Chapter 11 - Opioids Flashcards
analgesics vs anesthetics
anesthetics produce unconsciousness, analgesics do not
cultivation and use of opiates
Opium is an extract of poppy plant, have been used recreationally for thousands of years, common in popular remedies until the 20th century
what Act made narcotics illegal?
Harrison Act, passed in 1914. banned opiates and cocaine
Opiate vs Opioid
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
what is the principle active ingredient in opium?
Morphine, also contains codeine, thebaine, narcotine
Why is heroin more potent than morphine?
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
A molecule that binds to a receptor but produces less of a biological effect and has reduced risk of dependence
partial agonist
A molecule that can prevent or reverse the effect of opioids, ex.) naloxone and nalorphine
neutral agonist
Where do opioids have the most important effects?
CNS and gastrointestinal tract
Opioids effect on the gastrointestinal tract
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
adverse and fatal effects of opioids
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
At high doses the effects of opioids on what area of the brain are responsible for deaths due to overdose?
respiratory center of the brainstem
endogenous opioids are concentrated in areas related to
mood and pain
How was competition for the receptor shown?
Naloxone’s blocking effects can be overcome by increasing
concentrations of morphine
What are the four opioid receptor subtypes?
- μ-receptor
- δ-receptors
- κ-receptors
- NOP-R
μ-receptor
high affinity for morphine; have wide distribution in the brain and spinal cord
δ-receptors
predominantly found in forebrain structures; consistent with roles in modulation olfaction, motor integration, reinforcement, and cognitive function
κ-receptors
found in the striatum and amygdala, hypothalamus and pituitary; may participate in regulation of pain perception, gut mobility, and dysphoria
NOP-R
widely distributed in the CNS and PNS; receptor localization suggests a role in analgesia, feeding, learning, motor function, and neuroendocrine regulation
From Box 11.1 - what features make an analgesic “better” than morphine?
PZM 21 has analgesic effects that last longer than morphine, with fewer side effects. It causes less constipation, less respiratory depression
How are pain and stress regulation linked?
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.
opioid receptor mediated changes are?
Inhibitory
All four receptors are similar to proteins linked to what?
G proteins and second messenger (metabotropic)
opioids affect levels of what second messenger, which increases significantly during withdrawal?
cAMP
Postsynaptic inhibition
opens K+ channels - hyperpolarization
Axoaxonic inhibition
closes calcium Ca2+ channels - decreases amount of transmitter released
Presynaptic autoreceptors
reduce release of a co-localized transmitter
Pain is divided into two components. What are they, and how do they differ in their signaling?
First pain - an immediate, sensory component
Second Pain - emotional component
What is a noxious stimuli?
a stimulus strong enough to threaten the body’s integrity (cause damage to tissue)
How do opioids inhibit pain transmission?
at spinal and supra-spinal levels, mimic endogenous opioids
Opioids reduce transmission of pain signals at the spinal cord in two ways:
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
Opioid activity also occurs in supra-spinal locations
including sensory areas, limbic structures, and hypothalamus; may be responsible for the emotional component of pain
What does it mean that there was a “negative” correlation between opioid activity and pain scores?
PET imaging showed significant negative correlation between μ- opioid activity in the NAcc, amygdala, and thalamus and reported sensory pain scores.
How do opioids affect dopamine signaling, and where?
Opioid drugs inhibit inhibitory GABA cells, increasing mesolimbic cell firing and DA release in the NAcc.
Similar to alcohol withdrawal, withdrawal from opioids causes ____ because opioids generally ____ CNS activity
hyperactivity; depress
How did opioid use become an epidemic?
misleading and aggressive marketing of OxyContin to doctors and patients by the maker, Perdue Pharma
What are the current “street” options for the drug?
OxyContin, Heroin and counterfeit pills are now being adulterated with illicitly manufactured fentanyl, 50 times more potent than heroin
What are the current treatments for opioid addiction?
Detoxification which can be assisted by long-acting opioids (methadone), electroacupuncture, methadone maintenance program, medication-assisted treatment
