Midterm 2 Flashcards
How AMPH (amphetamines) are absorbed?
injected, ingested, snorted or smoked
Onset is fastest by ___ < ___< ___<___
Onset is fastest by smoking < injection < snorting < ingesting
Ice is to ___ what ___ is to cocaine
Ice is to meth what crack is to cocaine
Ice is ___ ___, ___ meth that has a half life of about __ hours
Ice is HCI salt, smokeable meth that has a half life of about 12 hours
Meth high lasts ___ than cocaine
Meth high lasts much longer than cocaine
Liver ___ metabolizes meth and AMPH (amphetamine)
Liver CYP2D6 metabolizes meth and AMPH (amphetamine)
4-HA and nor-ephedrine are ___
4-HA and nor-ephedrine are stimulants
4-HA activates ___ ____ ____ ___ (TAAR), stimulates ___ release and inhibits ___ ___ (MAO)
4-HA activates trace amino associated receptor (TAAR), stimulates NE release and inhibits monoamine oxidase (MAO)
AMPH can be broken down into ___ and ____
AMPH can be broken down into 4-HA and nor ephedrine
TAAR is an intracellular ____
TAAR is an intracellular GPCR (G-protein-coupled receptor)
Monoamine oxidase (MAO) degrades monoamine ____ like ___, NE, ___
Monoamine oxidase (MAO) degrades monoamine NTs like DA, NE, 5HT
AMPH/METH excretion via
kidney, sweat, saliva
Acute effects of AMPH: ___, energy, ___, grandiosity, ____ appetite
Acute effects of AMPH: euphoria, energy, aggression, grandiosity, decreased appetite
AMPH is sympathomimetic meaning that NE release is ____
AMPH is sympathomimetic meaning that NE release is increased
An acute effect of AMPH is that 5HT release ___ causing delusional parasitosis (i.e. ____) and ___ ___
An acute effect of AMPH is that 5HT release increases causing delusional parasitosis (i.e. bugs under skin) and perceptual disturbances
An acute effect of AMPH is that DA is ___ causing ___ activity
An acute effect of AMPH is that DA is increased causing locomotor activity
Punding
occurs at high doses of AMPH, repetitive meaningless behaviours; also common in Parkinson’s patients
AMPHs elevate __, ___, __ availability
AMPHs elevate DA, NE, 5HT availability
AMPH does not require ____-ergic ___ firing, unlike cocaine
AMPH does not require DA-ergic neuron firing, unlike cocaine
DAT transporter ___ meth into nerve ____
DAT transporter brings meth into nerve terminals
Meth can enter via DAT transporter and by ___
Meth can enter via DAT transporter and by diffusion
VMAT (vesicular monoamine transporter) pumps meth into ___ ___
VMAT (vesicular monoamine transporter) pumps meth into storage vesicles
Synaptic mechanism of AMPH (that results in spike of DA)
1) AMPH binds DAT and enters terminal (also defuses in)
2) MAO (monoamine oxidase) degrades cytoplasmic DA, NE, 5HT
3) VMAT transports AMPH into storage vesicles
4) DA is displaced from vesicles into cytoplasm
5) MAO bound by AMPH cannot degrade DA
6) AMPH-TAAR complex and cytoplasmic DA build-up reverse DAT
7)DA leaks across terminal membrane into synapse too
8) Resulting DA spike in synapse causes post-synaptic cell activation
AMPH mechanisms differ from cocaine for 2 main reasons:
1) ___ structure that allows ___ to complete transport
2) AMPH activates ___ ____ ____ called TAAR - TAAR activates ____-____ signalling that targets ___ which reverses transport
AMPH mechanisms differ from cocaine for 2 main reasons:
1) smaller structure that allows transporter to complete transport
2) AMPH activates additional intracellular GPCR called TAAR - TAAR activates phosphorylation-dependent signalling that targets DAT which reverses transport
Adverse effects of acute use of AMPH:
- ___ from contaminants
- combining with other drugs can ___ ____ effects
Adverse effects of acute use of AMPH:
- poisoning from contaminants
- combining with other drugs can enhance stimulant effects
Tolerance to AMPH is caused by ___, __, and ____ depletion via displacement of these NTs from terminals
Tolerance to AMPH is caused by DA , 5HT , and NE depletion via displacement of these NTs from terminals
Inhibition of tyrosine hydroxylase enzyme ____ synthesis of DA and NE
Inhibition of tyrosine hydroxylase enzyme reduces synthesis of DA and NE
Acute dosing reduces ___ function, which causes subsequent dose to have greatly reduced effects
Acute dosing reduces DAT function, which causes subsequent dose to have greatly reduced effects
Withdrawal of meth is similar to cocaine but both ___ and ___
Withdrawal of meth is similar to cocaine but both physical and psychological
