amphetamines Flashcards
what is amphetamine (1 word)
stimulant
what is methamphetamine
amphetamine derivative that enters the brain more rapidly
what is crystal meth
methamphetamine hydrochloride crystals - smokable
what are the psychological effects of methamphetamine
euphoria, energy, alertness (same as cocaine)
what is punding
repetitive meaningless behaviours
what weird thing happens at high methamphetamine doses
punding
what causes punding
too much DA in basal ganglia
what is the role of the basal ganglia
voluntary motor control and action selection
what medical condition is punding often found in and why
parkinson’s patients if medicine drastically increases DA levels
what is a bad psychological effect of amphetamine
unprovoked aggression and violence
what % of people have engaged in violent behaviour or suicide with methamphetamine
43% and 27%
can methamphetamine cause paranoia and hallucination
yes
what is a weird PSYCHOLOGICAL effect of methamphetamines
delusions of parasitosis
do methamphetamines have local anesthetic actions
no
do methamphetamines do anything to the sympathetic stimulation
yes, like cocaine (increased HR BP insomnia)
what are some physiological effects of methamphetamine
increase BP HR, tremours, headache, sweating
what happens to body temperature with methamphetamine
hyperthermia
what 4 things can cause death from methamphetamine
renal and hepatic failure, strokes, seizures
are amphetamines natural synthetic or semi
purely synthetic
what are 6 ways that amphetamines have been used medically
asthma weight loss depression ADHD narcolepsy stimulant (soldiers)
what 2 structures is amphetamine similar to
NA and DA
which receptors do amphetamines interact with and why
same transporters as DA and other NTs because of close structural similarity
why is methamphetamine the amphetamine of choice (3)
- extra methyl makes it easier to enter brain + more difficult to metabolize
- less peripheral more CNS effects
- smokeable
does amphetamine or methamphetamine have more CNS effects
methamphetamine
does amphetamine or methamphetamine have more PNS effects
amphetamine
does amphetamine or methamphetamine get in the brain easier
methamphetamines
does amphetamine or methamphetamine metabolized easier
amphetamines
why amphetamine easier to metabolize than methamphetamine
because meth has the extra methyl group
what form is meth smokable in
crystalline hydrochloride form
where does most methamphetamine come from
mexico
what is the starting molecule for methamphetamine synthesis
pseudophedrine
what kind of dangerous waste is made to make methamphetamine
lithium batteries, sodium, match heads (phosphorus), ammonia
how much water is made for every 1kg of produce
5-7kg
how much water is made for every 10kg of produce
50-70kg
what is a pro to the shake and bake / one pot method of making meth
less pseudophedrine is needed
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
the pattern of use for meth is similar to what drug
cocaine (orally, snorted, smoked, injected)
does meth or cocaine last longer
meth
does meth or cocaine have to be administered more often
cocaine
why does meth make a rapid tolerance
because there is rapid NT depletion with high doses
why is cocaines high shorter lasting than meth
because it doesnt stay in the brain for as long
which enzyme breaks down amphetamines
CYP2D6
what does CYP2D6 do to amphetamines
adds OH to make it more water soluble
which enzyme breaks down methamphetamines
CYP2D6
what does CYP2D6 break methamphetamines into
amphetamines or 4-hydroxymethamphetamine
what are the 3 metabolites of methamphetamines and amphetamines
4-HMA
4-HA
NE
(4-hydroxymethamphetamine, 4-hydroxyamphetaminem norephedrine)
what does norephedrine do
mimics the effects of adrenaline at adrenergic receptors (blood vessel effect)
what does 4-HA do
stimulates NA release, inhibits MAO, activates TAAR
what does 4-HMA do
MAYBE stimulates NA release, inhibits MAO, activates TAAR
what does TAAR stand for
trace amine associated receptor
what do 4-HMA 4-HA and NE do to the body (1 word
stimulation
what % of Caucasians are deficient in CYP2D6
10%
which metabolites stimulate NA release
4-HA and 4-HMA
which metabolites inhibit MAO
4-HA and 4-HMA
which metabolites activate TAAR
4-HA and 4-HMA
which metabolites mimic effects of adrenaline at adrenergic receptors
norephedrine
which NTs do amphetamines block the uptake of
DA NE and serotonin
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
do amphetamines need depolarization events for DA buildup to occur
no
does cocaine need depolarization events for DA buildup to occur
yes
what does VMAT stand for
vesicular monoamine transporter
how is amphetamine transported into NT storage vesicles
VMAT
what happens once amphetamines are pumped into nerve terminal
they are transported into vesicles
besides the transporters, what other receptors may be affected by amphetamines
nicotinic acetylcholine receptors
