Chapter 11 - Opioids

Question 1

analgesics vs anesthetics

Answer 1

anesthetics produce unconsciousness, analgesics do not

Question 2

cultivation and use of opiates

Answer 2

Opium is an extract of poppy plant, have been used recreationally for thousands of years, common in popular remedies until the 20th century

Question 3

what Act made narcotics illegal?

Answer 3

Harrison Act, passed in 1914. banned opiates and cocaine

Question 4

Opiate vs Opioid

Answer 4

Opiates are chemical compounds that are extracted or refines from natural plant matter ex.) Opium, Morphine, Heroin, cocaine. Opioids include both naturally and synthetically derived substances

Question 5

what is the principle active ingredient in opium?

Answer 5

Morphine, also contains codeine, thebaine, narcotine

Question 6

Why is heroin more potent than morphine?

Answer 6

Heroin is converted to morphine in the brain; when its injected it’s more potent bc it’s more lipid soluble and reaches the brain faster

Question 7

A molecule that binds to a receptor but produces less of a biological effect and has reduced risk of dependence

Answer 7

partial agonist

Question 8

A molecule that can prevent or reverse the effect of opioids, ex.) naloxone and nalorphine

Answer 8

neutral agonist

Question 9

Where do opioids have the most important effects?

Answer 9

CNS and gastrointestinal tract

Question 10

Opioids effect on the gastrointestinal tract

Answer 10

Opium and morphine have been used to treat diarrhea and can be life-saving in severe bacteria and parasitic diseases.
Constipation can be a side effect when used for pain management

Question 11

adverse and fatal effects of opioids

Answer 11

Adverse effects: dysphoria, restlessness and anxiety,
nausea and vomiting, sedative effects may lead to
unconsciousness; body temperature and blood
pressure fall; pupils become very constricted
Fatal effects: respiratory failure

Question 12

At high doses the effects of opioids on what area of the brain are responsible for deaths due to overdose?

Answer 12

respiratory center of the brainstem

Question 13

endogenous opioids are concentrated in areas related to

Answer 13

mood and pain

Question 14

How was competition for the receptor shown?

Answer 14

Naloxone’s blocking effects can be overcome by increasing
concentrations of morphine

Question 14

What are the four opioid receptor subtypes?

Answer 14

1. μ-receptor
2. δ-receptors
3. κ-receptors
4. NOP-R

Question 15

μ-receptor

Answer 15

high affinity for morphine; have wide distribution in the brain and spinal cord

Question 16

δ-receptors

Answer 16

predominantly found in forebrain structures; consistent with roles in modulation olfaction, motor integration, reinforcement, and cognitive function

Question 17

κ-receptors

Answer 17

found in the striatum and amygdala, hypothalamus and pituitary; may participate in regulation of pain perception, gut mobility, and dysphoria

Question 18

NOP-R

Answer 18

widely distributed in the CNS and PNS; receptor localization suggests a role in analgesia, feeding, learning, motor function, and neuroendocrine regulation

Question 19

From Box 11.1 - what features make an analgesic “better” than morphine?

Answer 19

PZM 21 has analgesic effects that last longer than morphine, with fewer side effects. It causes less constipation, less respiratory depression

Question 20

How are pain and stress regulation linked?

Answer 20

many types of stressors increase both CRF and POMC. CRF is released from the hypothalamus in response to stress, also causes rapid increase of POMC mRNA, POMC is a propeptide concentrated in areas related to pain modulation and mood.

Question 21

opioid receptor mediated changes are?

Answer 21

Inhibitory

Question 22

All four receptors are similar to proteins linked to what?

Answer 22

G proteins and second messenger (metabotropic)

Question 23

opioids affect levels of what second messenger, which increases significantly during withdrawal?

Answer 23

cAMP

Question 24

Postsynaptic inhibition

Answer 24

opens K+ channels - hyperpolarization

Question 25

Axoaxonic inhibition

Answer 25

closes calcium Ca2+ channels - decreases amount of transmitter released

Question 26

Presynaptic autoreceptors

Answer 26

reduce release of a co-localized transmitter

Question 27

Pain is divided into two components. What are they, and how do they differ in their signaling?

Answer 27

First pain - an immediate, sensory component Second Pain - emotional component

Question 28

What is a noxious stimuli?

Answer 28

a stimulus strong enough to threaten the body's integrity (cause damage to tissue)

Question 29

How do opioids inhibit pain transmission?

Answer 29

at spinal and supra-spinal levels, mimic endogenous opioids

Question 30

Opioids reduce transmission of pain signals at the spinal cord in two ways:

Answer 30

Inhibitory spinal interneurons release endorphins that inhibit activation of spinal projection neurons Descending modulatory pathways - inhibit projection neuron or excitatory interneuron, or excite inhibitory opioid neuron; most important pathway originates in the PAG in the midbrain

Question 31

Opioid activity also occurs in supra-spinal locations

Answer 31

including sensory areas, limbic structures, and hypothalamus; may be responsible for the emotional component of pain

Question 32

What does it mean that there was a “negative” correlation between opioid activity and pain scores?

Answer 32

PET imaging showed significant negative correlation between μ- opioid activity in the NAcc, amygdala, and thalamus and reported sensory pain scores.

Question 33

How do opioids affect dopamine signaling, and where?

Answer 33

Opioid drugs inhibit inhibitory GABA cells, increasing mesolimbic cell firing and DA release in the NAcc.

Question 33

Similar to alcohol withdrawal, withdrawal from opioids causes ____ because opioids generally ____ CNS activity

Answer 33

hyperactivity; depress

Question 34

How did opioid use become an epidemic?

Answer 34

misleading and aggressive marketing of OxyContin to doctors and patients by the maker, Perdue Pharma

Question 35

What are the current “street” options for the drug?

Answer 35

OxyContin, Heroin and counterfeit pills are now being adulterated with illicitly manufactured fentanyl, 50 times more potent than heroin

Question 36

What are the current treatments for opioid addiction?

Answer 36

Detoxification which can be assisted by long-acting opioids (methadone), electroacupuncture, methadone maintenance program, medication-assisted treatment