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PMCOL 305 > ecstacy > Flashcards

ecstacy Flashcards

1
Q

what class is ecstasy

A

an amphetamine even though it is often classified as a hallucinogen

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2
Q

what is the difference with methamphetamines and MDMA (structurally)

A

there is a methylenedioxy ring

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3
Q

what is the general effect of the methylenedioxyring compared to meth (2)

A

it reduces stimulant effects and produces more serotonergic effects

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4
Q

what is Molly

A

powder form of ecstasy

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5
Q

what is the precursor for ecstasy

A

safrole

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6
Q

what is safrole (where from)

A

an aromatic oil obtained from distillation of the root bark of sassafras

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7
Q

what have manufacturers started doing due to the scarcity of sassafras trees

A

started using different chemicals as a starting point

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8
Q

what is a risk when manufacturers use a different chemical as a starting point

A

increased risk of contamination with PMA

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9
Q

what is the administration with ecstasy

A

pill form

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10
Q

how can molly be administered and why

A

snorted because its a powder

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11
Q

what is the rate of onset for ecstasy and why

A

slow (up to 2 hours) because it is orally ingested

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12
Q

what is “stacking”

A

when you take multiple doses simultaneously

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13
Q

what can the dose range of MDMA pills be (content of actual ecstasy)

A

10-150mg

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14
Q

when do people feel the effects of ecstasy the most (what mg dose)

A

between 75-125mg

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15
Q

what % of people use ecstasy once per week

A

10%

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16
Q

is psychological or physical dependence more with ecstasy use

A

more psychological dependence

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17
Q

how long does the ecstasy high last

A

2-3 hours

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18
Q

what kind of mood changes with ecstasy

A

positive

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19
Q

what happens to defence mechanisms with ecstasy

A

less of them

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20
Q

what does entactogens mean

A

they are drugs that increase empathy for others

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21
Q

is ecstasy an entactogen

A

yes

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22
Q

what does ecstasy do to self esteem

A

increase

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23
Q

is ecstasy stimulant or depressant

A

stimulant

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24
Q

what kind of mental disease is ecstasy maybe good for

A

PTSD

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25
Q

how does ecstasy effect octapuses

A

increases their social interactions even though they are fairly solitary

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26
Q

what NT is most effected with ecstasy

A

serotonin

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27
Q

what does high levels of serotonin cause the release of

A

oxytocin

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28
Q

what is oxytocin

A

hormone that gives feeling of empathy and bonding

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29
Q

besides 5HT, what else does ecstasy cause the release of

A

cortisol

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30
Q

what is the % increase of cortisol with ecstasy

A

800% increase

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31
Q

when is peak cortisol released timed with ecstasy use (what symptoms correlated with)

A

excitement and happiness, lack of fatigue

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32
Q

why does cortisol cause a lack of fatigue

A

because cortisol can induce glucose release

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33
Q

what are 5 physiological effects of ecstasy

A

increase HR BP
hyperactivity
hyperthermia
bruxism -jaw clenching/grinding

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34
Q

what is bruxism

A

jaw clenching / grinding

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35
Q

what causes bruxism

A

excess 5HT release

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36
Q

what is the mechanism of action of ecstasy

A

blockade and reversal of serotonin transporters

but also DA and NE transporters

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37
Q

from NE DA 5HT block with ecstasy, name in order of potency of block

A

5HT > NA > DA

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38
Q

what is the affinity of ecstasy for 5HT transporter compared to the NA transporter

A

10X higher

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39
Q

does ecstasy bind to TAAR

A

yes

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40
Q

what happens once ecstasy binds to and effects TAAR

A

induces reversal of direction of transporters

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41
Q

what does ecstasy do to vesicles

A

leaks 5HT from vesicles into the nerve ending cytoplasm

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42
Q

what does ecstasy do to MAO

A

partial inhibition

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43
Q

why is ecstasy classified as a hallucinogen

A

because its an agonist at 5HT2A receptors

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44
Q

why is ecstasy an agonist at 5HT2A receptors

A

due to the methylenedioxy ring

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45
Q

what is the main hallucinogen receptor

A

5HT2A

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46
Q

what is the % increase of DA in rats NAc with ecstasy

A

200-300%

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47
Q

what is the % increase of 5Ht in rats NAc with ecstasy

A

1400%

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48
Q

where in the brain is there an increase in 5HT

A

in prefrontal cortex and NAc and other parts of he reward pathway

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49
Q

is ecstasy as reinforcing as cocaine or meth and why

A

not as much because less DA release comparatively

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50
Q

do you see much ecstasy addiction

A

not as much as like cocaine

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51
Q

besides 5HT DA NE

where does ecstasy also bind to (3)

