W12 MENTAL HEALTH 2 Flashcards
(220 cards)
1
Q
What is depression?
A
A mental illness that can linger for for more than 2 weeks; it significantly affects one’s ability to work, play, love
2
Q
Sx of depression
A
Having five of the following symptoms may inform a diagnosis of depression: depressed mood for 2+ weeks, loss of interest in things normally enjoyed, changes in appetite, changes in sleep patterns, restlessness or slowness, poor concentration, feelings of worthlessness or guilt, suicidal ideation or thoughts.
intangible sx
3
Q
Depression has physical manifestations, seen in the naked eye, or x-ray… provide examples
A
smaller frontal lobe and hippocampus, blunted circadian rhythms (REM/slow wave sleep cycles), abnormal regulation of hormones (high cortisol, deregulation of thyroid hormones)
4
Q
Which neurotransmitters are abnormally released/depleted during depression?
A
serotonin, norepinephrine, dopamine
5
Q
potential causes
A
mainly unknown, though, thought to be a genetic & environmental impact
6
Q
treatment options for depression
A
medications and behavioural-cognitive therapy to boost brain chemicals; in extreme cases, electro-simulation
7
Q
how does depression compare to general feelings of sadness
A
General sadness is a mood that comes and goes in most individuals. It is a natural part of life but is usually not as long lasting or as impactful as depression.
8
Q
Which neurotransmitters and brain structures mentioned as being of key interest in the physiology of depression?
A
The key interest in physiology of depression includes abnormal levels of certain monoamine neurotransmitters, blunted circadian rhythms and sleep patterns, as well as hormonal abnormalities. Smaller frontal lobes and hippocampal volumes of the brain are also important to note.
9
Q
list the processes during 5-HT nerve transmission
A
- serotonin (5-HT) is synthesised from tryptophan and loaded into vesicles via the vesicular monoamine transporter (VMAT)
- it then undergoes calcium-mediated exocytosis and is released into the synaptic cleft
- 5-HT then binds to the 5-HTr to induce a serotonergic effect
- 5-HT is then reabsorbed into the presynaptic cell via the serotonin transporter (SERT) and is reloaded into vesicles or degraded by monoamine oxidase (MOA)
10
Q
what does VMAT stand for, and what is its function
A
vesicular monoamine transporter; it is responsible for the uptake of cystosolic monoamines into synaptic vesicles in monoaminergic neurons
11
Q
what MAO stand for, and what is its function
A
monoamine oxidase; an enzyme involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.
12
Q
what is the monoamine theory of depression?
A
it states there is a deficiency of monoamine neurotransmitters within the brain. Deficiencies of key monoamines including serotonin (5-HT) and noradrenaline lead to symptoms of depression.
13
Q
what are TCAs
A
tricyclic antidepressants.
14
Q
what are available TCA medications (-ine, -in) (6)
[A, C, D, D, I, N]
A
amitriptyline, clomipramine, dosulepin, doxepin, imipramine, nortryptiline
15
Q
what is the overall effect of TCAs
A
Tricyclic antidepressants (TCAs) block the reuptake of serotonin (5-HT) and noradrenaline (NA) in presynaptic terminals, which leads to increased concentration of these neurotransmitters in the synaptic cleft, which leads to their anti-depressive effect. Additionally, they act as competitive antagonists on post-synaptic cholinergic, muscarinic, and histaminergic receptors (H1).
16
Q
what are the side effects of TCAs (6)
A
dry mouth, constipation, difficulty urinating, sedation, sexual complications, weight gain.
it is not a good idea to drink alcohol when depressed as it tends to worsen the depression. it also interacts with TCAs, increasing sedation.
17
Q
the side effects of TCAs are largely due to the…
A
interactions w non-monoamine associated receptors; the most common adverse effects including constipation, dizziness, and xerostomia (dry mouth)
18
Q
TCA side effects: Due to its blockade of cholinergic receptors, these drugs can lead to…
A
blurred vision, constipation, xerostomia, confusion, urinary retention, and tachycardia.
TCAs may also cause cardiovascular complications, including arrhythmias, such as QTc prolongation, ventricular fibrillation, and sudden cardiac death in patients with pre-existing ischemic heart disease.
19
Q
TCA side effects: Due to its blockade of alpha-1 receptors…
A
it can cause orthostatic hypotension and dizziness
20
Q
TCA side effects: Due to its blockade of histamine (H1) receptors…
A
causes sedation, increased appetite, weight gain, and confusion.
