Anti-Anxiety Drugs Flashcards
(106 cards)
1
Q
what are the 3 types of anxiety disorder?
A
- GAD
- Panic disorder
- Phobias
2
Q
what are 3 symptoms of GAD?
A
- muscle tension
- autonomic arousal
- vigilance
3
Q
what is GAD?
A
constant worry for >6 months
4
Q
what happens if you stop treatment for GAD?
A
relapse
5
Q
what are 4 characteristics of panic disorder?
A
- episodic
- recurrent
- brief
- extreme fear + stress symptoms
6
Q
what are 2 types of phobias?
A
- social –> ex. speaking in public
- specific –> ex. snakes, exams
7
Q
are drugs a cure for anxiety?
A
no
8
Q
what are the 4 types of possible drug treatments for GAD?
A
- antidepressants (SSRIs, SNRIs)
- benzodiazepines
- B blockers (if somatic)
- Busiprone
9
Q
what are the 2 types of possible drug treatments for panic disorder?
A
- benzodiazepines
- antidepressants
10
Q
what type of drug is used for social phobia?
A
B blockers
11
Q
what type of drug is used for specific phobias?
A
no drugs
12
Q
what are 4 risk factors for GAD?
A
- women >men
- civilian trauma
- low socioeconomic status
- middle-aged
13
Q
how did they determine that diazepam binds GABAA receptors?
A
radiolabelled diazepam and added it to rat brain
- diazepam was found in the same locations as the GABAA receptor
14
Q
does diazepam compete with GABA for GABAA receptors?
A
no –> diazepam binding increases in presence of GABA
15
Q
what were 3 possibilities for why diazepam binding increases in presence of GABA?
A
- GABA could be increasing the number of available receptors
- GABA could be increasing the affinity of diazepam
- both
16
Q
what are the axes of a scatchard plot?
A
X = amount of diazepam bound
Y = bound/free receptors
17
Q
what happens if a scatchard plot shows a change in slope?
A
there is a change in affinity for a receptor
18
Q
what happens if a scatchard plot shows a change in x-intercept?
A
there is a change in number of receptors
19
Q
how are the scatchard plots with and without GABA different? and what does this mean?
A
with GABA has steeper line –> GABA increased diazepam’s binding affinity
with GABA doesn’t have different x-intercept –> GABA does not affect the number of receptors
20
Q
how many subunits are in GABAA?
A
5
21
Q
how many GABA are required to bind GABAA receptor to open it?
A
2 GABA
22
Q
what is the relationship btwn GABA and diazepam and their affinities for GABAA receptor? how?
A
GABA and diazepam increase each other’s affinity for the receptor
via conformational changes that promote the binding of the other ligand
23
Q
what site does diazepam bind?
A
allosteric site
24
Q
what site does GABA bind?
A
orthosteric site
25
how do benzodiazepines affect GABA-induced hyperpolarization?
benzodiazepines INCREASE GABA's ability for hyperpolarization due to increased affinity
26
what occurs during GABA hyperpolarization?
1. GABA binds and opens GABAA
2. Cl- enters cell based on electrochemical gradient
3. cell becomes hyperpolarized
27
do GABAA channels open spontaneously?
usually no
28
describe the opening and closing of channels caused by GABA alone
channel opens and closes randomly
29
describe the opening and closing of channels caused by BZ alone
channel does not open at all
30
describe the opening and closing of channels caused by GABA and BZ
channel opens with increased frequency (BZ requires GABA to work)
31
describe the opening and closing of channels caused by GABA and barbiturates
channel opens for longer time (but barbiturates does not require GABA to work)
32
do benzodiazepines and barbiturates bind at the same site on GABAA?
no
33
when is IV diazepam used?
for epilepsy
34
describe the entry of BZ at the brain and periphery when injected thru IV
BZ rapidly enters the brain, then slowly redistributes to the periphery
it is fat-soluble so it quickly enters fatty brain/spinal cord with high blood supply
then reaches fat in periphery with lower blood supply
takes longer to equilibrate btwn brain and fat
fast onset and loss of effect
35
what is the problem with BZ metabolites?
they are active and have long half lifes
36
what is the main active BZ metabolites? what is its half life?