Withdrawal from meth includes ___,____,__,___,___
Withdrawal from meth includes cravings , depression, lethargy ,muscle pain ,abnormal sleep patterns
Chronic AMPH dosing causes reduced cell-surface expression of ___ for ___ and ___
Chronic AMPH dosing causes reduced cell-surface expression of transporters for DA and NE
Dependence is caused by TAAR activation that occurs ___ of reduced transporter expression
Dependence is caused by TAAR activation that occurs upstream of reduced transporter expression
Long-term consequences of amphetamine use include
Weight loss, skin breakdown, sores, picking, poor oral hygiene, tooth decay, jaw grinding tic
Contaminants in AMPH may be ___ or excessive NE symptom which causes activation of ___ receptors on vessels and activation of pre-synaptic ___ receptors on salivary gland neurons that leads to ___ saliva production
Contaminants in AMPH may be corrosive or excessive NE symptom which causes activation of α1 receptors on receptors and activation of pre-synaptic α2 receptors on salivary gland neurons that leads to reduced saliva production
DA depletion is significant in __, ___ and ___-__ brain regions
DA depletion is significant in movement, memory and decision-making brain regions
Another long-term consequence of amphetamine use is damage to __, __, ___ terminals
Another long-term consequence of amphetamine use is damage to DA, NE, 5HT terminals
As cells recover from MAO inhibition that occurs at __ ___ concentrations, elevated DA metabolism results in ___ ___ formation which damages cell membrane, __, ___
As cells recover from MAO inhibition that occurs at high AMPH concentrations, elevated DA metabolism results in reactive species formation which damages cell membrane, proteins, mitochondria
Excitotoxicity stresses neurons and induces cell death which results in ___ ___
Excitotoxicity stresses neurons and induces cell death which results in brain damage
Neuron loss in the limbic system underlies __-__ ___ in AMPH
Neuron loss in the limbic system underlies long-term symptoms in AMPH
Damage is measured by reduced volume= __number of neurons
Damage is measured by reduced volume= reduced number of neurons
___ losses correlate with word-recall issues in long-term meth users
hippocampal losses correlate with word-recall issues in long-term meth users
As DA-ergic neurons die meth addicts are ~75% more likely to develop ____
As DA-ergic neurons die meth addicts are ~75% more likely to develop Parkinsonism
AMPH may trigger nicotinic acetylcholine receptors (nAChRs),allowing __ influx leading to ___ __ species production and ___ ___
AMPH may trigger nicotinic acetylcholine receptors (nAChRs),allowing Ca influx leading to reactive oxygen species production and cellular stress
Forms of inhalants
gases and liquids that are inhaled directly or via an accessory e.g. rag, bag
Inhalants are mixtures of several ___ ____
Inhalants are mixtures of several lipophilic chemicals
Administration by inhalation includes…
huffing, sniffing and bagging
Inhalants have ___ and ___ distribution, similar to anesthetics
Inhalants have rapid and wide distribution, similar to anesthetics
The more volatile inhalants i.e. gases under standard conditions are mostly ___
The more volatile inhalants i.e. gases under standard conditions are mostly exhaled
Inhalants can reduce blood pH at higher doses= ___
Inhalants can reduce blood pH at higher doses= acidosis
Inhalants are metabolized by
Liver CYP2E1
Inhalants are excreted via
kidneys and breath
The acute effects of inhalants are similar to ___, ___, ___
The acute effects of inhalants are similar to alcohol, sedatives, hypnotics
Inhalants are __ for 15-45 minutes then after 1-2 hours ___, ___, ____,___ occurs first then ___, ___,___
Inhalants are biphasic for 15-45 minutes then after 1-2 hours euphoria, disinhibition, dizziness, light-headedness occurs first then drowsiness, disorientation, headaches
At low doses of inhalants there is ___ of motor circuits
At low doses of inhalants there is disinhibition of motor circuits
Other acute effects of inhalants include..
slurred speech and inebriation (drunkenness)
___, ___, ___ and ___ can happen at high doses of inhalants
Hallucinations, anesthesia , coma and death can happen at high doses of inhalants
Toluene leads to ___ and ___ via __ –> ___ pathway, elevated striatal DA levels
Toluene leads to reward and euphoria via VTA –> NAc pathway, elevated striatal DA levels
Toluene can be found in..
