Barbiturates Flashcards
1
Q
Anxiolytic
A
Reducing anxiety or tranquilizing
2
Q
Sedative
A
Calming, relaxing, or sleep inducing
3
Q
Hypnotic
A
Sleep inducing or sopoforic
4
Q
soporific
A
tending to induce drowsiness or sleep
5
Q
Normal anxiety is a
A
survival response leading to activation of the
sympathetic nervous system for fight-or-flight response to danger
6
Q
Anxiety is the
A
anticipation of potential danger
7
Q
anxiety is the Subjective unsettling feelings of
A
concern or worry
8
Q
Physiological responses of anxiety including
A
sympathetic activation
9
Q
anxiety range
A
Ranges from vague discomfort to intense sense of terror
10
Q
Acute anxiety in response to stressors can be
A
beneficial
11
Q
Moderate anxiety for exams drives
A
studying
12
Q
Anxiety for public speaking prompts
A
thorough preparation
13
Q
Chronic or excessive anxiety can cause
A
deterioration of performance and
distracting preoccupation with the agitation associated with anxiety
14
Q
Sympathetic effects of stress and anxiety
A
increased muscle tension, digestive problems, sleep disturbance
15
Q
Escalating anxiety
A
cycle due to performance decrease and fear of failure (driving further
anxiety)
16
Q
Anxiety has high comorbidity with depressive disorders and substance abuse 59%
A
of patients with major depressive disorder have a co-morbid anxiety disorder
17
Q
Anxiety has high comorbidity with depressive disorders and substance abuse 20%
A
of patients anxiety/mood disorder patients have a comorbid substance abuse
disorder (esp. alcohol)
18
Q
Rates of alcohol abuse highest with
A
social anxiety disorders
19
Q
GENERALIZED ANXIETY
DISORDER (GAD)
A
Symptoms of anxiety without identifiable cause
20
Q
GAD Persistent anxiety most of
A
each day for prolonged periods (weeks/months)
21
Q
GAD Constant
A
worry, predicting, anticipating, or imagining failure or
disastrous events
22
Q
physical symptoms of GAD (5)
A
muscle tension and agitation leading to
poor concentration, irritability, and sleep disturbances
23
Q
PANIC ATTACKS / PANIC
DISORDER
A
Experiencing physiological effects of fear reactions without
threatening stimulus
24
Q
PANIC ATTACKS / PANIC
DISORDER Accompanied by strong
A
sympathetic NS activation
25
PANIC ATTACKS / PANIC
DISORDER Accompanied by strong sympathetic NS activation
Increased heart rate, chest pain
* Sweating
* Shortness of breath, faintness
* Choking
* Fear of losing control or dying
26
Panic attack in response to a
cue can lead to phobia
27
Susceptibility for un-cued panic attacks leads to
panic disorder
28
Early anxiolytic and sedative hypnotic
drugs
alcohol & Bromides
29
Contemporary anxiolytic and sedative
hypnotics
* Barbiturates
* Benzodiazepines
30
Bromide toxicity
Bromides are sedative possibly through effects on Clbalance in the CNS
31
Bromides were the first effective
anticonvulsant
32
Bromides have the side effect of
decreased libido which coincidentally supported the prevailing notion (at the time) that epilepsy was caused by masturbation
33
* Bromide has a half-life of
~8-12 days making dosing
difficult and intoxication problematic
34
Bromism results from
bromide toxicity
35
Bromism results from bromide toxicity (5)
* Impaired thought and memory
* Drowsiness, dizziness
* Irritability, emotional disturbances
* Repulsive skin eruption (rash)
* Bromide psychosis (delirium, delusions, vivid
hallucinations, mania, lethargy, and coma)
36
Barbital was the first
psychoactive barbiturate synthesized in 1903 and marketed as
Veronal
37
Barbital found to have
relaxing and sopoforic effects
38
Barbital Long half-life meant
drowsiness extended for days
39
Phenobarbital was developed in 1912 and was noted to be
faster acting, of shorter duration, and having excellent anticonvulsant properties
40
Barbiturates can be classed
according to the
relative
lipophilicity of the compound.
41
Increasing the lipophilicity of
barbiturates results in
n faster
uptake into the brain and more
rapid sedation
42
Effects of barbiturates low doses
Anxiolytic and
tranquilizing at low
doses
43
Effects of barbiturates moderate doses
Sedating and sopoforic
44
effects of barbiturate's at high doses
Anesthetic at high doses
45
Ultrashort-acting barbiturates are
anaesthetic
46
Ultrashort-acting barbiturates are
anaesthetic - Highly
lipophilic
47
Ultrashort-acting barbiturates are
anaesthetic - names
Thiopental, hexobarbital
48
Ultrashort-acting barbiturates are
anaesthetic - IV administration results in
rapid uptake and sleep in 10-20 seconds
49
Ultrashort-acting barbiturates are
anaesthetic - Unconsciousness lasts ____ and
ends due to
20-30 minutes and
ends due to redistribution of lipophilic
barbiturates into fatty tissues
50
Short/intermediate-acting barbiturates
are
sedative
51
Short/intermediate-acting barbiturates
are sedative - Moderate
lipid solubility
52
Short/intermediate-acting barbiturates
are sedative - names
Amobarbital (Amytal) and pentobarbital
(Nembutal)
53
Short/intermediate-acting barbiturates
are sedative - Sleep in
20-40 minutes lasting 5-8 hours
54
Short/intermediate-acting barbiturates
are sedative - termination
depends on liver metabolism
55
Short/intermediate-acting barbiturates
are sedative - prescribed
for insomnia, high abuse
potential
56
Long-acting barbiturates are effective at
are effective for treating seizure
disorders and anxiety
57
Long acting barbiturates have low
lipophilicity
58
Long-acting barbiturates - names
Phenobarbital, mephobarbital
59
Long-acting barbiturates - onset
takes 1 or more hours
60
Long-acting barbiturates - metabolism
slow
61
Long-acting barbiturates lasting effects
10-12 hours
62
Side effects and safety margin of barbiturate's
Anxiolytic effects are accompanied by
cognitive side effects
63
* Anxiolytic effects of barbiturate's are accompanied by
cognitive side effects (3)
* Mental clouding
* Loss of judgement
* Slowed reflexes
64
barbituate Intoxication (high doses) leads to (3)
staggering, jumbled speech, impaired
thinking
65
barbituates cause
Coma and death due to respiratory
depression
66
REM and barbiturates
Alterations in REM sleep
67
barbiturate's and tolerance
Produce tolerance and dependence resulting in high abuse potential
68
Safety margin of barbiturate's
narrows due to
tolerance mechanisms
69
Despite their hypnotic effects,
barbiturates do not
induce restful
sleep.