NORDIAZEPAM
T1/2 = 30-200H
37
Which 3 drugs are used for short term procedures? why?
1. Alprazolam
2. Oxazepam
3. Lorazepam
they have shorter half lives
38
what are 2 additional factors that prolong the action of BZs?
1. diazepam is 99% bound to plasma proteins
2. enterohepatic recycling
39
how do plasma proteins prolong the action of diazepam?
99% is bound to plasma proteins --> acts as a reservoir to delay clearance
40
what can cause diazepam to be displaced from plasma protein?
if you take a drug that binds to the same plasma protein
41
what is enterohepatic recycling? and how does this prolong the action of BZs?
BZs go from GIT to liver, but enterohepatic circulation takes it and brings it back to GIT
the drug can also be glucuronidated in the liver then converted back in GIT
42
does diazepam cause more sedation or muscle relaxing effects?
causes more muscle relaxing effects than sedation (but sedation still present)
43
is it ideal for BZs to cause sedation?
no
44
what does alpha1 subunit cause?
sedation
45
what does alpha2 subunit cause?
anxiolytic effect
46
what does the sensitivity of GABAA receptor to BZs depend on?
depends on alpha and gamma subunits
47
describe the use of frog oocytes to see the effects of each GABAA subunit
A. inject cDNA into frog oocytes to produce specific GABAA subunits
B. can pick the subunits you want it to express/not express
C. test diff drugs and see which receptors they interact with
48
how many alpha subunits are there?
6
49
describe the distribution of different alpha subunits in the brain
each distributed differently but with some overlap
50
Which 2 alpha subunits do not bind BZs?
alpha4 and alpha6
51
what amino acid do alpha subunits that bind BZs have?
alpha subunits that bind BZs have HISTIDINE in its binding pocket
52
what amino acid do alpha subunits that do not bind BZs have?
alpha subunits that do not bind BZs have ARGININE in its binding pocket
53
what happens if you turn the histidine in an alpha subunit to arginine?
alpha subunit will no longer be able to bind BZs
54
what happens if there is a point mutation in GABAA receptors with alpha2
cannot bind BZs
55
describe the dark and light experiment with mice and mutated alpha2 GABAA receptor. what does this experiment signify?
- normal mice will hide in the dark
- mice w normal BZ will go into the light (reduced anxiety)
- mice w mutated BZ will hide in the dark (has anxiety)
therefore, alpha2 subunit is necessary for anxiolytic effect
56
how many BZs are in use?
20
57
what is the half life of midazolam?
2h
58
what is the half life of diazepam?
>24h
59
should BZs be used short term or longer term?
short term
60
why should BZs not be used long-term? (2)
- can lead to dependence
- can lead to withdrawal --> rebound anxiety, rebound seizures
61
what are 2 unwanted effects of BZs?
1. sedation
2. overdose (esp w alcohol)
62
what is flumazenil?
competitive antagonist for BZ binding site to reverse an overdose
63
what is busiprone?
5HT1A PARTIAL AGONIST
64
why may buspirone be better to use than BZs?
has none of the side effects of BZs
65
which of the 3 types of anxieties does buspirone work against?
- GAD
- somatic activity (a bit)
66
how long does buspirone take to work?
1-3 weeks
67
what is the main disadvantage of buspirone?
takes 1-3 weeks to take effect, whereas BZs take 15 min-2h to work
68
what are the 2 reasons that the buspirone effect is impossible to predict?
1. 5HT1A receptors can inhibit cell firing and release of 5HT but also mimics postsynaptic action of 5HT
2. partial agonists act as agonist or antagonist depending on 5HT tone
69
how does 5HT1A receptors inhibit cell firing and release?
5HT1A acts as an autoreceptor
70
what is the effect of buspirone if there is lots of 5HT?
buspirone will get in the way and act as an antagonist
71
what is the effect of buspirone if there is less 5HT?
buspirone will act as an agonist
72
what are the 2 endogenous agonists for beta adrenergic receptors?
1. NA
2. adrenaline
73
what is the target of beta blockers
beta adrenergic receptors
74
what are 4 locations of beta adrenergic receptors?
