Midterm 2 Flashcards
1
Q
How AMPH (amphetamines) are absorbed?
A
injected, ingested, snorted or smoked
2
Q
Onset is fastest by ___ < ___< ___<___
A
Onset is fastest by smoking < injection < snorting < ingesting
3
Q
Ice is to ___ what ___ is to cocaine
A
Ice is to meth what crack is to cocaine
4
Q
Ice is ___ ___, ___ meth that has a half life of about __ hours
A
Ice is HCI salt, smokeable meth that has a half life of about 12 hours
5
Q
Meth high lasts ___ than cocaine
A
Meth high lasts much longer than cocaine
6
Q
Liver ___ metabolizes meth and AMPH (amphetamine)
A
Liver CYP2D6 metabolizes meth and AMPH (amphetamine)
7
Q
4-HA and nor-ephedrine are ___
A
4-HA and nor-ephedrine are stimulants
8
Q
4-HA activates ___ ____ ____ ___ (TAAR), stimulates ___ release and inhibits ___ ___ (MAO)
A
4-HA activates trace amino associated receptor (TAAR), stimulates NE release and inhibits monoamine oxidase (MAO)
9
Q
AMPH can be broken down into ___ and ____
A
AMPH can be broken down into 4-HA and nor ephedrine
10
Q
TAAR is an intracellular ____
A
TAAR is an intracellular GPCR (G-protein-coupled receptor)
11
Q
Monoamine oxidase (MAO) degrades monoamine ____ like ___, NE, ___
A
Monoamine oxidase (MAO) degrades monoamine NTs like DA, NE, 5HT
12
Q
AMPH/METH excretion via
A
kidney, sweat, saliva
13
Q
Acute effects of AMPH: ___, energy, ___, grandiosity, ____ appetite
A
Acute effects of AMPH: euphoria, energy, aggression, grandiosity, decreased appetite
14
Q
AMPH is sympathomimetic meaning that NE release is ____
A
AMPH is sympathomimetic meaning that NE release is increased
15
Q
An acute effect of AMPH is that 5HT release ___ causing delusional parasitosis (i.e. ____) and ___ ___
A
An acute effect of AMPH is that 5HT release increases causing delusional parasitosis (i.e. bugs under skin) and perceptual disturbances
16
Q
An acute effect of AMPH is that DA is ___ causing ___ activity
A
An acute effect of AMPH is that DA is increased causing locomotor activity
17
Q
Punding
A
occurs at high doses of AMPH, repetitive meaningless behaviours; also common in Parkinson’s patients
18
Q
AMPHs elevate __, ___, __ availability
A
AMPHs elevate DA, NE, 5HT availability
19
Q
AMPH does not require ____-ergic ___ firing, unlike cocaine
A
AMPH does not require DA-ergic neuron firing, unlike cocaine
20
Q
DAT transporter ___ meth into nerve ____
A
DAT transporter brings meth into nerve terminals
21
Q
Meth can enter via DAT transporter and by ___
A
Meth can enter via DAT transporter and by diffusion
22
Q
VMAT (vesicular monoamine transporter) pumps meth into ___ ___
A
VMAT (vesicular monoamine transporter) pumps meth into storage vesicles
23
Q
Synaptic mechanism of AMPH (that results in spike of DA)
A
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
24
Q
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
A
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
25
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
26
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
27
Inhibition of tyrosine hydroxylase enzyme ____ synthesis of DA and NE
Inhibition of tyrosine hydroxylase enzyme reduces synthesis of DA and NE
28
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
29
Withdrawal of meth is similar to cocaine but both ___ and ___
Withdrawal of meth is similar to cocaine but both physical and psychological
30
Withdrawal from meth includes ___,____,__,___,___
Withdrawal from meth includes cravings , depression, lethargy ,muscle pain ,abnormal sleep patterns
31
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
32
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
33
Long-term consequences of amphetamine use include
Weight loss, skin breakdown, sores, picking, poor oral hygiene, tooth decay, jaw grinding tic
34
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
35
DA depletion is significant in __, ___ and ___-__ brain regions
DA depletion is significant in movement, memory and decision-making brain regions
36
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
37
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
38
Excitotoxicity stresses neurons and induces cell death which results in ___ ___
Excitotoxicity stresses neurons and induces cell death which results in brain damage
39
Neuron loss in the limbic system underlies __-__ ___ in AMPH
Neuron loss in the limbic system underlies long-term symptoms in AMPH
40
Damage is measured by reduced volume= __number of neurons
Damage is measured by reduced volume= reduced number of neurons
41
___ losses correlate with word-recall issues in long-term meth users
hippocampal losses correlate with word-recall issues in long-term meth users
42
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
43
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
44
Forms of inhalants
gases and liquids that are inhaled directly or via an accessory e.g. rag, bag
45
Inhalants are mixtures of several ___ ____
Inhalants are mixtures of several lipophilic chemicals
46
Administration by inhalation includes...
