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PMCOL 305 > Midterm 2 > Flashcards

Midterm 2 Flashcards

1
Q

How AMPH (amphetamines) are absorbed?

A

injected, ingested, snorted or smoked

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2
Q

Onset is fastest by ___ < ___< ___<___

A

Onset is fastest by smoking < injection < snorting < ingesting

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3
Q

Ice is to ___ what ___ is to cocaine

A

Ice is to meth what crack is to cocaine

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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

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5
Q

Meth high lasts ___ than cocaine

A

Meth high lasts much longer than cocaine

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6
Q

Liver ___ metabolizes meth and AMPH (amphetamine)

A

Liver CYP2D6 metabolizes meth and AMPH (amphetamine)

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7
Q

4-HA and nor-ephedrine are ___

A

4-HA and nor-ephedrine are stimulants

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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)

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9
Q

AMPH can be broken down into ___ and ____

A

AMPH can be broken down into 4-HA and nor ephedrine

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10
Q

TAAR is an intracellular ____

A

TAAR is an intracellular GPCR (G-protein-coupled receptor)

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11
Q

Monoamine oxidase (MAO) degrades monoamine ____ like ___, NE, ___

A

Monoamine oxidase (MAO) degrades monoamine NTs like DA, NE, 5HT

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12
Q

AMPH/METH excretion via

A

kidney, sweat, saliva

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13
Q

Acute effects of AMPH: ___, energy, ___, grandiosity, ____ appetite

A

Acute effects of AMPH: euphoria, energy, aggression, grandiosity, decreased appetite

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14
Q

AMPH is sympathomimetic meaning that NE release is ____

A

AMPH is sympathomimetic meaning that NE release is increased

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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

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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

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17
Q

Punding

A

occurs at high doses of AMPH, repetitive meaningless behaviours; also common in Parkinson’s patients

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18
Q

AMPHs elevate __, ___, __ availability

A

AMPHs elevate DA, NE, 5HT availability

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19
Q

AMPH does not require ____-ergic ___ firing, unlike cocaine

A

AMPH does not require DA-ergic neuron firing, unlike cocaine

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20
Q

DAT transporter ___ meth into nerve ____

A

DAT transporter brings meth into nerve terminals

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21
Q

Meth can enter via DAT transporter and by ___

A

Meth can enter via DAT transporter and by diffusion

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22
Q

VMAT (vesicular monoamine transporter) pumps meth into ___ ___

A

VMAT (vesicular monoamine transporter) pumps meth into storage vesicles

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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

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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

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25
Q

Adverse effects of acute use of AMPH:
- ___ from contaminants
- combining with other drugs can ___ ____ effects

A

Adverse effects of acute use of AMPH:
- poisoning from contaminants
- combining with other drugs can enhance stimulant effects

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26
Q

Tolerance to AMPH is caused by ___, __, and ____ depletion via displacement of these NTs from terminals

A

Tolerance to AMPH is caused by DA , 5HT , and NE depletion via displacement of these NTs from terminals

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27
Q

Inhibition of tyrosine hydroxylase enzyme ____ synthesis of DA and NE

A

Inhibition of tyrosine hydroxylase enzyme reduces synthesis of DA and NE

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28
Q

Acute dosing reduces ___ function, which causes subsequent dose to have greatly reduced effects

A

Acute dosing reduces DAT function, which causes subsequent dose to have greatly reduced effects

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29
Q

Withdrawal of meth is similar to cocaine but both ___ and ___

A

Withdrawal of meth is similar to cocaine but both physical and psychological

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30
Q

Withdrawal from meth includes ___,____,__,___,___

A

Withdrawal from meth includes cravings , depression, lethargy ,muscle pain ,abnormal sleep patterns

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31
Q

Chronic AMPH dosing causes reduced cell-surface expression of ___ for ___ and ___

A

Chronic AMPH dosing causes reduced cell-surface expression of transporters for DA and NE

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32
Q

Dependence is caused by TAAR activation that occurs ___ of reduced transporter expression

A

Dependence is caused by TAAR activation that occurs upstream of reduced transporter expression

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33
Q

Long-term consequences of amphetamine use include

A

Weight loss, skin breakdown, sores, picking, poor oral hygiene, tooth decay, jaw grinding tic

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34
Q

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

A

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

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35
Q

DA depletion is significant in __, ___ and ___-__ brain regions

A

DA depletion is significant in movement, memory and decision-making brain regions

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36
Q

Another long-term consequence of amphetamine use is damage to __, __, ___ terminals

A

Another long-term consequence of amphetamine use is damage to DA, NE, 5HT terminals

