Lecture 5 - Opioids Flashcards
pain’s primary function is to serve as a ____ system.
warning
central pain sensitization involves activation and recruitment of ____ and ____ surrounding nerve endings responsible for pain transmission
astrocytes, microglia
mediators released by glial cells feed into the central sensitization of ___ and ____ receptors, which are important in pain signalling
AMPA, NMDA
key brain regions expressing opioid receptors are the ____, the rostral ventral medulla, and the _____
Periaqueductal gray, DRG
opium contains two types of alkaloids:
phenanthrenes, benzylisoquinolines
some opioids, including methadone, mepiridine, and fentanyl do not have the ____ backbone. this may be beneficial when conisidering ____ ____
phenanthrene, opioid rotation
partial agonism of Mu-opioid receptors is conferred by ____ side groups such as in naloxone
bulky
Most opioids get metabolized by ____ enzymes in the liver. Important phase 2 metabolism is via ____. Patients with ____ dysfunction may have trouble excreting the compounds.
CYP, glucuronidation;
renal
what are the three opioid receptors? which one do most opioids act on?
mu, kappa, delta;
mu
the mu-opioid receptor gets activated by what endogenous compound?
endorphins
mu-opioid receptors are expressed at high concentrations in the brain and ___. this explains the very common side effect of ____.
GI;
constipation
Other side effects of opioids:
respiratory ____ due to action in the ___. ____ (eyes), CNS ____, ____ (skin), addiction
depression, brain stem;
miosis;
depression;
pruritis
what is the natural ligand for kappa receptors?
dynorphin
the problem with kappa agonists is that they produce strong ____. however, kappa receptors may play a strong protective role in ____
dysphoria;
addiction
what drug is a kappa-opioid receptord agonist and a mu opioid receptor antagonist?
pentazocine
butorphanol, nalbuphine, and buprenorphine are ____ receptor agonists and ____ receptor partial agonists
kappa;
mu
what is the natural ligand for delta opiod receptors?
enkephalins
delta-opioid receptors are upregulated during _____ stimulation
chronic;
potential use for chronic pain
what kind of receptors are mu-opioid receptors? binding causes ….
Gi;
inhibition of cAMP production
binding of opioid receptors activates ____ channels causing hyperpolarization. is this pre or post synaptic
GIRK (g-protein activated inwardly rectifying K channels);
post
binding of opioid receptors causes closure of ____ channels, inhibiting ___ release. pre or post synaptic?
calcium;
NT;
pre
tramadol is a ____ ____ agonist. it also inhibits what?
weak opioid;
serotonin, NE reuptake
tramadol is used in management of mild ____ pain
neuropathic
meperidine is used to treat ____. however, it has a toxic metabolite that is ___ toxic.
rigors;
neuro ie tremors, seizures, etc
methadone and levorphanol both block ____ receptors, making them clinically useful in chronic pain
NMDA (its upregulated)
methadone can cause what unwanted side effect?
what sort of half life does it have?
prolonged QT;
long AF
fentanyl, sufentanil, and remifentanil have a _____ onset. they are used for ____
fast;
surgery
postop/epidurally, what 2 opioids are used
hydromorphone, morphine
oxycodone, hydrocodone, oxycontin, and zohydro are used during management of pain because of _____
oral bioavailability
morphine is used to treat terminal cancer pain because of ____
cost (and not worrying about addictiveness)
what is senna/what does it do?
increases GI motility by promoting contraction;
used for constipation
polyethylene glycol (mirolax) and docusate are both ____
stool softeners
____ restricted opioid ____ have become a major strategy for dealing with opioid induced constipation
peripherally, antagonists;
ie alvimopan, methylnaltrexone
opioids release _____ from mast cells –> itchiness
histamine
tolerance does not develop for ___ and ___
miosis, constipation
opioids cause persistent _____ of adenylyl cyclase. in response, the cell ____ AC
`inhibition;
upregulates
upregulation of AC causes an increase in ____, leading to cellular ____ to the opioid effect
cAMP;
tolerance
in addition to an increase in cAMP, the cells increase expression of _____ involved in pain transmission. in the abscence of an opioid, both of these factors cause the patient to experience _____
receptors;
hyperalgesia
what should you do if a patient has opioid induced hyperalgesia
switch opioid class
or use methadone
interaction with ____ proteins (in addition of GPCR) may be the cause of constipation and respiratory depression
beta-arrestin
take great care in giving opioids to patients with seizure, ____, or ____ disorders
hepatic, respiratory
meperidine can cause _____ when administered with certain other drugs
serotonin syndrome (ie if with MAO or SSRIs)
2 types of opioid dependence? which occurs in all chronic users?
physical dependance, psychological;
physical occurs in all
what drug is used to treat opioid withdrawl in addiction therapy? what is it’s mechanism of action on the mu receptor?
buprenorphine; partial agonist
if a patient is already using a full agonist, buprenorphine will work as a ____ and can cause ____
antagonist, withdrawl
