Lecture 9/10- Opioids Flashcards
What is the definition of Analgesics?
Reduction of pain
What is the definition of anaesthesia?
Loss of sensation
What are narcotic analgesics?
Reduction of pain without loss of sensation but promotes sense of relaxation/sleep
Overdoses lead to comas/death
What are opiates?
Extract of opium poppy plant, and substances are directly derived from opium
What is produced after altering natural narcotics?
Related semisynthetic and synthetic compounds
What is the last stage of opium alteration?
Endogenous peptides acting on same receptors (opioid)
What are acute actions of opioids?
Analgesia
Respiratory depression
Euphoria
Decreased blood pressure
Reduced sex drive
What are some withdrawal symptoms of opioids?
Pain/ irritability
Dysphoria/ depression
Insomnia
Increased blood pressure
Hyperthermia
What are the 3 aspects of the molecular structure of opioids?
Heroin
Codeine
Naloxone
What is the molecular structure of heroin?
Added acetyl group to morphine structure w/ more lipophil.
Crosses blood-brain barrier more quickly and has strong high/euphoria.
In the brain, heroin is converted to morphine.
What is the molecular structure of Codeine?
Less analgesic, but also less die effects and less addictive
but still a very potent cough suppression.
What does Naloxone do?
Opioid receptor antagnist?
What is the history of opioids?
Medical use eg pain/coughing
Recreational use eg euphoria
What is the current opinion of Opioids?
Medical use is restricted and recreational is illegal
What is the opioid epidemic?
-High levels of opioid use esp. in USA -Opioids are main cause of overdose deaths in both US and UK, in UK 51% of all drug poisoning deaths were from opioids.
What are symptoms of opioid overdose?
Respiratory depression, hypothermia, Stupor (unresponsiveness)
How can opioid overdose be treated?
Opioid antagonist naloxone
What the 4 types of opioid receptor endogenous ligand?
Endomorphins
Enkephalins
Dynorphins
Nociceptin/orphanin
What is the endogenous ligand endomorphin?
Most commonly acted upon by opioid receptors.
-Widely distributed in brain eg thalamus, striatum, brain stem, hippocampus
-Has variety of effects eg analgesia, cardiovascular/respiratory depression.
What is the endogenous ligand Dynorphins?
Selectively act on kappa opioid receptor which mediates effects opposite to opioid receptor
Found in pituitary gland, hypothalamus
-Neuroendocrine function, water balance, temperature control
What protein are opioid receptors coupled up to?
Opioid receptors are G-protein coupled receptors
What does activation of opioid receptors do?
Inhibit neural activity/ neurotransmitter release of neurons carrying opioid receptor
What are the 3 ways opioid receptors inhibit neural activity?
Postsynaptic inhibition
Axoaxonic inhibition
Presynaptic auto receptors
What is postsynaptic inhibition?
Opioid receptors on post synaptic neuron leads to g-protein activation which opens potassium channel which inhibits neuron.
What is Axoaxonic inhibition?
Closes calcium channels which reduces neurotransmitter release as calcium influx into presynaptic terminal triggers neurotransmitter release
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
What is presynaptic auto receptors?
Inhibition of neurotransmitters release from presynaptic terminal.
What is chronic pain?
Pain that lasts or recurs for longer than 3 months; can be symptom or disease in itself
What are the 2 types of pain pathways?
Ascending
Descending
What is Nociception?
The neural process of encoding noxious stimuli eg stimuli causing tissue damage.
What happens in the Ascending pain pathway?
Dorsal horn of Spinal cord, Primary sensory neurons (PSN) in dorsal root ganglion (DRG).
Deals with first/fast and late/slow pain
What is First/fast pain in the ascending pain pathway?
PSNs with Adelta fibres -> Somatosensory cortex
What are the 2 ways opioid inhibit pain processing and what does it only apply to?
- Opioids disinhibit a descending pain pathway that inhibits pain.
- Opioids inhibit signal transmission in the ascending pain pathway.
Only applies to acute pain
What is late/slow pain in ascending pain pathways?
PSNs with C fibres -> Other cortical/sub cortical areas
What happens in the Descending pain pathway?
Originate in midbrain regions incl periaqueductal grey and inhibit pain processing.
Modulates experience with pain
What method can we use to measure levels?
Microdialysis can be used to measure if opioid administration increases dopamine release in nucleus accumbens
How do rewards affect dopamine transmission?
Rewards activate meso-corticolimbic dopamine transmission.
How do opioids increase dopamine release in nucleus accumbens?
Disinhibition of dopaminergic neurons in the VTA: opioids stimulate opioid receptors of GABA neurons, inhibiting GABA release by these neurons, thereby allowing an increase of dopaminergic VTA neurons.
What is Opioid modulation of meso-corticolimbic dopamine system?
Opioids can increase NAC dopamine release via mu-opioid receptors in the VTA.
-Opioids with preferential action on kappa-receptors can act presynaptically on dopamine terminals in NAC to reduce dopamine release.
What is the difference between reward and pleasure
Reward= something you want/desire
Pleasure= feeling of liking
What is the Nucleus accumbens shell?
Stimulation of opioid receptors increases ‘liking’, whereas stimulation of dopamine receptors reduces ‘liking’
What 2 adaptations created by repeated opioid use affect dependence?
Tolerance
Lt compensatory changes
What are the tolerance changes due to repeated opioid use?
Repeated use leads to acute effects which can lead to higher doses or stronger opioids
What are the LT compensatory changes due to repeated opioid use?
In the neural mechanisms, the response to repeated opioid use can lead to withdrawal symptoms w/o continued use.
What are the changes over time for prescription opioids?
-Since the late 90s early 2000s, heroin dependent patients in the US have mainly initiated opioid abuse with a prescription opioid.
-More recently, with reduction in supply of prescription opioids, heroin again gains in importance as initiating drug
What is detoxification?
Usually assisted by substitution with a long-acting opioid drug (methadone or buprenorphine) which has lower highs and less pronounced withdrawal symptoms
Reduces mortality from overdoses
What is the negative effect of detoxification?
Substitution drugs can have adverse effects and can interfere with normal life
What does treatment for full abstinence do?
Treatment for full abstinence w/ opioid antagonist (naloxone) will make opioid administration ineffective but requires highly motivated patients.
