Stimulants Flashcards
1
Q
…-containing sodas first appeared in 1885 with the introduction of Coca-Cola.
A
Caffeine
2
Q
Today, more than ..% of sodas on the market contain caffeine, most of which is synthetically manufactured.
A
60
3
Q
how much can does the GRAS say is safe
A
.02=71mg per can
4
Q
how did energy drinks get around the caffeine restrictions
A
marketing caffeinated drinks as dietary supplements, rather than as food products, to circumvent regulations on caffeine content.
5
Q
energy drinks have less caffeine than a cup coffee
A
yes but contain other stimulating ingredients likely not included in the caffeine count. not on label
6
Q
Energy drinks may also contain: …, such as taurine, tyrosine, L-carnitine, L-tryptophan, L-arginine, and L-theanine; vitamins, including A, B, C, and E; minerals, such as iron or calcium
A
amino acids
7
Q
Canada, energy drinks are regulated by Health Canada whose guidelines state that a single-serving container have no more than … caffine
A
180mg
8
Q
men consume more coffins
A
t
9
Q
Nutrition Examination Surveys showed that approxi-mately ..`% of children and adolescents aged 6–18 years consume caffeine.
A
75
10
Q
nowadays where are kids getting caffeine from
A
soda
tea
coffee
energy drinks
11
Q
when given for medical reasons, the purified drugs sometimes cause nausea and gastric irri-tation, especially in children. In such cases, the drugs may be given in the form of a …3
A
rectal suppository or by intramus-cular or intravenous routes
12
Q
what is coffin used for transdermally
A
anti-cellulite and anti-aging cosmetics and creams
13
Q
The methylxanthines are bases; how would you expect this to effect absorption
A
when they are dissolved in the acidic environment of the digestive tract, you might expect them to be highly ionized and, therefore, not lipid soluble (but very low Kpa= won’t ionize
14
Q
how easily are they absorbed
A
all of it is absorbed and quickly through stomach and small intestine
15
Q
how long after cup of coffee for peak blood levels
A
cleared from stomach in 20min peak blood levels 45 to 75min
16
Q
The caffeine in coffee, tea, energy drinks, and choco-late exists and is consumed in its … form. and …. for medical purposes
A
alkaloid, salts
17
Q
ask her about page 202
A
…
18
Q
does caffeine go through entire body
A
throughout the body’s tissues and reaches all organs, although the rates of entering and leaving the organs may vary
19
Q
About 10 to 30% of caffeine in the blood becomes bound to protein and trapped in the …
A
circu-latory system
20
Q
how easily does cat pass blood brain and placental barrier
A
super easy
21
Q
what is Theophylline used for
A
respiratory disorders
22
Q
what is theobromine used for
A
chocolate
23
Q
Theophylline and theobromine are slower to pass through the blood–brain barrier. why
A
are less lipid soluble than caffeine
24
Q
how do we get rid of caffeine
A
1% in urine
The remaining 99% is metabolized almost exclu-sively in the liver
25
what enzyme in liver breaks down caffeine
cytochrome P450 superfamily enzyme: CYP1A2
26
within vs between individuals how does the half life of caffeine breakdown differ
consistent in individual
| differ between average 5 hours to excrete all metabolites
27
There is evidence that caffeine’s half-life may be ...
dose-dependent (faster with lower dose= constant rate )
28
The addition of ...which itself contains 4–8% caffeine by weight, may prolong the half-life of caffeine
guaraná,
29
a number of factors affect the rate of caffeine metabo-lism and elimination from the body
genes
30
how do genes influence
The CYP1A2 gene carries instructions for building the caffeine-metabolizing cyto-chrome P450 enzyme. Individuals who express the CYP1A2*1A gene form are rapid caffeine metabolizers while those who carry the
CYP1A2*1F gene form are slow caffeine metabolizers = more effects
31
caf-feine metabolism is slowed by alcohol and grapefruit juice but speeded by broccoli, and smokers eliminate caffeine nearly twice as quickly as nonsmokers, slowed with antibiotics: why does this happen
The CYP1A2 enzyme can also be stimulated or inhib-ited by various foods and medications
32
how does caffeine digestion differ in females
hormones; longer half life after ovulation
contraceptives= longer half life
less elimination when pregnant
33
how does caffeine digestion differ in females
hormones; longer half life after ovulation
contraceptives= longer half life
less elimination when pregnancy increases half life
34
how much can do babies excrete
due to immaturity of the liver’s CYP1A2 enzyme system, and they excrete about 85% of caffeine unchanged in urine.= 100 hours
35
An adult-like pattern of caffeine metabolism and excretion does not develop until what age
about 7 to 9 months of age
36
how does half life differ in nonhuman species
Dif metabolism
| Dif enzymes and metabolites
37
The effects of the methylxanthines on neural functioning arise from their structural similarity to the neurotransmitter ...
adenosine.
38
how does caffeine interact with adenosine
is an adenosine receptor blocker (A1 and A2 receptor subtypes
39
where are A1 receptors in the brain
A1 receptors are distributed widely throughout the brain with the highest densities found in the hippocampus, cerebellum, cerebral cortex, and certain thalamic nuclei. Moderate densities are found in the sub-stantia nigra, neostriatum, ventral tegmental area, and nucleus accumbens
40
where are adenosine receptors
post and presynaptic
| heteroreceptor
41
what NT is A1 inhibiting (6)
inhibit neurotransmitter release from neurons producing acetylcholine, GABA, glu-tamate, norepinephrine, serotonin, and dopamine
42
Caffeine is an adenosine receptor blocker, exerting its effects mainly at ...2...receptor subtypes.
A1 and A2A
43
where are A2 receptors located
concen-trated in dopamine-rich regions of the brain, primarily the dorsal striatum and nucleus accumbens
44
is the rewarding effect of caffeine due to a direct or indirect effect
both
45
what does a low and high level of adenosine subjectively feel like
```
high= sleepy
low= alert
```
46
when is caffeine most effective
when adenosine levels are high
47
what NTs do caffeine effect indirectly
```
Ach = increases fight or flight
block inhibitory effects of glutamate
more nonep
other monomines (5HT and DA)
```
48
why can lots of caffeine cause siesires
Blockade of adenos-ine’s inhibitory effects on glutamate neurons helps explain why high doses of caffeine can lead to seizures.
