amphetamines Flashcards
1
Q
what is amphetamine (1 word)
A
stimulant
2
Q
what is methamphetamine
A
amphetamine derivative that enters the brain more rapidly
3
Q
what is crystal meth
A
methamphetamine hydrochloride crystals - smokable
4
Q
what are the psychological effects of methamphetamine
A
euphoria, energy, alertness (same as cocaine)
5
Q
what is punding
A
repetitive meaningless behaviours
6
Q
what weird thing happens at high methamphetamine doses
A
punding
7
Q
what causes punding
A
too much DA in basal ganglia
8
Q
what is the role of the basal ganglia
A
voluntary motor control and action selection
9
Q
what medical condition is punding often found in and why
A
parkinson’s patients if medicine drastically increases DA levels
10
Q
what is a bad psychological effect of amphetamine
A
unprovoked aggression and violence
11
Q
what % of people have engaged in violent behaviour or suicide with methamphetamine
A
43% and 27%
12
Q
can methamphetamine cause paranoia and hallucination
A
yes
13
Q
what is a weird PSYCHOLOGICAL effect of methamphetamines
A
delusions of parasitosis
14
Q
do methamphetamines have local anesthetic actions
A
no
15
Q
do methamphetamines do anything to the sympathetic stimulation
A
yes, like cocaine (increased HR BP insomnia)
16
Q
what are some physiological effects of methamphetamine
A
increase BP HR, tremours, headache, sweating
17
Q
what happens to body temperature with methamphetamine
A
hyperthermia
18
Q
what 4 things can cause death from methamphetamine
A
renal and hepatic failure, strokes, seizures
19
Q
are amphetamines natural synthetic or semi
A
purely synthetic
20
Q
what are 6 ways that amphetamines have been used medically
A
asthma weight loss depression ADHD narcolepsy stimulant (soldiers)
21
Q
what 2 structures is amphetamine similar to
A
NA and DA
22
Q
which receptors do amphetamines interact with and why
A
same transporters as DA and other NTs because of close structural similarity
23
Q
why is methamphetamine the amphetamine of choice (3)
A
- extra methyl makes it easier to enter brain + more difficult to metabolize
- less peripheral more CNS effects
- smokeable
24
Q
does amphetamine or methamphetamine have more CNS effects
A
methamphetamine
25
does amphetamine or methamphetamine have more PNS effects
amphetamine
26
does amphetamine or methamphetamine get in the brain easier
methamphetamines
27
does amphetamine or methamphetamine metabolized easier
amphetamines
28
why amphetamine easier to metabolize than methamphetamine
because meth has the extra methyl group
29
what form is meth smokable in
crystalline hydrochloride form
30
where does most methamphetamine come from
mexico
31
what is the starting molecule for methamphetamine synthesis
pseudophedrine
32
what kind of dangerous waste is made to make methamphetamine
lithium batteries, sodium, match heads (phosphorus), ammonia
33
how much water is made for every 1kg of produce
5-7kg
34
how much water is made for every 10kg of produce
50-70kg
35
what is a pro to the shake and bake / one pot method of making meth
less pseudophedrine is needed
36
what is a con to the shake and bake / one pot method of making meth
can cause explosions, flash fires if O2 enters bottle too quickly
37
the pattern of use for meth is similar to what drug
cocaine (orally, snorted, smoked, injected)
38
does meth or cocaine last longer
meth
39
does meth or cocaine have to be administered more often
cocaine
40
why does meth make a rapid tolerance
because there is rapid NT depletion with high doses
41
why is cocaines high shorter lasting than meth
because it doesnt stay in the brain for as long
42
which enzyme breaks down amphetamines
CYP2D6
43
what does CYP2D6 do to amphetamines
adds OH to make it more water soluble
44
which enzyme breaks down methamphetamines
CYP2D6
45
what does CYP2D6 break methamphetamines into
amphetamines or 4-hydroxymethamphetamine
46
what are the 3 metabolites of methamphetamines and amphetamines
4-HMA
4-HA
NE
(4-hydroxymethamphetamine, 4-hydroxyamphetaminem norephedrine)
47
what does norephedrine do
mimics the effects of adrenaline at adrenergic receptors (blood vessel effect)
48
what does 4-HA do
stimulates NA release, inhibits MAO, activates TAAR
49
what does 4-HMA do
MAYBE stimulates NA release, inhibits MAO, activates TAAR
50
what does TAAR stand for
trace amine associated receptor
51
what do 4-HMA 4-HA and NE do to the body (1 word
stimulation
52
what % of Caucasians are deficient in CYP2D6
10%
53
which metabolites stimulate NA release
4-HA and 4-HMA
54
which metabolites inhibit MAO
4-HA and 4-HMA
55
which metabolites activate TAAR
4-HA and 4-HMA
56
which metabolites mimic effects of adrenaline at adrenergic receptors
norephedrine
57
which NTs do amphetamines block the uptake of
DA NE and serotonin
58
what is the main difference with cocaine and amphetamines when it comes to DA buildup
cocaine needs NT release but amphetamines dont need NT release / depolarization events
59
do amphetamines need depolarization events for DA buildup to occur
no
60
does cocaine need depolarization events for DA buildup to occur
yes
61
what does VMAT stand for
vesicular monoamine transporter
62
how is amphetamine transported into NT storage vesicles
VMAT
63
what happens once amphetamines are pumped into nerve terminal
they are transported into vesicles
64
besides the transporters, what other receptors may be affected by amphetamines
nicotinic acetylcholine receptors
65
what are 2 ways that amphetamines enter the presynaptic terminals
transportation by DAT
| diffusion across the membrane (high concentrations)
66
