Opiates Flashcards
what are the 2 elements that comprise pain??
1- LOCAL IRRITATION- stimulation of peripheral nerves
2- RECOGNITION- of the pain within the CNS
what are the 4 stages of nociception pathways??
1- transduction/nociception
2- transmission
3- perception
4- modulation
what are peripheral nerve endings called?
nociceptors
where are nociceptors found?
within the skin, muscle, joints, bones and viscera
what do nociceptors respond to?
tissue injury
injury leads to?
localized biochemical change
describe the transmission stage:
signals are relayed to a second set of neurons in the dorsal horn of the spinal cord
neurotransmitters are used to relay the signal
they are excitatory because they activate or “excite” new signals in the second set of relay neurons
what neurotransmitters are used to relay the transmission signal?
glutamate and substance P
what are some excitatory transmitters?
substance P
calcitonin gene related peptide
aspartate, glutamate
what are some inhibitory transmitters?
GABA
glycine
somatostatin
A2 agonists
what are primary nociceptor fibers?
alpha delta fibers
C fibers
what is the brain responsible for?
perception of pain
describe the perception stage:
pain is perceived by an individual once all the incoming nervous messages are interpreted by the brain
this involves the integration of all the nociceptive impulses and the interpretation of what these mean
describe the modulation stage:
DESCENDING INHIBITION
areas in the midbrain can be stimulated to trigger nervous impulses that travel down the SC and release neurotransmitters (serotonin & NE) and the endogenous opioids
clamps down on pain response when appropriate
what do endogenous opioids do?
reduce the nociceptive transmissions and thus pain
what are descending connections that modulate incoming pain impulses?
fibers that descend from the BS to SC modulating incoming signals
neurotransmitters
opioid receptors
what neurotransmitters are responsible for mediating anti-nociceptive effects?
norepinephrine and serotonin
how is pain modulation achieved?
through dynorphins and change in opioid receptor number/activity
nociceptive pain can either be:
acute or chronic
nociceptive pain can only occur when:
all neural equipment is working properly
is the patient experiencing nociceptive pain?
how is nociceptive pain managed?
analgesic selection and overall treatment approach will depend on the type, duration and intensity of the pain
what is neuropathic pain?
pain that is the result of injury to the NS (CNS and/or PNS)
may occur after trauma as well as acute and chronic
while it may be intermittent, it is chronic
affects more than 2 million people in the US alone
notoriously difficult to treat!
what is allodynia?
the interpretation of non-painful stimuli as painful
what is hyperpathia?
an exaggerated and prolonged response to painful stimuli
what is the first choice for treating pain related to post-surgical, dental, trauma, visceral pain and cancer?
opioids
all opioids relieve, to some degree, moderate to severe acute and chronic pain
what are the 3 opioid receptors that are clinically important??
opioids act by stimulating _____ receptors mu, delta and/or kappa receptors
stimulation of the opiate receptors inhibits…
the transmission of pain signals and the stimulation of pain control circuits in the SC
what is released when an opioid receptor is stimulated?
endorphins (peptides)
how are endorphins produced?
produced by the pituitary and hypothalamus
selective for mu receptors
what are enkephalins?
produced throughout the CNS and peripheral nerve endings;
selective for delta
what are dynorphins?
found in some nerve endings;
selective for kappa
how do opioids “block” pain?
naturally derived or synthetic molecules that mimic the actions of the body’s endogenous opioid peptides
these substances bind to OPIOID RECEPTORS in the pain transmission and perception circuits to block both pain transmission and pain perception
what is the order of greatest to least analgesia produced by receptor activation?
mu>delta>kappa
what is the MOA of opioid agonists in the SC and the brain??
decreases Ca2+ influx in response to incoming AP.