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37
Q

As cells recover from MAO inhibition that occurs at __ ___ concentrations, elevated DA metabolism results in ___ ___ formation which damages cell membrane, __, ___

A

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

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38
Q

Excitotoxicity stresses neurons and induces cell death which results in ___ ___

A

Excitotoxicity stresses neurons and induces cell death which results in brain damage

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39
Q

Neuron loss in the limbic system underlies __-__ ___ in AMPH

A

Neuron loss in the limbic system underlies long-term symptoms in AMPH

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40
Q

Damage is measured by reduced volume= __number of neurons

A

Damage is measured by reduced volume= reduced number of neurons

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41
Q

___ losses correlate with word-recall issues in long-term meth users

A

hippocampal losses correlate with word-recall issues in long-term meth users

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42
Q

As DA-ergic neurons die meth addicts are ~75% more likely to develop ____

A

As DA-ergic neurons die meth addicts are ~75% more likely to develop Parkinsonism

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43
Q

AMPH may trigger nicotinic acetylcholine receptors (nAChRs),allowing __ influx leading to ___ __ species production and ___ ___

A

AMPH may trigger nicotinic acetylcholine receptors (nAChRs),allowing Ca influx leading to reactive oxygen species production and cellular stress

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44
Q

Forms of inhalants

A

gases and liquids that are inhaled directly or via an accessory e.g. rag, bag

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45
Q

Inhalants are mixtures of several ___ ____

A

Inhalants are mixtures of several lipophilic chemicals

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46
Q

Administration by inhalation includes…

A

huffing, sniffing and bagging

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47
Q

Inhalants have ___ and ___ distribution, similar to anesthetics

A

Inhalants have rapid and wide distribution, similar to anesthetics

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48
Q

The more volatile inhalants i.e. gases under standard conditions are mostly ___

A

The more volatile inhalants i.e. gases under standard conditions are mostly exhaled

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49
Q

Inhalants can reduce blood pH at higher doses= ___

A

Inhalants can reduce blood pH at higher doses= acidosis

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50
Q

Inhalants are metabolized by

A

Liver CYP2E1

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51
Q

Inhalants are excreted via

A

kidneys and breath

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52
Q

The acute effects of inhalants are similar to ___, ___, ___

A

The acute effects of inhalants are similar to alcohol, sedatives, hypnotics

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53
Q

Inhalants are __ for 15-45 minutes then after 1-2 hours ___, ___, ____,___ occurs first then ___, ___,___

A

Inhalants are biphasic for 15-45 minutes then after 1-2 hours euphoria, disinhibition, dizziness, light-headedness occurs first then drowsiness, disorientation, headaches

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54
Q

At low doses of inhalants there is ___ of motor circuits

A

At low doses of inhalants there is disinhibition of motor circuits

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55
Q

Other acute effects of inhalants include..

A

slurred speech and inebriation (drunkenness)

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56
Q

___, ___, ___ and ___ can happen at high doses of inhalants

A

Hallucinations, anesthesia , coma and death can happen at high doses of inhalants

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57
Q

Toluene leads to ___ and ___ via __ –> ___ pathway, elevated striatal DA levels

A

Toluene leads to reward and euphoria via VTA –> NAc pathway, elevated striatal DA levels

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58
Q

Toluene can be found in..

A

paints and glues

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59
Q

Motor effects by inhalants are regulated in part by ___ in the caudate putamen in mice

A

Motor effects by inhalants are regulated in part by GABA in the caudate putamen in mice

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60
Q

Toluene potentiates (increases power of) ___ and ___ neurotransmitters

A

Toluene potentiates GABA and glycine neurotransmitters

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61
Q

Toluene inhibits __ ___ receptors and ___

A

Toluene inhibits NMDA Glu receptors and nAChRs

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62
Q

Toluene causes direct activation of ___ __-ergic projections to the NAc which leads to ___-mediated reinforcement

A

Toluene causes direct activation of VTA DA-ergic projections to the NAc which leads to DA-mediated reinforcement

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63
Q

The NMDA __-containing channels are most sensitive

A

The NMDA 2B-containing channels are most sensitive

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64
Q

Cultured hippocampal neurons are insensitive to __ in presence of toluene

A

Cultured hippocampal neurons are insensitive to ACh in presence of toluene

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65
Q

An acute adverse effect of intoxication by inhalation includes ___ of the heart to ___

A

An acute adverse effect of intoxication by inhalation includes sensitization of the heart to epinephrine

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66
Q

Cardiac dysrhythmias caused by intoxication to inhalants is a result of inhibited __ of voltage-gated __ and __ channels

A

Cardiac dysrhythmias caused by intoxication to inhalants is a result of inhibited inactivation of voltage-gated Na+ and Ca2+ channels

