Nonopioids Analgesics (Exam 2) Flashcards
Nonopioid Analgesic Classes
NSAIDs
Acetylsalicylic acid (Aspirin)
Acetaminophen (Tylenol)
Cannabinoids
NSAIDs
MoA
inhibit an enzyme Cycloxygenase responsible for prostaglandin & thromboxane synthesis
Antipyretic, analgesic, and anti-inflammatory.
Acetylsalicylic acid (Aspirin)
MoA
similar to NSAIDS but irreversible inhibitor of COX
binds permanently & destroy (longer HLoE & long term issues)
Acetaminophen (Tylenol)
similar to NSAIDS
but not anti-inflammatory
? inhibit COX but not in periphery. Probably CNS.
(Periphery: H2O2 inhibits TYLENOL)
T/F
Aspirin is a reversible COX inhibitor.
False
NSAIDS = reversible
Acetylsalicylic acid (Aspirin) = irreversible
T/F
Aspirin’s effects last longer than ibuprofen.
True
Aspirin’s COX inhibitory effects are irreversible
Cannabinoids
receptors
specific receptors
(All Gi/0 type)
CB1: brain & SC
CB2: mainly immune
Cannabinoids
limitations
Research weak
CBD (cannabidiol) oil questionable. Some degree of pain relief.
Analgesia d/t sedation
Analgesic dose also causes too much sedation/fxnl limitation
Centrally Acting Nonopioid Analgesics
a2-Adrenergic Agonists:
Clonidine
Dexmedetomidine
Acetylcholinesterase Inhibitors (AChEI’s)
BZDs:
Midazolam
Anesthetics:
Ketamine
Conopeptides:
Ziconotide
GABA Agonists:
Baclofen
Others (weaker proof of benefit):
Ketorolac (NSAID)
Gabapentin
Magnesium Sulfate
Calcitonin
Adenosine
Octreotide
Tramadol
Droperidol
a2-Adrenergic Agonists
MoA
↓NE release in multiple pathways (CNS pain pathways)
stimulate pre-synaptic a2 receptors
↓
block vesicle fusion & NE release from pre-synaptic terminal.
a2-Adrenergic Agonists
Major effect on pain is on…
sympathetic preganglionic neuronal activity
Clonidine
partial a2 receptor agonist
Neuraxial use: cancer, non-cA, post-op pain.
use w/ LAs: potentiate effects
synergistically w/ opioids
Black-box warning for neuraxial administration in obstetrics due to maternal hemodynamic instability.
clonidine
T/F
Norepi can inhibits its own release
True
Norepi can bind to a2 receptor and prevents vesicle and NT release
(Precedex can do this bc its an a2 agonist)
Which is more potent?
Clonidine
Dexmedetomidine
Dexmedetomidine
Dexmedetomidine
a2 receptor agonist
Fewer systemic & HD SEs vs clonidine
a/w demyelination following epidural dosing
Acetylcholinesterase Inhibitors (AChEI’s)
Neostigmine
Blocks ACh metab in synapse
by blocking post-syn sites where ACh would normally bind to and be metabolized
↓
more free ACh in synapse
Intrathecal: released ACh continues to stimulate muscarinic receptors = minor pain relief
adjunct w/ intrathecal LAs & opioids
high SE profile may outweigh small benefit
AChase is located on the (pre/post) synaptic membrane
post
ACh is broken down into…
choline
acetic acid
(Dont confuse w/ Suxx metab)
adrenergic vs. cholinergic
cause of inhibition/limited action
adrenergic: uptake carrier (reuptake of Norepi)
cholinergic: enzyme breaks down substance @ post-syn membrane (AChase)
Form in which ACh is taken back up by neuron for reuse
choline
Neostigmine can provide pain relief. Why is its use for this purpose not common?
high SE profile may outweigh small benefit
T/F
BARBs can be used for pain relief.
False
enhance pain response
Ketamine
Analgesic (anesthetic & subanesthetic doses)
Neuraxial +/- LAs: effective post-op pain relief
synergism w/ opioids
Ketamine
noncompetitively inhibits NMDA of…
secondary afferent neurons in SC dorsal horn
Ketamine
SEs
sedation
headache
possible psychotic rxn
transient burning back pain during admin
Ketamine
benefits
lack of CV SE’s & respiratory depression
Midazolam
MoA
Receptors & their location
GABAA: ↑ inhibition & block pain transmission
act in dorsal horn (high [ ] GABAAr; Lamina II)
opioid receptor activity: stimulates release of endogenous opioids
Can we give Versed neuroaxially?
No proven neurotoxic effects
location of high [ ] of GABA(A) receptors
dorsal horn; laminae II
(Conopeptides)
Ziconotide (Prialt)
structure
25 AA polypeptide derived from conotoxin (from marine snail)
Ziconotide (Prialt)
(Conopeptides)
selective antagonist of neuronal (N-type) voltage-gated Ca channels in presynaptic nerve terminals in the dorsal horn.
block nerve transmission by blocking NE release
sympatholytic
IV: ↓ MAP & SBP
intrathecal: minimal effect
Only currently FDA approved nonopioid for IT use to treat neuropathic pain.
Ziconotide (Prialt)
Ziconotide (Prialt)
SEs
limitations
> 90%
dizziness, confusion, ataxia, memory impairment, suicide ideations
High costs and SE’s limit use.
last resort
GABA(B)
G protein complex system
Sympatholytic
blocks SNS & norepi
Baclofen (Lioresal)
GABA(B) agonist
via G-protein system
↓
activate K channels & hyperpolarize internal membrane
inhibitory effects like GABAA but diff moA
Acts in lamina II & III (DH) presynaptically to inhibit depolarization & decrease Ca entry
↓
decreases afferent pain transmission
T/F
Baclofen (Lioresal) is a GABA(A) agonist.
False
GABA(B)
B for Baclofen
GABA(B) conducts which ion?
K
Baclofen
uses
Intrathecal: chronic pain syndrome from MS & complex regional pain syndrome
back pain (with root compression)
spasticity (ie: cerebral palsy)
Use with Bupivocaine: ↓ postop opioid use
Baclofen
SEs
sedation
drowsiness
nausea
headache
weakness
Rare but serious:
rhabdomyolysis
multiple organ failure
A/w rhabdomyolysis & multiple organ failure
Baclofen
Gabapentin
precursor of GABA; weak pain relief
Adenosine is considered “other”
has its own receptor type
Magnesium Sulfate & Calcitonin
for pain relief
Controls Ca and thus ability to stimulate neurons
Droperidol use
neuroleptic anesthesia