21
Q
Noting the side-effects of TCAs, what other conditions could they be used to treat? (8)
A
migraine prophylaxis, obsessive-compulsive disorder (OCD), insomnia, anxiety, and chronic pain, especially neuropathic pain conditions such as myofascial pain, diabetic neuropathy, and postherpetic neuralgia. TCAs are also the second-line treatment for fibromyalgia after the failure of other treatments.
22
Q
what are SNRIs
A
serotonin and noradrenaline reuptake inhibitors (SNRIs); antagonises reuptake transporters of both noradrenaline and serotonin
23
Q
what are current SNRIs available in Australia (-xine, -xetine) (3)
A
venlafaxine, desvenlafaxine, and duloxetine
24
Q
describe the mechanism of action of SNRI medication
A
SNRIs antagonism both 5-HT and noradrenergic re-uptake transporters, increasing the concentrations of both neurotransmitters in synapses.
25
what is the difference between TCAs and SNRIs
The major differences between TCAs and SNRIs comes down to their reduced side effects. SNRIs have minimal affinity and therefore minimal antagonism for the H1 histaminergic and muscarinic receptors. This means there are reduced sedation and cardiovascular effects.
26
what are SSRIs
selective serotoninergic reuptake inhibitors (SSRIs)
27
what are current SSRIs available in Australia (-pram, -xetine...) (6)
citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
28
which type of medication for depression is usually first-line
SSRIs
29
what do SSRIs mainly act on
serotonergic synapses
30
what transporter do SSRIs block
SERT (serotonin reupdate transporter)
31
what is the result of SSRI
increased serotonin available for postsynaptic nerve transmission
32
what are some common side effects of SSRI
nausea (esp. in the first wk of treatment), difficulty going to sleep, nervousness, headaches, sexual problems.
33
what is an example of a pre-synaptic autoreceptor on serotonergic neurons
5-HT1A
34
what is the role of autoreceptors
they detect the presence of serotonin that is released into the synaptic gap following an action potential by the serotonergic neuron itself
35
Activation of the autoreceptor leads to gradual _________ in serotonin release – a ________ feedback process.
reduction; negative
36
Activation of postsynaptic 5-HT1A receptors mediates _______ (e.g., _______) properties, whereas activation of _____ autoreceptors is implicated in delay of therapeutic onset of antidepressants.
therapeutic; antidepressant; raphe
37
hypothalamic 5-HT1A receptors are involved in ____________ and ___________ control
thermoregulation; neuroendocrine
38
septum/___________ receptors control ___ release and aspects of memory function
hippocampal; ACh
39
SSRI treatment results in ______ concentrations of _________ and over time it is thought the auto-receptors are downregulated and ___________.
higher; serotonin; desensitised
40
why do antidepressants take 2-4 weeks to be effective
the 5-HT1A autoreceptor desensitization model: inhibition of serotonin reuptake increases serotonin concentration, which causes a downregulation of 5HT1A receptors. After the number of 5HT1A receptors is reduced, the neuron is less inhibitided to release more serotonin in the synaptic space.
41
what are MAOIs
irreversible monoamine oxidase inhibitors (MAOIs) (the oldest drug class of antidepressants)
42
what MAOIs are currently available in Aus (2)
phenelzine, tranylcypromine
43
summarise the MAOI mechanism of action
MAOIs prevent monoamine degradation, so they are packaged more quickly into synaptic vesicles for re-release. this enhances the speed with which the pre-synaptic neuron can respond to an action potential and therefore alleviates the presumed deficiency
44
what is the difference between MAO-A and MAO-B
MAO-A: works on noradrenaline and serotonin
MAO-B: metabolises dopamine within the CNS
45
where is else is MAO-A located and what does it metabolise
digestive tract; tyramine
46
list some food that contain tyramine
cheese, yeast, beer, some wines, avocados, yoghurt, soy sauce
47
what is the interaction between food that contain tyramine and MAOIs
as MAOIs inhibit MAO-A, the normal metabolism of tyramine is inhibited. tyramine will then be absorbed into the blood supply, making its way to the BBB. tyramine can then pass through the reuptake transporters for noradrenaline and subsequently displace NA from its synapses, lading to its unregulated release into synapses. this can lead to a hypertensive crisis. which could be fatal due to its sudden increase in blood pressure, heart rate, heart palpitations, and sweating.