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67
Q

__ i.e. propane/butane are common causes of ER visits

A

Lighters i.e. propane/butane are common causes of ER visits

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68
Q

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

A

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

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68
Q

___ is especially prevalent with glue sniffing

A

trauma is especially prevalent with glue sniffing

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69
Q

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

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

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70
Q

Structural changes in hippocampus as a result of inhalation can happen as quickly as ___

A

Structural changes in hippocampus as a result of inhalation can happen as quickly as 4 days

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71
Q

40-day 200 ppm toluene cycle causes ___ __ in hippocampal __ and ___ regions which correlate with ___ ___

A

40-day 200 ppm toluene cycle causes neuronal death in hippocampal CA1 and CA3 regions which correlate with memory loss

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72
Q

Long-term damage of brain regions like __ ___, ___, ___ and ___ is a result of inhalant abuse

A

Long-term damage of brain regions like basal ganglia, cerebellum, thalamus and pons is a result of inhalant abuse

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73
Q

Myelin loss (a long-term health risk associated with inhalant abuse) results in __ ___, __ __ and cerebellar ataxia i.e. clumsy voluntary movements

A

Myelin loss (a long-term health risk associated with inhalant abuse) results in cognitive decline, slower processing and cerebellar ataxia

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74
Q

Because myelin is a ___ substance (70% ___), __ accumulate

A

Because myelin is a fatty substance (70% lipid), inhalants accumulate

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75
Q

Ecstasy was synthesized in 1912 by __ at Merck (a drug company)

A

Ecstasy was synthesized in 1912 by Kollisch at Merck (a drug company)

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76
Q

Alexander ___ published first pharmacological ecstasy in 1960 at DOW Chemicals

A

Alexander Shulgin published first pharmacological ecstasy in 1960 at DOW Chemicals

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77
Q

MDMA/Ectasy can be derived from natural sources like being extracted from cured ___ ___, ___ ___, or ___ ___ root bark or synthetic sources

A

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

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78
Q

Ecstasy aka 3,4- methylenedioxymethamphetamine is classified as a ___, similarity to mescaline

A

Ecstasy aka 3,4- methylenedioxymethamphetamine is classified as a hallucinogen, similarity to mescaline

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79
Q

MDMA/Ecstasy is excreted by

A

the kidneys, 20% unchanged

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80
Q

MDMA is an ___ / an ____ (type of psychoactive drug known to impact the emotional and social behavior of the user)

A

MDMA is an empathogen/ an entactogen

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81
Q

Acute effects of MDMA include __, __ __, __, __ self-esteem

A

Acute effects of MDMA include euphoria, emotional empathy, energy, enhanced self-esteem

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82
Q

MDMA is ___ : increases heart rate, hyperthermia, diaphoresis

A

MDMA is sympathomimetic : increases heart rate, hyperthermia, diaphoresis

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83
Q

In a higher dose, MDMA acts as a serotonin ___, causing an increase in serotonin release and blocking its uptake

A

In a higher dose, MDMA acts as a serotonin agonist, causing an increase in serotonin release and blocking its uptake

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84
Q

Because MDMA is a 5HT 1B/2 ___ it causes __ (jaw grinding) and increased ___

A

Because MDMA is a 5HT 1B/2 agonist it causes bruxism (jaw grinding) and increased locomotion

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85
Q

MDMA/ Ecstasy reverses ___ transporter and also blocks __ and __ transporters

A

MDMA/ Ecstasy reverses 5HT transporter and also blocks NE and DA transporters

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86
Q

MDMA __ cortisol which is correlated with feelings of __ and ___, increases blood glucose too

A

MDMA increases cortisol which is correlated with feelings of excitement and happiness, increases blood glucose too

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87
Q

MDMA shifts activation towards ___ ___ (thoughtfulness), decreases ___ activity (fear, rage)

A

MDMA shifts activation towards ventral striatum (thoughtfulness), decreases amygdala activity (fear, rage)

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88
Q

___ exemplify pro-social effects of MDMA

A

Cephalopods exemplify pro-social effects of MDMA

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89
Q

Tolerance of MDMA is due to a decrease in __ transporter activity (__ and ___ too)and depletion of neurotransmitters

A

Tolerance of MDMA is due to a decrease in 5HT transporter activity (DA and NE too), transporter expression decreasing and depletion of neurotransmitters

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90
Q

MDMA withdrawal results in the inability to ___ and can be ___ –> “suicide Tuesdays”

A

MDMA withdrawal results in the inability to thermoregulate and can be lethal –> “suicide Tuesdays”

