41: Opiod Analgesics Flashcards
what 5 things are opiods traditionally used for?
euphoria analgesia sedation relief from diarrhea cough suppression
opium combined with alcohol =
laudanum
the exudate from poppy seeds containing 20 biologically active components including morphine and codeine
opium
drug extracted from the exudate of the poppy
opiate
natural or synthetic drug that binds to opiod receptors producing agonist effects
opioid
term used to characterize pharmacological compounds used to treat moderate to severe pain
narcotic
natural opiods occur …
- in the exudate of the opium poppy
- as endogenous endorphins, enkephalins and dynorphins
all non-natural opiods are derived from…
morphine and precursor compounds
located outside the spinal cord and responsible for central interpretation of pain - supraspinal analgesia
Mu1
located throughout the CNS- brainstem and spinal cord
responsible for supraspinal and spinal analgesia, respiratory depression, constipation, physical dependence, and euphoria
Mu2
three endogenous opiod receptors
Mu
Kappa
Delta
what gprtn is assocaited with opiod receptor activation
Gi/Go
upon opiod receptor activation, the Gi/Go coupling results (3)
- inhibition of adenyly cyclase
- reduced opening of presynaptic voltage-gated Ca2+ channels resulting in loss of intracellular calcium and decreased release of neurotransmitters
- increase postsynaptic opening of K+ channels (hyperpolarization and decreased firing)
mechanisms of analgesia on the ascending pain pathways (3)
1) inhibition of afferent pain transmission (blockade of pain impulses from the periphery to the brain)
2) peripheral effects (activation of opiod receptors on distal ends of afferent neurons decreases their activation and excitability)
3) dorsal horn of the spinal cord (reduction in incoming pain signaling and reduction in pain signaling up the spinal cord)
how do opiods work presynaptically v. postsynaptically?
presynaptic : opiods block release of pain-mediating Nt from afferent neurons via inhibtion of Ca channels
postsynaptic: opioids inhibit activation of afferent neurons via increased K conductance that leads to hyperpolarization
how do opioids work in descending pathways?
opiods block inhibtior GABAergic interneurons to produce disinhibiton
leads to enhanced inhibition of nociceptive processing in the spinal cord and overall pain relief
site of action of opioids
periaqueductal gray-midbrain
rostral ventral medulla - brainstem
locus coeruleus - pons in brainstem
reduce both sensory and affective aspects of pain
analgesia
what special precaution needs to be taken with use of opiods in head trauma?
increased pCO2 –> reflexive cerebral vasodilation
respiratory depression is a general pharmacological effect of opioids and leads to reduction in respiratory center sensitivity to pCO2 tension
do opioids cause dilated or constricted pupils?
miosis - constriction of pupils
why do opiods cause cough suppression?
suppress the cough center in the brain – action is predominately via the brainstem chemoreceptor trigger zone
what is the main GI effect of opioids?
constipation
relieve diarrhea by decreasing gut motility and increasing the tone of intestinal smooth muscle
how do opioids affect the uterus and urinary tract?
diminished force of contractions in labor
urinary retention
what are the cardiovascular effects of opioids?
hypotension
bradycardia
urticaria (hives) may be a side effect of opioid use. why?
histamine release – stimulates mast cell degranulation and release of histamin causing urticaria, itching, diaphoresis and vasodilation
what is a contraindication for meperidine use?
MAOi drug interaction with opioids
hyperpyrexic rxn including hypertension
dextromethorphan
cough suppressant
diphenoxylate
antidiarrheal agent
loperamide
antidiarrheal agent
tramadol
mu agonist plus 5HT/Ne uptake inhibitor
pros and cons of mixed opioid agonist-antagonists
mixed act differently at specific opioid receptors
pros: provide adequate analgesia with less risk of side effects and addiction
cons: enhanced psychotropic effects
which mixed opioid agonist-antagonist is a partial activator of mu rec, blocks kappa rec.
buprenorphine
all the others activate kappa rec. and block or partially activate mu rec
which receptors does morphine work on?
mu
kappa
delta
latency to onset and duration of action for morphine
15-60;
3-6 hrs
PO administration -other routes are preferred
7-10x more potent analgesic than morphine
hydromorphone
which opioid is transdermal?
fentanyl
works 72 hours transdermal
more potent than morphine and hydromorphone
what happens when a normal person takes opioid antagonists?
in normal individuals with no opiates present, these drugs produce no effects
what drug would you use to reverse effects of acute opioid overdose?
naloxone (opioid antagonist)
IV produces a reversal of CNs and respiratory depression within 30 sec
what drug might be used as a maintenance drug for addicts in treatment programs?
naltrexone (opioid antagonist)
PO administration with long duration of inhibitory action
physiological tolerance involves changes in…
decrease in number and sensitivity of opioid receptors
what is cross-tolerance?
tolerance to one drug produces tolerance for another drug
one who is tolerant to morphine will also be tolerant to the analgesic effect of fentanyl and other opioids
primary pharmacologic intervention used to treat opioid addiction
methadone
substituted for heroin and slowly withdrawn with milder withdrawal symptoms