what are 2 ways that amphetamines enter the presynaptic terminals
transportation by DAT
diffusion across the membrane (high concentrations)
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
why can amphetamines go through DAT unlike cocaine
it is smaller and more structurally similar to DA
what does MAO do
degrades DA NE E 5HT
what happens once VMAT brings amphetamines into vesicles
they induce the vesicles to spew out DA into the cytoplasm
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
what does interactions with TAAR cause
DAT pumps in reverse so that DA is pumped into the synapse
what causes DAT to pump in reverse
amphetamines interactions with TAAR
with amphetamines, what are 2 ways DA leaves the pre-synaptic neuron
1-DAT in reverse
2-diffusion
does cocaine interact with TAAR
no
what causes TAAR to let DAT run in reverse
G protein cascade, phosphorylation of DAT lets it be reversed
does amphetamines or cocaine have a higher DA release in NAc
amphetamines
what are 2 other pathways (besides dopaminergic) that gives the effect of amphetamines
noradrenergic and serotonergic pathways
what is tyrosine hydroxylase
enzyme in DA and NA synthesis pathway
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
what does a single dose of amphetamines do to DAT function
decreases its function
what does chronic amphetamine use do to DAT expression
less DAT expression on the cell-surface
what does chronic amphetamines do to cell surface transporter expression
decreases - DAT and for NE too
what causes the effects of less transporters on the cell surface from amphetamines
TAAR activation
does amphetamines cause brain damage, what kind
yes, profound changes in brain structure
what kind of terminals are reduced with amphetamine use
Dopamiergic, serotonergic and noradrenergic terminals are reduced
with amphetamines, are Dopamiergic, serotonergic and noradrenergic terminals reduced temporarily or permanently
likely permanently
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
what does excessive glutamate release cause
toxic environment that leads to neuronal cell death (excitotoxicity)
what do amphetamines do to glutamate release
cause excessive glu release
what causes excitotoxicity
excess glu release
does meth cause neuronal loss
yes
where does meth cause neuronal loss
globally, but mainly in hippocampal, limbic and cingulate system
what does the cingulate system do (4)
learning memory emotion motivation
which type of meth users get the most significant neuronal loss
people will early onset schizo and dementia
what kind of tests will show correlation with hippocampal volume loss
word-recall
what happens to brain / long-lasting changes with amphetamine use
death of dopaminergic neurons
what is brain damage from amphetamines similar to (which disease) and why
parkinsons because that is a loss of DA neurons
is there an increased risk of parkinsons with cocaine use, how much
no none
is there an increased risk of parkinsons with amphetamines use, how much
yes 76% increase
what happens when amphetamines bind to nAChR (1st step)
they let Ca++ into the neuron
what happens when Ca++ enters neuron from amphetamines activating nAChR
cascade of events leading to increased levels of ROS
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
what happens with you use nAChR receptor blockers with amphetamines
there is less ROS damage and prevents some neuronal damage IN VITRO
which specific nAChR subunit may be most implicated in ROS formation
alpha 7!!!
which ion flows through when nAChR is acticated
Ca++
what happens with increase Ca++ in ACh cells
triggers increased levels of ROS
what are 5 symptoms of withdrawal from amphetamines
anhedonia, fatigue, mood volatility, vegetative state, intense cravings
what is anhedonia
inability to feel pleasure
what causes anhedonia in withdrawal
because tyrosine hydroxylase is inhibited so less DA is made
how long can amphetamine withdrawal last
12 months
what does length of amphetamine withdrawal link to
decree of brain damage/dysfuntion
what may cause someone to never recover from amphetamines
if dopaminergic neurons were destroyed
what are 2 possible causes of meth mouth
contaminants in meth, lack of saliva
why may the contaminants in meth cause meth mouth
because many meth components are highly corrosive
why does meth cause a lack of saliva
vasoconstriction in gums
what causes vasoconstriction in gums
excess NA onto alpha1 receptors on blood vessels AND activation of inhibitory alpha2 presynaptic neurons in salivary glands
what does amphetamine do to alpha1 (salivary glands)
excess NA stimulation causes vasoconstriction
what does amphetamine do to alpha2 (salivary glands)
they are inhibitory presynaptic, so activating them reduces saliva flow
what happens when alpha2 isnt activated (normal circumstances)
NA causes saliva flow
alpha2 is inhibitory presynaptic
what does alpha2 activation in saliva glands cause
less saliva flows