70
sleep - Short term use results in
rapid sleep
onset but decreased Stage 3 & 4 sleep.
71
Chronic use decreases
REM sleep and
stage 3 & 4 sleep and increases
spontaneous awakenings.
72
Illicit use
High abuse potential due to rapid tolerance
and dependence
73
Illicit use * Often used in conjunction with
amphetamines
74
Often used in conjunction with
amphetamines
Amphetamines during the day (uppers or
pep-pills)
Barbiturates at night (downers or goofballs)
75
High potential for interactions with
ethanol
76
Decreasing safety margin with tolerance
leads to
high potential for overdose
77
Synaptic effects of barbiturates - Barbiturates act at the
GABA-A receptor
78
at the
barbiturate binding site
Positive allosteric
modulation
79
barbiturate's and GABA affinity
Increases GABA affinity
80
channel open time and barbituates
Prolongs open time
81
High doses -Synaptic effects of barbiturates
– GABA mimetic (opens GABAA in absence of GABA)
82
Barbiturate drug effects
Barbiturates are CNS depressants and cause
broad increases in inhibitory neurotransmission
83
Barbiturate drug effects - Anticonvulsant by
decreasing general
excitability
84
Barbiturate drug effects - Important effects in the
reticular formation
85
Pontine
normally activates cortical centres
86
Medullary
– normally supresses cortical centres
87
Balance of barbiturate effect in the reticular
formation - Medullary first
euphoria resulting from cortical activation (disinhibitory)
88
Balance of barbiturate effect in the reticular
formation - pontine first
relaxation, drowsiness, sleep from
cortical depression (inhibitory)
89
Barbiturate abuse - Paradoxically, barbiturates decrease
mesolimbic DA release in the NAc through effects on VTA GABA interneurons.
90
Barbiturates can be demonstrated to
reinforce through
microinjection into the
VTA (operant self-administration)
suggesting the same neural substrates
for addictions as other abused substances.
91
Pentobarbital administration inhibits
NAc dopamine release and can inhibit ketamine induced dopamine release.
92
Barbiturate tolerance
Tolerance develops through metabolic and pharmacodynamics mechanisms
93
Metabolic tolerance - enzymes
Barbiturates induce microsomal enzymes leading to greater liver metabolism
94
Metabolic tolerance: drug dose
Increased drug dose required to achieve same blood levels
95
Metabolic tolerance - cross tolerance
Leads to cross-tolerance among different barbiturates
96
Barbiturate tolerance Pharmacodynamic tolerance - cellular
Cellular changes in GABAA receptor function and expression
97
Pharmacodynamic tolerance - dosage
Greater barbiturate dose required to elicit inhibitory effect
98
Tolerance to sedative, anxiolytic and hypnotic effects are more
pronounced than tolerance to respiratory
depression
99
intoxication induced with doses
4-12 times above therapeutic dose
100
Peak sedative effect in
30-90 minutes
101
Fully awake
4 hours after dose
102
Period of cognitive impairment
– inarticulate speech, clouded thought,
coarse tremors of hand, depressed superficial reflexes, depression or mania
103
Dependence induced by
increasing doses every 12 hours for 92-140 days
104
Dependence trials resulted in
continuous mild intoxication in
most cases
105
Dependence trials resulted in continuous mild intoxication in
most cases
Confusion, inability to perform normal tasks
* Unkempt living quarters and decreased self-care
* Irritable, aggressive, and quarrelsome
* Staggering, frequent falls and injuries
106
Barbiturate withdrawal - 12-16 hours
12-16 hours after last dose subjects appeared to sober
107
Barbiturate withdrawal - 24-36 hours
24-36 hours after last dose increasing anxiety and weakness developed
108
24-36 hours after last dose increasing anxiety and weakness developed
* At peak subjects could not stand unassisted
* Drop in blood pressure – fainting on standing
* Tremors, anorexia, vomiting, abdominal distress, insomnia, weight loss,
increased startle response, hyperreflexia
109
withdrawal - Significant appearance of
convulsions and psychosis
110
Rebound hyperactivity
Since barbiturates enhance GABAA
function, rebound results in
hyperexcitability and convulsions
111
Psychosis developed 3-5 days after
withdrawal lasting as long as
9 days
112
Psychosis developed 3-5 days after
withdrawal lasting as long as 9 days
* Delirium, agitation, insomnia,
confusion, disorientation, auditory
and visual hallucinations
* High BP, temperature, pulse
113
Withdrawal is typically managed
clinically
114
Intermediate acting barbiturates replaced with
long acting drug (typically phenobarbital)
115
Phenobarbital weaned
over a long period to
minimize severity of withdrawal