what is the difference with amphetamines and cocaines interaction with DAT
amphetamines actually are transported into the nerve endings unlike cocaine which just inhibits DAT
67
why can amphetamines go through DAT unlike cocaine
it is smaller and more structurally similar to DA
68
what does MAO do
degrades DA NE E 5HT
69
what happens once VMAT brings amphetamines into vesicles
they induce the vesicles to spew out DA into the cytoplasm
70
what 2 things allow DA to accumulate in the nerve ending from amphetamines
1-vesicles spew out all DA
| 2- MAO is inhibited so it can't break down the free DA
71
what does interactions with TAAR cause
DAT pumps in reverse so that DA is pumped into the synapse
72
what causes DAT to pump in reverse
amphetamines interactions with TAAR
73
with amphetamines, what are 2 ways DA leaves the pre-synaptic neuron
1-DAT in reverse
| 2-diffusion
74
does cocaine interact with TAAR
no
75
what causes TAAR to let DAT run in reverse
G protein cascade, phosphorylation of DAT lets it be reversed
76
does amphetamines or cocaine have a higher DA release in NAc
amphetamines
77
what are 2 other pathways (besides dopaminergic) that gives the effect of amphetamines
noradrenergic and serotonergic pathways
78
what is tyrosine hydroxylase
enzyme in DA and NA synthesis pathway
79
what happens to tyrosine hydroxylase with amphetamine use and why
inhibited because the nerve endings see massive amounts of DA so you want to downregulate the synthesis pathway
80
what does a single dose of amphetamines do to DAT function
decreases its function
81
what does chronic amphetamine use do to DAT expression
less DAT expression on the cell-surface
82
what does chronic amphetamines do to cell surface transporter expression
decreases - DAT and for NE too
83
what causes the effects of less transporters on the cell surface from amphetamines
TAAR activation
84
does amphetamines cause brain damage, what kind
yes, profound changes in brain structure
85
what kind of terminals are reduced with amphetamine use
Dopamiergic, serotonergic and noradrenergic terminals are reduced
86
with amphetamines, are Dopamiergic, serotonergic and noradrenergic terminals reduced temporarily or permanently
likely permanently
87
what causes amphetamine damage to brain cells
free DA forming ROS when metabolized by MAO (even though it is inhibited) which causes damage of cell membranes proteins and mitochondria
88
what does excessive glutamate release cause
toxic environment that leads to neuronal cell death (excitotoxicity)
89
what do amphetamines do to glutamate release
cause excessive glu release
90
what causes excitotoxicity
excess glu release
91
does meth cause neuronal loss
yes
92
where does meth cause neuronal loss
globally, but mainly in hippocampal, limbic and cingulate system
93
what does the cingulate system do (4)
learning memory emotion motivation
94
which type of meth users get the most significant neuronal loss
people will early onset schizo and dementia
95
what kind of tests will show correlation with hippocampal volume loss
word-recall
96
what happens to brain / long-lasting changes with amphetamine use
death of dopaminergic neurons
97
what is brain damage from amphetamines similar to (which disease) and why
parkinsons because that is a loss of DA neurons
98
is there an increased risk of parkinsons with cocaine use, how much
no none
99
is there an increased risk of parkinsons with amphetamines use, how much
yes 76% increase
100
what happens when amphetamines bind to nAChR (1st step)
they let Ca++ into the neuron
101
what happens when Ca++ enters neuron from amphetamines activating nAChR
cascade of events leading to increased levels of ROS
102
which receptor may be a leading factor in brain damage from amphetamines (like the cause of the damage)
nAChR - cascade of events leads to ROS release
103
what happens with you use nAChR receptor blockers with amphetamines
there is less ROS damage and prevents some neuronal damage IN VITRO
104
which specific nAChR subunit may be most implicated in ROS formation
alpha 7!!!
105
which ion flows through when nAChR is acticated
Ca++
106
what happens with increase Ca++ in ACh cells
triggers increased levels of ROS
107
what are 5 symptoms of withdrawal from amphetamines
anhedonia, fatigue, mood volatility, vegetative state, intense cravings
108
what is anhedonia
inability to feel pleasure
109
what causes anhedonia in withdrawal
because tyrosine hydroxylase is inhibited so less DA is made
110
how long can amphetamine withdrawal last
12 months
111
what does length of amphetamine withdrawal link to
decree of brain damage/dysfuntion
112
what may cause someone to never recover from amphetamines
if dopaminergic neurons were destroyed
113
what are 2 possible causes of meth mouth
contaminants in meth, lack of saliva
114
why may the contaminants in meth cause meth mouth
because many meth components are highly corrosive
115
why does meth cause a lack of saliva
vasoconstriction in gums
116
what causes vasoconstriction in gums
excess NA onto alpha1 receptors on blood vessels AND activation of inhibitory alpha2 presynaptic neurons in salivary glands
117
what does amphetamine do to alpha1 (salivary glands)
excess NA stimulation causes vasoconstriction
118
what does amphetamine do to alpha2 (salivary glands)
they are inhibitory presynaptic, so activating them reduces saliva flow
119
what happens when alpha2 isnt activated (normal circumstances)
NA causes saliva flow
alpha2 is inhibitory presynaptic
120
what does alpha2 activation in saliva glands cause
less saliva flows