A

adrenergic receptors
H1 (histamine)
nAChR type alpha 7

52
Q

what happens when ecstasy binds to adrenergic receptors

A

cardiovascular effects and hyperthermia

53
Q

what happens when ecstasy binds to histamine type 1 receptors

A

acetylcholine release –> excitation (think= anti-histamines make you sleepy, so this wakes you up)

54
Q

what happens when ecstasy binds to alpha7 nAChR

A

partial agonist to increase NT release

55
Q

which enzyme metabolizes ecstasy

A

CYP2D6

56
Q

what % of ecstasy is metabolized by CYP2D6

A

80%

57
Q

what % of ecstasy is excreted unchanged in urine

A

20%

58
Q

how is ecstasy metabolized (what % is handled in what ways)

A

80% CYP2D6

20% excreted unchanged in urine

59
Q

is ecstasy or amphetamine metabolism more complicated

A

ecstasy

60
Q

how many metabolites of ecstasy are there

A

9

61
Q

what do lots of the ecstasy metabolites cause

A

apoptosis

62
Q

what is apoptosis

A

programmed cell death

63
Q

what causes the random pattern of ecstasy toxicity

A

the wide range of CYP activity in humans - some more susceptible to production of harmful metabolites than others

64
Q

how does ecstasy tolerance happen

A

decrease in transporter activity (5HT and also DAT and NAT)

65
Q

what happens to transporters at neuronal membrane with ecstasy

A

decrease

66
Q

what are 4 adverse effects following ingestion of ecstasy

A

depression, anxiety, hallucinations and paranoia

67
Q

how severe is ecstasy withdrawal

A

it can be severe

68
Q

what are 4 side effects of ecstasy withdrawal

A

lethargy, irritability, memory loss, panic

69
Q

why can there be lots of depression after ecstasy use

A

exhausted the supply of NTs such as 5HT and DA

70
Q

can ecstasy damage be lethal

A

yes

71
Q

what causes serotonin syndrome

A

abnormally high levels of 5HT

72
Q

what are 7 symptoms of serotonin syndrome

A

high BP HR, muscle rigidity, severe perspiration, delirium, diarrhea, hyperthermia, rhabdomyolysis

73
Q

what are 4 ways you can die with serotonin syndrome

A

kidney failure, convulsions, shock, death

74
Q

which drugs is ecstasy dangerous to take with

A

drugs that increase 5HT like psychiatric SSRIs

75
Q

what is weird about SSRIs and ecstasy in animal models

A

they found that SSRIs can be protective

76
Q

what is the leading cause of death for ecstasy

A

hyperthermia

77
Q

what are 2 things that make ecstasy induced hyperthermia extra lethal

A

physical exertion and warm environment

78
Q

how does excess 5HT from ecstasy cause hyperthermia

A

CNS dysregulation of body temperatures (the body doesnt know how to regulate heat anymore)

79
Q

how does excess NE from ecstasy cause hyperthermia

A

adrenergic alpha1: vasoconstrict=retain heat

adrenergic beta3: mitochondria uncoupling=generate heat

80
Q

how does NE on alpha1 cause hyperthermia

A

because it causes vasoconstriction and heat retention

81
Q

how does NE on beta3 cause hyperthermia

A

mitochondrial uncoupling, generation of heat

82
Q

how does excess DA from ecstasy cause hyperthermia

A

not sure but it does!!!!

