Opioids Flashcards
drugs that reduce pain without producing unconsciousness
narcotic analgesics
The main active ingredient in opium
morphine
Opium has other molecules like ____, ____ and ____, and the small differences in structure determine the _____ and side effects
codeine, thebaine, narcotine, effectiveness
heroin was made by adding two ____ groups to morphine, making it more _____ soluble. It reaches the brain _____, making it more ____ than morphine when injected due to increased ______. It is converted to _____ in the brain. Some opium derivatives are _______, or modified versions of opium ingredients. Other narcotics are entirely ____ and may have very different chemical structures
acetyl, lipid, faster, potent, bioavailability, morphine, semi-synthetic, synthetic
opioid receptors were first discovered using ______ binding assays, before the ____ ligands were identified. Opioid receptors are also in the ____. Selective ones were used to identify receptor subtypes: _____, ____, ____ and _____. Receptor subtypes have distinct _____ in the brain and spinal cord, suggesting they mediate a wide variety of effects. All are ____ ______ metabotropic receptors that inhibit ____ ______
radioligand, endogenous, gut, mu, delta, kappa, NOP-R, distributions, Gi protein-linked, adenylyl cyclase-cAMP
The mu receptor has a high affinity for ____, and regional distribution reflects its effects. Receptors in the medial ______, ____ ____, _____, _____, and ___ ____ mediate the analgesia. Receptors in the ____ mediate cardiovascular / respiratory control, ____ control, and nausea / vomiting. Receptors in the ___ and striatum have a role in sensorimotor integration.
morphine, thalamus, periaqueductal grey, raphe, LC, spinal cord, brainstem, cough, thalamus
mu receptors in the NAcc mediate feeding _____ _______. They mediate pleasurable aspects of ____ foods. Blocking these receptors results in reduction of ____ pleasure. Opioids are also released during _____ encounters
positive reinforcement, fatty, hedonic, sexual
the delta receptor is predominately in _____ structures. The locations suggests roles in ______, motor _____, ________ and _____ function. Reduced delta activity causes ____ in animals. A considerable number of areas overlap with ____ receptors, suggesting modulation of analgesia.
forebrain, olfaction, integration, reinforcement, cognitive, anxiety, mu
the kappa receptor are located in the _____, _____ and ______. They may participate in the regulation of _____ perception, _____ motility, and ______. They were initially identified by binding to ______
striatum, amygdala, hypothalamus, pain, gut, dysphoria, ketocyclazocine
an opioid analog that produces hallucinations and dysphoria
ketocyclazocine
Nociceptin / orphanin FQ receptors are widely distributed in the ____, ___ areas, thalamus, ___ ___ and spinal cord. The receptors are similar to other opioid receptors but do not ____ opioid drugs. Their locations suggest a role in _____, feeding, ____, ____ function, ____ and neuroendocrine regulation. Activation in the ___ _____ produces less _____ vs mu receptors but also has minimal ____ potential and causes less _____ ______. Above the spinal cord, these receptors can produce _______
cortex, limbic, raphe nuclei, bind, analgesia, learning, motor, reward, spinal cord, analgesia, abuse, respiratory depression, hyperalgesia
peptide transmitters that bind to opioid receptors were discovered in the _____ and was called _____. Multiple peptides that activate these receptors were later discovered and called _______.
1970s, enkephalin, endorphins
endogenous opioid peptides are synthesized from larger ____ peptides which are ___ into smaller peptide transmitters in the _____. These _______ contain the amino acid sequence for both endogenous opiates and other transmitters.
precursor, cleaved, terminal, propeptides
some opioid transmitters are released via long _____ projection systems, while other are released by ______ circuit neurons
axonal, local
different variants of endogenous peptides exist such as _____ or ___, met or _________. Endogenous opioid peptides are often _____ with other NTs in the nerve terminals and can be simultaneously released with ____ or ______.
dynorphin-A, B, leu-enkephalin, co-released, Glutamate, GABA
endogenous opiates are not _____ for a receptor subtype, but instead show a _____ preference. the _____ receptor is preferentially activated by endorphins and somewhat selectively activated by ______. The delta receptor is preferentially activated by ____ and _____. The Kappa receptor is preferentially activated by ______.
selective, relative, mu, endomorphins, endorphins, enkephalins, dynorphins
a class of endogenous opiate; propeptide has not been isolated yet
endomorphins
opiates inhibit neural activity in several ways. In postsynaptic inhibition, receptors activate a ____ protein that opens _____ channels causing ______. They can also use presynaptic ________ that activate G proteins that close ____ channels, reducing transmitter _______. They can also use presynaptic autoreceptors to reduce the release of ______ NTs, resulting in a reduced postsynaptic effect
G, K+, hyperpolarization, heteroreceptors, Ca2+, release, co-localized
a partial agonist that is less potent than morphine but also has the risk of respiratory depression and dependence
buprenorphine
opioid antagonists that are fast acting and used for opioid overdose as they prevent or reverse the effects of opioid drugs
naloxone, naltrexone
____ ____ antagonists are harder to dose and disrupt regular functions by opioids
non competitive
endogenous opioids and opioid drugs bind to receptors and inhibit ____ _____ transduction at multiple sites. Within the spinal cord, (_____ ____), opioid _____ can inhibit pain projection neurons. Opioids can also activate _____ pathways originating in the brain that project to the spine to either ______ inhibit pain projection neurons, or inhibit _____ interneurons that synapse onto pain projection neurons.
