
Allodynia - innocous syimuli cause pain response
hyperalgesia - exaggerated response to noxious stimuli
what analgesics act on the brain?
GABA/ pregablin
opiods
TCA
SNRI
what alagesics act on the perihperal sites
lidocaine
NSAIDS
Capsaicin
GABA MOA
Attache to alpha 2 - delt subunit and reduce influx of calcium into presynaptic cells, causing less firing and less realese of excitatory neurtransimottors
cell depolarization
TCA examples
amitriplyline or nortriplyline
SNRI examples
duloxetine and venlafaxine
(duloxetine is ebtter)
How do anti depressants work?
Block reuptake of NE and serotonin 5HT in the synaptic cleft
NE - associated with pain relief
1. spinal cord
2. increased NE acts on LC
Nocieceptice circuit
transduction - trasnmission - modultaion perception
inflamtory mediators
bradykins, serotonin, prostagladins, and leukotrines
NSAID MOA
Stop the formation of prostagladnins whihc allows for swelling inflammation, rises in temperature and redness. They do so by blocking COX! and COX2 whihc are key in PG formation
COX1 vs COX 2
COX1 - physiologic
- GI protection
- platlet aggreagtion
COX2 - inflammatory
SE of NSAID
- Hypertension - reduce blood flow
- Kidney damage
- increased risk of MI / stroke
What are opioids?
any compound that binds to opiate receptor
opiates vs synthetic opiiods
opiates: morphine, codeine, opium
Semi-synthtic - fentanyl, methadone, tramadol
opioids MOA
bind to G- protein coupled receptors all through out body and blcok pain messages
can also bind to endogenous peptides involved in pain modulation
- decreas cAMP
- efflux of potassium ( decreased posy synptic K)
- decrease presynaptic Ca2+
- inhibit substance P
Cause hyperpolarization of neuron can’t fire
what opioid receptor is involved in analgesic
Mu recpetor
Distinguish betwen full and partial agonist and antagonist wiuth examples
- greater activation, fully bind
methadone, morphine, oxycodone - low intrinsic activity, ceiling in agonts activity, plateua
buprnorphine - bind fully but do not activate
naloxone
what should be noted about anti-depressants dosing for pain?
it’s in lower dosages
what areas are affected by opiods?
CNS and PNS
What are common side effects with opoids?
peristalsis (leading to constipation), itch, mental clouding, hallucinations, dizziness fatigue, swelling, rashes, hives
What are some concerns with opioids side effects?
repsiratory depression, recpetors in cardiac tissues so bradycardia, hypotension
if we are taking a higher dose opiod do we have more less or the same number of side effects?
more - as dose increases
explain the concept of tolerance and a concern for taking opiods after being opiod free for a while
the bain adjust to opiods so we need more and more in order to get the same relief or effect from them
if we were taking opioid then stop we may loss our tolerance so resume the same dose as before could lead to an overdose
what are the two theroies on opioid tolerance
- opioids become less sesnitive to the drug
- neurons remove opiods receptors from the cell wall, so less available binding
if we develop tolerance what should we do?
increase the dose
how does opiod dependance work?
it’s a neurobehaviorual disorder characterized by repeated compulsive seeking of opioids whihc develops into a physical dependance
rank the rate from fastets to slowest route to the brain for drugs
injection, inhalation, ingestion
what two drug class work by decreasing substance P and glumatte
opiods and pregablin