49
what explains coffins psychomotor and reinforcing effects
dopamine
50
how does caffeine increase dopamine
blocks A1 receptors located on dopamine terminals = more release of dopamine
51
what is a heteroreceptor
a receptor regulating the synthesis and/or the release of mediators other than its own ligand.
52
what are receptor mosaics
two or more receptors are attached to each other and consequently influence one another’s operation
53
what does caffeine have to do with receptor masaics
The operation of receptor mosaics com-prised of adenosine and dopamine (A1–D1 and A2A–D2) receptors is impacted by caffeine so that dopamine neuro-transmission is enhanced in the striatum
54
what happens when you combine alc with caffeine
alc increased adenosine by enhancing Neurotransmission
| caf antagonizes aden receptors= feel less drunk and more alert
55
why do alc beverages with caffeine increase desire to drink those beverages
Like caffeine, alcohol enhances dopamine neurotransmission. The joint actions of caffeine and alco-hol on dopamine activity= reinforcement
56
what does it mean to say can has discriminitive stimulus properties
stimulus that has stimulus control over behavior because the behavior was reliably reinforced in the presence of that stimulus in the past.
57
what does psychomotor stimulants mean
stim CNS through brain chemical
58
The methylxanthines stimulate the release of... from the adrenal glands and increase sympathetic nervous system activity, with accompanying physiological changes in ...3
epinephrine
| vascular tone, heart rate, and body temperature
59
caffeine increase blood pressure
t but only in newbies
60
what is tachycar-dia
condition that makes your heart beat more than 100 times per minute (only from high dose consumption in nonaccustom ppl)
61
At doses of 5 to 10 cups of coffee per day, caffeine can cause ....
sensory distur-bances, such as ringing in the ears and seeing flashes of light, as well as mild delirium and excitement.
62
The regula-tory centers of the ... are also stimulated by high doses of caffeine, producing an increase in the rate and depth of breathing.
medulla (used for babies born with breathing problems)
63
what does caffeine do outside the CNS
direct actions on the muscles: smooth (involuntary) mus-cles tend to relax, and striated (voluntary) muscles increase in strength
64
theophylline: Smooth muscle relaxation results in ...
dilation of the bronchi of the lungs and a decrease in airway resistance
65
which blood vessels does cad dilate which does it constrict
dilate: endothelial cells (those that line arterial walls),
| constrict in brain
66
Adenosine-receptor binding can produces vasodilation or vasoconstriction?`
either , depending on the target organ and the type of receptor activated.
67
At moderate doses (~250 mg), caffeine produces ... and can reduce cerebral blood flow by as much as 30%
vasoconstriction
68
what does caffeine do the headaches
Because dilation of cerebral blood vessels is associated
| with headache, caffeine administration can alleviate head-ache pain and is added to many over-the-counter analgesics.
69
which coffee drinkers have the most headaches
low
moderate less headaches
high less headaches
70
how long does it take adenosine to up regulate receptors in number and sensitivity
as little as 2 cups of coffee per day for 5 days
71
T: coffee withdrawal condition marked by fatigue, flushing, nausea, anxiety, and headache.
abstinence syndrome
72
what causes abstinence syndrome
dilation of blood vessels in brain
| inhibitory actions of more adenosine
73
inhibitory actions of adenosine on the release of other neurotransmitter molecules, including ..4
serotonin, norepinephrine, acetylcholine, and dopamine
74
what does caffeine do to peeing
more pee
less sensitive to full bladder
more flow and rate
75
how can you explain the diuretic effects of coffee
adenosine regulates kidney function
76
how can the confusing positive and negative subjective effects of caffeine be explained
depends on conditions
77
what conditions make for positive effects
```
if have been not using coffee (not from withdrawal though)
low doses
positive reinforcer (genetic?)
```
78
how do the subjective effects of theobromine compare o caffeine
same effects to less extent
same quickness of effects
bad effects 5- 10 h later not like caffeine
79
how was the subjective experience of caffeine on cacaine usurers different
There was a dose-related increase in rat-ings of “liking,” “drug effect,” “high,” and “good effects.” thought it was cocaine
80
what does high doses of caffeine feel like
anxiety and panic
81
why does high caffeine cause anxiety
particular A2c receptor in some peoples genes (due to effect on adenosine receptors)
82
what does glucose do when it interacts with caffeine
reduce hostility effect of caffeine but increase tension effect of caffeine
83
The addition of ... counter-acts caffeine’s stimulatory impact on mood, fatigue, alert-ness, and vigor
taurine
84
In combination with caffeine, ..., which is also present in tea, increases alertness and decreases head-ache
L-theanine
85
in energy drinks: ..., is often taken in herbal-supplement capsules and is associated with subjective improvements in well-being, anxiety, depression, energy, and alertness
Ginkgo biloba
86
in energy drinks: ... has been found to increase anxiety and panic
Yohimbine
87
why can't we trust participants subjective reports of cognitive effects of caffeine
they have better mood and confidence so will think they preformed better without supporting results (no better on go no go task
88
what are the effects of coffee withdrawal
higher levels of sleepiness, lower mental alertness, and performed more poorly on reaction time and recognition memory tasks
89
does drinking caffeine have an impact on cognitive performance for non users
no just sleepiness due to anxiety (better cog performance in reg users due to return to baseline)
90
Researchers often find that caffeine is capable of
reversing decrements in performance caused by boredom and fatigue, certain drugs, caffeine withdrawal, and even the common cold
t
91
Caffeine has what 2 positive effects
improves attention and speeds both simple and choice reaction times.