pain signal, spinal analgesia, interneurons, descending, directly, excitatory
opioid drugs can work in the brain or the _____, and the net effect is to reduce the spinal cord neuron’s activity. Opioids activate two descending pain-inhibiting pathways originating in the ______ ______. This area is rich with opioid peptides and _____. Stimulation induces ____ that can be attenuated by opioid _______. Opioid projections from this area _____ _____ and ____ ____ descending projections that suppress pain signals in the spinal cord. It is very effective because it targets multiple _____.
spine, periaqueductal grey, receptors, analgesia, antagonists, disinhibit, raphe, locus coeruleus, sites
Opioid activity occurs in other _____ locations such as the ____, ____ and ____ areas, which may mediate ______, ______ and or _____ components of pain.
supraspinal, sensory, limbic, hypothalamic, emotional, autonomic, neuroendocrine
_______ can activate the endogenous opioid system, while ____ suppresses this effect.
acupuncture, nalaxone
the central effects of opioids are related to the ___ and rate of _____. Therapeutic opioids are administered _____ or _____, resulting in slower absorption and are not as _____. Recreational opiates are often administered through more rapid means such as ____, ______ and ______.
dose, absorption, orally, intramuscularly, euphoric, snorting, subcutaneous, IV
At low / moderate doses, opiates produce pain ______, constricted _____, ____, inability to _____, and _____ sleep
relief, pupils, drowsiness, concentrate, dreamy
At higher doses, opiates produces an abnormal state of ____ or _____
elation, euphoria
At the highest doses, opiates have ____ effects that may lead to ____ and _____. This is due to suppression of the brainstem’s ___ ______.
sedative, unconsciousness, death, respiratory centre
Other aversive effects of opiates include ____, _____, _____, ____ and ____ (gut). Compared to other drugs such as alcohol, tobacco and psychostimulants, the ___ ___ toxic effects of opiates are less ______ except for the risk of ____ and issues with ____ administration. Recent work suggests that long-term ____ deficits are associated with chronic ____ abuse
dysphoria, restlessness, anxiety, nausea, constipation, long term, severe, overdose, IV, cognitive, heroin
Animals readily self-administer opiates in a similar ____ to humans. Direct stimulation of the _____ receptors underlies most of the pleasurable and some of the ____ properties of these drugs, while kappa _____ are aversive.
pattern, mu, reinforcing, agonists
opioids also activate the _____ DA pathway and this also contributes to _____ ______. Mu receptor activation inhibits ____ neurons in the _____, which leads to ______ of DA neuron firing and increase of _____ release. In contrast, kappa receptor activation on DA terminals in the _____ reduces DA release, which may mediate their _____ effects
mesolimbic, opioid reinforcement, GABA, VTA, disinhibition, DA, NAcc, aversive
Tolerance to different effects of opioids develop at different _____. Tolerance to _______ and ______ develops relatively quickly, while tolerance to _____ or ___ ____ develops more slowly.
rates, analgesia, pleasure, constipation, pupil dilation
tolerance to opioids is primarily _______, meaning the body and brain are engaging in _____ activity to maintain homeostasis. ___ ___ also occurs
pharmacodynamic, compensatory, cross tolerance
withdrawal from opioids produces a rebound ______ of CNS functions, as they are the _____ of the acute action of opioids. This includes ____ and _____, ______ and hostility. They are extremely unpleasant but not __ ____. Symptoms are typically the worst of the _____ or ___ day and dissipate after ____ days. Withdrawal severity varies by the type of opioid drug. ____ and ____ have severe withdrawal symptoms, while ___ and ____ have less severe symptoms.
hyperactivity, opposite restlessness, insomnia, fearfulness, life threatening, 2nd, 3rd, 7, morphine, heroin, methadone, buprenorphine
re-administering the same opioid drug or other opioids during withdrawal will ____ or ____ the symptoms.
reduce, eliminate
There are ____ reports of death by withdrawal symptoms
few
Withdrawal symptoms can be precipitated by opioid _______, either systemically or directly into certain brain _____.
antagonists, nuclei
Different brain systems mediate different aspects of withdrawal. Opioid antagonists in the ___ or _____ (hyperactivity) triggers _____ withdrawal in dependent rats. Contrarily, reducing ____ activity can reduce withdrawal ______. Infusions of antagonists in the _____ (hyperactivity) or _____ can precipitate aversive ______ effects of opioid withdrawal. This is tested in conditioned place _____, in which animals will avoid environments associated with _____ and spend more time in neutral environments
LC, PAG, physical, NE, severity, NAcc, amygdala, emotional, aversion, withdrawal
Tolerance / withdrawal to opioid drugs drugs can be observed at the ___ ____ level. In cell cultures, morphine inhibits synthesis of ______, With repeated treatment over ___ days, cells adapt by producing _____ of it. Removing the morphine or adding ______ can result in a rebound ______ in levels.
single cell, cAMP, 2, more, naloxone, increase
Morphine reduces the firing of ____ neurons but with repeated exposure, they ____ firing as an adaptation. Stimulating morphine _____ with naltrexone causes a rebound ____ in LC firing rate above normal levels. However, naltrexone alone in a _______ rat produces no difference in LC firing
LC, increase, withdrawal, increase, morphine-naive