huffing, sniffing and bagging
47
Inhalants have ___ and ___ distribution, similar to anesthetics
Inhalants have rapid and wide distribution, similar to anesthetics
48
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
49
Inhalants can reduce blood pH at higher doses= ___
Inhalants can reduce blood pH at higher doses= acidosis
50
Inhalants are metabolized by
Liver CYP2E1
51
Inhalants are excreted via
kidneys and breath
52
The acute effects of inhalants are similar to ___, ___, ___
The acute effects of inhalants are similar to alcohol, sedatives, hypnotics
53
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
54
At low doses of inhalants there is ___ of motor circuits
At low doses of inhalants there is disinhibition of motor circuits
55
Other acute effects of inhalants include..
slurred speech and inebriation (drunkenness)
56
___, ___, ___ and ___ can happen at high doses of inhalants
Hallucinations, anesthesia , coma and death can happen at high doses of inhalants
57
Toluene leads to ___ and ___ via __ --> ___ pathway, elevated striatal DA levels
Toluene leads to reward and euphoria via VTA --> NAc pathway, elevated striatal DA levels
58
Toluene can be found in..
paints and glues
59
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
60
Toluene potentiates (increases power of) ___ and ___ neurotransmitters
Toluene potentiates GABA and glycine neurotransmitters
61
Toluene inhibits __ ___ receptors and ___
Toluene inhibits NMDA Glu receptors and nAChRs
62
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
63
The NMDA __-containing channels are most sensitive
The NMDA 2B-containing channels are most sensitive
64
Cultured hippocampal neurons are insensitive to __ in presence of toluene
Cultured hippocampal neurons are insensitive to ACh in presence of toluene
65
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
66
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
67
__ i.e. propane/butane are common causes of ER visits
Lighters i.e. propane/butane are common causes of ER visits
68
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
68
___ is especially prevalent with glue sniffing
trauma is especially prevalent with glue sniffing
69
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
70
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
71
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
72
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
73
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
74
Because myelin is a ___ substance (70% ___), __ accumulate
Because myelin is a fatty substance (70% lipid), inhalants accumulate
75
Ecstasy was synthesized in 1912 by __ at Merck (a drug company)
Ecstasy was synthesized in 1912 by Kollisch at Merck (a drug company)
76
Alexander ___ published first pharmacological ecstasy in 1960 at DOW Chemicals
Alexander Shulgin published first pharmacological ecstasy in 1960 at DOW Chemicals
77
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
78
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
79
MDMA/Ecstasy is excreted by
the kidneys, 20% unchanged
80
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
81
Acute effects of MDMA include __, __ __, __, __ self-esteem
Acute effects of MDMA include euphoria, emotional empathy, energy, enhanced self-esteem
82
MDMA is ___ : increases heart rate, hyperthermia, diaphoresis
MDMA is sympathomimetic : increases heart rate, hyperthermia, diaphoresis
83
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
84
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
85
MDMA/ Ecstasy reverses ___ transporter and also blocks __ and __ transporters
MDMA/ Ecstasy reverses 5HT transporter and also blocks NE and DA transporters
86
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
87
MDMA shifts activation towards ___ ___ (thoughtfulness), decreases ___ activity (fear, rage)
MDMA shifts activation towards ventral striatum (thoughtfulness), decreases amygdala activity (fear, rage)
88
___ exemplify pro-social effects of MDMA
Cephalopods exemplify pro-social effects of MDMA
89
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
90
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"
91
Dependence on MDMA is more ___ than __
Dependence on MDMA is more psychological than physical
92
Biased agnoism in 5HT2C receptor agonism may underlie MDMA's ___ ___ risk
Biased agnoism in 5HT2C receptor agonism may underlie MDMA's low addiction risk
93
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
94
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
95
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
96
___ is the most common cause of overdose death
hyperthermia is the most common cause of overdose death
97
___ 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)
98
Long-term health effects of MDMA are ___ and ___ deficits
Long-term health effects of MDMA are memory and attention deficits
99
Yeast has a ___ generation time
Yeast has a fast generation time
100
Yeast is ___ for long-term storage, and __ for use
Yeast is dried for long-term storage, and rehydrated for use
101
Yeast has genomes that __ ___
Yeast has genomes that fully sequenced
102
Yeast is a model organism for __, __ __ and ___
Yeast is a model organism for aging, DNA repair and brewing
103
Yeast has __ ___ strains available which optimizes it for application
Yeast has multiple unique strains available which optimizes it for application
104
___% ethanol is toxic to yeast
15% ethanol is toxic to yeast
105
___ concentrates the concentration of alcohol to __%+
distillation concentrates the concentration of alcohol to 40%+
106
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
107
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
108
Common molecules found in wine, beer and scotch are
anthocynanins, terpenes, tannins, vitamins and polyphenols
109
4 categories of alcohol use
1) Abstinent
2) Moderate
3) Bingeing
4) Heavy (Alcoholic)
110
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
111
How much ethanol (EtOH) in a standardized drink?
