Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medicine Sem 3 > Case 8 > Flashcards

Case 8 Flashcards

1
Q

what are the 3 functional subdivisions of the striatum?

A
  1. Sensorimotor - Putamen
  2. Associative – Globus Pallidus
  3. Limbic/Ventral - Ventral Tegmental Area
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the four main dopamine pathways?

A
  1. Nigrostriatal dopamine pathway
  2. Mesocortical dopamine pathway
  3. Mesolimbic dopamine pathway
  4. Tuberofundibular dopamine pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

nigrostriatal dopamine pathway

  • projects from where to where
  • part of what NS
  • controls what
A
  • The nigrostriatal dopamine pathway projects from the substantia nigra to the basal ganglia or striatum.
  • It is part of the extrapyramidal nervous system. (part of motor system causing involuntary actions)
  • It controls the motor function and movement.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

deficiencies in dopamine in the nigrostriatal pathway causes what? what can dopamine deficiency in the basal ganglia also produce?

A
  • movement disorders including Parkinson’s disease, characterized by rigidity, akinesia/bradykinesia and tremor
  • akathisia (a type of restlessness), and dystonia (twisting movements especially of the face and neck)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how can these movement disorders of the nigrostriatal pathway be replicated?

A

by drugs that block D2 receptors in this pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is hyperactivity of dopamine in the nigrostriatal pathway (associative striatum)?

A

 Emotional behaviours – positive symptoms of psychosis, such as delusions and hallucinations.
 Motivation, pleasure and reward.
 Hyperkinetic movement disorders.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

chronic blockade (?) of D2 receptors in the nigrostriatal pathway may result in what?

A

hyperkinetic movement disorder known as neuroleptic-induced tardive dyskinesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

the increase in dopamine associated with schizophrenia occurs where?

A

in the associative striatum of the nigrostriatal pathway and not in the mesolimbic pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

where does the mesocortical pathway project from and to?

A

from the ventral tegmental area to areas of the prefrontal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the mesocortical pathway associated with?

A

 Mediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) of schizophrenia.
 Mediating affective symptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia.
 Mediating negative symptoms (DLPFC and VMPFC) of schizophrenia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what might cognitive and some negative symptoms of schizophrenia be due to?

A

deficit of dopamine activity in mesocortical projections to dorsolateral prefrontal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what might affective and other negative symptoms be due to?

A

deficit of dopamine activity in mesocortical projections to ventromedial prefrontal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does the behavioural deficit state suggested by negative symptoms implies what?

A

underactivity or lack of proper functioning of mesocortical dopamine projections that may be the consequence of neurodevelopmental abnormalities in the NMDA glutamate system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the effect of increasing dopamine in the mesocortical pathway on schizophrenia?

A

might improve negative, cognitive, and affective symptoms

 However, since there is hypothetically an excess of dopamine elsewhere in the brain – within the mesolimbic pathway (associative striatum of nigrostriatal pathway) – any further increase of dopamine in that pathway would actually worsen positive symptoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

where does the mesolimbic pathway project from and to?

A

projects from the dopaminergic cell bodies in the ventral tegmental area (ventral striatum) to axon terminals in one of the limbic areas of the brain, namely the nucleus accumbens in the ventral striatum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what does deficient function of the mesolimbic pathway lead to?

A
  • loss of motivation and interest
  • anhedonia
  • lack of pleasure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

treating patients with antipsychotics can produce what in terms of negative symptoms?

A

worsening of negative symptoms and a state of ‘neurolepsis’ that looks very much like negative symptoms of schizophrenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

since the prefrontal cortex does not have a high density of D2 receptors, this implicates possible deficient functioning within the mesolimbic dopamine system causing what?

A

inadequate reward mechanisms, exhibited as behaviours such as anhedonia and drug abuse, as well as negative symptoms, exhibited as lack of rewarding social interactions and lack of general motivation and interest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

where does the tuberoinfundibular pathway project from and to?

A

from the hypothalamus to the anterior pituitary gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

normally what does the tuberoinfundibular pathway do? what happens in the postpartum state? what are elevated prolactin levels associated with? what problems can occur after antipsychotic use?

