EXAM 2 Opioid analgesics and antagonists Dr. Pond

Question 1

Which opioid receptors are primarily found in the area of nociception and reward?

Answer 1

Mu (μ) receptors
analgesia, reward (euphoria)!!!, sedation, respiratory
depression, miosis, inhibition of GI motility, modulation of hormone release

Delta (δ) receptors
-> Mediate analgesia and modulation of hormone release

Question 2

How are Kappa (κ) receptors: from the others?

Answer 2

-Unique anatomical distribution and unique pattern of physiologic action

-produces dysphoria (opposite of mu receptor)
-Increase psychotomimesis (hallucinations, delusions)
-also causes sedation, and slow GI transition

Question 3

Target of endogenous opioid peptides

Answer 3

endorphins (large peptide) -> mu receptors
enkephalins (5 AS) -> delta receptors
dynoprhines (dynorphin A and B) -> kappa receptors

but all peptides bind to all receptors with some affinity

Question 4

What are the differences between the enkephalins?

Answer 4

Tyr-Gly-Gly-Phe-…

5-AS-peptide
Met-enkephalin
Leu-enkephalin

Question 5

What is the name of the newly discovered opioid peptide?

Answer 5

Orphanin FQ or nociceptin
-> binding ORL1

Question 6

What is the propeptide from which endorphins are derived?

Answer 6

Pro-opiumelanocortin -> ß endorphin

-> also contains ACTH: adrenocorticotropic hormone (stimulates the release of cortisol)

Question 7

What type of receptors are opioid receptors?
Metabotropic or ionotropic?

Answer 7

Metabotropic -> interacts with ion channels and changes the memrabne potential
->interact with enzymes (adenylate cyclase)

Question 8

What are the effects of opioid receptors?

Answer 8

-inhibit adenylate cyclase (blocks: ATP -> cAMP conversion)
-activation of K+ channels (IPSP) on postsynaptic neuron
-inactivation of voltage-gated Ca2+-channels axoaxonic (blocking NT release)

-> inhibitory effect

Question 9

Where in the pain transmission are opioid receptors located?

Answer 9

-Primary nociceptors
-Secondary afferent neurons within the dorsal horn of SC
-Tertiary afferent neurons of the thalamus
-Cerebral cortex (target of thalamic neurons)

Question 10

How do opioids work on the descending pathway?

Answer 10

it inhibits the inhibitor (GABA) of the descending (inhibitory) pathway

GABA would inhibit the descending pathway -> but it blocked by opioids

opioids blocks voltage gated Ca2+channels and prevents GABA release

Question 11

What is the primary reward pathway in the brain?

Answer 11

mesolimbic dopamine pathway

VTE (reward) to nucleus accumbens (reward)

Question 12

What are the functions of endogenous opioids?

Answer 12

-mediate stress-induced analgesia (ACTH is produced together with ß-endorphin)

-may contribute to the regulation of appetite drives (for food, water, or sex), endocrine function, and perhaps memory