Opioid Analgesics 1

Question 1

What are the general indications for opiates?

Answer 1

• Moderate to severe dental pain - that cannot be managed effectively by NSAIDS
• Those whom NSAIDS are contraindicated

Question 2

What term is used to describe opiates, their antagonists, and the receptors stimulated by opioid drugs?

Answer 2

Opioids

Question 3

How can opioids be classified?

Answer 3

• Mechanism of action:
  
  • Agonists, partial agonists, mixed opioids (agonists/antagonists), antagonists
• Chemical structure
• Degree of efficacy that they produce

Question 4

What are opioids mechanism of action?

Answer 4

• They bind to receptors in both CNS and spinal cord
• Produce altered perception of pain reaction

Question 5

True or false: opioid receptors that mediate specific pharmacologic effects and adverse reactions are stimulated to varying degrees by individual opioids?

Answer 5

True

Question 6

Where do opiates have their analgesic effect?

Answer 6

On the descending pain-modulating circuit - where there’s a lot of endogenous opioid peptides

Question 7

Where do systemic opiates produce analgesia?

Answer 7

At widely distributed sites throughout the CNS

Question 8

In the pain modulatory system, what neurotransmitter is used?

Answer 8

Serotonin

Question 9

What activates the descending pathway circuit of pain?

Answer 9

• Noxious stimuli
• Pain
• Pyschological factors (placebo responders)
• Opioids

Question 10

The analgesia system is mediated by what 3 major componenets, where chemical mechanisms of opioid analgesics will take place?

Answer 10

1. Periaquaductal grey matter (midbrain)
2. Nucleus raphe magnus (medulla)
3. Pain inhibitory neurons (dorsal horns of the spinal cord)

Question 11

In addition to the opiate receptors - what other kind of receptors or connections are there in the descending pathways?

Answer 11

Noradrenergic and serotonergic receptors

Question 12

Which projections are Serotonergic? And what are they highly sensitive to?

Answer 12

Projections from the periaqueductal gray matter (PAG) and RVM (rostroventral medulla)

Highly sensitive to morphine

Question 13

What projections are noradrenergic?

Answer 13

Projections from the dorsolateral pons - application of Norepinephrine to spinal cord blocks noxious stimuli in dorsal horn

Question 14

What are the 3 groups of endogenous opioids?

Answer 14

1. Endophins
2. Enkephalins
3. Dynorphins

Question 15

What 3 different receptors do the endogenous opioids act through?

Answer 15

1. Mu
2. Delta
3. Kappa

They are G protein-coupled receptors

Question 16

Where are the endogenous opioid peptides produced?

Answer 16

In the pituitary gland and the hypothalamus

Question 17

The endophrins cross-top in the limbic system, what is an indication of this?

Answer 17

When people get emotional when they take opioids

Question 18

Which endogenous opioid is expressed in cells in the arcuate nucleus of the hypothalamus and in the brainstem, act via mu and influences appetite and sexual behavior?

Answer 18

Beta-endorphins

Question 19

Which endogenous opioid is widely distributed throughout the brain and acts via mu and delta?

Answer 19

Enkephalins

Question 20

Which endogenous opioid is found in the spinal cord and in many parts of the brain, including the hypothalamus, acts via kappa?

Answer 20

Dynorphins

Question 21

What are endorphins derived from and what do they produce?

Answer 21

Derived from precursor molecules and produce opiate-like effects.

Question 22

Where are endorphins found?

Answer 22

In the gut (pancreatic islet cells), sympathetic nervous system, adrenal medullary chromaffin cells, CNS

MU receptors

Question 23

Naturally occuring endorphins as well as opioid medications act via the mu receptors found in where?

Answer 23

The gastrointestinal tract - why you can get constipation from opioids (slows down the GI tract)

Question 24

What are the first isolated compounds on enkephalins?

Answer 24

• Leucine-enkephalin
• Methionine-enkephalin

Question 25

What do enkephalins act like?

Answer 25

Mimic opiate activity - weaker analgesics

Question 26

Enkephalins may be responsible for what?

Answer 26

Producing analgesia in placebo responders and acupuncture - act via mu and delta

Question 27

What causes the side effects of opioid use (respiratory depression, pupil constriction, decrease body temp and gut motility)?

Answer 27

Opiate receptors found in tissues outside the CNS - that are NOT involved in analgesia

Question 28

What kind of scan can you do to show opiate receptor activity in the brain?

Answer 28

PET - positron emission tomography

Question 29

Recognition site of receptor is highly _________? And the analgesic action of opioid drugs is stereospecific, what isomer have biological activity?

Answer 29

Specific

Levo-isomers have biological activity

Question 30

What are the 5 subtypes of opioid receptors?

Answer 30

1. Mu
2. Delta
3. Kappa
4. Epsilon
5. Sigma (no longer classified as opioid receptor: responds to NMDA agonists - extas)

Question 31

When you want good analgesia, what receptor do you have to bind to? What is bad about that?

Answer 31

Mu1 - it’s the dependence receptor

Question 32

What are the functions of Mu1 and Mu2?

Answer 32

• Mu1
  
  • Supraspinal analgesia
  • Euphoria
  • Physical dependence
• Mu2
  
  • Respiratory depression

Question 33

When patients take opiates for pain, do they automatically become dependent?

Answer 33

No- once the pain wears off (after 3 days) then they continue taking the opiates and the dependence comes in with the same Mu1 receptors

Question 34

What’s the tradeoff for opioid receptor function of MU receptors?

Answer 34

• Drugs that bind to Mu exhibit the best analgesic properties - but they have the risk of addiction and respiratory depression

Question 35

What happens if you decrease the drug’s affinity for Mu?

Answer 35

Then you decrease the risk for addiction, but you also decrease the level of analgesia.