92
how does adding glucose to caffeine change cognitive impacts
increase sustained attention and improve verbal memory vs only improving reaction time in just café's
93
... in combi-nation with caffeine, has been found to reduce symptoms of caffeine withdrawal
Taurine,
94
caffeine alone decreased mental fatigue and improved informa-tion processing, while the addition of ... further enhanced cognitive performance, as demonstrated by improvements in reaction time, working memory, long-term memory, and a decrease in headache
L-theanine in tea
95
caf-feine lowers the acoustic arousal threshold while sleeping so that people wake up more easily in response to a sound in the night.
t
96
does tolerance influence how disturbing can is to sleep
yes less disruptive (at first very disruptive
97
T: is a sleep-inducing center. When it is active, it causes sleep by generating synchronous activity in the cortex, which shows up on an EEG as slow waves
ventrolateral preoptic nucleus (VLPO)
98
are the wake or sleep centres in coms with the cortex
flip flops between them
99
how does Adenosine influence sleep and wake centres
a buildup of adenosine is one trigger that can activate the sleep cen-ter= caffeine blocks this activity
100
is caffeine a reinforcer
yes
101
what changes the reinforcing value of caffeine
your caf history
102
people don't show café's preference if you haven't had coffee in past week
t
103
people actively avoid caffeine withdrawal and seek the effects of caffeine.
t
104
what factors contribute to the reinforcing properties of caffeine (how likely you are to choose it)
dependance to avoid withdrawal
positive effects
dose
task requirements
105
Coffee drinkers show a low-ered risk of developing type 2 diabetes.
t but decaf did too...
106
benefits of coffee consumption
diabetes
weight loss
cancer prevention
less coronary heart disease
107
why weight loss
increase metabolic rate energy expenditure, lipid degeneration, and thermogene-sis
108
dangers of caffeine consumption
cardiac disease
109
how does how you prepare coffee influence heart disease
One study has shown that boiled coffee contains a substance that raises cholesterol levels, but filtered coffee does not contain this factor
110
a positive relationship between caffeine consumption and cardiovascular disease, but only in indi-viduals with ...
“slow metabolizing” form of the CYP1A2 enzyme gene
111
common adverse reactions to energy drinks?
Common reactions include elevations in blood pressure and heart rate, and minor cognitive effects such as insomnia
112
what are the hazards of standard consumption of energy drinks
flushing, headache, dizziness, tremor, hyperventilation, renal failure, vomiting, diarrhea, incontinence, fluctuations in blood pressure, fainting, anaphylactic shock, heart palpitations, chest pain, heart attack, hemorrhage, stroke, disorientation, spontaneous abortion, depression, anxiety, aggression, blindness, deafness, hallucinations, and convulsions
113
if energy drinks have same caffeine as cup of coffee why the extreme effects? 4
consumed rapidly
adol and young adults
can't confirm caffeine intake due to other caffeine substances not listed
correlated with doing stupid sit
114
how much caffeine will kill you
150–200 mg/kg of body weight= 5000 to 50,000mg (Hodgman, 1998) or about 80–100 mg of caffeine per liter of blood
115
addition of taurine decrease caffeine fatalities
f The addition of taurine, for instance, to caffeine potentiates increases in blood pressure and caffeine-induced cardiac muscle contraction
116
how does caffeine kill you 3
ventricular fibril-lation, convulsions, and/or respiratory collapse.
117
does APA say there's such thing as caffeine use disorder
intoxication and withdrawal syndromes, but excludes from potentially causing a “use disorder.” (WHO includes caffeine dependance syndrome)
118
3 criteria that must be met to prove can use disorder
(1) a persistent desire or unsuccessful efforts to reduce or control caffeine use; (2) continued caffeine use despite it causing or exacerbating an existing physical or psychological problem; and (3) withdrawal symptoms upon cessation or reduction of caffeine intake.
119
caffeine produces symptoms of intoxication: how?
restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal distur-bance, muscle twitching, rambling flow of thought and speech, tachycardia or cardia arrhythmia, periods of inex-haustibility, and psychomotor agitation
120
Chronic administration of caffeine causes an upregulation in both the number and sensitivity of ...
adenosine receptors
121
caffeine has less effect on heavy drinkers of cof-fee than on nondrinkers.
t
122
individuals who are most resistant to the effects of caffeine might also be the ones who become heavy coffee drinkers.
maybe but might be tolerance
123
how long till tolerance
The sleep-disrupting effects of caffeine show toler-ance within 7 days and the subjective effects are tolerated within 4 days
124
The effects of caf-feine on the body also build tolerance at different rates
t
125
Caffeine withdrawal symptoms include: ...7
headache; fatigue or drowsiness; dysphoria, depressed mood, or irritability; difficulty concentrating; and flu-like symptoms including nausea, vomiting, or muscle pain and stiffness
126
Like ..., withdrawal is feature of drug dependence.
tolerance
127
most common coffee withdrawal symptom?
headache
128
higher dose = what effect to withdrawal
faster tolerance
129
how long does withdrawal last
2-9 days
130
how long can withdrawal headaches last
up to 3 weeks
131
is it likely that caffeine use disorder will gain equal footing with other substance use disorders contained in the DSM?
no big business and is so widespread in normal functioning people
132
how can you take meth
- orally
- injected
- snorted
- smoked
- anal and vag suppository
133
Following oral administration, meth-amphetamine bioavailability is ~...%. Its psychoactive effects can be felt within about ...minutes following ingestion and reach their peak at about ... hours.
67
20-60
3
134
when meth is smoked These routes result in drug bio-availability of ~...%
peak subjective effects?
peak blood level?
80–100
15 -20 min
2- 3 hours
135
When snorted, cardiovascular and peak sub-jective effects of methamphetamine are felt within ... minutes, though peak blood plasma concentrations are reached nearly ... hours later
5–15
| 4
136
why the difference between subjective effects and peak plasma in meth
acute tolerance
137
meth injection..
| subjective effects?
10 min (2 min for cardiovascular effects)
138
how long does effects of meth last
up to 8 hours
139
how efficient is chewing the plant route of admin for cathinone
highly efficient; nearly 90% of plant constituents are released by chewing
140
chewing cathinone subjective effects? peak blood level?
begin at 30–60 minutes of chewing, as blood levels of cathinone begin to rise, and last for about 3 hours. Peak blood plasma concentrations are attained within about 1.5–3.5 hours
141
how do cathinones compare to amphetamines
Compared to the amphetamines, cathinones are less lipo-philic and therefore less able to penetrate the blood–brain barrier, requiring higher doses to produce reinforcing effects
142
... is pro-duced as a white or off-white powder that is most com-monly snorted
Methcathinone
143
Cocaine has a pKa of ...