48
how can you avoid a MAOI induced hypertensive crisis
tyramine-restricted diet, consideration of administration of MAOIs via a transdermal patch [it does not inhibit MAO-A]
49
common side effects of MAOIs
dry mouth, nausea, diarrhoea or constipation, headache, insomnia, drowsiness, dizziness or light-headedness, and possible skin reactions at the patch site
50
less common side effects of MAOIs
hypotension, reduced sexual desire/difficulty achieving orgasm, weight gain, muscle cramps
51
what are NASSAs
noradrenergic and specific serotonergic antidepressants (NASSAs)
52
what is one example of NASSA
mirtazapine
53
summarise NASSA mechanism of action [2 mechanism of actions]
In adrenergic neurons, NASSAs have an affinity for and antagonist effects against the NA alpha2 autoreceptors, which leads to downregulation/desensitization in the long term and a net increase in noradrenaline release in synapses.
In serotonergic neurons, NA influences increase synaptic release of 5-H. NASSAs are antagonists of postsynaptic 5-HT2 and 5-HT3 receptors. This leads to increased action on the 5-HT1 receptors, which stabilises mood.
54
list side effects of NASSAs [7]
dry mouth, increased appetite and weight gain, headaches, drowsiness, nausea, vomiting, diarrhoea, and constipation
55
how long should we try a treatment before we know whether it is working or not?
allowing time to observe clinical response, some agents may require 2-3 month trial. These changes may be positive, non-optimal or negative due to side effects experienced. The GP may continue the current dose, alter it up or down, or discontinue and/or switch to a new drug class. The goal is to achieve “remission” of the severe depressive symptoms such that other means of support can be added (e.g., counselling, mindfulness).
56
If medication(s) can be optimised for the patient, it is likely that “maintenance” will be achieved for at least _ months – __.
9; 1 year
57
when are relapses more likely to happen when taking anti-depressants
12 weeks - 9 months
58
in depression, remission can also be associated with...
return to euthymia - feeling true to oneself
59
When a patient is in remission/recovery for more than ___ year, their medication may be reduced gradually over a _-_ week period.
one; 4-6
60
what is recurrence in depression
where symptoms reuturn after recovery
61
what is serotonin syndrome
elevated serotonin levels; mild or severe
62
what causes serotonin syndrome
antidepressant medications, St. John's Wort, some cough medications, MDMA, migraine medications and other drugs, and intentional overdose of antidepressant medications
63
mild sx of serotonin syndrome
sweating, fever, agitation, confusion, anxiety, tachycardia, diarrhoea, tremors, poor coordination
64
full sx of serotonin syndrome
hyperthermia, shivering diaphoresis
hypomania, hyper-vigilance
hypertension
hyperflexia, clonus, myoclonus
65
severe sx of serotonin syndrome
hyperthermia (>40 degrees C), seizures, coma, death, rigidity
66
psychotherapy is a non-pharmacological ways to improve mental health, this involves:
cognitive behavioural therapy (CBT), stress mgt, relaxation strategies, effective sleep habits
67
electroconvulsive therapy (ECT) is a non-pharmacological way to improve mental health, this is:
a fast treatment for severe depression when the situation is thought to be life-threatening or after all other treatment options have failed.
68
what is a side effect of ECT
mild memory loss
69
T/F
ECT is one of the most effective treatments for depression
T
70
T/F
the effects of ECT are long-term without the requirement of further pharmacological/non-pharmacological assistance like antidepressants and therapy
F
71
During ECT the patient is placed under light _______ ______ and given _______ ______
general anaesthetics; muscle relaxants
72
T/F
antidepressants improve sx in about 40-60 out of 100 people
T
73
about __% of people who took an antidepressant had a relapse in 1-2 years
23
74
T/F
there may be strong components within families for depression
T
75
Deficiencies of which two central nervous system neurotransmitters may be linked to depressed mood, and which drugs are generally the first choice for the treatment of depression?
noradrenaline and serotonin; SSRIs
76
T/F
increased intraventricular conduction time is a side effect associated with TCAs as a result of blocking adrenergic receptors, muscarinic cholinergic receptors, or H1 receptors?