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91
Q

Dependence on MDMA is more ___ than __

A

Dependence on MDMA is more psychological than physical

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92
Q

Biased agnoism in 5HT2C receptor agonism may underlie MDMA’s ___ ___ risk

A

Biased agnoism in 5HT2C receptor agonism may underlie MDMA’s low addiction risk

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93
Q

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

A

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

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94
Q

Combining MDMA with ___ (antidepressants) reduces its effects due to competition for ____ transporters

A

Combining MDMA with SSRI (antidepressants) reduces its effects due to competition for 5HT transporters

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95
Q

Combining MDMA with ___ inhibitors can potentiate (make stronger) effects of MDMA due to increased ___ availability

A

Combining MDMA with MAO inhibitors can potentiate effects of MDMA due to increased NT availability

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96
Q

___ is the most common cause of overdose death

A

hyperthermia is the most common cause of overdose death

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97
Q

___ 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 ___)

A

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)

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98
Q

Long-term health effects of MDMA are ___ and ___ deficits

A

Long-term health effects of MDMA are memory and attention deficits

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99
Q

Yeast has a ___ generation time

A

Yeast has a fast generation time

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100
Q

Yeast is ___ for long-term storage, and __ for use

A

Yeast is dried for long-term storage, and rehydrated for use

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101
Q

Yeast has genomes that __ ___

A

Yeast has genomes that fully sequenced

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102
Q

Yeast is a model organism for __, __ __ and ___

A

Yeast is a model organism for aging, DNA repair and brewing

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103
Q

Yeast has __ ___ strains available which optimizes it for application

A

Yeast has multiple unique strains available which optimizes it for application

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104
Q

___% ethanol is toxic to yeast

A

15% ethanol is toxic to yeast

105
Q

___ concentrates the concentration of alcohol to __%+

A

distillation concentrates the concentration of alcohol to 40%+

106
Q

Proof is __ the alcohol (ethanol) content by volume e.g. a whisky with 50% alcohol is __-proof whiskey

A

Proof is twice the alcohol (ethanol) content by volume e.g. a whisky with 50% alcohol is 100-proof whiskey

107
Q

The two main methods for indicating the alcoholic content of a beverage are ___ (ABV) and ___

A

The two main methods for indicating the alcoholic content of a beverage are alcohol-by-volume (ABV) and proof

108
Q

Common molecules found in wine, beer and scotch are

A

anthocynanins, terpenes, tannins, vitamins and polyphenols

109
Q

4 categories of alcohol use

A

1) Abstinent
2) Moderate
3) Bingeing
4) Heavy (Alcoholic)

110
Q

Bingeing is __or __ drinks on one occasion in the last __ days for men or women

A

Bingeing is 5 or 4 drinks on one occasion in the last 30 days for men or women

111
Q

How much ethanol (EtOH) in a standardized drink?

A

13.98 g

112
Q

ethanol is absorbed in the __ __

A

ethanol is absorbed in the small intestine

113
Q

food ___ retention time of ethanol in the stomach which __ absorption of it

A

food increases retention time of ethanol in the stomach which slows absorption of it

114
Q

low pH does/does not alter ethanol

A

low pH does not alter ethanol

115
Q

Alcohol distributes through ___ tissues

A

Alcohol distributes through aqueous tissues

116
Q

volume available for distribution determines ___

A

volume available for distribution determines BAC (blood alcohol content)

117
Q

higher proportion of body fat = ___ BAC after 1 drink

A

higher proportion of body fat = higher BAC after 1 drink

118
Q

The average man is __% water and average woman is __% water

A

The average man is 53.4% water and average woman is 48.5% water

119
Q

BAC is slightly higher in ___ than ___

A

BAC is slightly higher in females than males

120
Q

Ethanol is ___ ___ throughout tissues

A

Ethanol is freely distributed throughout tissues

121
Q

Acute effects of EtOH are __

A

Acute effects of EtOH are biphasic

122
Q

What causes the phases of the acute effect of EtOH

A

metabolism

123
Q

EtOH ___ sociability and ___ anxiety especially in adolescent animals

A

EtOH increases sociability and decreases anxiety especially in adolescent animals

124
Q

EtOH brain effects

A

inhibits decision-making and judgements
unstable mood and heightened emotion
decreased anxiety
increased aggression
increased addiction

125
Q

EtOH mouth effects

A

increased salivation and appetite

126
Q

EtOH stomach effects

A

increased gastric HCI secretion
increased insulin sensitivity in non-diabetics

127
Q

Other EtOH acute effects

A

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
Q

EtOH blood effects

A

dilated blood vessels of skin
reduced blood clotting
increased HDL (cholesterol) levels