A

• Normally, these neurons inhibit prolactin release.
• In the postpartum state, however, the activity of these dopamine neurones is decreased.
• Prolactin levels can therefore rise during breastfeeding so that lactation will occur.
• Elevated prolactin levels are associated with:
o Breast pathology (galactorrhoea/ enlargement); amenorrhea (loss of ovulation and menstrual periods)/ sexual dysfunction.
• Such problems can occur after antipsychotics that block D2 receptors are used.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is schizophrenia?

A

• ICD-10: “a severe and enduring mental disorder, with fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually maintained, although cognitive deficits may evolve in the course of time”.
 This is accompanied by high levels of social dysfunction, inability to maintain employment, depression and suicide.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how is schizophrenia characterised?

A

Schizophrenia is a major psychosis.
 It is characterised by a disintegration of the process of thinking, of contact with reality, and of emotional responsiveness.
 The condition can spontaneously remit, run a course with infrequent or frequent relapses, or become chronic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is prognosis of schizophrenia?

A

this is improved with antipsychotic drugs but usually follows a relapsing and remitting course, and has a high incidence of depression and suicide

  • No cure
  • Ten years after initial diagnosis, approx. 50% of people diagnosed with schizophrenia are either noted to be completely recovered or improved to the point of being able to function independently
  • 25% are improved, but require a strong support network, and an additional 15% remain unimproved and are typically hospitalised
  • 10% see no way out except through death – suicide

Overall weighted life expectancy was 64.7 years
People with schizophrenia often die at a considerably younger age than the rest of the population – reasons for this include: late diagnosis and poor treatment of physical illnesses, metabolic side effects of antipsychotic medication, unhealthy lifestyle and high risk of suicide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are the symptoms of schizophrenia?

A

Positive (type 1) Symptoms - Psychosis
• These are characterised by the existence of an abnormal phenomenon.
• These include delusions, hallucinations, thought disorder, bizarre behaviour and catatonia.
• These symptoms are associated with acute episodes.

Negative (type 2) Symptoms - Deficit
• These are characterised by the absence or reduction of normal function and reactions.
• These include apathy, affective blunting, poverty of speech (alogia), inability to experience pleasure (anhedonia), lack of desire to form relationships (asociality), social withdrawal, impaired judgement, lack of motivation (avolition), lack of interest in personal hygiene, difficulty in planning and impaired problem solving.
• These symptoms underlie the severe disability associated with chronic schizophrenia.

Cognitive Impairments
• Particularly memory and executive functions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is a delusion? what are the different types?

A

• Delusion – “a fixed, false belief, unshakeable by superior evidence to the contrary, and out of keeping with a person’s cultural norms”.
• Patients may persist with different types of delusions:
 Reference – e.g. people are always talking about ‘me’.
 Persecution – e.g. people are out to kill me.
 Control – e.g. my body is not under my control, I am a puppet.
 Bizarre and impossible – e.g. think you are a tree.

  • grandiosity (mania in bipolar disorder) – you have special powers
  • hypochondriacal or somatic (various, often depression) – referred to your body – I believe I have a rat inside by leg
  • nihilistic (usually psychotic depression) – I’m dead, my head is empty
  • guilt (usually psychotic depression) – look back on little things and they develop such a huge presence that they start to believe that they don’t deserve to live because of that, or they think they are responsible for all the evil in the world
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are hallucinations? what are the different types?

A
  • Hallucination – a perception, internally generated, in the absence of an external stimulus.
  • Hallucinations can occur in any sensory modality: hearing (auditory –most common), vision (visual), taste (gustatory), smell (olfactory), somatosensory (tactile), kinaesthetic (body position), temperature, pressure.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

how is schizophrenia classified?

A

 Paranoid Schizophrenia – dominated by delusions and hallucinations (positive symptoms).
 Residual Schizophrenia – predominant negative symptoms.

Paranoid schizophrenia:

  • Most common
  • Largely defined by the presence of auditory hallucinations or delusional thoughts about persecution or conspiracy
  • Often diagnosed late into illness because they often look normal to others – only when experience a major stressful event in your life that exposes your paranoid thoughts to family

Disorganised or hebephrenic schizophrenia:

  • Confused thought process
  • Ability to maintain logical thinking is largely affected

Catatonic schizophrenia:

  • Catatonic stupor: dramatic reduction in activity – waxy flexible may develop as well
  • Catatonic excitement: hyperactivity and presence of stereotypic behaviour – repetitive but purposeless actions

Undifferentiated schizophrenia:
- May have some signs of paranoid, hebephrenic or catatonic schizophrenia, but doesn’t obviously fit into one of these types alone

Residual schizophrenia:
- Predominantly negative symptoms

Schizoaffective disorder:

  • Mixture of schizophrenia and either depression or bipolar disorder
  • Mental illness in its own right
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

describe the epidemiology of schizophrenia.