8.6
144
It is also common for those who self-administer coca in this way to mix the leaves with wood ashes or ground shells, which are alka-line why is this beneficial for cocaine injestion
raises the pH of the saliva and the digestive tract, consequently reducing drug ionization and increasing its absorption
145
is cocaine ever consumed orally
only when chewing not pure cocaine
146
Peak blood plasma levels of cocaine are reached within about... minutes to ...hours of chewing
25 min to 2 hours
147
3 ways cocaine is taken
to improve absorption and enhance subjective effects, it is nearly always injected, snorted, or smoked.
148
why is cocaine rarely smoked
Because heat degrades the drug before it reaches the point of vaporiza-tion
149
why add Hcl salt like baking soda to cocaine before smoking
will free the HCl base from the salt, thereby removing the ionic charge from the molecules of cocaine, and increasing its lipid solubility. When the water evaporates, crystalline chunks are left
150
benefits of having cocaine in rock from
has a much lower melting point and can be heated in pipes or other devices, and its vapors inhaled.
151
When injected intravenously or smoked as crack,
peak blood plasma levels of cocaine are reached very quickly, within ... minutes subjective effects are felt within... minutes of smoking crack and within ... minutes of injecting cocaine snorting within...
2–5
1–2
3–4
10-15
152
does smoking or snorting crack lead to more bioavalibiility
snorting nothing lost as smoke
153
The absorption of methylphenidate varies consider-ably between individuals. name 2 ways
bioavailability
| development
154
how readily do amphetamines cross the blood brain barrier
easily
155
```
put in order of highest to lowest concentrations of metham in the body
lungs
liver
heart
pancreas
brain
```
The highest concentrations of metham-phetamine occur in the kidneys and lungs, followed by the stomach, pancreas, spleen, and liver, with lower concentra-tions in the heart and brain
156
when are peak brain concentrations when smoking or injecting methamphetamine stimulants
9 min
157
peak brain concentrations for cocaine?
concentrate more in brain = 4.5 min
158
a greater total percentage of a cocaine dose enters the brain compared to a dose of methamphetamine
t
159
oral vs injection peak brain concentration for methylphenidate
oral 1 hour
| injection 8-20 min
160
The excretion of amphetamines from the body depends a great deal on the ..
pH of the urine.
161
how does Ph of urine effect?
more acidic= ionized and excreted
| basic= drug reabsorbed and dealt with by liver
162
what does the acidity of unine do to half life
more acidic decreases half life
| basic prolongs it
163
Approximately ...% of a dose of amphetamine is excreted unchanged in urine
30–40
164
amphetamines have behaviourally active metabolites
t but don't contribute to subjective effects
165
all the ways amph is eliminated
urine
sweat
saliva
liver!!!!
166
is the half life longer for oral/ intravenous or snorted/ smoked
longer in snorted or smoked = less quick effects
167
Approximately 70% of a dose of methamphetamine is excreted in urine within 24 hours what are the 3 things being excreted
unchanged methamphetamines
metabolites
amphetamine (from most to least)
168
how long metham detectable in urine
1 week metabolites longer
169
The metabolism of methamphetamine doesn’t appear to be altered by repeated drug use what does this tell us
tolerance is not enzymatic (pharmacokinetic) but pharmacodynamic
170
how does cocaine half life compare to amphetamines
short ! 60 min
171
what does half life depend on
route of admin
individual differences
ph of urine
172
intravenous vs intranasal half life for cocaine?
longer in nasal longer again in oral
173
how much cocaine excreted unchaged in urine
not much!
174
how long canine detectable in urine
depends on route but 1.5- 3 days unless chronic doses 10 days
175
The half-life of methylphenidate is age-dependent what's Dif
shorter in kids 2.5 vs 3.5 hours
176
how is methylphenidate excreted
inactive metabolite
177
what is common to all psychomotor drugs
ability to impact neurotransmission at the monoaminergic synapses
178
Moneraminergic: what are the 5 monoamine neurotransmitters
serotonin, dopamine, norepinephrine, epinephrine, and histamine.
179
what is neuropharocology
the study of how drugs affect cellular function in the nervous system, and the neural mechanisms through which they influence behavior.
180
T: the study of how drugs affect cellular function in the nervous system, and the neural mechanisms through which they influence behavior.
neuropharocology
181
Following monoamine release and receptor-activation,
| neurotransmission is terminated both by ...2
the activity of spe-cific enzymes in the synaptic cleft
| the reabsorption of neurotransmitter molecules into the presynaptic neuron.
182
what enzymes terminal activity in cleft
monoamine oxi-dase (MAO) and catechol-O-methyltransferase (COMT)
183
Reabsorption is achieved via special reuptake transporter molecules called ...
monoamine transport-ers (MATs). = large protéine molecules on pre terminal
184
Each monoamine has its own special transporter
t but MATs are structurally very similar to one another and are therefore capable of transporting molecules of each other’s neurotransmitter but lower affinity for them
185
MATs belong to a family of transporter proteins called
| ...-dependent substrate-specific neuronal membrane trans-porters.
Na+/Cl
186
how do NA cl dependant substrate-specific neuronal membrane trans-porters. use the gradient
use the power of the ionic gradient that exists between the outside and inside of a neuron to transport molecules of neurotransmitter from the synaptic cleft into the presynaptic axon terminal
187
T: —a receptor located on the outer mem-brane of the transporter complex that binds its relevant monoamine
substrate recognition site
188
Because the concentration of any monoamine will be much higher inside the axon terminal relative to outside in the synaptic space, simple gradient forces will not move the monoamine to the inside of the cell. how is this counteracted
MATs additionally bind Na+ and Cl-ions, which form a chemical complex with the monoamine, and rely on the motive force of the inward-directed Na+ ion gradient to transport molecules of monoamine into the neuron, against their own outward-directed concentration gradi-ent
189
When a molecule of monoamine binds to its recogni-tion site on the transporter, a conformational change is trig-gered that causes the MAT to shift from an ...
outward-facing to an inward-facing conformation
190
describe the normal operation of a MAT protien
A molecule of monoamine neurotransmitter attaches to the MAT and is moved into the cell. This reduces the concentration of monoamine molecules in the
synaptic cleft. Once inside the cell, the monoamine is transported into the synaptic vesicle by a vesicular monoamine transporter 2 (VMAT2).
