Stimulants Flashcards
(95 cards)
1
Q
What types of transmitters do amphetamine & cocaine effect?
A
all monoamines!
DA, NE, EPI, 5-HT
2
Q
What happens when stimulants are used at low doses?
A
Increased attention / mood
3
Q
What happens when stimulants are used at higher doses?
A
Decreased activity / mood
4
Q
What happens with chronic high doses of stimulants?
A
Schizophrenia-like state
5
Q
What are the differences between schizophrenic brains and chronic stimulant brains?
A
Schizophrenic brains have lower DA concentrations in some parts
6
Q
How long does it take to remove symptoms with antipsychotics in stimulant-induced psychotic states?
Schizophrenia-induced?
A
Stimulant-induced: Hours
Schizophrenia-induced: Weeks
7
Q
What effects will tolerate with stimulants? Why?
A
Reinforcing effects
Due to regionally specific receptor downregulation at postsynaptic sites
8
Q
What effects will sensitize with stimulants?
Why?
A
Motor and psychosis-inducing effects
Due to downregulation of presynaptic autoreceptors
9
Q
What breaks down monoamines?
A
MAO (monoamine oxidase)
10
Q
What is the ED50 of amphetamine?
A
10mg (narcolepsy)
20-30mg (adhd)
250mg (abuse)
11
Q
What is the LD50 of amphetamine?
A
200mg
12
Q
What is the TI of amphetamine?
A
7-15
13
Q
What is TI?
A
LD50 / ED50
14
Q
What is the half-life of cocaine?
A
60min
15
Q
What is the ED50 of cocaine?
A
~3mg dose
16
Q
What is the LD50 of cocaine?
A
~50mg
17
Q
What is the TI of cocaine?
A
~15
18
Q
What are the effects of amphetamine?
A
Increase release of newly-synthasized DA
Cause vesicles to release DA into cytoplasm
19
Q
What does amph do to DT (dopamine transporter)?
A
Phosphorylates it
DA is then pumped out of the cell
20
Q
What does Amphetamine block?
A
MAO
21
Q
What is MAO?
A
monoamine oxidase
Degradation enzyme responsible for inactivating monoamines
22
Q
What does cocaine do?
A
Blocks transporter (compared to amphetamine, which reverses it)
23
Q
What is the crucial difference between cocaine / amphetamine?
A
You need action potentials with cocaine
24
Q
What does cocaine do if near a sodium channel?
A
Blocks it (local anesthetic)
25
What does cocaine do if near a 5-HT transporter?
Blocks it (and other monoamine transporters)
26
Why doesn't cocaine always block ion channels, so that it doesn't have an effect at the synapse?
You need much higher concentrations of cocaine to block ion channels
27
What is the medial forebrain bundle?
Axons from the midbrain to the forebrain
mesoaccumbens axons
mesocortical axons
mesolimbic axons
Monoamine projections to the forebrain
28
How (generally) do amphetamines help with ADHD?
Interaction between NE and DA
29
What are synapses en passante?
Synapses 'in passing'
Swelling in the middle of an axon containing voltage-gated Ca2+ channels
Cause release sites in the axon itself
30
What is Volume Conduction?
Communication not specific to a synapse
Release neurotransmitter into extracellular space, making a 'gradient' of changed activation
31
What are the most diverse group of ion channels?
K+ channels
32
What is a current shunt?
| Na+ shunt, K+ shunt
As quickly as Na+ comes in, K+ goes out (K+ driving force affected by Na+)
Keeps membrane voltage stable
33
What are EPSPs in relation to shunts?
Overwhelming the ability of the leak channels to compensate for Na+
34
What is the general rule for D1/D2 receptors?
```
D1 = excitatory
D2 = inhibitory
```
35
What is the effect of blocking shunt for NE/DA in relation to ADHD?
Signals better able to come in
Noise blocked
36
What is a metaphor for increasing NE release for a state-change?
Increase volume: make signal stronger, noise weaker
37
What's happening in the neuron when you change signal-to-noise by adding amphetamine?
Less random activation (shunts, DA)
Cell is more excitable (state-change, depolarization)
Higher likelihood of action potential, but less random noise
38
How addictive are psychostimulants?
Among the most readily addictive substances known
39
What happens when you have low levels of D4 receptors?
'need the buzz you get from seeing what's over the next mountain'
More apt to explore, more apt to desire novel experiences
40
How do NE transporters relate to DA?
They're great at picking up DA - can reduce DA levels
Only one enzyme away from NE
41
How to DA transporters relate to NE?
Not great at picking up NE
NE is already farther along in the cascade chain than DA, so you can't synthesize DA from NE
42
How much caffeine does a 6-oz cup of coffee have?
74-83mg/5-oz cup (tall is 12-oz)
43
What might help in infant sleep apnea?
Caffeine
44
Which receptors does caffeine antagonize?
A-1 and A-2Aa adenosine receptors
45
Where are the adenosine receptors we're interested found?
Terminal boutons
| But they're there all over the nervous system
46
Where is adenosine released?
Postsynaptically, propagates BACKWARD to terminal bouton
47
What do A-1 receptors do when activated?