paints and glues
Motor effects by inhalants are regulated in part by ___ in the caudate putamen in mice
Motor effects by inhalants are regulated in part by GABA in the caudate putamen in mice
Toluene potentiates (increases power of) ___ and ___ neurotransmitters
Toluene potentiates GABA and glycine neurotransmitters
Toluene inhibits __ ___ receptors and ___
Toluene inhibits NMDA Glu receptors and nAChRs
Toluene causes direct activation of ___ __-ergic projections to the NAc which leads to ___-mediated reinforcement
Toluene causes direct activation of VTA DA-ergic projections to the NAc which leads to DA-mediated reinforcement
The NMDA __-containing channels are most sensitive
The NMDA 2B-containing channels are most sensitive
Cultured hippocampal neurons are insensitive to __ in presence of toluene
Cultured hippocampal neurons are insensitive to ACh in presence of toluene
An acute adverse effect of intoxication by inhalation includes ___ of the heart to ___
An acute adverse effect of intoxication by inhalation includes sensitization of the heart to epinephrine
Cardiac dysrhythmias caused by intoxication to inhalants is a result of inhibited __ of voltage-gated __ and __ channels
Cardiac dysrhythmias caused by intoxication to inhalants is a result of inhibited inactivation of voltage-gated Na+ and Ca2+ channels
__ i.e. propane/butane are common causes of ER visits
Lighters i.e. propane/butane are common causes of ER visits
Aerosol-evoked cardiac arrest as a result of intoxication is caused by (1-5 = movement to heart)
1) rapid chilling of the __ (liquid-to-gas phase change of inhalants)
2) mucosal oedema and laryngospasm cause __ (i.e. low levels of oxygen in body tissues)
3) Irritate descending __ nerve
4) Elevated __ released onto heart
5) Bradycardia and cardiac arrest
Aerosol-evoked cardiac arrest as a result of intoxication is caused by (1-5 = movement to heart)
1) rapid chilling of the larynx (liquid-to-gas phase change of inhalants)
2) mucosal oedema and laryngospasm cause hypoxia
3) Irritate descending vagal nerve
4) Elevated ACh released onto heart
5) Bradycardia and cardiac arrest
___ is especially prevalent with glue sniffing
trauma is especially prevalent with glue sniffing
A mechanism that causes long-term inhalant abuse: subunit composition change/ neuroadaptation causes altered sensitivity of channels to __ __—-> ACh attenuation (reduced) initially, but ___ occurs after each withdrawal period
A mechanism that causes long-term inhalant abuse: subunit composition change/ neuroadaptation causes altered sensitivity of channels to drug binding—-> ACh attenuation initially, but excitotoxicity occurs after each withdrawal period
Structural changes in hippocampus as a result of inhalation can happen as quickly as ___
Structural changes in hippocampus as a result of inhalation can happen as quickly as 4 days
40-day 200 ppm toluene cycle causes ___ __ in hippocampal __ and ___ regions which correlate with ___ ___
40-day 200 ppm toluene cycle causes neuronal death in hippocampal CA1 and CA3 regions which correlate with memory loss
Long-term damage of brain regions like __ ___, ___, ___ and ___ is a result of inhalant abuse
Long-term damage of brain regions like basal ganglia, cerebellum, thalamus and pons is a result of inhalant abuse
Myelin loss (a long-term health risk associated with inhalant abuse) results in __ ___, __ __ and cerebellar ataxia i.e. clumsy voluntary movements
Myelin loss (a long-term health risk associated with inhalant abuse) results in cognitive decline, slower processing and cerebellar ataxia
Because myelin is a ___ substance (70% ___), __ accumulate
Because myelin is a fatty substance (70% lipid), inhalants accumulate
Ecstasy was synthesized in 1912 by __ at Merck (a drug company)
Ecstasy was synthesized in 1912 by Kollisch at Merck (a drug company)
Alexander ___ published first pharmacological ecstasy in 1960 at DOW Chemicals
Alexander Shulgin published first pharmacological ecstasy in 1960 at DOW Chemicals
MDMA/Ectasy can be derived from natural sources like being extracted from cured ___ ___, ___ ___, or ___ ___ root bark or synthetic sources
MDMA/Ectasy can be derived from natural sources like being extracted from cured Ocotea pretiosa, Sassafras albidum, or Cinnamomum parthenoxylon root bark or synthetic sources
Ecstasy aka 3,4- methylenedioxymethamphetamine is classified as a ___, similarity to mescaline
Ecstasy aka 3,4- methylenedioxymethamphetamine is classified as a hallucinogen, similarity to mescaline
MDMA/Ecstasy is excreted by
the kidneys, 20% unchanged
MDMA is an ___ / an ____ (type of psychoactive drug known to impact the emotional and social behavior of the user)
MDMA is an empathogen/ an entactogen
Acute effects of MDMA include __, __ __, __, __ self-esteem
Acute effects of MDMA include euphoria, emotional empathy, energy, enhanced self-esteem