191
what stimulant is a MAT reuptake blocker 2 (blocks keeping inward facing)
cocaine methylphenidate
192
how do amphetamines work on MAT
substrate-releasing agent
193
how do substrate releasing agents work
Molecules of the substrate-releasing agent are transported across the neuronal membrane by the MAT. Once inside the cell, they are taken into synaptic vesicles and subsequently reverse VMAT2 action, causing a release of stored monoamines into the cytosol of the axon terminal. Substrate-releasing agents also provoke a reversal of MAT action and cause the channel of the MAT to stay open, allowing monoamines to diffuse rapidly into the synaptic cleft.
194
T: The process of packaging monoamine molecules in vesicles is accomplished by the action of another trans-porter, one that is embedded in the membrane of the synap-tic vesicle.
VMAT2 vesicular monoamine transporter 2
195
Psychostimulant drug molecules have physico-chemical properties similar to those of the monoamine neurotransmitters. how does this change there function
competitive substates = alter function at MAT and VMAT2
196
Cocaine and methylphenidate are equally potent inhibitors of DATs.
t
197
at least ...% of transporters must be blocked for users to experience a cocaine-induced high. what receptor>
47
| dopamine
198
other than dopamine what else does cocaine block
NE and 5-HT more than DA
199
what are the 2 dopamine systems
motor activity and reinforcement and motivation
200
At high doses, many of the monoamine reuptake inhibiting compounds actually produce dysphoric and aversive effects
t
201
Bupropion is rather similar to cocaine and methylphenidate, in terms of its potency as a DAT inhibitor, yet its administration does not increase sub-jective “drug liking” what does this suggest about cocaine
cocaine and methylphenidate may have an additional, long-overlooked mechanism of action.
202
what is a inverse agonists
a ligand that binds to the same receptor-binding site as an agonist and not only antagonizes the effects of an agonist but, moreover, exerts the opposite effect by suppressing spontaneous receptor signaling
203
how does cociane and methelphenidates compare with DAT in binding affinity
6-7 times greater
204
how do receptor response differ for dopamine on DAT compared to cocaine and methylphenidate on DAT
dopamine: recapture of monoamine from cleft into cell
cocaine: opposite conformational shift to keep monoamine in synapse during AP
205
would a pure competitive DAT inhibitor create more or less effect compared to DAT inverse agonists like cocaine
less = no influx of Dopamine out of the cell
206
would a pure competitive DAT inhibitor (bupropion) create more or less effect compared to DAT inverse agonists like cocaine
less = no influx of Dopamine out of the cell
207
2 amphetamines?
l-and d-isomers, as well as methamphetamine
208
amphetamines are structural analogs of monoamine NT, what is the relationship between monomines and them
compete for transport into cell (regulated by concentration)
209
how do amped enter presynaptic neuron?
binding to a transporter protein, along with Na+ and Cl-ions
210
why don't cocaine and methylphenidate go into presynaptic neuron
too large to pass through transporter
211
how are mono effected by amphetamines
slowed transport into pre cell due to competition
212
increasing concentration of amph increases ...
drug molecules that get inside cell
213
amph and methamphetamine are best at inhibiting which receptor? NET, DAT or SERT
NET most potent, DAT then SERT
214
how does the function of d-amphetamine vs l-amphetamine relate to their behavioural effects
l= less effective in DA and NE reuptake and 5 HT
| D: better at DA less good at NE
215
how do amphetamines affinity for VMAT2 influence monotones concentration
prevent the transport of mono-amines from the cytosol into vesicles, causing a buildup of unpackaged neurotransmitter molecules in the axon termi-nal.
216
how do amph release mon into vesicle
distrust PH = release into cell due to higher concentration in cell due to reversal of VMAT2
217
why are amph considered competitive substrate-releasing agents.
by causing reverse transport of mono
218
why does Na+ plays a role in the displacement of monoamines
every molecule of amph getting in comes with a few NA = gradient doesn't allow for more monamines
219
AMPH disruption of Na+ distri-bution, combined with the outward monoamine gradient, forces a ...
reversal in the direction of transporter action. = Nt out of cell
220
second proposal for how amph release monodies
A second mechanism has also been proposed whereby amphet-amines induce rapid, brief bursts of monoamine efflux through the transporter protein, which acts momentarily as an open channel. This allows monoamine to flow out of the cell at a high rate
221
Methamphetamine is less potent than d-or l-amphetamine
f more
222
another effect exerted by the amphetamines is an inhibition of activity of MAO, how does this effect monomies
the enzyme that normally degrades any molecules of monoamine that float free in the cytosol of the cell
223
what's the difference between substrate releasing agents and reuptake inhibitors in terms of impact
autoreceptors shut down substrate release for classic inhibition but not for substrate melee
224
all these amph reactions create what effect
rapid huge dopamine concentration = reinforcing and addictive
225
because cocaine blocks SERTs and NETs in the same way that antidepressants do, it has have antidepressant properties
f cocaine dependence is strongly associated with depression
226
...... are structurally similar
| to amphetamine and methamphetamine, so it is no sur-prise that their effects are also analogous.
cathinone and methcathinone
227
both cathinones and amphet and methamphetamines drugs act as monoamine substrate-releasing agents and enhance ..., and, to a lesser extent,...
DA, NE
| 5 HT
228
how do cat differ from amph
less potent
229
difference between epinephrine and nonep?
While epinephrine has slightly more of an effect on your heart, norepinephrine has more of an effect on your blood vessels
230
what is the effect of the Psychomotor stimulant drugs effect on epinephrine
strong cardiovascular effects that result from psychostimulant use
231
why is cocaine an anesthesia
cocaine has the ability to block Na+ ion channels in cell membranes, which prevents the conduction of action potentials along nerve axons
232
forgetting of what they learned when the effects of the drug wear off, suggesting that amphet-amine causes ..
dissociation
233
what NT plays largest role in discriminative effects of amph
dopamine
234
what are unconditioned behaviours of amphetamines at low and high doses
```
low= increase locomotion
high= sterotyped behaviours = no purpose
```
235
what other drugs in stem family produce unconditioned behaviour
Both khat and cathinone enhance aggressive behavior of isolated rats
methacatha
236
T: a stereotypical motor behavior in which there is an intense fascination with repetitive handling and examining of mechanical objects, such as picking at oneself or taking apart watches and radios
punding
237
Because psychomotor stimulants activate the ..., they produce elevations in heart rate and blood pressure, increase body temperature, and cause pupil dilation
sympathetic nervous system
238
psychomotors daalde or constrict everthing
dilate
239
their ability to dilate made them useful to treat...
asthma
240
When stimulants are used for their psycho-active properties, most of the sympathomimetic effects are considered unpleasant. what are some of these symptoms
abdominal cramps, nausea, vomiting, tremors, and exacerbate motor tics
241
... has stronger CNS effects and fewer peripheral effects than d-and l-amphetamine or cocaine.