This decreases release of excitatory neurotransmitters such as glutamate
activation of the opioid receptor increases K+ efflux and decreases the response of the post-synatpic neuron to excitatory neurotransmitters
what are the clinical effects of mu opiate receptors?
euphoria
physical dependence
respiratory depression
supraspinal analgesia
what are the clinical effects of kappa opiate receptors?
miosis (close eyes, constrict pupil)
sedation
spinal analgesia
respiratory depression
what are the clinical effects of sigma opiate receptors?
dysphoria- unhappy, emotional state
hallucinations
respiratory stimulation
vasomotor stimulation
what are additional (9) pharmacologic effects of opiates?
anti-tussive (exception= meperidine)- used to prevent/relieve cough
alterations in smooth muscle tone: increase smooth muscle tone while inhibiting peristalsis in the gut
inhibit parasympathetic stimulation: affects the intestines (mechanism: blocks ACh release)
decrease urine formation: opiates stimulate the secretion of anti-diuretic hormone (ADH)
miosis: pinpoint pupil
mood alteration: euphoria/dysphoria
respiratory depression: via direct effect on respiratory centers (primarily associated with mu receptors)
nausea/emetic effect: via direct stimulation of chemoreceptor trigger zone (CTZ)
direct release of histamine: hives, itching, flushing
how are opioids classified?
1- SOURCE: natural, semisynthetic, synthetic
2- POTENCY: strong, intermediate, weak
3- SPECIAL FEATURES
what is the potency and effectiveness of morphine?
strong potency
poor oral effectiveness
releases histamine (bc it’s a base
what is the potency and effectiveness of codeine?
intermediate potency as an analgesic
high potency as antitussive
good oral effectiveness
often combined with non-narcotics
excellent variety of dosage forms
what are 3 semisynthetic narcotics?
heroine
dihydromorphine (Dilaudid)
oxycodone (OxyCotin, Percocet)
what is the potency and effectiveness of heroin?
high potency
acetyl groups facilitate passage across BBB
better C/P ratio
more prevalent street narcotic
heroin= diacetyl morphine
what is the potency and effectiveness of dihydromorphone?
high potency
excellent C/P ratio
what is the potency and effectiveness of oxycodine?
used in well over 40 products
can be combined with non-narcotics
short-acting
widely abused
what is a synthetic narcotic?
methadone (Dolophine)
what is the potency and effectiveness of methadone?
potency equal to morphine (strong)
very long half life
accumulates if taken once daily
can produce steady-state plasma concentration that is both analgesic and will prevent withdrawal
used for both chronic pain management & maintenance programs/weaning
what opiate has the highest potency?
codeine
morphine
fentanyl
methadone
FENTANYL
what is tolerance?
a given drug loses its effectiveness over time and an increase dose is required to produce desired therapeutic effect
what is physical dependence?
dependence on a given drug to maintain normal homeostasis of the body
example: chronic opioid use/administration
what is drug withdrawal?
a set of symptoms that are consistent with the stoppage of a drug which produces physical dependence
physical symptoms of opiate withdrawal include: excessive yawning lacrimation rhinorrhea restlessness increased pain sensitivity nausea vomiting diarrhea cramps muscle aches sweating dysphoric mood
how do opioid antagonists work?
antagonists attach to the opioid receptor and displace the agonist
what are examples of opioid antagonists?
naloxone (Narcan)
naltrexone (Trexan, Vivitrol) or nalmefene
what is the MOA of naloxone?
competitive blocking of mu and kappa receptors
parenteral use only; very quick action
when and how is naltrexone used?
orally effective; long acting
used in treatment programs to prevent addicts from getting high on street narcotics
can be used to reduce craving, relapse and drinking in alcohol-troubles persons
what are questions on a standard questionnaire: pain assessment?
onset when and how did the pain start?
location/site where is pain located?
what has happened since onset?
characteristics/quality of pain: describe the pain
severity?
unpleasantness/distress: how unpleasant is the pain?
are there any other symptoms? (numbness, weakness, bowel/bladder dysfunction, insomnia, etc?
does the pt suffer from depression?
anxiety?
what makes the pain worse? better?
impact of function and activities. how are work and ADLs affected?
response to past treatments?
does the pt smoke? drink? drugs? how much/often?
how is the pt coping with the pain?
what are 2 natural opiates?
morphine and codeine