129
Q

EtOH kidney effects

A

inhibited anti-diuretic hormone and increased urination

130
Q

EtOH reproductive effects

A

inconsistent effects on reproductive system

131
Q

EtOH causes vaso____

A

EtOH causes vasodilation

132
Q

EtOH causes ____ gastric/salivary secretions

A

EtOH causes increased gastric/salivary secretions

133
Q

EtOH causes loss of stomach mucosal lining leading to ___

A

EtOH causes loss of stomach mucosal lining leading to ulcers

134
Q

EtOH affects neurotransmitters…

A

GABA, Glutamate, Dopamine and endogenous opioids

135
Q

___% of EtOH is metabolized in the liver, __% is excreted untouched by breath, urine, skin etc. , ___% metabolized in stomach, ___% other

A

90% of EtOH is metabolized in the liver, 2% is excreted untouched by breath, urine, skin etc. , 3% metabolized in stomach, 5% other

136
Q

When driving under the influence the amount of alcohol exhaled is ____ the concentration in the blood, this is set as the ___ of ___ ____ tests (BrAC)

A

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
Q

what % of alcohol is lethal

A

0.4-0.5%

138
Q

The ___ are also a common side-effect of excessive drinking EtOH

A

The spins are also a common side-effect of excessive drinking EtOH

139
Q

Steps that alcohol causes the spins

A

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
Q

over-suppressed/decreased activity by high dose ethanol leads to ___ ___ amnesia

A

over-suppressed/decreased hippocampal activity by high dose ethanol leads to transient anterograde amnesia

141
Q

Hippocampal dentate gyrus neurons are ___ to
ethanol damage

A

Hippocampal dentate gyrus neurons are susceptible to
ethanol damage

142
Q

Chronic alcoholism can coincide with ___
___ (e.g. thiamine)

A

Chronic alcoholism can coincide with nutritional
deficiencies (e.g. thiamine)

143
Q

Alcohol-related brain damage (ARBD) is driven by
__-____ signaling that induces ___ ___ and death

A

Alcohol-related brain damage (ARBD) is driven by
pro-inflammatory signaling that induces cellular damage and death

144
Q

metabolites are ___

A

metabolites are toxic

145
Q

Dropping BAC ….
- ____ GABA A receptor IPSPs
- Blocks ___ (GluN) receptor EPSPs
- Blocks select __ channels

A

Dropping BAC ….
- Potentiates/enhances GABA A receptor IPSPs
- Blocks NMDA (GluN) receptor EPSPs
- Blocks select Ca channels

146
Q

Alcohol acute –> chronic effects (How tolerance is developed):
- GABA A receptor functions ____
- NMDA (GluN) receptors ___-regulated
- Ca channel receptors ___-regulated

A

Alcohol acute –> chronic effects (How tolerance is developed):
- GABA A receptor functions decrease
- NMDA (GluN) receptors up-regulated
- Ca channel receptors up-regulated

147
Q

Metabolic tolerance of EtOH causes ___ levels to go up

A

Metabolic tolerance of EtOH causes CYP2E1 levels to go up

148
Q

CYP2E1 knockout prevents ___-induced liver damage

A

CYP2E1 knockout prevents EtOH-induced liver damage

149
Q

Overactive CYP2E1 induces ___ EtOH damage

A

Overactive CYP2E1 induces more EtOH damage

150
Q

Alcohol withdrawal syndrome (AWS) have symptoms that are both __ and ___

A

Alcohol withdrawal syndrome (AWS) have symptoms that are both physical and psychological

151
Q

Physical syndromes of a hangover/AWS

A

headache, diarrhea, fatigue, restlessness, nausea

152
Q

Psychological syndromes of a hangover/AWS

A

haziness, slower thought/cognition, impaired reaction times and poor reasoning

153
Q

Congener

A

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
Q

Hangover severity increases with increased ___ content

A

Hangover severity increases with increased congener content

155
Q

Brandy results in a ___(Stronger/weaker) hangover than vodka

A

Brandy results in a stronger hangover than vodka

156
Q

Symptom(s) of stage 1 of alcohol withdrawal

A

elevated heart rate/bp, diaphoresis(sweating), tremors , no appetite, insomnia

157
Q

Symptom(s) of stage 2 of alcohol withdrawal

A

hallucinations

158
Q

Symptom (s) of stage 3 of alcohol withdrawal

A

delusions, delirium, amnesia, tremens peak 3-4 days after last drink

159
Q

Symptom (s) of stage 4 of alcohol withdrawal

A

seizures

160
Q

Alcohol withdrawal is ___ severe than most other drugs e.g. heroin, meth

A

Alcohol withdrawal is more severe than most other drugs e.g. heroin, meth

161
Q

Goal of treatment for AWS/hangover is to prevent withdrawal stages __ and __

A

Goal of treatment for AWS/hangover is to prevent withdrawal stages 3 and 4

162
Q

___ or ___ is used for reducing AWS severity

A

Benzodiazepines or ketamine is used for reducing AWS severity

163
Q

Clonidine is a pre-synaptic __ adrenegic ___ that prevents excessive neurotransmitter released (reducing over-excitation from AWS)