13.98 g
112
ethanol is absorbed in the __ __
ethanol is absorbed in the small intestine
113
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
114
low pH does/does not alter ethanol
low pH does not alter ethanol
115
Alcohol distributes through ___ tissues
Alcohol distributes through aqueous tissues
116
volume available for distribution determines ___
volume available for distribution determines BAC (blood alcohol content)
117
higher proportion of body fat = ___ BAC after 1 drink
higher proportion of body fat = higher BAC after 1 drink
118
The average man is __% water and average woman is __% water
The average man is 53.4% water and average woman is 48.5% water
119
BAC is slightly higher in ___ than ___
BAC is slightly higher in females than males
120
Ethanol is ___ ___ throughout tissues
Ethanol is freely distributed throughout tissues
121
Acute effects of EtOH are __
Acute effects of EtOH are biphasic
122
What causes the phases of the acute effect of EtOH
metabolism
123
EtOH ___ sociability and ___ anxiety especially in adolescent animals
EtOH increases sociability and decreases anxiety especially in adolescent animals
124
EtOH brain effects
inhibits decision-making and judgements
unstable mood and heightened emotion
decreased anxiety
increased aggression
increased addiction
125
EtOH mouth effects
increased salivation and appetite
126
EtOH stomach effects
increased gastric HCI secretion
increased insulin sensitivity in non-diabetics
127
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
128
EtOH blood effects
dilated blood vessels of skin
reduced blood clotting
increased HDL (cholesterol) levels
129
EtOH kidney effects
inhibited anti-diuretic hormone and increased urination
130
EtOH reproductive effects
inconsistent effects on reproductive system
131
EtOH causes vaso____
EtOH causes vasodilation
132
EtOH causes ____ gastric/salivary secretions
EtOH causes increased gastric/salivary secretions
133
EtOH causes loss of stomach mucosal lining leading to ___
EtOH causes loss of stomach mucosal lining leading to ulcers
134
EtOH affects neurotransmitters...
GABA, Glutamate, Dopamine and endogenous opioids
135
___% 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
136
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)
137
what % of alcohol is lethal
0.4-0.5%
138
The ___ are also a common side-effect of excessive drinking EtOH
The spins are also a common side-effect of excessive drinking EtOH
139
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
140
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
141
Hippocampal dentate gyrus neurons are ___ to
ethanol damage
Hippocampal dentate gyrus neurons are susceptible to
ethanol damage
142
Chronic alcoholism can coincide with ___
___ (e.g. thiamine)
Chronic alcoholism can coincide with nutritional
deficiencies (e.g. thiamine)
143
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
144
metabolites are ___
metabolites are toxic
145
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
146
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
147
Metabolic tolerance of EtOH causes ___ levels to go up
Metabolic tolerance of EtOH causes CYP2E1 levels to go up
148
CYP2E1 knockout prevents ___-induced liver damage
CYP2E1 knockout prevents EtOH-induced liver damage
149
Overactive CYP2E1 induces ___ EtOH damage
Overactive CYP2E1 induces more EtOH damage
150
Alcohol withdrawal syndrome (AWS) have symptoms that are both __ and ___
Alcohol withdrawal syndrome (AWS) have symptoms that are both physical and psychological
151
Physical syndromes of a hangover/AWS
headache, diarrhea, fatigue, restlessness, nausea
152
Psychological syndromes of a hangover/AWS
haziness, slower thought/cognition, impaired reaction times and poor reasoning
153
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
154
Hangover severity increases with increased ___ content
Hangover severity increases with increased congener content
155
Brandy results in a ___(Stronger/weaker) hangover than vodka
Brandy results in a stronger hangover than vodka
156
Symptom(s) of stage 1 of alcohol withdrawal
elevated heart rate/bp, diaphoresis(sweating), tremors , no appetite, insomnia
157
Symptom(s) of stage 2 of alcohol withdrawal
hallucinations
158
Symptom (s) of stage 3 of alcohol withdrawal
delusions, delirium, amnesia, tremens peak 3-4 days after last drink
159
Symptom (s) of stage 4 of alcohol withdrawal
seizures
160
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
161
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
162
___ or ___ is used for reducing AWS severity
Benzodiazepines or ketamine is used for reducing AWS severity
163
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)
164
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
165
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
166
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
167
The NAc has 2 regions ...
