Lecture 11: Psychostimulants Flashcards
1
Q
3 therapeutic effects of psychostimulants
A
- local anesthetic
- ADHD treatment
- narcolepsy
2
Q
how do stimulants exert their behavioral effect? where?
A
augmenting DA action
activity in NA
3
Q
low dose effects of PS induce ___
A
behavior-activating response akin to normal emergency reaction (sympathomimetic drugs)
4
Q
3 physiological effects of sympathomimetic drugs
A
- increased BP and HR
- blood flow shifts from skin and organs to muscles
- oxygen and blood glucose levels rise
5
Q
4 positive CNS effects of PS
A
- elevated mood
- reduced fatigue/increased energy
- decreased appetite
- improved task performance
6
Q
3 negative effects of PS
A
anxiety
irritability
insomnia
7
Q
3 high dose negative effects of PS
A
anxiety
irritability
psychotic behavior
8
Q
PS used historically for 5 reasons
A
- endurance
- sense of wellbeing
- reduce fatigue
- increased stamina
- alleviate hunger
9
Q
cocaine is the ___ most popular illegal drug in US
A
2nd
10
Q
estimated cocaine market in US exceeds ____
A
$70 billion
11
Q
Harrison Narcotic Act
A
1914; banned incorporation of cocaine into medicines and beverages
12
Q
cocaine related ER visits were second only to ___
A
illicit drug use combined with alcohol
13
Q
3 types of cocaine
A
E. coca leaves
Cocaine HCl
Cocaine base (crack, freebase)
14
Q
crack is soluble in (3)
A
alcohol
acetone
ether
15
Q
% cocaine in coca paste
A
60-80%
16
Q
% cocaine in E. coca leaves
A
1%
17
Q
how many mgs of cocaine per line?
A
25mg; snort 50-100mg at a time
18
Q
how much of cocaine HCl is absorbed through snorting? what inhibits it?
A
20-30%
cocaine is a vasoconstrictor
19
Q
plasma level peak of cocaine
A
30-60 min
20
Q
how long does cocaine persist in plasma?
A
6 hours
21
Q
for smoked cocaine freebase, absoprtion is ___
A
rapid and complete
22
Q
onset and persistance of smoked freebase
A
5 min; 30 min
23
Q
onset of IV powder cocaine
A
30-60s
24
Q
cocaine metabolite. how long can it be detected in urine?
A
benzoylecgonine
detected in urine 48h after use; 2 weeks in chronic users
25
when combined with alcohol, cocaine is metabolized to...
cocaethylene
26
effects of cocaethylene (3)
1. can be more active/longer lasting than cocaine
2. blocks DA reuptake transporter
3. increases risk of toxicity
27
cocaine MoA
potentiates actions of DA and 5HT by blocking active reuptake
28
mice lacking ___ do not self administer cocaine
dopamine reuptake transporter
29
8 low-dose cocaine effects
1. alertness
2. motor hyperactivity
3. tachycardia
4. vasoconstriction
5. hypertension
6. bronchodilation
7. increased blood glucose levels
8. blood flow shift to muscles
30
cocaine psychological response first 30 min
1. euphoria
| 2. enhanced self-consciousness and boastfulness
31
cocaine psych response next 60-90 min
mild euphoria mixed with protracted anxiety
32
8 risks/complications of acute cocaine use
1. racing thoughts/speech
2. depression
3. suppressed appetite
4. delayed sleep
5. movement disorders
6. seizures
7. depletion of oxygen (cerebral ischemia)
8. intracranial hemorrhage
33
toxic paranoid psychosis (4)
1. anxiety
2. sleep deprivation
4. repetitive compulsive behavior
4. altered perception of reality, violent responses to imagined persecution
34
cocaine psychosis (8)
1. paranoia
2. impaired reality testing
3. stereotyped, compulsive, repetitive behavior
4. vivid hallucinations
5. irritability
6. extreme psychomotor activation
7. impaired relationships
8. disturbances in eating and sleeping
35
how old do cocaine dependent people tend to be?