A

Clonidine is a pre-synaptic α2 adrenegic agonist that prevents excessive neurotransmitter released (reducing over-excitation from AWS)

164
Q

Propranolol is a __ adrenergic ___ that reduces sympathetic effects and tremor seen in AWS

A

Propranolol is a β adrenergic antagonist that reduces sympathetic effects and tremor seen in AWS

165
Q

Disulfiram inhibits ___ ___, causing build-up of __ and the aim of it is to prevent ___use but does not decrease ___

A

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
Q

Naltrexone and nalmefene aopioid antagonists are used as treatments for AWS because they prevent ___-ergic reward

A

Naltrexone and nalmefene aopioid antagonists are used as treatments for AWS because they prevent DA-ergic reward

167
Q

The NAc has 2 regions …

A

the core and shell

168
Q

___ brain volume in alcoholics compared to healthy controls because ___ ___ off

A

reduced brain volume in alcoholics compared to healthy controls because neurons die off

169
Q

Gross changes in brain health and appearance is induced by ___/___ production in the brain

A

Gross changes in brain health and appearance is induced by ROS/acetaldehyde production in the brain

170
Q

Changes in the brain caused by alcohol affects __ metabolism, ___ synthesis, ___ formation all of which damage neurons and cause ___ death

A

Changes in the brain caused by alcohol affects glucose metabolism, protein synthesis, myelin formation all of which damage neurons and cause cell death

171
Q

Hyperactive __ systems cause ___ via excessive Ca influx leading to __ ___

A

Hyperactive Glu systems cause excitotoxicity via excessive Ca influx leading to cell death

172
Q

People with low baseline __-___ levels are prone to drinking more alcohol

A

People with low baseline beta-endorphin levels are prone to drinking more alcohol

173
Q

Heavy drinkers often suffer from ___

A

Heavy drinkers often suffer from malnutrition

174
Q

EtOH contains __ energy than carbs and proteins

A

EtOH contains more energy than carbs and proteins

175
Q

CYP2E1 produces ___ ____ like ___ and ___

A

CYP2E1 produces reactive species like acetaldehyde and ROS

176
Q

ROS reacts with __-___ systems under controlled conditions

A

ROS reacts with anti-oxidant systems under controlled conditions

177
Q

At elevated levels, __-___ systems are overwhelmed

A

At elevated levels, anti-oxidant systems are overwhelmed

178
Q

If the cell cannot detoxify, it becomes ___, __ leads to __ & __ damage, __, cell death

A

If the cell cannot detoxify, it becomes stressed, stress leads to membrane & DNA damage, cancer, cell death

179
Q

Metabolic switch in the liver caused by EtOH abuse results in ___ ___ disease

A

Metabolic switch in the liver caused by EtOH abuse results in fatty liver disease

180
Q

Fatty liver disease progresses to ___

A

Fatty liver disease progresses to cirrhosis

181
Q

Cirrhosis is characterized by a ___ ___ state and cell death

A

Cirrhosis is characterized by a chronic inflammatory state and cell death

182
Q

TGF-beta cytokine production by infiltrating immune cells triggers ___ changes

A

TGF-beta cytokine production by infiltrating immune cells triggers transcriptional changes

183
Q

__% of cancers are linked to alcohol consumption

A

50% of cancers are linked to alcohol consumption

184
Q

The ___ ___ ___ is susceptible to cancer because microflora contribute to EtOH metabolism

A

The upper GI tract is susceptible to cancer because microflora contribute to EtOH metabolism

185
Q

acetaldehyde concentrations are __ in the blood

A

acetaldehyde concentrations are higher in the blood

186
Q

4MP is an ___ ___ (ADH) __

A

4MP is an alcohol dehydrogenase (ADH) inhibitor

187
Q

Mechanism of oncogenesis/tumors because of alcohol

A

1) acetaldehyde interferes with DNA synthesis and repair
2) Binds and inactivates DNA repair proteins
3) Causes mutations and chromosomal abnormalities

188
Q

Cardioprotective effects:
- __ doses, 1 drink per 1-2 days
- wine several ___ ___, increases ___ which prevents lipid deposition in arteries (anti-atherosclerotic), decreases ___ ___