A
  • Constant prevalence around the world = 1%.
  • No significant influence of culture, ethnic background or socio-economic group. There is a slightly increased prevalence in urban areas.
  • No overall difference exists between the sexes.
  • The average age of onset appears to be earlier in men (15-25 years) than in women (20-30 years).
  • Men have a poorer response to treatment than women, and a worse long-term outcome.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how is schizophrenia diagnosed?

A

ICD-10 Diagnostic Criteria:
 At least 1 first-rank symptom (for at least 1 month):
1. Thought echo, thought insertion or withdrawal, or thought broadcasting.
(Thought echo – a voice repeating your thoughts after you think it)
(Thought insertion – your thoughts belong to someone else)
(Thought broadcasting – others can hear your thoughts)
2. Delusions of control, influence or passivity, clearly referred to body or limb movements or specific thoughts, actions or sensations.
3. Auditory hallucinations giving a running commentary or discussing the patient between themselves, hallucinatory voices from parts of the body.
4. Persistent delusions that are completely impossible.

 Or at least 2 second-rank symptoms (at least 1 month):

  1. Other persistent hallucinations in any modality.
  2. Thought disorder (neologisms, loosening or breaks in the train of thought resulting in incoherent or irrelevant speech).
  3. Catatonic behaviour (posturing, waxy flexibility, mutism, stupor, catatonic excitement).
  4. Negative symptoms, not due to depression or medications.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what are the risk factors for schizophrenia?

A

• Schizophrenia has a significant genetic component.
 Relatives of schizophrenic patients have a higher risk of developing the illness compared to the 1% rate in general population.

• There is a higher risk of schizophrenia for people born in winter months and also after viral epidemics, which may affect development in utero.

Genetics:

  • Tends to run in families but no single gene thought to be responsible
  • Different combinations of genes make people more vulnerable to the condition
  • In identical twins, if one twin develops schizophrenia the other twin has a one in two chance of developing it too

Pregnancy and birth complications:
- People who develop schizophrenia are more likely to have experienced complications before and during their birth, such as: a low birth weight, premature labour, a lack of oxygen (asphyxia) during birth

Triggers:

  • Stress – main psychological triggers of schizophrenia are stressful life events
  • Drug abuse – particularly cannabis, cocaine, LSD or amphetamines, may trigger symptoms of schizophrenia in people who are susceptible
  • Studies shown teenagers under 15 who use cannabis regularly, especially ‘skunk’ and other more potent forms of the drug, are up to four times more likely to develop schizophrenia by the age of 26
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

summarise the 4 dopamine pathways and what they’re involved in

A

Dopamine neurons have 4 major projections:
1. Nigrostriatal pathway
 Substantia nigra → caudate and putamen. It has 2 main branches which are:
 Dorsal striatum - motor (involuntary) control Parkinson’s Disease.
 Associative striatum - learning, habituation, memory, attention, motivation, emotion, and volition.

  1. Mesolimbic pathway
     Ventral Tegmental Area in midbrain to limbic regions associated with reward, motivation, affect and memory.
     Include ventral striatum (nucleus accumbens), amygdala, hippocampus & medial prefrontal cortex.
  2. Mesocortical pathway
     VTA to frontal cortex, including dorsolateral prefrontal cortex (DLPFC).
     Cognitive function, motivation & emotional response.
  3. Tuberoinfundibular pathway
     Tuberal region to median eminence (infundibular region at top of pituitary stalk).
     DA acts to inhibit prolactin release from pituitary.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

summarise the 4 dopamine pathways and what they’re involved in

A

Dopamine neurons have 4 major projections:
1. Nigrostriatal pathway
 Substantia nigra (SNc) → caudate and putamen.
It has 2 main branches which are:
 SNc -> Dorsal (sensorimotor) striatum - motor (involuntary) control Parkinson’s Disease.
 SNc -> Associative (mid) striatum - learning, habituation, memory, attention, motivation, emotion, and volition. (PD)