MDMA is ___ : increases heart rate, hyperthermia, diaphoresis
MDMA is sympathomimetic : increases heart rate, hyperthermia, diaphoresis
In a higher dose, MDMA acts as a serotonin ___, causing an increase in serotonin release and blocking its uptake
In a higher dose, MDMA acts as a serotonin agonist, causing an increase in serotonin release and blocking its uptake
Because MDMA is a 5HT 1B/2 ___ it causes __ (jaw grinding) and increased ___
Because MDMA is a 5HT 1B/2 agonist it causes bruxism (jaw grinding) and increased locomotion
MDMA/ Ecstasy reverses ___ transporter and also blocks __ and __ transporters
MDMA/ Ecstasy reverses 5HT transporter and also blocks NE and DA transporters
MDMA __ cortisol which is correlated with feelings of __ and ___, increases blood glucose too
MDMA increases cortisol which is correlated with feelings of excitement and happiness, increases blood glucose too
MDMA shifts activation towards ___ ___ (thoughtfulness), decreases ___ activity (fear, rage)
MDMA shifts activation towards ventral striatum (thoughtfulness), decreases amygdala activity (fear, rage)
___ exemplify pro-social effects of MDMA
Cephalopods exemplify pro-social effects of MDMA
Tolerance of MDMA is due to a decrease in __ transporter activity (__ and ___ too)and depletion of neurotransmitters
Tolerance of MDMA is due to a decrease in 5HT transporter activity (DA and NE too), transporter expression decreasing and depletion of neurotransmitters
MDMA withdrawal results in the inability to ___ and can be ___ –> “suicide Tuesdays”
MDMA withdrawal results in the inability to thermoregulate and can be lethal –> “suicide Tuesdays”
Dependence on MDMA is more ___ than __
Dependence on MDMA is more psychological than physical
Biased agnoism in 5HT2C receptor agonism may underlie MDMA’s ___ ___ risk
Biased agnoism in 5HT2C receptor agonism may underlie MDMA’s low addiction risk
Some dangers of acute use of MDMA include:
- bad trips involve ___, ___, ___, ___
- 5HT syndrome causing increased heart rate and BP, muscle ___, hyper-diaphoresis, ____, diarrhea, ____ that can lead to ___ failure, ____ and death
Some dangers of acute use of MDMA include:
- bad trips involve depression, anxiety, hallucination, paranoia
- 5HT syndrome causing increased heart rate and BP, muscle rigidity, hyper-diaphoresis, delirium, diarrhea, rhabdomyolysis that can lead to kidney failure, convulsion and death
Combining MDMA with ___ (antidepressants) reduces its effects due to competition for ____ transporters
Combining MDMA with SSRI (antidepressants) reduces its effects due to competition for 5HT transporters
Combining MDMA with ___ inhibitors can potentiate (make stronger) effects of MDMA due to increased ___ availability
Combining MDMA with MAO inhibitors can potentiate effects of MDMA due to increased NT availability
___ is the most common cause of overdose death
hyperthermia is the most common cause of overdose death
___ or low Na in blood caused by larger water intake due to hyperthermia (because of MDMA use) can result in ___ ___ (swelling) leading to ___ and ___ ___ (compressed ___)
Hyponatremia or low Na in blood caused by larger water intake due to hyperthermia (because of MDMA use) can result in cerebral edema (swelling) leading to vomiting and respiratory arrest (compressed brainstem)
Long-term health effects of MDMA are ___ and ___ deficits
Long-term health effects of MDMA are memory and attention deficits
Yeast has a ___ generation time
Yeast has a fast generation time
Yeast is ___ for long-term storage, and __ for use
Yeast is dried for long-term storage, and rehydrated for use
Yeast has genomes that __ ___
Yeast has genomes that fully sequenced
Yeast is a model organism for __, __ __ and ___
Yeast is a model organism for aging, DNA repair and brewing
Yeast has __ ___ strains available which optimizes it for application
Yeast has multiple unique strains available which optimizes it for application
___% ethanol is toxic to yeast
15% ethanol is toxic to yeast
___ concentrates the concentration of alcohol to __%+
distillation concentrates the concentration of alcohol to 40%+
Proof is __ the alcohol (ethanol) content by volume e.g. a whisky with 50% alcohol is __-proof whiskey
Proof is twice the alcohol (ethanol) content by volume e.g. a whisky with 50% alcohol is 100-proof whiskey
The two main methods for indicating the alcoholic content of a beverage are ___ (ABV) and ___
The two main methods for indicating the alcoholic content of a beverage are alcohol-by-volume (ABV) and proof
Common molecules found in wine, beer and scotch are
anthocynanins, terpenes, tannins, vitamins and polyphenols
4 categories of alcohol use
1) Abstinent
2) Moderate
3) Bingeing
4) Heavy (Alcoholic)
Bingeing is __or __ drinks on one occasion in the last __ days for men or women
Bingeing is 5 or 4 drinks on one occasion in the last 30 days for men or women
How much ethanol (EtOH) in a standardized drink?