A

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
Q

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 __

A

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
Q

What are some medical uses for opioids

A

used for pain- an anti- nociceptive (blocks detection of painful stimulus), blocks afferent transmission in the spinal cord/brainstem

191
Q

Opioids can be __ and ___ when used appropriately

A

Opioids can be safe and effective when used appropriately

192
Q

Lethal mix= __ + ___

A

Lethal mix= opioids + sedatives

193
Q

Naloxone is an ___ ___ (OR) antagonist

A

Naloxone is an opioid receptor (OR) antagonist

194
Q

Methadone is a ___ ___

A

Methadone is a μ (mu) agonist (activates)

194
Q

Methadone is a ___ ___

A

Methadone is a μ (mu) agonist (activates)

195
Q

Who are first responders

A

firefighters and EMS

196
Q

3 types of major opioids

A

1) Natural
2) Semi-synthetic
3) Synthetic

197
Q

Natural opioid sources: ___- alkaloid-laden latex, __, ___

A

Natural opioid source: opium- alkaloid-laden latex, morphine, codeine

198
Q

Semi-synthetic opioid sources: __, __-___/-morphone, ___, __, __ ,___

A

Semi-synthetic opioid sources: heroin, hydro-codone/-morphone, oxycodone, krokodil, buprenorphine, etorphine

199
Q

Synthetic opioid sources: __, ___,__,__

A

Synthetic opioid sources: methadone, meperidine, tramadol, fentanyl

200
Q

Opium is a key source for many narcotics including __ and ___

A

Opium is a key source for many narcotics including morphine and codeine

201
Q

Morphine is __x __ potent than opium

A

Morphine is 10x more potent than opium

202
Q

__ converts codeine to morphine in brain and __

A

CYP2D6 converts codeine to morphine in brain and liver

203
Q

__% of Caucasians have deficient ___ –> codeine having no effect

A

10% of Caucasians have deficient CYP2D6 –> codeine having no effect

204
Q

__% of population has overactive CYP2D6 –> __ ___

A

2% of population has overactive CYP2D6 –> morphine intoxication

205
Q

Semi-synthetic means

A

produced by modifying a naturally- derived chemical

206
Q

Heroin has 2 __ groups which make the molecule 10x more __

A

Heroin has 2 acetyl groups which make the molecule 10x more lipophilic

207
Q

Early 1960s resulted in the synthesis of ___ which can reverse morphine effects

A

Early 1960s resulted in the synthesis of naloxone which can reverse morphine effects

208
Q

Candace __ and Sol __ discovered __ ___ in the brain

A

Candace Pert and Sol Snyder discovered opioid receptors in the brain

209
Q

Pert and Snyder found 4 classes of pre- and post-synaptic opioid receptors which were __, ___, __ and __

A

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)

210
Q

Pre-synaptic receptors modulate ___ ___ (e.g. DA, NE, GABA)

A

Pre-synaptic receptors modulate NT release (e.g. DA, NE, GABA)

211
Q

Post-synaptic receptors alter __ __

A

Post-synaptic receptors alter membrane potential

212
Q

__ different peptide ligands, endorphins are known

A

18 different peptide ligands, endorphins are known

213
Q

Endogenous opioids are involved in ___, ___ __, __, __, __, _, __ and __ dependence

A

Endogenous opioids are involved in pain, emotional responses, euphoria, eating, memory, stress , seizures and alcohol dependence

214
Q

μ opioid receptors (MORs) are expressed in..

A

VTA, NAc, PAG, Hypothalamus, LC, Brainstem, Pupils and GI tract

215
Q

Most opioids bind ___ receptors

A

Most opioids bind μ receptors

216
Q

μ opioid receptors (MORs) are involved in

A

reward, addiction, analgesia- reduces pain (euphoria/Anxiolytic- to reduce anxiety, respiration, BP, nausea, itch, constriction and constipation

217
Q

δ opioid receptors (DORs) are expressed in the..

A

neocortex, striatum, NAc, Substantia nigra, olfactory bulb

218
Q

δ(delta) opioid receptors (DORs) are bound by

A

enkephalins

218
Q

δ(delta) opioid receptors (DORs) are bound by

A

enkephalins

219
Q

κ opioid receptors (KORs) are expressed in the …

A

pituitary, hypothalamus, PAG, spinal cord

220
Q

κ opioid receptors (KORs) are bound by __, __, __ and ___

A

κ opioid receptors (KORs) are bound by endorphins, dynorphins, PCP and ketamine

221
Q

Orphan opioid receptor (ORL-1 i.e. opioid receptor-like 1) are expressed in

A

limbic system and spinal cord

222
Q

ORL1 or orphan opioid receptors are bound by __

A

buprenorphine

223
Q

Illegal fentanyl comes mostly from __ to Canada

A

Illegal fentanyl comes mostly from Asia to Canada

224
Q

Fentanyl looks like __ ___

A

Fentanyl looks like 80mg oxycontin (painkiller)