  1. Mesolimbic pathway
     Ventral Tegmental Area in midbrain to limbic regions associated with reward, motivation, affect and memory.
     Include ventral striatum (nucleus accumbens), amygdala, hippocampus & medial prefrontal cortex.
  2. Mesocortical pathway
     VTA to frontal cortex, including dorsolateral prefrontal cortex (DLPFC).
     Cognitive function, motivation & emotional response.
  3. Tuberoinfundibular pathway
     Tuberal region to median eminence (infundibular region at top of pituitary stalk).
     DA acts to inhibit prolactin release from pituitary.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

dopamine receptors

  • what are the different types
  • what does each do
  • where is each found
A

• There are a few postsynaptic dopamine receptors.
• Dopamine receptors are divided in two families: D1 receptors and D2 receptors.
 D1 receptors activate adenylyl cyclase.
 D2 receptors inhibit the formation of cAMP by inhibiting adenylyl cyclase.

  • D2 receptor is divided into long and short versions depending on whether it is a pre-synaptic autoreceptor which is a short version, or postsynaptic receptors on other neurones which are long.
  • Each ‘D’ receptor is region specific with some overlap.
  • D2 receptors affect dopamine synthesis, metabolism and release.
  • D3 receptors affect dopamine release.

D1-like receptor family:

  • D1
  • D5

D2-like receptor family:

  • D2 (L+S)
  • D3
  • D4

D1 receptor family:
- D1 – motor striatum, associative striatum, ventral striatum, cerebral cortex
- D5 – hippocampus, hypothalamus
D2 receptor family:
- D2 (L+S – long and short depending on whether presynaptic autoreceptors or postsynaptic receptors) – motor striatum, associative striatum, ventral striatum
- D3 – ventral striatum, associative striatum, hippocampus, amygdala
- D4 – frontal cortex, medulla, midbrain, amygdala

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what usually happens if there is a decrease in dopamine in the DLPFC? what usualy happens if there’s an increase in release of dopamine at the striatum? what happens in schizophrenia?

A
  • Usually, if there is a decrease in dopamine in the DLPFC, it feeds back to the striatum, causing an increased release of dopamine there.
  • The same is for the reverse – if there is an increase in the release of dopamine at the striatum, it causes a decrease in the dopamine in the DLPFC.
  • In schizophrenia, this creates a vicious cycle, where, first, there is a decrease in the levels of dopamine in the DLPFC, which leads to an increase in the striatal dopamine, which then causes a further decrease in the dopamine levels in the DLPFC.

• It is important to note that these DA dysregulation are secondary to another dysfunction of the brain.
 Rather, it is secondary to a more proximal abnormality e.g. in GABA or glutamate systems.

35
Q

what usually happens if there is a decrease in dopamine in the DLPFC? what usually happens if there’s an increase in release of dopamine at the striatum? what happens in schizophrenia? what is important to remember?

A
  • Usually, if there is a decrease in dopamine in the DLPFC, it feeds back to the striatum, causing an increased release of dopamine there.
  • The same is for the reverse – if there is an increase in the release of dopamine at the striatum, it causes a decrease in the dopamine in the DLPFC.
  • In schizophrenia, this creates a vicious cycle, where, first, there is a decrease in the levels of dopamine in the DLPFC, which leads to an increase in the striatal dopamine, which then causes a further decrease in the dopamine levels in the DLPFC.

• It is important to note that these DA dysregulation are secondary to another dysfunction of the brain.
 Rather, it is secondary to a more proximal abnormality e.g. in GABA or glutamate systems.

36
Q

what is the dopamine hypothesis for schizophrenia?

A
  • The current version of the hypothesis proposes that psychosis is associated with increased dopamine presynaptic function in the nigrostriatal pathway (particularly the part that projects to the associative subdivision of the striatum) rather than the mesolimbic system.
  • Dopamine abnormalities are believed to be secondary or ‘knock-on’ effects of a more primary abnormality perhaps in the glutamate or GABA systems in dorsolateral prefrontal cortex.
  • Excessive DA release in striatum during illness exacerbations (during psychosis)
  • positively correlated with positive symptoms – the more dopamine, the more symptoms
  • correlated with good treatment response to antipsychotic drugs
  • Inadequate DA in frontal cortex (all the time)
  • associated with deficits in cognitive function e.g. working memory
37
Q

