Lecture 13 - Opioids Flashcards
1
Q
What are opioids
A
- drugs that act at the opioid receptor
- have been used since ancient times
- still harvested from opium poppies
2
Q
Actions of opioids
A
- analgesia
- euphoria
- impaired cough reflex
- constipation
3
Q
Side effects of opioids
A
- respiratory depression
- nausea and vomiting
- dependence
- miosis
- pruritis
4
Q
Opioid receptor
A
- GPCR
- agonist action is inhibitory - causes K+ to leave the cell
- 3 kinds of receptors that all share the same intracellular signaling but different clinical respomse
- prevents neurotransmitter release
- also inhibits adenylyl cyclase
5
Q
K-opioid receptor
A
- produce analgesia
- also dysphoria, including hallucinations, and diuresis
- evidence suggests k-agonist are better in females than males
6
Q
- d-opioid receptor
A
- some analgesia
- activation may produce seizures
- receptors may not usually reside on the cell surface
7
Q
- u-opioid receptor
A
- strong analgesia, constipation, nausea, respiratory depressin, reduced cough reflex, tolerance and dependence
- most drugs target this reeptor
- naloxone and naltrexone are antagonists at the u-receptor
8
Q
Sites of opioid action for analgesia
A
- PAG
- spinal chord
9
Q
Sites of opioid action for euphoria
A
- NA
- VTA
10
Q
Site of opioid action for respiratory depression, antitussive, nausea/vomiting
A
- Medulla
11
Q
Endogenous opioids
A
- proenkephalin -> enkephalin (expressed in PAG)
- prodynorphin -> Dynorphin
- pro-opiomelanocortin -> b-endorphin
12
Q
Why does u-inhibition int he PAG activate the descending analgesic pathway
A
- u-receptor is extressed largely on GABA neuron
- inhibition of GABA neuron by morphine thus leads to reduced inhibition by GABA neurotransmitter and more release of neurotransmitters in spinal chord -> reduce release of substance P and glutamate -? Less excitable SC neurons
13
Q
Where else do opioids act
A
- Forebrain: lateral sensory system (thalamus, cortex), medial system emotional responses (limbic system)
- midbrain and brainstem: descending systems (PAG, raphe nuclei)
- spinal cord: sensory modulation (dorsal horn)
14
Q
How do opioids lead to euphoria
A
- dopamine is a catecholamine
- mesolimbic system is important for reward
- VTA-NA synaptic input
- opioids increase dopamine release in NA to produce reward and euphoria
- kappa receptors are on dopaminergic neurons ->will inhibit Dopa release -> dysphoria
15
Q
Opioid antagonists: Naloxone
A
- short acting
- low oral bioavailability
- used for reversal of opioid overdose
- used in combined therapy with agonist to reduce constipation