F
77
The ‘cheese reaction’ is characterised by flushing of the skin, sweating, and tachycardia when taking oral antidepressants. It is directly related to the effect of:
tyramine. which displaces noradrenaline from presynaptic vesicles, leading to a sympathetic response
78
The ‘cheese reaction’ is characterised by flushing of the skin, sweating, and tachycardia when taking oral antidepressants. It is directly related to the effect of:
elevated levels of 5-HT and NA caused by re-uptake inhibition and receptor blockade
79
anxiety is a reaction to our _____; a stop-reaction to the impulses that ____ and other core emotions create inside the body
emotions; fear
80
physical and psychological sx of anxiety
Feeling nervous, restless, or tense
Having a sense of doom
Increased heart rate
Shortness of breath
Sweating
Dizziness
Ear ringing
Trouble concentrating
Trouble sleeping
Gastrointestinal (GI) distress
Having difficulty controlling worry/ruminating
Having the urge to avoid things that trigger anxiety
Feeling insecure
80
physical and psychological sx of anxiety
Feeling nervous, restless, or tense
Having a sense of doom
Increased heart rate
Shortness of breath
Sweating
Dizziness
Ear ringing
Trouble concentrating
Trouble sleeping
Gastrointestinal (GI) distress
Having difficulty controlling worry/ruminating
Having the urge to avoid things that trigger anxiety
Feeling insecure
81
physical sx anxiety and depression share [3]
GI upset
Appetite and weight changes
Sleep difficulty
82
mental sx anxiety and depression share [2]
Difficulty concentrating
Irritability
83
how do stress and anxiety compare?
stress is short-term and is a response to a recognised threat
anxiety is long term where there is not an identifiable trigger
84
generalised anxiety disorder (GAD) is characterized by
increased motor tension (eg, fatigability, trembling, restlessness, muscle tension), autonomic hyperactivity (eg, shortness of breath, rapid heartbeat, high heart rate, dry mouth, cold hands, dizziness), and increased vigilance and scanning (eg, feeling keyed up, increased startling, impaired concentration)
85
T/F
in GAD men experience more psychologic sx (i.e. irritability, sense of impending doom), whereas women develop more physical pain (i.e. chest pain, palpitations, and shortness of breath)
T
86
list risk factors for GAD [8]
gender, childhood trauma, physical illness, stress, personality disorder, genetics, substance abuse, family discord
87
define generalised anxiety disorder (GAD)
persistent and excessive worry that tends to interfere w daily activities
88
define social anxiety disorder
intense anxiety about being embarrassed or rejected in social situations
89
define phobia (as a type of anxiety)
persistent and excessive fear around a particular object, activity, or situation
90
define panic disorder
the main sx is panic attacks, physical and psychological distress episodes
91
what causes anxiety disorders
the exact cause is not fully known, however there are a number of factors that appear to contribute to its development:
1. Brain chemistry: imbalances is neurotransmitters
2. Genetics: some research suggests that family history plays a part in increasing the chances of a person developing anxiety disorder
3. Environment: trauma and stressful evens such as abuse, the death of loved one, divorce, changing jobs or schools, may trigger anxiety disorders. The use of, and withdrawal from, addictive substances such as alcohol, caffeine and nicotine can also worsen anxiety. Some of these substances may in fact be used to “self-medicate” mental health stresses.
92
the _______ within the brain may respond with heightened outputs to triggers linked to anxiety
amygdala
93
list 4 neurotransmitters involved in depression
noradrenaline, serotonin, dopamine and GABA
94
T/F
barbiturates are prone to physical and psychological dependence and addiction
T
95
T/F
barbiturates have a very narrow therapeutic window between beneficial and potentially lethal effects
T
96
T/F
barbiturates do not cause withdrawal sx
F
withdrawal symptoms are severe
97
T/F
tolerance to barbiturates can cause respiratory depression
F
tolerance may develop to calming effects but not to respiratory depression
98
T/F
due to effects of alcohol on GABAA receptors, combining barbiturates and alcohol is potentially lethal
T
99
what is a potential first line treatment for anxiety
benzodiazepines (BNZs) (used as needed for a period of time, usually in combination w counselling)
100
what do BNZs do in the brain?
activates GABAergic receptors in the amygdala and hippocampus to bring on a sense of relaxation.
BNZs are taken systemically (cannot target them to specific brain regions yet) -> in the brainstem, activation of the GABAA receptors in the respiratory centres are thought to slow breathing.