glutamate in schizophrenia

  • what is glutamate
  • what are the receptors
  • what is model of symptoms of schizophrenia
A
  • Glutamate is the most abundant excitatory neurotransmitter in the CNS.
  • Receptors: NMDA, AMPA, kainate, mGluR1-8
  • NMDA receptor hypofunction is a model for positive, negative and cognitive symptoms of schizophrenia.
  • It predicts that hypoactivity of NMDA receptor function → excessive glutamate release which leads to glutamate excitotoxicity → impaired neuronal development → worsening of schizophrenia and disease progression.
  • Decrease NMDA receptor function:
     glu excitotoxicity -> impaired neuronal development -> disease progression
     DA dysregulation via glu-DA interactions
38
Q

what causes NMDA dysfunction and what can it lead to?

A 
Genetic factors:
- neuroregulin 
- dysbindin 
- DAAO/G72 
- isolated variants 
Environmental factors:
- pre/perinatal insult 
- developmment neurotoxicity 
- activity/nutritional status 
- metabolic variation

Effects:

  • sensory deficits
  • generalised cognitive deficits
  • impaired learning & memory
  • thought disorder
  • negative symptoms
  • position symptoms
  • gaiting deficits
  • executive dysfunction
  • dopamine dysregulation -> positive symptoms, gating deficits, executive dysfunction
39
Q

summary:

  • relapse of positive symptoms associated with what
  • can predict what
  • cognitive deficit associated with what
  • what would ideal antipsychotic do
A
  • Relapse of positive symptoms associated with ↑ DA in associative striatum. This increase can be detected up to 3 years before onset of first episode schizophrenia.
  • Can’t currently predict conversion to schizophrenia with adequate sensitivity and specificity by PET.
  • Cognitive deficits (e.g. WM) associated with ↓mesocortical DA (in the DLPFC).
  • Ideal antipsychotic would reduce associative striatum DA release without impairing DA function in mesocortical (cognitive impairment), sensorimotor striatum (EPS) or limbic striatum (worsening of negative symptoms) regions.
40
Q

what antipsychotic medications proven effective at doing? how are they used?

A
  • In schizophrenia, antipsychotic medications are proven effective in treating acute psychosis and reducing the risk of future psychotic episodes.
  • The treatment of schizophrenia thus has two main phases: an acute phase, when higher doses might be necessary in order to treat psychotic symptoms, followed by a maintenance phase, which is usually life-long.
41
Q

antipsychotics

  • what do they do
  • different types
  • examples
  • side effects of different types
A

• The treatment is aimed to decrease dopamine binding to the D2 dopamine receptor.
• The drugs can be divided into:
 Typical (old) antipsychotics - chlorpromazine
 Atypical (new) antipsychotics – resperidone
• Antipsychotics all reversible antagonists at D2 dopamine receptors.
 They block the excessive production & release of dopamine in psychosis.
• Dopamine is released by nigrostriatal neurones and moderates striatal function.

Side effects of typical
- Shaking, trembling, muscle twitches, muscle spasms
Side effects of both
- Drowsiness, weight gain (particularly atypical), blurred vision, constipation, lack of sex drive, dry mouth

42
Q

what is the threshold for antipsychotic efficacy? how do different antipsychotics provide this efficacy?

A

65% D2 receptor occupancy

different antipsychotics can provide this efficacy at different doses

43
Q

how does D2R occupancy patterns over time differ between antipsychotics? dose range for efficacy vs overdose?

A

 Resperidone and olanzapine D2R occupancy is relatively sustained over 24 hours.

  • Clozapine and quetiapine D2R occupancy declines more quickly
  • Means you don’t need to block them all day
  • For antipsychotic efficacy, a drug must block more than 65% of D2 receptors in the associative striatum for an adequate proportion of the time
  • This does not need to be continuous (i.e. 24 hr/day) – some APs (e.g. clozapine, quetiapine) only achieve this intermittently – the optimum duration is not yet known

 Typical antipsychotics have a narrow dose range for efficacy vs overdose.
 Atypical antipsychotics have a wide dose range for efficacy vs overdose.

44
Q

where does increase in dopamine levels occur? where does D2R occupancy occur? what does occupancy treat? what is extrastriatal D2R occupancy associated with?