13.98 g
ethanol is absorbed in the __ __
ethanol is absorbed in the small intestine
food ___ retention time of ethanol in the stomach which __ absorption of it
food increases retention time of ethanol in the stomach which slows absorption of it
low pH does/does not alter ethanol
low pH does not alter ethanol
Alcohol distributes through ___ tissues
Alcohol distributes through aqueous tissues
volume available for distribution determines ___
volume available for distribution determines BAC (blood alcohol content)
higher proportion of body fat = ___ BAC after 1 drink
higher proportion of body fat = higher BAC after 1 drink
The average man is __% water and average woman is __% water
The average man is 53.4% water and average woman is 48.5% water
BAC is slightly higher in ___ than ___
BAC is slightly higher in females than males
Ethanol is ___ ___ throughout tissues
Ethanol is freely distributed throughout tissues
Acute effects of EtOH are __
Acute effects of EtOH are biphasic
What causes the phases of the acute effect of EtOH
metabolism
EtOH ___ sociability and ___ anxiety especially in adolescent animals
EtOH increases sociability and decreases anxiety especially in adolescent animals
EtOH brain effects
inhibits decision-making and judgements
unstable mood and heightened emotion
decreased anxiety
increased aggression
increased addiction
EtOH mouth effects
increased salivation and appetite
EtOH stomach effects
increased gastric HCI secretion
increased insulin sensitivity in non-diabetics
Other EtOH acute effects
reduced time to fall asleep, less deep sleep, less REM sleep
Impaired memory
Impaired balance and coordination
Vision impeded and inhibited taste and smell
Reduced perception of pain
EtOH blood effects
dilated blood vessels of skin
reduced blood clotting
increased HDL (cholesterol) levels
EtOH kidney effects
inhibited anti-diuretic hormone and increased urination
EtOH reproductive effects
inconsistent effects on reproductive system
EtOH causes vaso____
EtOH causes vasodilation
EtOH causes ____ gastric/salivary secretions
EtOH causes increased gastric/salivary secretions
EtOH causes loss of stomach mucosal lining leading to ___
EtOH causes loss of stomach mucosal lining leading to ulcers
EtOH affects neurotransmitters…
GABA, Glutamate, Dopamine and endogenous opioids
___% of EtOH is metabolized in the liver, __% is excreted untouched by breath, urine, skin etc. , ___% metabolized in stomach, ___% other
90% of EtOH is metabolized in the liver, 2% is excreted untouched by breath, urine, skin etc. , 3% metabolized in stomach, 5% other
When driving under the influence the amount of alcohol exhaled is ____ the concentration in the blood, this is set as the ___ of ___ ____ tests (BrAC)
When driving under the influence the amount of alcohol exhaled is 1/2100th the concentration in the blood, this is set as the basis of roadside breathalyzer tests (BrAC)
what % of alcohol is lethal
0.4-0.5%
The ___ are also a common side-effect of excessive drinking EtOH
The spins are also a common side-effect of excessive drinking EtOH
Steps that alcohol causes the spins
1) EtOH permeates endolymph and cupula
2) BAC starts to decline
3) EtOH diffuses (diffusion is inversely proportional to density) out of cupula before endolymph
4) Cupula is now more dense than endolymph and does not stabilize when lying down
5) Sensory fibres are activated- brain interprets activity as motion
over-suppressed/decreased activity by high dose ethanol leads to ___ ___ amnesia
over-suppressed/decreased hippocampal activity by high dose ethanol leads to transient anterograde amnesia
Hippocampal dentate gyrus neurons are ___ to
ethanol damage
Hippocampal dentate gyrus neurons are susceptible to
ethanol damage
Chronic alcoholism can coincide with ___
___ (e.g. thiamine)
Chronic alcoholism can coincide with nutritional
deficiencies (e.g. thiamine)
Alcohol-related brain damage (ARBD) is driven by
__-____ signaling that induces ___ ___ and death
Alcohol-related brain damage (ARBD) is driven by
pro-inflammatory signaling that induces cellular damage and death
metabolites are ___
metabolites are toxic
Dropping BAC ….
- ____ GABA A receptor IPSPs
- Blocks ___ (GluN) receptor EPSPs
- Blocks select __ channels
Dropping BAC ….
- Potentiates/enhances GABA A receptor IPSPs
- Blocks NMDA (GluN) receptor EPSPs
- Blocks select Ca channels
Alcohol acute –> chronic effects (How tolerance is developed):
- GABA A receptor functions ____
- NMDA (GluN) receptors ___-regulated
- Ca channel receptors ___-regulated
Alcohol acute –> chronic effects (How tolerance is developed):
- GABA A receptor functions decrease
- NMDA (GluN) receptors up-regulated
- Ca channel receptors up-regulated
Metabolic tolerance of EtOH causes ___ levels to go up
Metabolic tolerance of EtOH causes CYP2E1 levels to go up
CYP2E1 knockout prevents ___-induced liver damage