2nd messenger
Increase K+ efflux
Decrease Ca2+ influx
(decrease exocytosis)
48
Where are there lots of A1 receptors?
HC, striatum, septum, frontal/cingulate cortex
49
What brain region is affected first in Alzheimer's?
Septum
50
What type of neurons mainly exist in the septum?
Cholinergic
51
What is a higher dose of caffeine?
~500mg+
52
What can caffeine do at higher doses?
Hallucinations, paranoia, mania/depression
53
Where in the brain is caffeine less potent?
Brainstem
2-10 cups
54
Where in the brain is caffeine not very potent?
Spinal cord - need 20-50 cups (tremor/seizures)
55
What is the LD50 of caffeine?
~200 cups of coffee (15g)
56
Where is caffeine metabolized?
Cytochrome p-450 in the liver, excreted in urine
| Overlaps with alcohol breakdown enzymes
57
What are the three significant metabolites of caffeine?
Paraxanthine (lose a methyl group at the top right)
Theobromine (lose a methyl group between ketones)
Theophylline (lose a methyl group on the bottom left)
58
How does cocaine absorption compare to amphetamine?
It's worse (less fat-soluble)
59
How is the "signal" increased in signal-to-noise by amphetamine?
Blocking the NeT
60
What does blocking the NeT by amphetamines do physically in the PfC to strengthen "signal"?
NE increases effect transmitters like GLU have at synapses
61
How is "noise" decreased by amphetamine?
Blocks DAT
62
How does blocking DAT decrease "noise"?
cAMP alteration in ion channels (primarily K+)
Suppresses K+ conductance that normally amplifies irrelevant inputs
63
How popular is nicotine?
#3 most used drug in the world
64
What is the current therapeutic relevance of nicotine?
NO relevance
(Reduces nicotine withdrawal...)
may help tourette's, parkinson's, alzheimer's, schizophrenia
65
Where do you lose cholinergic neurons with alzheimer's?
Septum
66
What does nicotine do?
Cholinergic agonist
67
Differences between ACh and Glu?
Glutamate is everywhere, has refined effect of NDMA
Ach is very specific to specific parts of the brain (e.g. cholinergic neurons of the septum)
68
How is nicotine usually injested?
Orally or by inhalation
69
What is the solubility of nicotine?
Both fat and water-soluble
70
How fast does nicotine hit the brain with inhalation?
3 min
| peak levels within 10 min
71
What is the ED50 of nicotine?
.5-1mg
| cigarette is 8mg
72
What is first-pass metabolism like for nicotine?
HIGH. 90% metabolized in liver by cytochrome P450
73
In what medium is nicotine eliminated?
Urine
74
What is the half life of nicotine?
1/2 hr
75
Why does tolerance to nicotine develop in the liver?
hepatic enzyme activation
76
What is the LD50 of nicotine?
60mg
77
What are lethal effects of nicotine produced by?
Paralysis of respiratory muscles
Nicotinic receptors get overstimulated
78
What happens to quiescent (dormant) nAchRs in the presence of nicotine?
Upregulated, they're activated
79
What happens in ongoing activation of nAChRs by nicotine?
Desensitizes ongoing activation
Acting as an antagonist now
80
How does long-term antagonistic effects of nicotine work?
Nicotine pushes receptors into an inactive state after long enough exposure
81
Where in the pons do you see lots of nitcotinic Ach receptors?
Locus coeruleus
| Lots of NE released there
82
What is causing the rewarding effects of nicotine?
Stimulation of mesolimbic DA neurons by nicotinic cholinergic neurons
83
What is the chemical source of arousal by nicotine?
nACh activation of LC/Brainstem neurons involved in sleep/wake
Activation of cortical/thalamic neurons
84
What does amphetamine do to MAO?
Blocks it, this increases synaptic DA levels
85
Why might amphetamine and cocaine cause toleration of rewarding/reinforcing effects?
Not as many DA receptors in specific parts of the brain
86
What is cocaines' solubility like?
Less lipid soluble than amphetamine
| Both lipid and water soluble (facilitate entering brain)
87
Which monoamine transporters does cocaine block?
5-HT, DA
88
Cocaine acts as a local anesthetic. What does it do to ion channels that causes this?
Gets charged (+)
When it's charged (+), gets stuck inside sodium channels, blocking Na+ from entering
89
What is DATKi? How is it relevant to cocaine?
A knock-in DA transporter not sensitive to cocaine
Cocaine doesn't block it, so it recycles DA just as easily, so cocaine has less effect
90
How fast is the GI absorption of caffeine?
99% in 45 min (fast)
91
How fast is the GI absorption of caffeine?
99% in 45 min (fast)
92
Where are A1 and A-2a found?
presynaptically (terminal boutons)
93
What happens when adenosine binds to A-1 receptors?
2nd messenger signals increase K+ efflux, decrease Ca2+ influx
This decreases exocytosis
94
Where in the brain are A-1 receptors generally found?
Limbic + memory system:
HC, striatum, septum, frontal/cingulate cortex
95
The neurons of which part of the brain does caffeine have the greatest effect on?
Cortical neurons - big increase in cortical activity