Methamphetamine
242
what do they do for food consumption
decrease it compensated later with excessive eating
243
these stem activate serotonin 5-HT1B and 5-HT2C receptors what is behavioural consequence
feelings of being full
244
users are annoyed when pending is interrupted
t
245
punding and stereotyped behavior are caused by stimula-tion of the ..., which has input into the extrapyramidal motor system
nigrostriatal DA system
246
everyone experiences pleasurable effects form amphetamines
f some say anxiety (those who like and want do it again)
247
One of the most noticeable effects of the amphetamines is that they ...
improve mood make people feel good
| a clear, organized mind; and a desire to get to work and accomplish things
248
These subjective effects peaked at .. hours for the amphetamines and at ... hours for methylphenidate, and had largely disappeared by ... hours, even when adminis-tered at the higher doses
2,3,5
249
intense feelings of pleasure called rushes account for the general feeling good produced by amph
f different effect but depend on how fast drug gets to brain in what concentration
250
rushes often have a ... component
sexual (feels like orgasm)
251
When cocaine is injected intravenously, its subjective
| effects are identical to those of intravenously administered amphetamines
t but shorter acting
252
3 main effects on subjective experience
feel talkative friendly
stimulated
like the drug
253
Peak subjective ratings of “high” occur during the rush
f shortly after the rush dissipates
254
how fast does tolerance to cocaine rushes happen
rapid but still feels good
255
Subjective reports of “good” effect and “high” are greater after injecting it intravenously
f after smoking cocaine (faster peak)
256
numbing sensation called the freeze can be felt within a couple of minutes for what cocaine route of admin
nasal
257
Peak subjective effects are reached in just under 15 minutes for what cocaine route
nasal
258
methylphenidate’s binding sites and mechanisms of action are nearly identical to those of cocaine so why the Dif effects
slower acting longer half life = less abuse
259
subjective effects of Khat chewing
positive stim effects followered by agitation, restlessness, anxiety, and depression as the hours-long chewing session reaches its end but can't sleep
260
Humans can quite readily learn to discriminate amphet-amine and other psychomotor stimulants from a placebo and Dif stimulants
f only placebo
261
what are stimulations effects on sleep
made to prevent fatigue = can create insomnia
262
stim sensory effects? 2
amphetamines increase auditory and visual acuity
| passage of time underestimated = seems longer
263
go pills = amphetamines improve performance
no better than coffee but increase aggression and willingness to fight
264
response speed and short-term memory, accuracy on boring tasks, sustained vigilance are better on amphetamines
t but worse when have to attend to more than one thing
265
T: attention becomes overwhelmed and this decreases a per-son’s ability to gather information effectively. People focus attention on only one event and fail to notice other things happening in the environment
tunnel vision
266
on what tasks do stimulants harm performance
tasks that require cognitive flexibility and the ability to adopt new strategies
267
the performance enhancing properties of stem are better with higher dosages
f At higher doses, most of the simple beneficial effects of stimulants are lost and peo-ple become impatient, more easily distracted, and show impaired judgment.
268
stem improve athletic performance
t = why its banned
269
cold meds could give you stimulations false negatives why
act as bronchodilators and are found in cold prepara-tions, cough syrups, and decongestants
270
do cold meds containing l-methamphetamine have any performance enhancing effects
no
271
what are amphetamines influence on driving
more likely to be killed more than any other drug (less for cocaine)
272
people on amphetamines are just as bad driving at night as in day
f worse in day due to more stimuli no effect on night driving
273
6 effects of ADHD
response inhibition, vigilance, timing, working memory, planning, decision-making, and mem-ory storage
274
how many ADHD kids have impulsivity into adulthood
Roughly 65% of individuals with ADHD in childhood or adolescence
275
The estimated prevalence of ADHD in adults is somewhere between ...
2 and 3%
276
3 stimulants used to treat ADHD
d-amphetamine, then methylphenidate, and most recently lisdexamfetamine
277
ADHD medications drugs primarily target .... systems (dopamine and norepinephrine), which are believed to be dysfunctional in individuals with ADHD.
catecholamine neurotransmitter
278
Why do stimulants work of aa drug defined by hyperactivity
differences in resting catecholamine level
279
methylphenidate and amphetamine are ... blockers
catecholamine
competitively inhibit DAT and NET reuptake = more DA and NE in cleft
stimulate D2 autoreceptors
negative feedback reduce DA singling on post cell
280
when stressed catecholamine hormone signals production what 3 NT
dopamine; norepinephrine; and epinephrine
281
how do stimulants reduce background noise
steady vs tsk related firing when on drug
282
Increases in extra-cellular dopamine levels is bad for ADHD
f might also enhance the motiva-tional salience of a cognitive task in which an individual is engaged
283
The relationship between catecholamine activity levels and cognitive functioning follows an inverted U-shape curve what does this mean
deficits, as well as excesses, of DA and NE can impair cognition (bad to take if you don't have. deficit)
284
does Methylphenidate work for ppl whose DA is too low
no
285
how is cognition effected if you don't have ADHD and take pill
selective attention and distractibility
| better sustained attention
286
short term and LT memory is improved with methylphenidate
f no ST
| some LT for people with severe deficits
287
stim improve cog and behavioural flexibility
f
288
unprescribed stimulants has been found to com-promise study habits, lower motivation, and contribute to attention problems
f
289
T: cocaine is usually taken in large quantities for brief periods of time that are followed by periods of abstinence.
run–abstinence cycle
290
most common drug mix is the a combination of cocaine (or amphetamine) and heroin. :T
speed ball
291
what is so pleasant about the speed ball
heroin reduces the jitteriness that cocaine arouses by stim-ulating the sympathetic nervous system, and the cocaine diminishes the sleepiness or nod caused by heroin (cocaine often mixed with Benzos)
292
pure cocaine has a long history of self admin
t but less so for pure cocaaine (run absent cycles more common)then oral cocaine
293
what is amphetamines pattern of self admin
run ab cycles but depends on why your taking eg present sleep or pleasure
294
In the 1960s, this pattern of use characterized the peak user or speed freak who might inject amphetamine every few hours for days on end. what is likely to happen on this run
amphetamines psychosis = punding and paranoia
| eventual crash
295
why recent increase in amphetamines use
adderall
296
guess which line is what drug figure 10-4 p 236
..