CYP2E1 knockout prevents EtOH-induced liver damage
Overactive CYP2E1 induces ___ EtOH damage
Overactive CYP2E1 induces more EtOH damage
Alcohol withdrawal syndrome (AWS) have symptoms that are both __ and ___
Alcohol withdrawal syndrome (AWS) have symptoms that are both physical and psychological
Physical syndromes of a hangover/AWS
headache, diarrhea, fatigue, restlessness, nausea
Psychological syndromes of a hangover/AWS
haziness, slower thought/cognition, impaired reaction times and poor reasoning
Congener
a minor chemical constituent especially one that gives a distinctive character to a wine or liquor or is responsible for some of its toxic effects
Hangover severity increases with increased ___ content
Hangover severity increases with increased congener content
Brandy results in a ___(Stronger/weaker) hangover than vodka
Brandy results in a stronger hangover than vodka
Symptom(s) of stage 1 of alcohol withdrawal
elevated heart rate/bp, diaphoresis(sweating), tremors , no appetite, insomnia
Symptom(s) of stage 2 of alcohol withdrawal
hallucinations
Symptom (s) of stage 3 of alcohol withdrawal
delusions, delirium, amnesia, tremens peak 3-4 days after last drink
Symptom (s) of stage 4 of alcohol withdrawal
seizures
Alcohol withdrawal is ___ severe than most other drugs e.g. heroin, meth
Alcohol withdrawal is more severe than most other drugs e.g. heroin, meth
Goal of treatment for AWS/hangover is to prevent withdrawal stages __ and __
Goal of treatment for AWS/hangover is to prevent withdrawal stages 3 and 4
___ or ___ is used for reducing AWS severity
Benzodiazepines or ketamine is used for reducing AWS severity
Clonidine is a pre-synaptic __ adrenegic ___ that prevents excessive neurotransmitter released (reducing over-excitation from AWS)
Clonidine is a pre-synaptic α2 adrenegic agonist that prevents excessive neurotransmitter released (reducing over-excitation from AWS)
Propranolol is a __ adrenergic ___ that reduces sympathetic effects and tremor seen in AWS
Propranolol is a β adrenergic antagonist that reduces sympathetic effects and tremor seen in AWS
Disulfiram inhibits ___ ___, causing build-up of __ and the aim of it is to prevent ___use but does not decrease ___
Disulfiram inhibits acetaldehyde dehydrogenase, causing build-up of acetaldehyde and the aim of it is to prevent alcohol use but does not decrease craving
Naltrexone and nalmefene aopioid antagonists are used as treatments for AWS because they prevent ___-ergic reward
Naltrexone and nalmefene aopioid antagonists are used as treatments for AWS because they prevent DA-ergic reward
The NAc has 2 regions …
the core and shell
___ brain volume in alcoholics compared to healthy controls because ___ ___ off
reduced brain volume in alcoholics compared to healthy controls because neurons die off
Gross changes in brain health and appearance is induced by ___/___ production in the brain
Gross changes in brain health and appearance is induced by ROS/acetaldehyde production in the brain
Changes in the brain caused by alcohol affects __ metabolism, ___ synthesis, ___ formation all of which damage neurons and cause ___ death
Changes in the brain caused by alcohol affects glucose metabolism, protein synthesis, myelin formation all of which damage neurons and cause cell death
Hyperactive __ systems cause ___ via excessive Ca influx leading to __ ___
Hyperactive Glu systems cause excitotoxicity via excessive Ca influx leading to cell death
People with low baseline __-___ levels are prone to drinking more alcohol
People with low baseline beta-endorphin levels are prone to drinking more alcohol
Heavy drinkers often suffer from ___
Heavy drinkers often suffer from malnutrition
EtOH contains __ energy than carbs and proteins
EtOH contains more energy than carbs and proteins
CYP2E1 produces ___ ____ like ___ and ___
CYP2E1 produces reactive species like acetaldehyde and ROS
ROS reacts with __-___ systems under controlled conditions
ROS reacts with anti-oxidant systems under controlled conditions
At elevated levels, __-___ systems are overwhelmed
At elevated levels, anti-oxidant systems are overwhelmed
If the cell cannot detoxify, it becomes ___, __ leads to __ & __ damage, __, cell death
If the cell cannot detoxify, it becomes stressed, stress leads to membrane & DNA damage, cancer, cell death
Metabolic switch in the liver caused by EtOH abuse results in ___ ___ disease
Metabolic switch in the liver caused by EtOH abuse results in fatty liver disease
Fatty liver disease progresses to ___
Fatty liver disease progresses to cirrhosis
Cirrhosis is characterized by a ___ ___ state and cell death
Cirrhosis is characterized by a chronic inflammatory state and cell death
TGF-beta cytokine production by infiltrating immune cells triggers ___ changes
TGF-beta cytokine production by infiltrating immune cells triggers transcriptional changes