A

• The increase in dopamine levels occur in the associative striatum, yet D2R occupancy occurs in the limbic (ventral) striatum.
 D2 receptor occupancy in striatum treats positive psychotic symptoms but not negative symptoms.
• Extrastriatal D2 receptor occupancy is not associated with any measures of treatment response or side effects. D2 receptor occupancy in unwanted regions is currently unavoidable.

45
Q

what are the adverse effects of D2R anatognism in the dopaminergic pathways? and at what occupancy?

A

• D2 receptor antagonism in the dopaminergic pathways gives rise to a range of related side effects ( at >72% D2 receptor occupancy):
1. Nigrostriatal motor pathway – Parkinsonism and other extrapyramidal side effects (EPSE)
2. Mesolimbic pathway – excessive blockade leads to worsening of the negative symptoms.
3. Mesocortical pathway – may exacerbate low dopamine, leading to deterioration in cognitive function.
4. Tuberoinfundibular pathway – hyperprolactinaemia secondary to antipsychotics.
 It is clinically difficult to achieve efficacy without hyperprolactinaemia.

• These antipsychotics can also antagonise other receptors (muscarinic, alpha-2-adrenergic and 5-HT2 receptors), leading to receptor-mediated side effects.

  • Threshold for raised prolactin: >72% D2 receptor occupancy
  • EPSE: >78% D2 receptor occupancy
  • Clinically difficult to achieve efficacy without hyperprolactinaemia
  • Second-generation antipsychotics easier to achieve efficacy without EPSE
46
Q

resperidone

  • what is it
  • effective for treating what
  • mechanism of action
  • what does it bind to
  • side effects
A
  • Atypical antipsychotic drug with high affinity for 5-HT and dopamine D2 receptors.
  • Risperidone is effective for treating the positive and negative symptoms of schizophrenia owing to its “loose” binding affinity for dopamine D2 receptors and additional 5-HT antagonism compared to first generation antipsychotics, which are strong, non-specific dopamine D2 receptor antagonists.

• Mechanism of Action:
 Blockade of dopaminergic D2 receptors in the ventral striatum, alleviating positive symptoms of schizophrenia such as hallucinations and delusions.
 Blockade of serotonergic 5-HT2 receptors in the mesocortical tract, causes an excess of dopamine, resulting in an increase in dopamine transmission, and an elimination of core negative symptoms.
 Dopamine receptors in the nigrostriatal pathway are not affected by risperidone and extrapyramidal effects are avoided.
 Like other 5-HT2 antagonists, risperidone also binds at alpha(1)-adrenergic receptors and, to a lesser extent, at histamine H1 and alpha(2)-adrenergic receptors.

• Side Effects:
 Hypotension, weight gain, rash, vomiting, constipation.

47
Q

clozapine

  • what is it
  • mechanism of action
  • side effects
A

• Atypical antipsychotic.

  • Licensed for treatment resistant schizophrenia (TRS)
  • TRS if two antipsychotics fail or can’t be tolerated at full dose
  • About 20% of early Sz, maybe 30% eventually eligible
  • Weight gain – sometimes the thinnest people gain the most weight

• Mechanism of Action:
 Combination of antagonistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex.
 D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.

• Side Effects:
 Sedation, hunger, hypersalivation, diabetes (‘dirty drug’)
- Rare side effect: agranulocytosis
- Hence rigorous blood monitoring regime
-meds can’t be dispensed without clear FBC
-no depot (injections), needs specialist service

48
Q

what are the major side effects of antipsychotics?

A
  • Elevated serum prolactin levels – antagonism of dopamine receptors in the tuberoinfundibular pathway
  • Parkinsonian symptoms – antagonism of dopamine receptors in the nigrostriatal pathway
  • Weight gain – antagonism of histamine H1 and serotonin 5-HT2c receptors plus effects on leptin
  • Deterioration in working memory – antagonism of dopamine receptors in the mesocortical pathway
  • Blurred near vision – antagonism of muscarinic M1 acetylcholine receptors
  • Sedation – antagonism of H1 and alpha-adrenergic receptors
49
Q

cannabis

  • what is it
  • what does it contain
  • receptors
  • what activates the receptors
A
  • Cannabis is a dried female flower of Cannabis sativa.
  • The plant contains several psychoactive substances, the most significant being the terpenoid Δ-9-tetrahydrocannabinol (THC).