297
Andean Natives who reg-ularly chew coca leaves have few health problems.
t
298
why might users have a yellow complexion
mild jaundice caused by liver disease.
299
what happens with prolonged nasal use
ulceration of mucous membrane progress to the extent that openings appear in the septum (the membrane separating the nostrils).
300
During runs, users don't report discomfort
f disturb-ing physiological and psychological symptoms
301
The most commonly experi-enced side effects of methylphenidate use in children include ...
headache, dizziness, drowsiness, sleep disturbance, irritability, abdominal pain, nausea, vomiting, diarrhea, cough, motor tics, and an increase in blood pressure and heart rate.
302
what does methlphen do to appetite
restricts it along with growth restriction
303
In adults, the use of oral amphetamine for short peri-ods have what negative effects
restless dizzy confusion
304
High-dose, chronic stimulant use has the potential to cause serious harm, especially if administered ..
intravenously
305
high dose chronic use has what effects
heart rate
blood pressure = internal bleeding or hemorrhage
brain damage
depression when off drug
306
why brain damage
rupture small blood vessels in brain
307
Compared to amphetamine or cocaine, the use of ... can be even more harmful, both in the short and long term
meth-amphetamine
308
Methamphetamine abuse is associated with ..., a deterioration of skeletal muscle
rhabdomyolysis
309
what is meth mouth (can happen with other stimulants)
dental decay from dry mouth due tosympa NS activity and teeth grinding
310
sensation of bugs on skin
formication
311
Methamphetamine users report high levels of ..., including depression, suicidal ideation, anxiety, psychosis, difficulty controlling anger, and violent behavior
psychiatric symptoms
312
Chronic khat chewing hasn't shown many adverse effects
f
heart problems gastrointestinal problems, urinary retention, hyper-thermia, blurred vision, dizziness, insomnia, headache, cog functioning, depression etc
313
Chronic khat chewing hasn't shown many adverse effects
f
heart problems gastrointestinal problems, urinary retention, hyper-thermia, blurred vision, dizziness, insomnia, headache, cog functioning, depression etc
314
which stem has most neurotoxic effects on the brain
methamphetamine
315
T: toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system.
neurotoxicity
316
what region is most effected in brain by amphetamines
regions containing dopamine and Seretonin producing cells
317
neurotoxic effects only occur from large doses
f Damage is more readily inflicted by large drug doses and binge-like intake, though a slower trajectory of escalating drug intake also results in deleterious effects
318
The loss of DATs that occurs as a result of methamphetamine use could be caused by what 2 things
down regulation of transporter proteins or
| dopamine cell degiation
319
In addition to affecting dopamine cells in the ...,
| methamphetamine exposure can produce long-term dam-age to dopamine and serotonin cells within the ...2
striatum
| hippocam-pus and prefrontal cortex
320
decreases in the expression of tyrosine hydroxylase and tryptophan hydroxylase from amphetamines use tell us what
enzymes involved in the biosynthesis of DA and 5-HT= less
321
Methamphetamine-induced neurotoxicity is associated with the cognitive symptoms of drug abuse.
t but also the , subjective, and psychomotor symptoms
322
The loss of dopamine cells in the striatum correlates with the presence and severity of 3
psychotic symp-toms, memory deficits, and impaired psychomotor coordi-nation.
323
The severity of psychotic symptoms from methamphetamine os correlated with ...
diminished DAT and SERT density
324
Brain abnormalities resulting from methamphetamine abuse are permanent for life
persist well beyond the period of drug administration but recover with abstinence
325
The degree to which ... function recovers during abstinence is predictive of therapeutic outcomes.
striatal dopa-mine
326
T: When taken in high doses or used frequently for extended periods, cocaine, khat, methamphetamine, and amphet-amine can elicit psychotic behavior in otherwise healthy people.
monomine psychosis
327
how similar is mon psychosis to schiz
indistinguishable
328
what are the positive symptoms of mon psycho
positive= auditory and visual hall
329
which are positive vs negative symptoms
delusions of reference, persecution, and grandeur; odd speech; flattened affect anxiety and agitation; depression and extreme paranoia that sometimes evokes hostility and violence, triggered by a belief that danger is imminent.
delusions of reference, persecution, and grandeur; odd speech; anxiety and agitation; and extreme paranoia that sometimes evokes hostility and violence, triggered by a belief that danger is imminent.
330
In countries such as Yemen and Ethiopia where khat chewing is customary, two forms of khat psychosis are rec-ognized.
manic psychosis
| schizophreniform psychosis
331
T: paranoid, persecutory, and referential delusions; thought alienation; auditory hallucinations; a tendency to isolate oneself from others; fear and anxiety; a hostile perception of the environment; and aggressive behavior
schizophreniform psychosis
332
T:It is marked by hyperactivity, talkative-ness, shouting, grandiose delusions, flight of ideas and tangential thought processes, and a highly liable mood that fluctuates from euphoria to anger
manic psychosis
333
The psychotic symptoms most frequently experienced by regular metham-phetamine users are ...3
delusions, hallucinations, and odd speech.
