Pharm- Opiods and Pain Flashcards
how do NSAIDs relieve pain?
inhibit cyclooxygenase (COX) to prevent thromboxane and prostaglandin formation, which thereby prevents pain sensory nerve ending stimulation
how does the descending pain pathway mitigate pain?
it descends from the periaqauductal gray region (PAG) and Raphe Magnus to inhibitory neurons in the substantia gelatinosa of the spinal cord (in the dorsal horn)
they release endogenous opioides, mainly enkephalin, which hyperpolarizes afferent pain neuron axons
where are endorphins found and describe them?
they’re found in the brainstem and hypothalamus, and they’re relatively stable to protease degradation
Where and how do opiates relieve pain?
free endings of sensory pain fibers: hyperpolarize
axons of primary nerve fibers in spinal cord: hyperpolarize, prevent neurotransmitter release
thalamus: hyperpolarize, no NT release
PAG and Raphe Magnus: activate descending pain pathway
cortex: loss of consciousness
How are opiates metabolized?
Mainly in liver with significant first pass
main mechanism is conjugation with glucuronide at the 3- position
if conjugated with glucuronide only at the 6- position then it is even more potent
a less significant mechanism is N-demethylation
What is necessary for codeine to be effective?
CYP2D6
it metabolizes codeine to morphine
if patient doesn’t have 2D6 then codeine is useless
how is it excreted?
mostly in urine
what receptor is the target of opiates?
the mu opioide receptor
chronic activation of it leads to tolerance and dependence
activation of it also causes euphoria
list the natural opiates
morphine, codeine
synthetics include methadone, meperidine, fentanyl,
propoxyphene, hydromorphone, oxycodone
name the opiate antagonist
naloxone must be used via IV b/c it’s completely inactivated by the liver
naltrexone can be taken orally and is used for opiate addiction
how does activation of mu opioide receptor prevent pain transmission from primary pain neurons?
increased K+ permeability and reduced Ca2+ conductivity
what can opiate overdose cause?
respiratory depression
relieved with naloxone, though opiates have longer durations then naloxone so mulitple doses may be necessary
can cause death
name the cough suppressant morphine-like substances
codeine
dextromethorphan (in robatussin and other cough syrups, no effect on opioide receptors)
what opiate is used for anesthesia?
fentanyl
artificial ventilation is required, and has no muscle relaxant effects (must be combined with succinylcholine)
advantages: no peripheral vasodilation (useful in cardiac surgery) and rapidly reversible by naloxone
disadvantagesL needs muscle relaxant, consciousness may not be fully lost so combined with N2O
side effect on GI? name an opiate which targets GI effects
constipation
loperamide is used as an antidiuretic and has little CNS effect
what’s used for neuropathic pain that’s not relieved by anything else?
ziconotide
heroin
a close relative of natural morphine except it enters the CNS more quickly and produces more euphoria
hydromorphone
dilaudid, can be used for exntended release oral capsule, highly abused
fentanyl
very potent, short duration, used for anesthesia
buprenorphine
a partial agonist at mu opioide receptors, mild analgesia alone but antagonistic effects when used with morphine