__% of cancers are linked to alcohol consumption
50% of cancers are linked to alcohol consumption
The ___ ___ ___ is susceptible to cancer because microflora contribute to EtOH metabolism
The upper GI tract is susceptible to cancer because microflora contribute to EtOH metabolism
acetaldehyde concentrations are __ in the blood
acetaldehyde concentrations are higher in the blood
4MP is an ___ ___ (ADH) __
4MP is an alcohol dehydrogenase (ADH) inhibitor
Mechanism of oncogenesis/tumors because of alcohol
1) acetaldehyde interferes with DNA synthesis and repair
2) Binds and inactivates DNA repair proteins
3) Causes mutations and chromosomal abnormalities
Cardioprotective effects:
- __ doses, 1 drink per 1-2 days
- wine several ___ ___, increases ___ which prevents lipid deposition in arteries (anti-atherosclerotic), decreases ___ ___
Cardioprotective effects:
* low doses, 1 drink per 1-2 days
* wine several beneficial antioxidants, increases HDL which prevents lipid
deposition in arteries (anti-atherosclerotic), decreases platelet aggregation
Cardiotoxic effects:
* cardiomyopathies at ___ EtOH doses
* direct modulator of Ca release→inhibits SR Ca release, negative inotropic effect
* acetaldehyde __ protein synthesis, heart has __ protein turnover due to muscle fibre and beating function; also damages __
Cardiotoxic effects:
* cardiomyopathies at high EtOH doses
* direct modulator of Ca release→inhibits SR Ca release, negative inotropic effect
* acetaldehyde inhibits protein synthesis, heart has high protein turnover due to muscle fibre and beating function; also damages mitochondria
What are some medical uses for opioids
used for pain- an anti- nociceptive (blocks detection of painful stimulus), blocks afferent transmission in the spinal cord/brainstem
Opioids can be __ and ___ when used appropriately
Opioids can be safe and effective when used appropriately
Lethal mix= __ + ___
Lethal mix= opioids + sedatives
Naloxone is an ___ ___ (OR) antagonist
Naloxone is an opioid receptor (OR) antagonist
Methadone is a ___ ___
Methadone is a μ (mu) agonist (activates)
Methadone is a ___ ___
Methadone is a μ (mu) agonist (activates)
Who are first responders
firefighters and EMS
3 types of major opioids
1) Natural
2) Semi-synthetic
3) Synthetic
Natural opioid sources: ___- alkaloid-laden latex, __, ___
Natural opioid source: opium- alkaloid-laden latex, morphine, codeine
Semi-synthetic opioid sources: __, __-___/-morphone, ___, __, __ ,___
Semi-synthetic opioid sources: heroin, hydro-codone/-morphone, oxycodone, krokodil, buprenorphine, etorphine
Synthetic opioid sources: __, ___,__,__
Synthetic opioid sources: methadone, meperidine, tramadol, fentanyl
Opium is a key source for many narcotics including __ and ___
Opium is a key source for many narcotics including morphine and codeine
Morphine is __x __ potent than opium
Morphine is 10x more potent than opium
__ converts codeine to morphine in brain and __
CYP2D6 converts codeine to morphine in brain and liver
__% of Caucasians have deficient ___ –> codeine having no effect
10% of Caucasians have deficient CYP2D6 –> codeine having no effect
__% of population has overactive CYP2D6 –> __ ___
2% of population has overactive CYP2D6 –> morphine intoxication
Semi-synthetic means
produced by modifying a naturally- derived chemical
Heroin has 2 __ groups which make the molecule 10x more __
Heroin has 2 acetyl groups which make the molecule 10x more lipophilic
Early 1960s resulted in the synthesis of ___ which can reverse morphine effects
Early 1960s resulted in the synthesis of naloxone which can reverse morphine effects
Candace __ and Sol __ discovered __ ___ in the brain
Candace Pert and Sol Snyder discovered opioid receptors in the brain
Pert and Snyder found 4 classes of pre- and post-synaptic opioid receptors which were __, ___, __ and __
Pert and Snyder found 4 classes of pre- and post-synaptic opioid receptors which were μ (mu), δ (delta), κ (kappa) and ORL-1 (opioid receptor like-1)
Pre-synaptic receptors modulate ___ ___ (e.g. DA, NE, GABA)
Pre-synaptic receptors modulate NT release (e.g. DA, NE, GABA)
Post-synaptic receptors alter __ __
Post-synaptic receptors alter membrane potential
__ different peptide ligands, endorphins are known
18 different peptide ligands, endorphins are known
Endogenous opioids are involved in ___, ___ __, __, __, __, _, __ and __ dependence
Endogenous opioids are involved in pain, emotional responses, euphoria, eating, memory, stress , seizures and alcohol dependence
μ opioid receptors (MORs) are expressed in..
VTA, NAc, PAG, Hypothalamus, LC, Brainstem, Pupils and GI tract
Most opioids bind ___ receptors
Most opioids bind μ receptors
μ opioid receptors (MORs) are involved in
reward, addiction, analgesia- reduces pain (euphoria/Anxiolytic- to reduce anxiety, respiration, BP, nausea, itch, constriction and constipation
δ opioid receptors (DORs) are expressed in the..
