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