pain and opioid analgesics Flashcards
drugs that relieve pain without major impairment of other senses
analgesics
block all sensation
anesthetics
the path of the ‘pain signal’
nociceptor detects painful stimuli–>synapse at dorsal horn in spinal cord–>ascending pathway to brain
how can pain signaling be decreased by descending inhibition?
decending pathways from medulla cause release of enkephalins (endogenous opioids)
how is pain signaling increased by peripheral and central sensitization?
something not normally painful becomes painful (showering after sunburn–>allodynia)
a normally painful stimulus is more painful that usual (pricked with a pin–>hyperalgesia)
causes are both peripheral AND central–>tissue damage, inflammation, nerve damage, enhanced ascending pathway activity (central sensitization)
what are the NTs involved in pain transmission w/in the spinal cord?
- glutamate–> directly acts on AMPA and NMDA receptors, and directly depolarizes post-synaptic neuron
- substance P–> peptide that allows channels to open more readily
what are the major mechanisms for pain control?
- activate opioid receptors (body’s natural pain control mechanism)
- decrease production of inflammatory mediators that sensitize pain fibers: NSAIDs
opioids
cmpds that activate the body’s endogenous opioid receptors to produce analgesia (morphine and codeine)
opioid receptors and endogenous ligands
mu: responsible for most analgesic effects
kappa: dysphoria and hallucination at high doses
delta: not well understood, maybe role in analgesia?
endogenous peptide ligands: endorphins, enkephalins, dynorphins
what type of receptors are the opioid receptors?
their cellular and physiological effects?
GPCR coupled to Gi
cellular: inhibit adenylyl cyclase–>decrease cAMP–>open K+ and close Ca2+ channels
physiological: inhibition of NT release at prononiceptive synapses; release of inhibition on descending pathways (‘release th brakes’)
acts of opioids on brain, spinal cord, and peripheral nociceptors, brainstem
brain: decreased emotional suffering
spinal cord: decreased activation of ascending pathways
peripheral nociceptors: decreased activation
brainstem: increased activity of descending inhibitory pathways
opioid adverse effects
- respiratory depression
- abuse/addiction
- pruritis
- N/V, constipation
morphine
- opioid natural/semisynthetic
- prototype drug
hydromorphone (dilauded)
- efficacy to morphine?
- potency compared to morphine?
- water solubility characteristic?
- opioid natural/semisynthetic
- simillar efficacy to morphine
- approx. 10x potency
- better water solubility allows lower IV volume
oxycodone
- efficacy?
- good ___ ____
- opioid natural/semisynthetic
- somewhat lower efficacy
- good oral bioavailability
codeine
- efficacy?
- prodrug issue?
- opioid natural/semisynthetic
- low efficacy
- prodrug susceptible to CYP2D6 pharmacogenetics
fentanyl
- fast or slow acting?
- potent vs. not?
- short or long duration of action?
- what is it used for? transdermal patch vs. lollipops?
- synthetic opioids
- fast acting
- very potent
- SHORT duration of action (vs. methadone)
-used in pain control during procedures, transdermal patch for pain management, lollipops for peds patients
methadone
- used to treat?
- long or short duration of action?
- synthetic opioid
- used to treat addiction but also for pain
- very LONG duration of action (vs. fentanyl)
loperamide
-describe effect at normal vs. high dose
- antidiarrheal
- effect at normal dose restricted to GI tract
- activation of mu receptors in GI tract reduces contraction and decreases secretions
- potential for abuse!
tramadol
- parent cmpd MOA?
- cytochrome issue?
- adverse effects?
parent cmpd MOA: inhibits serotonin and NE reuptake (SNRI)
- weak mu agonist
- CYP2D6 converts tramadol into a mu agonist 300x more potent than parent cmpd
adverse effects: dependence potential; a lesser known drug of abuse, lowers seizure threshold
naloxone
- treats?
- adverse effects?
- opioid antagonist
- tx overdose
- cause precipitated withdrawal in ppl who are physically dependent
buprenorphine
- tx?
- (+) naloxone effects?
- partial mu agonist with high potency
- helps wean patients off opioids by preventing severe withdrawal sxs
- can precipitate withdrawal if full agonist in patient’s system
- naloxone to deter IV and intranasal abuse; sublingual film, if injected/snorted, naloxone blocks opioid receptors–>withdrawal
Understand the relationship between tolerance, physical dependence, and addiction
tolerance: dose may need to increase over time to continue relieving pain, or may need to switch to a different drug
physical dependence: body has adapted to drug and can get opioid withdrawal
addiction: lack of impulse control over taking drug, and person seeks it despite negative consequences (family, job, etc.)
morphine
prototype drug