1. heart
2. blood vessels in muscle
3. bronchi
4. brain
75
what is the most common type of beta blocker?
propranolol
76
what do beta blockers require to have an effect?
requires presence of agonist to have an effect --> i.e. acts preferentially when SNS is overactive
77
describe the experiment for stage fright and results of BP and HR and self-evaluation
Test 1 and 2: random order of propranolol and placebo
Test 3: beta agonist
HR: placebo has same HR as beta agonist, but higher than propranolol
BP: unchanged across all 3 drugs
self-evaluation --> most thought they played better w B blocker
78
if propranolol lowers HR, how does this affect sympathetic activity?
propranolol is decreasing sympathetic activity
79
why did the beta agonist not increase HR compared to placebo?
could be because it was the 3rd performance so they felt more comfortable --> poor control
80
what are 5 adverse effects of propranolol?
1. bronchoconstriction
2. cardiac failure
3. blocks warning signs of hypoglycemia
4. physical fatigue
5. bad dreams
81
describe bronchoconstriction due to propranolol and the cause
- occurs in asthma patients
- inhalers mimic fight or flight to open the airways which is blocked by propranolol
82
describe cardiac failure due to propranolol
- occurs in ppl with heart disease
- if SNS is what is allowing heart to function, blocking this = fatal
83
what type of ppl does propranolol block warning signs of hypoglycemia?
diabetic patients
84
what are the warning signs of hypoglycemia that are blocked by propranolol? (2)
1. increased pulse rate
2. increased sympathetic tone
85
why does propranolol cause physical fatigue?
blocks oxygen supply to muscle
86
what is pindolol?
partial agonist at beta adrenergic receptor
87
what is the role of pindolol? when does it have little effect?
blunts EXCESSIVE sympathetic tone
(little effect if low sympathetic tone)
88
what is psychic anxiety?
anxiety in brain
89
what is somatic anxiety?
anxiety in periphery --> tremors, sweating
90
what is the effect of diazepam on somatic and psychic anxiety?
diazepam reduces both types of anxiety
91
what is the effect of propranolol on somatic and psychic anxiety?
propranolol only reduces somatic anxiety NOT psychic anxiety
92
why does propranolol have effects only against somatic anxiety?
propranolol only blocks peripheral effects of SNS, doesn't really affect brain
93
how does the efficacy of BZs, buspirone, and SSRIs differ?
all are similar
94
what is not known about the efficacy of antidepressants?
we don't know efficacy beyond 12 weeks --> i.e. don't know efficacy with chronic use
95
what does the choice of drug depend on? (2)
1. adverse effects + risks
2. if need fast onset
96
which drug is useful for short-term/immediate treatment?
diazepam
97
which drug is useful for long-term treatment?
use diazepam + SSRIs until SSRI effect kicks in, then wean off diazepam
98
what drug is considered second-line treatment? why
beta-blockers
second line bc certain patients and situations where they shouldn't be used
99
what is the elevated plus maze and what does it show?
- closed sections are dark --> mice like to be here
- open sections are bright and high up --> mice don't like to be here
if anxiety drug works, mice will spend more time in the open arms
100
what is optogenic stimulation?
modify neurons so they express a light-sensitive gene
then can inhibit/stimulate neurons with light to control neuron activity
101
describe what optogenetic stimulation of the amygdala-hippocampus pathway showed
inhibiting pathway --> less anxiety --> more time in open arms
stimulating pathway --> more anxiety --> less time in open arms
therefore, stimulation of the amygdala-hippocampus pathway is responsible for anxiety response
102
describe the 3 stages of the fear-potentiated startle response
1. training --> pair light and shock
- light comes on before shock
2. testing --> noise
- mouse jumps due to loud noise
3. testing --> pair light and noise
- mouse jumps MORE bc conditioned to associated light with shock
103
what are 3 advantages of fear-potentiated startle response?
1. detect broad range of anxiolytics
2. can test old and new drugs
3. reveals brain mechanisms
104
what system is the amygdala part of?
limbic system
105
describe the fear-potentiated startle response in the brain
the conditioned visual stimulus and the unconditioned shock stimulus meet at the amygdala
this combined with loud noise sends signal to muscles to jump
106
where is the origin of many symptoms of anxiety that are acted on by propranolol and BZs?
amygdala