225
Q

Fentanyl is sold as __

A

heroin

226
Q

Fentanyl is __x __ potent than morphine

A

Fentanyl is 100x more potent than morphine

227
Q

Fentanyl is __- __x __ potent than heroin

A

Fentanyl is 40- 50x more potent than heroin

228
Q

Fentanyl is highly lipo__

A

Fentanyl is highly lipophilic

229
Q

Fentanyl derivatives are ___ ___ potent

A

Fentanyl derivatives are even more potent

230
Q

Fentanyl derivatives have higher potency because they have increased affinity for __ receptors and enhanced ___ ___ __ ___

A

Fentanyl derivatives have higher potency because they have increased affinity for mu receptors and enhanced entry into the brain

231
Q

Street opioids are often ___ with additional adulterants like ___

A

Street opioids are often contaminated with additional adulterants like fentanyl

232
Q

Most opioids undergo extensive __-___ ___ in the liver before entering the systemic circulation reducing their ___

A

Most opioids undergo extensive first-pass metabolism in the liver before entering the systemic circulation reducing their bioavailability

233
Q

Chasing the dragon method

A

heating up tin foil and inhaling fumes, commonly smoked in a pipe

234
Q

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

A

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
Q

The effect of chasing the dragon method seems to be because of __ ___

A

The effect of chasing the dragon method seems to be because of metal toxicity (from the fumes of the tin foil)

236
Q

To inject heroin…

A

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
Q

Heroin injection leaves __ ___ because of the damage to __ by the needle, the drug, injection __, ___ or ‘__’ (blood being re-injected)

A

Heroin injection leaves track marksbecause of the damage to vessels by the needle, the drug, injection rate, infection or ‘flushing’

238
Q

Heroin injection results in __ blood flow, __ and __ to form

A

Heroin injection results in uneven blood flow, thrombosis and clots to form

239
Q

Most opioids are not lipophilic which means they do not readily cross the ___

A

Most opioids are not lipophilic which means they do not readily cross the BBB

240
Q

Opioids are metabolized in the __ and __, and excreted by ___ and __

A

Opioids are metabolized in the liver and brain , and excreted by kidneys and feces

241
Q

Heroin is metabolized to ___ in the brain

A

Heroin is metabolized to morphine in the brain

242
Q

the 2 MAM (monoacetylmorphine) intermediates are ___ and ___

A

the 2 MAM (monoacetylmorphine) intermediates are 3-MAM and 6-MAM

243
Q

_-MAM binds MOR while _-MAM does not

A

6-MAM binds MOR while 3-MAM does not

244
Q

_-MAM is not naturally occurring and used in legal cases to establish heroin use

A

6-MAM is not naturally occurring and used in legal cases to establish heroin use

245
Q

Acute effects of opioids to the skin

A

lowered body temperature, flushed skin and itching

246
Q

Opioids cause __ pupils opposite to other drugs because of __ and __ receptors in the oculomotor nucleus

A

Opioids cause constricted pupils opposite to other drugs because of μ and kappa receptors in the oculomotor nucleus

247
Q

Effects of opioids on medulla

A

lowers BP(hypotension) bronchoconstriction, itching from histamine release

248
Q

Effects of opioids on brain

A

euphoria, well-being and tranquility, mental clouding, impaired judgement, decreased attention and memory

249
Q

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

A

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
Q

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

A

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
Q

Mu, delta and kappa opioid receptors (ORs) come from separate ___ __

A

Mu, delta and kappa opioid receptors (ORs) come from separate Opr genes

252
Q

ORL orphan display __ __

A

ORL orphan display structural homology

253
Q

Most opioid effects are due to __ signaling

A

Most opioid effects are due to mu signaling

254
Q

All endogenous opioids contain an N-___ ___ residue

A

All endogenous opioids contain an N-terminal tyrosine residue

255
Q

Morphine structure mimics ___

A

Morphine structure mimics tyrosine

256
Q

All opioid receptors (Ors) are ___ linked via ___

A

All opioid receptors (Ors) are GPCRs linked via Gi/o

257
Q

Chronic exposure to morphine results in __-__ coupled receptor kinase (GRK)-__ ___ of opioid receptors and binding of __ __→desensitization

A

Chronic exposure to morphine results in G-protein coupled receptor kinase (GRK)-mediated phosphorylation of opioid receptors and binding of β arrestin→desensitization

PMCOL 305 (3 decks)

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