the core and shell
168
___ brain volume in alcoholics compared to healthy controls because ___ ___ off
reduced brain volume in alcoholics compared to healthy controls because neurons die off
169
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
170
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
171
Hyperactive __ systems cause ___ via excessive Ca influx leading to __ ___
Hyperactive Glu systems cause excitotoxicity via excessive Ca influx leading to cell death
172
People with low baseline __-___ levels are prone to drinking more alcohol
People with low baseline beta-endorphin levels are prone to drinking more alcohol
173
Heavy drinkers often suffer from ___
Heavy drinkers often suffer from malnutrition
174
EtOH contains __ energy than carbs and proteins
EtOH contains more energy than carbs and proteins
175
CYP2E1 produces ___ ____ like ___ and ___
CYP2E1 produces reactive species like acetaldehyde and ROS
176
ROS reacts with __-___ systems under controlled conditions
ROS reacts with anti-oxidant systems under controlled conditions
177
At elevated levels, __-___ systems are overwhelmed
At elevated levels, anti-oxidant systems are overwhelmed
178
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
179
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
180
Fatty liver disease progresses to ___
Fatty liver disease progresses to cirrhosis
181
Cirrhosis is characterized by a ___ ___ state and cell death
Cirrhosis is characterized by a chronic inflammatory state and cell death
182
TGF-beta cytokine production by infiltrating immune cells triggers ___ changes
TGF-beta cytokine production by infiltrating immune cells triggers transcriptional changes
183
__% of cancers are linked to alcohol consumption
50% of cancers are linked to alcohol consumption
184
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
185
acetaldehyde concentrations are __ in the blood
acetaldehyde concentrations are higher in the blood
186
4MP is an ___ ___ (ADH) __
4MP is an alcohol dehydrogenase (ADH) inhibitor
187
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
188
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
189
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
190
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
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Opioids can be __ and ___ when used appropriately
Opioids can be safe and effective when used appropriately
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Lethal mix= __ + ___
Lethal mix= opioids + sedatives
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Naloxone is an ___ ___ (OR) antagonist
Naloxone is an opioid receptor (OR) antagonist
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Methadone is a ___ ___
Methadone is a μ (mu) agonist (activates)
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Methadone is a ___ ___
Methadone is a μ (mu) agonist (activates)
195
Who are first responders
firefighters and EMS
196
3 types of major opioids
1) Natural
2) Semi-synthetic
3) Synthetic
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Natural opioid sources: ___- alkaloid-laden latex, __, ___
Natural opioid source: opium- alkaloid-laden latex, morphine, codeine
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Semi-synthetic opioid sources: __, __-___/-morphone, ___, __, __ ,___
Semi-synthetic opioid sources: heroin, hydro-codone/-morphone, oxycodone, krokodil, buprenorphine, etorphine
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Synthetic opioid sources: __, ___,__,__
Synthetic opioid sources: methadone, meperidine, tramadol, fentanyl
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Opium is a key source for many narcotics including __ and ___
Opium is a key source for many narcotics including morphine and codeine
201
Morphine is __x __ potent than opium
Morphine is 10x more potent than opium
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__ converts codeine to morphine in brain and __
CYP2D6 converts codeine to morphine in brain and liver
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__% of Caucasians have deficient ___ --> codeine having no effect
10% of Caucasians have deficient CYP2D6 --> codeine having no effect
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__% of population has overactive CYP2D6 --> __ ___
2% of population has overactive CYP2D6 --> morphine intoxication
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Semi-synthetic means
produced by modifying a naturally- derived chemical
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Heroin has 2 __ groups which make the molecule 10x more __
Heroin has 2 acetyl groups which make the molecule 10x more lipophilic
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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
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Candace __ and Sol __ discovered __ ___ in the brain
Candace Pert and Sol Snyder discovered opioid receptors in the brain
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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)
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Pre-synaptic receptors modulate ___ ___ (e.g. DA, NE, GABA)
Pre-synaptic receptors modulate NT release (e.g. DA, NE, GABA)
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Post-synaptic receptors alter __ __
Post-synaptic receptors alter membrane potential
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__ different peptide ligands, endorphins are known
18 different peptide ligands, endorphins are known
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Endogenous opioids are involved in ___, ___ __, __, __, __, _, __ and __ dependence
Endogenous opioids are involved in pain, emotional responses, euphoria, eating, memory, stress , seizures and alcohol dependence
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μ opioid receptors (MORs) are expressed in..