101
list common BNZs (-pam, -lam) [8]
alprazolam, chlordiazepoxide, clobazam, clonazepam, diazepam, flurazepam, lorazepam, nitrazepam
102
agomelatine is an ________ on melatonin receptors (MT1 and MT2) which are concentrated in a brain region called the suprachiasmatic necleus (SCN)
agonist
103
As sleep disruption is a symptom of depression, it is thought that activation of the MT1 and MT2 receptors by _________ may improve overall well-being.
agomelatine
104
In addition to the SCN, melatonin receptors (MT1 and MT2) also exist in the ___________ and ________ _______, and agomelatine is thought to provide ___________ effects via interactions in each of these brain regions.
hippocampus; frontal cortex; antidepressant
105
T/F
melatonin dysfunction is involved in anxiety and depression
F
only depression
106
T/F
agomelatine is an agonist on MT1 and MT2 receptors, while serving as an antagonist on 5HT2C receptors elsewhere
T
107
Buspirone is a non-___________ that works as a _______ _______ at 5-HT1A receptors.
benzodiazepine; partial agonist
108
buspirone may take up to ___ week for effectiveness, and does not tend to be associated with ________ symptoms when stopped.
1; withdrawal
109
In addition to buspirone, SSRIs and SNRIs can be effective treatment for...
GAD, phobias, social anxiety, OCD and PTSD
110
what class is imipramine
TCA
111
T/F
imipramine has positive effects in 50% of panic disorder patients
F
it's 60-70%
112
T/F
medication is the most effective anxiety treatment
F
a combination of medication and therapy is most effective
113
In the treatment of anxiety, benzodiazepines are preferred over barbiturates, because benzodiazepines:
(a) do not induce physical dependence
(b) act at GABAA receptors
(c) have a higher therapeutic index than barbiturates
(d) are more likely to cause drug interactions than barbiturates
(e) are better absorbed orally than barbiturates
C
114
Which of the following statements pertaining to the treatment of anxiety using either benzodiazepines (e.g. temazepam) or non-benzodiazepines (e.g. zolpidem) is INCORRECT?
(a) Both drug classes bind to GABA\vA\v receptors and function as positive allosteric modulators
(b) Physical or psychological dependence may occur with frequent use of either of these drug classes
(c) Episodes of sleep driving, sleep eating or sleep walking have been reported by users of zolpidem
(d) Combining either of these drug classes with alcohol is potentially dangerous, as they affect the same receptor targets
(e) Both of these drug classes have a range of half-life values, which may lead to the patient feeling ‘fuzzy’ in the morning if their medication is taken late in the evening
D
115
Which of the following statements about treatment strategies used to treat anxiety is INCORRECT?
(a) Barbiturates have been associated with life-threatening respiratory depression
(b) Patients taking Z-hypnotics or benzodiazepines may consume moderate amounts of alcohol safely
(c) Agomelatine is thought to affect melatonin receptors, as well as to antagonise 5-HT2C receptors
(d) The benefits of cognitive behavioural therapy (CBT) can outlast the benefits of pharmacological intervention
(e) Zolpidem produces sedative effects in patients by binding to the GABAA alpha subunits
B
116
Which of the following statements regarding anxiety and its treatments is INCORRECT?
(a) Buspirone does not affect GABAA receptors and is used to treat anxiety
(b) Ideally, drug treatment should be combined with cognitive behavioural therapy to alleviate anxiety
(c) Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, are useful to treat anxiety disorders
(d) Some benzodiazepines are useful to relieve generalised anxiety disorder (GAD)
(e) Monoamine oxidase inhibitors decrease the concentrations of neurotransmitters involved in stress and anxiety
E
117
what does bipolar mean
two extremes; elation and depression
118
there are two types of bipolar disorder, what is the difference
type 1 will likely experience "full manic" and may or may not have a major depressive episodes
type 2 will experience "hypomania" [less severe than full mania] and will have a major depressive episode
119
what causes bipolar disorder?
disrupted neural pathways; neurons create a network that's impossible to navigate -> abnormal thoughts and behaviours
This is attributed to the overabundance of DOPAMINE
120
does bipolar run in the family
typically; but there isn't a single gene that causes bipolar, it is usually created by interactions of multiple genes
121
what medication is usually used for bipolar disorder
lithium and antipsychotics, as well as electroconvulsive therapy
122
how is bipolar disorder acquired? (in relation to medications)
meds such as alcohol intoxication, drug withdrawal, antidepressants, drugs that enhance dopamine activity, non-prescription weight loss drugs, St. John's wort, and others
123
how is bipolar disorder acquired? (in relation to medical conditions)
endocrine or hormonal dysregulation, infections, CNS disorders and others
124
how is bipolar disorder acquired? (in relation to environmental factors)
sleep deprivation, bright light therapy, and deep brain stimulation (DBS)
125
what is meant by manic episodes
times of exceptional energy, extreme happiness, poor to little sleep, restlessness, and risk-taking behaviour.