12-39 years
36
cocaine users are usually dependent on at least ___ drugs
3
37
___ of cocaine users are male
75%
38
on personality tests, cocaine users tend to be (4)
reckless
rebellious
low tolerance for frustration
craving for excitement
39
___ of cocaine users have anxiety disorders
30%
40
___ of cocaine users are clinically depressed
67%
41
___ of cocaine users exhibit paranoia
25%
42
cocaines vasoconstrictive effects can cause what in the fetus? (3)
1. increased blood pressure
2. intracerebral hemorrhage
3. premature birth
43
fetus exposure to cocaine can lead to (2) later in life
1. behavioral/emotional problems
| 2. increased vulnerability to substance use in adolescence
44
when cocaine crosses the placental barriers, can lead to (2)
1. destructive brain lesions
| 2. sudden infant death syndrome
45
effects of cocaine neurotoxicity (3)
1. psychomotor slowing and slowed reactions
2. subclinical brain damage; early onset demention
3. upregulation of heat shock protein expression, causes damage in BBB
46
3 pharmacological strategies in cocaine dependency
1. block euphoria
2. reduce withdrawal/depressive symptoms
3. enhance PFC cortical projections
47
compounds that regulate ____ are in early clinical trial for cocaine dependency (2 examples)
glu transmissions from frontal cortex to VTA and NA
| topiramate and lamotrigine
48
7 drugs for cocaine dependency
1. disulfiram (antabuse, blocks aldehyde dehydrogenase)
2. naloxone (opiate antag)
3. methylphenidate
4. wellbutrin
5. modafinil
6. antidepressants (not SSRIs)
7. antiepileptic neuromodulators (increase GABA by inhibiting GABA transminase enzyme; attenuates DA levels in NA and reduces cravings)
49
3 problems with cocaine vaccine
1. need enough antibodies to bind to all bloodstream cocaine
2. long lasting needed to reduce number of readministrations
3. vaccine should be well tolerated
50
only ___ of those vaccinated for cocaine attained high enough antibody levels
38%
51
MoA of amphetamine (3)
1. DA and NE release from presynaptic nerve terminals
| 2. amphet causes transporters to run in reverse, leading to release of vesicular DA into cytoplasm and synaptic cleft
52
what causes stereotypical, repetitive, compulsive behavior from amphetamines?
increased DA in basal ganglia
53
4 low dose effects of amphet
1. increased BP and HR
2. increased alertness, euphoria, excitement, wakefulness
3. loss of appetite
4. improved task performance
54
4 moderate dose effects of amphet (not BP/HR, alertness/euphoria, appetite loss, task perform)
1. tremors/restlessness
2. worsening production of anxiety disorders/panic disorders/obsessive behavior
3. paranoid psychosis
4. insomnia
55
6 chronic use, high dose effects of amphet (not anxiety, insomnia, tremors)
1. stereotypical behaviors
2. sudden violent outbursts
3. paranoid delusions
4. severe anorexia/weight loss
5. skin sores from neglected healthcare
6. indirect negative fx by poor eating and sleeping
56
2 withdrawal symptoms of amphet?
1. increased appetite/weight gain
| 2. severe depression
57
methamphetamine can be easily synthesized from obtainable chemicals like ___
pseudoephedrine
58
ice
crystalline, smokable form of meth (like crack)
59
half life of meth
12 hours
60
2 high dose effects of meth
violent behavior
| paranoid/psychotic behavior
61
2 effects of meth repeated dosing
1. long lasting decrease in DA and 5HT in brain from damage to 5HT and DA nerve terminals
2. neuronal death; replacement with astroglia and microglia
62
chronic meth use has what 4 effects on the brain?
1. reduces hippocampal volume
2. increases size of ventricles
3. decreases gray matter
4. increases white matter
63
how does meth cause BBB breakdown? what are the effects?
causes hyperthermia
| increases numbers of WBCs in brain, initiating neuronal damage
64
6 nonamphet behavioral stimulants
1. ephedrine
2. pseudophedrine
3. ritalin
4. provigil (modafinil)
5. nuvigil (armodafinil)
6. kat
65
use of ephedrine
anesthesiology to increase BP
| releases epinephrine, elevating BP and heart rate
66
use of pseudoephedrine
used to relieve nasal congestion
67
2 actions of ritalin
1. blocks presynaptic DA transporter
| 2. slightly increases DA release
68
after 60 min of oral admin, ritalin effect is ___
blocks 50% of DA transporters
69
what accounts for low rate of positive reinforcement from ritalin?
slow uptake into brain
70
modafinil MoA (2)
1. blocks dopamine transporter
| 2. elevation of hypothalamic histamine levels
71
3 FDA approved uses of modafinil
1. narcolepsy
2. shift-work sleep disorder
3. obstructive sleep apnea
72
khat; how is it consumed?
east african flowering shrub
| can be chewed or brewed as tea
73
3 effects of khat
1. excitement
2. loss of appetite
3. euphoria
74
active ingredients in khat
1. cathinone
| 2. cathine
75
what does cathinone do?
increases DA levels in CNS
76
what does cathine do?
mild psychostimulant
77
differences in cocaine vs. amphetaine action
1. cocaine: potentiates action of DA and sereotonin by blocking active reuptake
2. amphetamine: causes release of DA from vesicles and cause DAT to run in reverse
78
effects of meth related 5HT damage (3)
1. anxiety
2. depression
3. aggression
79
DA damage from meth use makes users vulnerable to ___
neurodegenerative disorders like parkinson's
80
what 3 parts of the brain are most damaged by meth BBB breakdown?
most severe in
1. amygdala,
2. hippocampus, and
3. caudate-putamen
81
where does cocaine increase DA activity?
nucleus accumbens
82
where does amphetamine increase DA activity?
nucleus accumbens
83
meth MoA (2)
1. release of DA from vesicles
| 2. causes DAT to run in reverse