83
Q

how long does how does ecstasys effect on thermoregulated last

A

long after the drug has left the body

84
Q

what happens once rats are exposed to ecstasy over 3 to 4 days (body temp) then 4-6 weeks later are exposed to high ambient temperature

A

they have an impaired ability to thermoregulate

85
Q

what is hyponatremia

A

low sodium in blood

86
Q

what triggers excessive thirst

A

hyperthermia

87
Q

what is water intoxication

A

huge water intake in short period of time, dilution of sodium in blood

88
Q

why can ecstasy increase water retention

A

it can trigger excessive release of ADH

89
Q

what are 2 ways that ecstasy can cause hyponatremia

A

1- hyperthermia can trigger excessive thirst

2- can trigger ADH release (water retention)

90
Q

what are 4 ways that hyponatremia can kill you

A

cerebral edema (cells absorbing too much water)
vomiting
coma
respiratory arrest (compression of brain stem)

91
Q

does ecstasy cause permanent neuronal loss

A

its controversial and contradictory

92
Q

what happens to SERT in ecstasy users

A

there are less of them

93
Q

where is most SERT lost in the brain in ecstasy users

A

occipital cortex and hippocampus

94
Q

why is it not sure if ecstasy kills off neurons

A

you dont know if you have fewer neuron or just fewer SERT proteins

95
Q

did they find volume loss (neuron loss) in ecstasy users

A

no not significant

96
Q

what is produced as a byproduct of ecstasy metabolism by MAO

A

hydrogen peroxide

97
Q

what does hydrogen peroxide form

A

hydroxyl radicals

98
Q

what can hydroxyl radicals do

A

damage lipids and proteins

99
Q

what does 5-HIAL do

A

reactive thing that damages proteins and lipids

100
Q

what is 5-HIAL

A

a breakdown product of 5HT

101
Q

what is the MAO reaction with 5HT

A

5HT –MAO–> H2O2 + 5-HIAL

102
Q

what breaks down 5-HIAL

A

aldehyde dehydrogenase

103
Q

what happens when you have ecstasy with alcohol

A

the byproduct 5-HIAL will compete with alcohol for aldehyde dehydrogenase and that will cause more damage

104
Q

what does damage to mitochondria from 5-HIAL cause

A

damage to nerve terminals and eventual cell death (damaged mitochondria cause trigger apoptosis)

105
Q

what can metabolism of ecstasy itself cause

A

quinones and semiquinones

106
Q

what do quinones and semiquinones do

A

produce large amounts of ROS

107
Q

what is the relationship between death and ecstasy dose

A

there isnt a clear relationship - sudden illness and death can occur even after small doses

108
Q

what causes some users to have fatal reactions even to very small doses

A

rare combination of variability in genes for metabolic enzymes - may lead to increased production of toxic metabolites

109
Q

what is PMA action timing compared to ecstasy

A

it has a more delayed reaction

110
Q

how potent is PMA compared to ecstasy

A

it is more potent

111
Q

what is a negative of PMA

A

it is neurotoxic

112
Q

what is a mechanism of action of PMA

A

MAO inhibitor

113
Q

what are 3 effects of PMA

A

hypoglycemia, hyperkalemia, hyperthermia

114
Q

what is the difference of PMA and PMMA (structural)

A

PMMA has an extra methyl group, more similar to meth

115
Q

is PMA or PMMA more toxic

A

likely equal

116
Q

what is the methamphetamine version of PMA

A

PMMA

117
Q

what is N-benzylpiperazine

A

synthetic compound from a family used in plastics, pesticides, resins (deworming cattle)

118
Q

what is the mechanism of action of N-benzylpiperazine

A

increases mainly DA and NE release, minor 5HT release

119
Q

what drug does N-benzylpiperazine mimic the most

A

amphetamines

120
Q

what does N-benzylpiperazine lack in terms of trying to mimic MDMA

A

not a big 5HT impact, so not the big empathy experience

121
Q

what does overdose of N-benzylpiperazine look like

A

seizures and cardiac distress hours after ingestion

122
Q

what is the mechanism of action of 3-trifluoromethylphenylpiperazine (TFMPP)

A

serotonin efflux through serotonin transporter

123
Q

what two drugs are often combined to mimic MDMA

A

3-trifluoromethylphenylpiperazine (TFMPP)

N-benzylpiperazine

124
Q

what kind of NT release does 3-trifluoromethylphenylpiperazine (TFMPP) mimic to MDMA

A

it produces both the DA and 5HT level increase that MDMA does

125
Q

what does 3-trifluoromethylphenylpiperazine (TFMPP) cause in animal models

A

rats going into convulsions

126
Q

what is 3-trifluoromethylphenylpiperazine (TFMPP) often a main ingredient of

A

E or molly

PMCOL 305 (26 decks)

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