The sx may be so severe that hospital care is needed. Someone with a manic episode is likely to be diagnosed w bipolar Type 1 disorder.
126
lithium works as a ____ stabiliser
mood
127
lithium is thought to ______ (+/-) inhibitory neurotransmission via ____
increase; GABA
128
lithium is thought to ________ (+/-) excitatory neurotransmission via g_______ and d_______
decrease, glutamate and dopamine
129
at the level of the neuron, lithium inhibits voltage-sensitive sodium ion channels. how does it do this?
Li+ mimics Na+ but is not a substrate for Na-K-ATPase. it may accumulate in cells
130
at the level of the neuron, lithium modulates GPCR second messenger systems. how does it do this?
it inhibits inositol monophosphate which blocks the phosphoinositide pathway
[hypothesis: an overactive InsP signal transduction pathway underlies mania]
131
T/F
lithium at the synaptic level promotes the inhibtory neurotransmission of dopamine
F
Li+ inhibits the excitatory neurotransmission of dopamine
132
T/F
lithium at the synaptic level promotes the inhibtory neurotransmission of dopamine
F
Li+ inhibits the excitatory neurotransmission of dopamine
133
T/F
Lithium inhibits the excitatory neurotransmission of glutamate
T
134
T/F
Lithium inhibits the excitatory neurotransmission of GABA
F
Li+ promotes inhibitory neurotransmission of GABA
135
T/F
schizophrenia is rather a disruption of thought processes than manifestation of another personality
T
136
what are positive sx of schizophrenia (occurs in people with schizophrenia, but in the general population)
delusions, hallucinations, disordered speech and behaviour
137
list 6 symptoms associated with schizophrenia
1. delusions
2. hallucinations
3. thinking difficulties
4. loss of drive
5. blunted or inappropriate emotions
6. social withdrawal
138
what is the function of basal ganglia
involved in movement and emotions and in integrating sensory information
139
abnormal functioning of the basal ganglia in schizophrenia is thought to contribute to...
paranoia and hallucinations [excessive blockade of dopamine receptors in the basal ganglia by traditional antipsychotic medicines leads to motor side effects]
140
what is the function of the frontal lobe
critical problem solving, insight and other high-level reasoning
141
Perturbations in schizophrenia lead to difficulty in planning actions and organising thoughts in what part of the brain?
frontal lobe
142
the limbic system is involved in e____
emotion
143
how do disturbances due to schizophrenia affect the limbic system
contributes to agitation
144
the auditory system enables humans to _____ and understand _____
hear; speech
145
In schizophrenia, overactivity of the speech area (called Wernicke’s area) can create auditory hallucinations—the illusion that internally generated thoughts are real voices coming from the outside. What part of the brain is affected
auditory system
146
the occipital lobe processes information about the v_____ w______
visual world
147
disturbances to the occipital lobe in schizophrenia can contribute to such difficulties as..
interpreting complex images, recognising motion, and reading emotions on others' faces
148
the hippocampus mediates l______ and m_______ f______, intertwined functions that are _______ in schizophrenia
learning; memory formation; impaired
149
As a neurotransmitter, the monoamine _ _ _ _ _ _ __ plays key roles along its neural tracts.
dopamines
150
what are the four dopamine pathways in the brain:
1. mesocortical
2. nigrostriatal
3. mesolimbic
4. tuberoinfundibular
151
in the mesocortical pathway, dopamine influences
perception, cognition and social behaviour
152
in the nigrostriatal pathway, dopamine has influence over
control of fine movements and initiation of movement
153
in the mesolimbic pathway, dopamine is thought to be involved in
emotion and memory, pleasurable sensations and reward, the euphoric effects of addictive substances, as well as psychotic sx, such as delusions and hallucination
154
in the tuberoinfundibular pathway, dopamine normally inhibits the release of
prolactin
155
summarise the life cycle of dopamine
1. tyrosine is enzymatically converted to levadopa (L-DOPA). levadopa undergoes decarboxylation to form dopamine (DA).
2. within the presynaptic neuron, DA is packaged into vesicles via VMAT-2
3. when released into the synaptic gap, DA can then bind to post-synaptic receptors (either D1-like or D2-like)
4. it is ultimately recycled by reuptake via the DA transporter, or catabolized by catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO) enzymes
156
out of the DA receptors, which is the predominant subtype in the brain?
involved in mood, emotional stability in the limbic system as well as movement control in the basal ganglia.