VTA, NAc, PAG, Hypothalamus, LC, Brainstem, Pupils and GI tract
215
Most opioids bind ___ receptors
Most opioids bind μ receptors
216
μ opioid receptors (MORs) are involved in
reward, addiction, analgesia- reduces pain (euphoria/Anxiolytic- to reduce anxiety, respiration, BP, nausea, itch, constriction and constipation
217
δ opioid receptors (DORs) are expressed in the..
neocortex, striatum, NAc, Substantia nigra, olfactory bulb
218
δ(delta) opioid receptors (DORs) are bound by
enkephalins
218
δ(delta) opioid receptors (DORs) are bound by
enkephalins
219
κ opioid receptors (KORs) are expressed in the ...
pituitary, hypothalamus, PAG, spinal cord
220
κ opioid receptors (KORs) are bound by __, __, __ and ___
κ opioid receptors (KORs) are bound by endorphins, dynorphins, PCP and ketamine
221
Orphan opioid receptor (ORL-1 i.e. opioid receptor-like 1) are expressed in
limbic system and spinal cord
222
ORL1 or orphan opioid receptors are bound by __
buprenorphine
223
Illegal fentanyl comes mostly from __ to Canada
Illegal fentanyl comes mostly from Asia to Canada
224
Fentanyl looks like __ ___
Fentanyl looks like 80mg oxycontin (painkiller)
225
Fentanyl is sold as __
heroin
226
Fentanyl is __x __ potent than morphine
Fentanyl is 100x more potent than morphine
227
Fentanyl is __- __x __ potent than heroin
Fentanyl is 40- 50x more potent than heroin
228
Fentanyl is highly lipo__
Fentanyl is highly lipophilic
229
Fentanyl derivatives are ___ ___ potent
Fentanyl derivatives are even more potent
230
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
231
Street opioids are often ___ with additional adulterants like ___
Street opioids are often contaminated with additional adulterants like fentanyl
232
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
233
Chasing the dragon method
heating up tin foil and inhaling fumes, commonly smoked in a pipe
234
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
235
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)
236
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
237
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'
238
Heroin injection results in __ blood flow, __ and __ to form
Heroin injection results in uneven blood flow, thrombosis and clots to form
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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
240
Opioids are metabolized in the __ and __, and excreted by ___ and __
Opioids are metabolized in the liver and brain , and excreted by kidneys and feces
241
Heroin is metabolized to ___ in the brain
Heroin is metabolized to morphine in the brain
242
the 2 MAM (monoacetylmorphine) intermediates are ___ and ___
the 2 MAM (monoacetylmorphine) intermediates are 3-MAM and 6-MAM
243
_-MAM binds MOR while _-MAM does not
6-MAM binds MOR while 3-MAM does not
244
_-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
245
Acute effects of opioids to the skin
lowered body temperature, flushed skin and itching
246
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
247
Effects of opioids on medulla
lowers BP(hypotension) bronchoconstriction, itching from histamine release
248
Effects of opioids on brain
euphoria, well-being and tranquility, mental clouding, impaired judgement, decreased attention and memory
249
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
250
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
251
Mu, delta and kappa opioid receptors (ORs) come from separate ___ __
Mu, delta and kappa opioid receptors (ORs) come from separate Opr genes
252
ORL orphan display __ __
ORL orphan display structural homology
253
Most opioid effects are due to __ signaling
Most opioid effects are due to mu signaling
254
All endogenous opioids contain an N-___ ___ residue
All endogenous opioids contain an N-terminal tyrosine residue
255
Morphine structure mimics ___
Morphine structure mimics tyrosine
256
All opioid receptors (Ors) are ___ linked via ___
All opioid receptors (Ors) are GPCRs linked via Gi/o
257
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
