Lecture 5 - Opioids

Question 1

pain’s primary function is to serve as a ____ system.

Answer 1

warning

Question 2

central pain sensitization involves activation and recruitment of ____ and ____ surrounding nerve endings responsible for pain transmission

Answer 2

astrocytes, microglia

Question 3

mediators released by glial cells feed into the central sensitization of ___ and ____ receptors, which are important in pain signalling

Answer 3

AMPA, NMDA

Question 4

key brain regions expressing opioid receptors are the ____, the rostral ventral medulla, and the _____

Answer 4

Periaqueductal gray, DRG

Question 5

opium contains two types of alkaloids:

Answer 5

phenanthrenes, benzylisoquinolines

Question 6

some opioids, including methadone, mepiridine, and fentanyl do not have the ____ backbone. this may be beneficial when conisidering ____ ____

Answer 6

phenanthrene, opioid rotation

Question 7

partial agonism of Mu-opioid receptors is conferred by ____ side groups such as in naloxone

Answer 7

bulky

Question 8

Most opioids get metabolized by ____ enzymes in the liver. Important phase 2 metabolism is via ____. Patients with ____ dysfunction may have trouble excreting the compounds.

Answer 8

CYP, glucuronidation;

renal

Question 9

what are the three opioid receptors? which one do most opioids act on?

Answer 9

mu, kappa, delta;

mu

Question 10

the mu-opioid receptor gets activated by what endogenous compound?

Answer 10

endorphins

Question 11

mu-opioid receptors are expressed at high concentrations in the brain and ___. this explains the very common side effect of ____.

Answer 11

GI;

constipation

Question 12

Other side effects of opioids:

respiratory ____ due to action in the ___. ____ (eyes), CNS ____, ____ (skin), addiction

Answer 12

depression, brain stem;
miosis;
depression;
pruritis

Question 13

what is the natural ligand for kappa receptors?

Answer 13

dynorphin

Question 14

the problem with kappa agonists is that they produce strong ____. however, kappa receptors may play a strong protective role in ____

Answer 14

dysphoria;

addiction

Question 15

what drug is a kappa-opioid receptord agonist and a mu opioid receptor antagonist?

Answer 15

pentazocine

Question 16

butorphanol, nalbuphine, and buprenorphine are ____ receptor agonists and ____ receptor partial agonists

Answer 16

kappa;

mu

Question 17

what is the natural ligand for delta opiod receptors?

Answer 17

enkephalins

Question 18

delta-opioid receptors are upregulated during _____ stimulation

Answer 18

chronic;

potential use for chronic pain

Question 19

what kind of receptors are mu-opioid receptors? binding causes ….

Answer 19

Gi;

inhibition of cAMP production

Question 20

binding of opioid receptors activates ____ channels causing hyperpolarization. is this pre or post synaptic

Answer 20

GIRK (g-protein activated inwardly rectifying K channels);

post

Question 21

binding of opioid receptors causes closure of ____ channels, inhibiting ___ release. pre or post synaptic?

Answer 21

calcium;
NT;
pre

Question 22

tramadol is a ____ ____ agonist. it also inhibits what?

Answer 22

weak opioid;

serotonin, NE reuptake

Question 23

tramadol is used in management of mild ____ pain

Answer 23

neuropathic

Question 24

meperidine is used to treat ____. however, it has a toxic metabolite that is ___ toxic.

Answer 24

rigors;

neuro ie tremors, seizures, etc

Question 25

methadone and levorphanol both block ____ receptors, making them clinically useful in chronic pain

Answer 25

NMDA (its upregulated)

Question 26

methadone can cause what unwanted side effect? | what sort of half life does it have?

Answer 26

prolonged QT; | long AF

Question 27

fentanyl, sufentanil, and remifentanil have a _____ onset. they are used for ____

Answer 27

fast; | surgery

Question 28

postop/epidurally, what 2 opioids are used

Answer 28

hydromorphone, morphine

Question 29

oxycodone, hydrocodone, oxycontin, and zohydro are used during management of pain because of _____

Answer 29

oral bioavailability

Question 30

morphine is used to treat terminal cancer pain because of ____

Answer 30

cost (and not worrying about addictiveness)

Question 31

what is senna/what does it do?

Answer 31

increases GI motility by promoting contraction; | used for constipation

Question 32

polyethylene glycol (mirolax) and docusate are both ____

Answer 32

stool softeners

Question 33

____ restricted opioid ____ have become a major strategy for dealing with opioid induced constipation

Answer 33

peripherally, antagonists; ie alvimopan, methylnaltrexone

Question 34

opioids release _____ from mast cells --> itchiness

Answer 34

histamine

Question 35

tolerance does not develop for ___ and ___

Answer 35

miosis, constipation

Question 36

opioids cause persistent _____ of adenylyl cyclase. in response, the cell ____ AC

Answer 36

`inhibition; | upregulates

Question 37

upregulation of AC causes an increase in ____, leading to cellular ____ to the opioid effect

Answer 37

cAMP; | tolerance

Question 38

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 _____

Answer 38

receptors; | hyperalgesia

Question 39

what should you do if a patient has opioid induced hyperalgesia

Answer 39

switch opioid class or use methadone

Question 40

interaction with ____ proteins (in addition of GPCR) may be the cause of constipation and respiratory depression

Answer 40

beta-arrestin

Question 41

take great care in giving opioids to patients with seizure, ____, or ____ disorders

Answer 41

hepatic, respiratory

Question 42

meperidine can cause _____ when administered with certain other drugs

Answer 42

serotonin syndrome (ie if with MAO or SSRIs)

Question 43

2 types of opioid dependence? which occurs in all chronic users?

Answer 43

physical dependance, psychological; physical occurs in all

Question 44

what drug is used to treat opioid withdrawl in addiction therapy? what is it's mechanism of action on the mu receptor?

Answer 44

buprenorphine; partial agonist

Question 45

if a patient is already using a full agonist, buprenorphine will work as a ____ and can cause ____

Answer 45

antagonist, withdrawl