D2
157
D1 and D5 DA receptors belong to which receptor family
D1
158
D2 receptors include which other subtypes
D2, D3, D4
159
The D1 receptor family increases ________
cyclic AMP
160
The D2 receptor family decreases ______, increases ______, decreases ________
cyclic AMP, K+ currents, voltage-gated Ca2+ currents
161
The D1 receptor family _________ cyclic AMP
increases
162
The D2 receptor family _________ cyclic AMP, _________ K+ channels, _________ voltage-gated Ca2+ currents
decreases, increases, increases
163
In schizophrenia, the mesocortical pathway is ________, leading to _________ symptoms (affective flattening, avolition)
hypodopaminergic; negative
164
In schizophrenia, the mesolimbic pathway is ______________, leading to ________ symptoms (delusions, hallucinations, disorganized thought, speech, and behaviour).
hyperdopaminergic; positive
165
inhibition of the nigrostratial pathway causes the ________ side effects of antipsychotic drugs
extrapyramidal
166
Mesolimbic pathway:
- Dopamine travels from the m________ tegmental area to the nucleus _________.
- Increased activity in this pathway may cause delusions, hallucinations, and other so-called ______ symptoms of schizophrenia.
midbrain; accumbens; positive
167
Mesocortical pathways:
- Decreased activity in the pathway that goes from the midbrain to the _______ ______ _______ can cause apathy, withdrawal, lack of motivation and pleasure, and other so-called _______ symptoms of schizophrenia.
- Mesocortical __________ also _______ the mesolimbic pathway.
prefrontal lobe cortex; negative; dysfunction; disinhibits
168
Tuberoinfundibular pathway:
- The pathway from the _______ to the _______ inhibits the release of ______.
- Inhibition of this pathway leads to elevated serum ______ levels.
hypothalamus; pituitary; prolactin; prolactin
169
describe the mechanism of action of antipsychotic drugs on the mesocortical pathway
D2 receptor antagonism by typical antipsychotics can cause or worsen negative and cognitive symptoms
170
describe the mechanism of action of antipsychotic drugs on the mesolimbic pathway
D2 receptor antagonism by antipsychotic drugs reduces positive symptoms
171
describe the mechanism of action of antipsychotic drugs on the nigrostriatal pathway
D2 receptor antagonism by antipsychotic drugs can result in EPS (extrapyramidal sx)
172
describe the mechanism of action of antipsychotic drugs on the tuberoinfundibular pathway
D2 receptor antagonism by typical antipsychotics can increase prolactin levels
173
there are two general categories of antipsychotic drugs:
1. typical first-gen antipsychotics (FGA)
2. atypical second-gen antipsychotics (SGA)
174
typical antipsychotics are modelled on ___ receptor antagonism
D2
175
side effects of typical antipsychotics include... (2)
- extrapyramidal sx (EPS)
- tardive dyskinesia (TD)
176
atypical antipsychotics are modelled on ___ and ___ receptor antagonism
5HT2; D2
177
side effects of atypical antipsychotics include...
- weight gain
- sedation
- risk of diabetes
178
Older _______ ____ drugs reduce the enhanced activity of ________ in the _________ pathway by working as c_______ ________ antagonists at D2 receptors, thus reducing _________ symptoms
typical FGA; dopamine; mesolimbic; competitive reversible; positive
179
is CHLORPROMAZINE a typical antipsychotic or atypical antipsychotic?
typical antipsychotic
180
Chlorpromazine is an _________ for __ receptors
antagonist; D2
181
chlorpromazine is also an antagonist for m_______ (_1), h________ (H_), _-__ and alpha-_-________ receptors
muscarinic (M1); histaminic (H1); 5-HT; alpha-2-adrenergic receptors
182
Blocking the D2 receptors of the striatum can lead to...
extrapyramidal symptoms
183
extrapyramidal symptoms resemble which disease?