334
which halluncinations most common?
auditory
visual
tactile
335
the symptoms of mono-amine psychosis are transient what does this mean
don't have lasting effects and go away when you stop use (in some people they persist)
336
how does relapse influence chronic users psychotic symptoms
In chronic methamphet-amine users, behavioral sensitization to the drug’s effects means that even a small dose is capable of triggering a relapse of psychotic symptoms
337
Psychotic symptoms may also be triggered during periods of meth-amphetamine abstinence by environmental stressors
t
338
Sensitization to methamphetamine psychosis is caused by what
neurotoxic effects = DAT density in striatum and prefrontal cortex
339
what do psychomotor stimulants do to sex drive
rev it when doing drug disinterest when off
340
what do psychomotor stimulants do to baby when pregnant
birth abnormalities
| low birth weight, increased pregnancy complications, pre-term delivery, and perinatal infant mortality
341
cocaine use causes this. the placenta detaches prematurely:T
abruptoplacental
342
some evidence that prenatal exposure to cocaine affects .... 6
childhood IQ, short-term memory, and ver-bal reasoning, particularly in male offspring , more behavioural problems
343
why might cocaine users be unable to stand up, or may collapse but not lose con-sciousness
Users who take large doses of cocaine commonly experience muscle weakness and respiratory depression
344
what determines lethal dose 2
cardiovascular susceptibility and route of admin
345
how much cocaine will kill average person
1200 mg when cocaine is taken intranasally (depends on how much in brain not dose)
140 and 1650 mg of drug taken orally methamphetamine
346
2 phases of cocaine overdose
1. excitement followed by vommiting headache convulsions
| 2. pass out, resritory depends and cardiac failure
347
how long does death by cocaine take
Death may be very rapid, within 2 to 3 minutes, or it may take as long as half an hour
348
Chlorpromazine, an antipsychotic, is also very effective as an antagonist of the toxic effects of cocaine
t
349
certain individuals might be highly resistant to the euphoric effects of the drug are less likely to OD
f more likely to try and get the high
350
T: ntense cardiovascular effects that can be fatal when the drug is injected or inhaled in concentrated form
cocaine sudden-death syndrome
351
Common signs of methamphetamine overdose include
dilated pupils, shivering, high fever, hypertension, rapid or laboured breathing, chest pain
352
Altered mental status is common in ...poisoning and most often include agitation, suicidal ideation, and psycho-sis
methamphetamine
353
overdose deaths have occurred after as little as .. mg of methamphetamine administered intravenously
20
354
reasons for overdose fatalities? 7
most commonly result from multisys-tem organ failure, pulmonary congestion, cerebrovascular hemorrhage, and acute cardiac failure, though deaths have also been attributed to sepsis resulting from dirty injections and by asphyxia by aspiration of vomit
355
what accounts for more than 40% of meth deaths?
homocide and suiside
356
The subjective effects of amphetamine and cocaine tend to be greater when blood levels of the drug are rising compared to when they are falling what is this a sign of
acute tolerance
357
T: With the pattern of use that occurs during bingeing cocaine quickly loses its ability to cause rushes and gradually becomes incapable of improving mood
coke out
358
what develops acute tolerance what doesn't
no for cardiovascular
| yes for subjective effects
359
why do runs come to an end
coke out= loss of subjective pleasure
360
pre-exposure to amphetamine decreased the drug’s ..., but not its ..., as a discriminative stimulus
potency
| effectiveness
361
which amph and cocaine effects are short acting vs no tolerance
short: apetitite, heart and blood pressure, effects
no: sleep
362
any sensitization with stimulations?
stereotypes behaviours and psychosis
363
After a single dose of amphetamine or cocaine, the high is typically followed by a crash, is this withdrawal?
no, occurs quicker in cocaine vs amphetamines
364
is there withdrawal with cocaine and amphetamines
After chronic heavy use, abrupt discontinuation of amphetamine or cocaine can last weeks to months
365
what are symptoms of withdrawal
depression, increased appetite, insomnia anxiety, agitation, and panic; drug craving; and cog-nitive impairment
366
Withdrawal from psychomotor stimulants can also
| disrupt performance why?
reduced cortical activation
| failure to activate ventromedial cortex
367
after 1 year of amphetamines abstinence cortical activation returned to normal
f continued decreased in dorsolateral prefrontal cortical activation
368
what are treatments
detox= acute withdrawal (few weeks
| pharmacotherapies that treat withdrawal
369
3 common behavioural treatments
cognitive behav-ioral therapy, contingency management, and community reinforcement
370
T: teaches strat-egies for rational thinking, avoidance of maladaptive behavior, and relapse prevention
CBT very effective
371
T: uses conditioned rewards, such as vouchers for goods and services as operant technique for abstinence
contingency management works better than com with rewards = in long run
372
T: uses social rein-forcement, such as praise and encouragement from one’s family and social group
community reinforcement
373
T: drugs should block with-drawal symptoms, reduce craving for psychomotor stimu-lants, and block the effect of a psychomotor stimulant should it be taken.
pharmacotherapies
374
what are different drug pharmacotherapies 5
```
moDafinil
bupropion
methylphenidate
oral D amphetamine
naltrexone
```
375
T: —it stimulates dopamine, norepinephrine, and glutamate
| and histamine w limited abuse potential
modfinil
376
how effective is modafinil
There have been encouraging but inconclusive results with cocaine treatment
x methamphetamines
377
T: is an antidepressant. DAT and NET blocker Its ability to enhance dopamine transmission in the nucleus accumbens and prefrontal cortex is the proposed mechanism by which the drug may reduce craving and the cognitive deficits associated with withdrawal.
Bupropion only effective on meth with light users
378
why does methylphenidate help stimulant addicts = reduces amphetamines and peth cravings
It is a cocaine-like blocker of DATs and NETs with little effect on SERTs and is reported to have less abuse potential than cocaine and the amphetamines
379
T: Oral is a safer route of administration and dampens fluctuations in blood drug levels, which are what cause rushes and euphoria= decrease dependance in meth
oral D amphetamines
380
T: is an opioid antagonist, and the endogenous opioid system is implicated as a mecha-nism of drug reward = amphetamines users
naloxone
381
what treatments work best
behavioral and psychosocial
382
what is the logic behind a immunization
stimulate the immune system to create antibodies that would bind to molecules of
cocaine. This would prevent the drug from passing through the blood–brain barrier to enter the central ner-vous system, thereby blocking its effect.
383
One of the difficulties in developing a vaccine for a
| drug is... 3
the immune system normally only creates antibodies for large protein molecules, but drugs like cocaine and methamphetamine are small non-protein mol-ecules.
need many antibodies
levels drop after a few moths