neocortex, striatum, NAc, Substantia nigra, olfactory bulb
δ(delta) opioid receptors (DORs) are bound by
enkephalins
δ(delta) opioid receptors (DORs) are bound by
enkephalins
κ opioid receptors (KORs) are expressed in the …
pituitary, hypothalamus, PAG, spinal cord
κ opioid receptors (KORs) are bound by __, __, __ and ___
κ opioid receptors (KORs) are bound by endorphins, dynorphins, PCP and ketamine
Orphan opioid receptor (ORL-1 i.e. opioid receptor-like 1) are expressed in
limbic system and spinal cord
ORL1 or orphan opioid receptors are bound by __
buprenorphine
Illegal fentanyl comes mostly from __ to Canada
Illegal fentanyl comes mostly from Asia to Canada
Fentanyl looks like __ ___
Fentanyl looks like 80mg oxycontin (painkiller)
Fentanyl is sold as __
heroin
Fentanyl is __x __ potent than morphine
Fentanyl is 100x more potent than morphine
Fentanyl is __- __x __ potent than heroin
Fentanyl is 40- 50x more potent than heroin
Fentanyl is highly lipo__
Fentanyl is highly lipophilic
Fentanyl derivatives are ___ ___ potent
Fentanyl derivatives are even more potent
Fentanyl derivatives have higher potency because they have increased affinity for __ receptors and enhanced ___ ___ __ ___
Fentanyl derivatives have higher potency because they have increased affinity for mu receptors and enhanced entry into the brain
Street opioids are often ___ with additional adulterants like ___
Street opioids are often contaminated with additional adulterants like fentanyl
Most opioids undergo extensive __-___ ___ in the liver before entering the systemic circulation reducing their ___
Most opioids undergo extensive first-pass metabolism in the liver before entering the systemic circulation reducing their bioavailability
Chasing the dragon method
heating up tin foil and inhaling fumes, commonly smoked in a pipe
Chasing the dragon method is linked to ____, which causes brain tissue to look __ with __ or referred to as ___. This can progress to __ (loss of body movements), __ (lack of interest/concern), ___(restlessness) and to the complete inability to speak or move
Chasing the dragon method is linked to leukoencephalopathy (disease of the white matter of the brain), which causes brain tissues to look spongy with holes or referred to as spongiform. This can progress to ataxia, apathy, akathisia and to the complete inability to speak or move
The effect of chasing the dragon method seems to be because of __ ___
The effect of chasing the dragon method seems to be because of metal toxicity (from the fumes of the tin foil)
To inject heroin…
it is mixed with some water in a spoon, acid or heat is used to dissolve it, drawn up through a cotton ball to remove particulates
Heroin injection leaves __ ___ because of the damage to __ by the needle, the drug, injection __, ___ or ‘__’ (blood being re-injected)
Heroin injection leaves track marksbecause of the damage to vessels by the needle, the drug, injection rate, infection or ‘flushing’
Heroin injection results in __ blood flow, __ and __ to form
Heroin injection results in uneven blood flow, thrombosis and clots to form
Most opioids are not lipophilic which means they do not readily cross the ___
Most opioids are not lipophilic which means they do not readily cross the BBB
Opioids are metabolized in the __ and __, and excreted by ___ and __
Opioids are metabolized in the liver and brain , and excreted by kidneys and feces
Heroin is metabolized to ___ in the brain
Heroin is metabolized to morphine in the brain
the 2 MAM (monoacetylmorphine) intermediates are ___ and ___
the 2 MAM (monoacetylmorphine) intermediates are 3-MAM and 6-MAM
_-MAM binds MOR while _-MAM does not
6-MAM binds MOR while 3-MAM does not
_-MAM is not naturally occurring and used in legal cases to establish heroin use
6-MAM is not naturally occurring and used in legal cases to establish heroin use
Acute effects of opioids to the skin
lowered body temperature, flushed skin and itching
Opioids cause __ pupils opposite to other drugs because of __ and __ receptors in the oculomotor nucleus
Opioids cause constricted pupils opposite to other drugs because of μ and kappa receptors in the oculomotor nucleus
Effects of opioids on medulla
lowers BP(hypotension) bronchoconstriction, itching from histamine release
Effects of opioids on brain
euphoria, well-being and tranquility, mental clouding, impaired judgement, decreased attention and memory
Physiological effects of opioids on reproduction:
GnRH, LH and FSH levels are ___ –> decreased __, impotence and __ (absence of period cycle)
___ ___ syndrome (NAS)–> babies are __, vomit, __, ___ and ___ distress. They require close attention and put in NICU, __ __ reduces hospital time
Physiological effects of opioids on reproduction:
GnRH, LH and FSH levels are reduced –> decreased libido, impotence and amenorrhea (absence of period cycle)
Neonatal abstinence syndrome (NAS)–> babies are irritable, vomit, diarrhea, seizures and respiratory distress. They require close attention and put in NICU, physical contact reduces hospital time
Physiological effects of opioids on GI tract:
Isometric muscle contractions __ bowel movements and secretions leading to __
Constrict __ and sphincters of __, stimulate __-___ hormone release leading to decrease in urination
Physiological effects of opioids on GI tract:
Isometric muscle contractions reduce bowel movements and secretions leading to constipation
Constrict ureter and sphincters of bladder, stimulate anti-diuretic hormone release leading to decrease in urination
Mu, delta and kappa opioid receptors (ORs) come from separate ___ __
Mu, delta and kappa opioid receptors (ORs) come from separate Opr genes
ORL orphan display __ __
ORL orphan display structural homology
Most opioid effects are due to __ signaling
Most opioid effects are due to mu signaling
All endogenous opioids contain an N-___ ___ residue
All endogenous opioids contain an N-terminal tyrosine residue
Morphine structure mimics ___
Morphine structure mimics tyrosine
All opioid receptors (Ors) are ___ linked via ___
All opioid receptors (Ors) are GPCRs linked via Gi/o
Chronic exposure to morphine results in __-__ coupled receptor kinase (GRK)-__ ___ of opioid receptors and binding of __ __→desensitization
Chronic exposure to morphine results in G-protein coupled receptor kinase (GRK)-mediated phosphorylation of opioid receptors and binding of β arrestin→desensitization