Parkinson's
184
symptoms of D2 receptor antagonism include: (4)
- shuffling gait
- tremor at rest
- rigidity
- stooped posture
185
what are clinical effects at the dopamine D2 receptors when blocked
positive psychotic sx (hallucinations, delusions)
adverse effects: extrapyramidal sx and prolactin levels
186
what are clinical effects at the blocking of serotonin 5-HT1A receptors
balances D2 blockade and attenuates extrapyramidal sx
[possible role in circadian rhythm and hallucinations]
187
what are clinical effects at the blocking of serotonin 5-HT2A receptors
possible role in anxiety, cognition, mood
188
what are clinical effects when blocking serotonin 5-HT7 receptors
possible role in circadian rhythm, mood, thermoregulation, learning, memory, and endocrine regulation
189
what are clinical effects when the alpha-adrenergic alpha-1 receptor is blocked
dizziness, drowsiness, orthostatic hypotension
190
what are clinical effects when the H1 receptor is blocked
sedation, weight gain, impaired cognition
191
what are clinical effects when the muscarinic (M1) receptor is blocked
deficits in memory and cognition, constipation, blurred vision, dry mouth , drowsiness, tachycardia, urinary retention
192
haloperidol and other butyrophenones (non-phenothiazine compounds) are typical or atypical?
typical
193
haloperidol _____ both D2 and D1 receptors to reduce _____ symptoms
antagonises; positive
194
T/F
Atypical Second-Generation Antipsychotics (SGAs) were designated as being “atypical” in that they did not have a strong tendency towards EPS side effects.
T
195
T/F
The antagonism of D2 receptors is increased relative to the typical compounds, and the method of titrating the concentration in a patient was no longer effective.
F
it is decreased
196
in typical antipsychotics, they have a greater affinity for and/or longer binding time w D2 receptors, what does this mean in terms of its side effects
this results in a "slow off" or unbinding and an increased risk of EPS
197
atypical SGAs bind to D2 receptors bit more loosely, resulting in...
a "fast off" and a reduced risk of EPS
198
what are 2 advantages of atypical antipsychotic medications over typical counterparts?
1. reduced D2 receptors, and are also 5-HT2A receptor antagonists, and 5-HT1A receptor agonists
2. more effective against both positive and negative sx of shizophrenia, whereas typical FGAs predominanty address the positive sx.
199
medications that block 5-HT2A receptors have been linked to:
- increased food intake [weight gain]
- dyslipidaemia (increased mean total cholesterol serum levels)
- hypertriglyceridemia: increased triglyceride levels
- increased risk of T2DM
200
clozapine and olanzapine (atypical antipsychotics) have the greatest affinity for 5-HT2 receptor antagonism, which means...
the weight gain element is greatest
201
clozapine is a _____-_____ antagonist
serotonin-dopamine
202
clozapine has a ____ affinity for 5-HT2A receptors and _____ affinity for D2 receptors
high; low
203
T/F
at therapeutic doses of clozapine, there is no EPS
T
204
what other receptors in the brain are also antagonised by clozapine?
muscarinic ACh, alpha-adrenergic, H1 receptors
205
patients using clozapine report weight ____, osteo_____, and an increased tendency towards ______
gain, -porosis, T2DM
206
what agranulocytosis and its relationship w clozapine
the death of granulocytes involved in the immune response
this led to a number of patient deaths; patients on clozapine are now required to regularly submit for haematological monitoring of granulocytopenia before agranulocytosis develops
207
risperidone is a _____-_____ antagonist
serotonin-dopamine
208
relative to haloperidol, risperidone has a very _____ affinity for 5-HT2A receptors and a _____ affinity for D2 receptors
high; low
209
T/F
at therapeutic doses of resperidone, EPS can occur
F
no EPS
210
T/F
Collateral binding of risperidone with other receptors contributes to side effects however there is less muscarinic ACh antagonism compared to clozapine.
T
211
aripiprazole is a ______ agonist for D2 and 5-HT2A receptors
partial
being a partial agonist means that it activates both types but elicits a reduced response compared to natural neurotransmitter
212
aripiprazole is also a partial agonist at ______, ____ and ________ receptors. it has no affinity for cholinergic muscarinic (M1) receptors
5-HT1A, H1, alpha1-adrenergic
213
T/F
A partial agonist can be considered to be a 'modulator', adjusting levels depending on whether they are too high or too low.
T
214
how does aripiprazole reduce positive sx
partial agonism in the mesolimbic pathway is postulated to reducing hyper-dopaminergic interactions
215
how does aripiprazole reduce negative sx
partial agonism in the mesocortical pathway increases the dopaminergic activity back to normal levels
216
T/F
aripiprazole has quite adverse side effects
F
generally safe and well tolerated with minimal side effects
217
aripiprazole is metabolised by CYP___ and CYP___
3A4, 2D6
218
If aripiprazole is co-administered with medications that inhibit CYP3A4 or CYP2D6 , the dose is ______.
halved
219
If aripiprazole is co-administered with medications that induce CYP3A4, drug doses need to be evaluated based on perceived _____.
efficacy