• There are two types of cannabinoid receptors involved in the role of cannabis in psychosis:
 CB1 receptors – mediate most effects of cannabinoids on the CNS (also in the lungs, liver and kidneys).
 These are involved in physiological processes such as appetite, pain-sensation, mood and memory.
 These receptors are responsible for the euphoric and anticonvulsive effects of cannabis.
 CB2 receptors – found in the PERIPHERY and are expressed mainly in the immune system and in hematopoietic cells.

• Cannabinoid receptors are activated by:

  1. Plant cannabinoids (produced by the cannabis plant) – THC – through the production of an endocannabinoid (a ligand known as anadamide)
  2. Endocannabinoids (produced by humans)
50
Q

how does THC work?

A

Plant Cannabinoids (THC) and Ligand (Anandamide):

  • As THC enters the brain, it causes the user to feel euphoric – or high – by acting on the brain’s reward system.
  • THC activates the reward system by stimulating brain cells to release dopamine.

• Mode of action of THC (Euphoria):
 Increases the release of dopamine in the brain.
 This causes stimulation of the D2 dopamine receptors in the striatum.
 This causes an increase in the formation and release of a ligand called anandamide.
 Anandamide activates cannabinoid receptors.
 This leads to the euphoria.

• THC also disrupts coordination and balance by binding to CB1 receptors in the cerebellum and basal ganglia.

51
Q

endocannabinoids

  • what are they
  • where produced
  • mode of actions
A

• Endocannabinoids are substances produced in the brain.
• They are used in retrograde signalling between neurons, in to temporarily reduce the amount of conventional neurotransmitter released.
 Their production is Ca2+ dependent.
 They are produced in post-synaptic GABA neurons.

• Mode of action of Endocannabinoids (Euphoria):
 GABA is released into the synaptic cleft and binds to the ‘endocannabinoid source’ (where the endocannabinoids are produced).
 This leads to the production of endocannabinoids.
 Endocannabinoids released from the depolarised post-synaptic GABA neuron bind to CB1 receptors in the pre-synaptic GABA neuron and cause a reduction in GABA release.
 This causes a decrease in the inhibitory effects in the brain, thus leading to euphoria.
 This is called “endocannabinoid-mediated depolarisation-induced suppression of inhibition”.

• Mode of action of Endocannabinoids (Anticonvulsive):
 Cannabinoids are thought to have regulatory role in the striatum in terms of glutamatergic signals from the corticostriatal fibres.
 Intense firing of corticostriatal neurones leads to release of glutamate which causes as influx of Ca2+ ions in the post-synaptic membrane.
 Constant glutamate release causes Ca2+ ions to build up in the post-synaptic membrane.
 This accumulation causes Ca2+ ions to synthesise endocannabinoids in the medium-sized striatal spiny neurones.
 These stimulate CB1 receptors on the pre-synaptic corticostriatal fibres leading to a decreased release of glutamate.

52
Q

what is the Mental Health Act?

A

Mental Health Act 1983 (Sections 2 and 3)
• The Mental Health Act covers the reception, care and treatment of mentally disordered persons, the management of their property and other related matters.
• It provides legalisation by which people diagnosed with a mental disorder can be detained in hospital or police custody and have their disorder assessed or treated against their wishes, unofficially known as “sectioning” (detainment).
• The Act has been reviewed and amended by the Mental Health Act 2007.

53
Q

when does detainment happen?

A

• For detainment to happen, certain professionals must agree that the patient has a mental disorder that requires them to stay in hospital.
 Assessment and treatment is given if needed.
 Only carried out when own safety or someone else’s is at risk.

54
Q

what are the three conditions that need to be met before an appropriate compulsory section form is signed?

A

the patient must be:

  1. Suffering from a mental disorder
  2. At risk to his/her health or safety and/or other people’s safety
  3. Unwilling to accept hospitalization voluntarily
55
Q

Section 2

  • when is a patient placed under Section 2
  • what’s the process - what must happen
  • admission to hospital must be arranged within how many days of the last medical examination
  • length of detainment
  • can it be renewed
A

• The patient is placed under Section 2 if they have not been assessed in hospital before or if they have been assessed in hospital for a long time.

• An application for admission to hospital under section 2 must be made by an Approved Mental Health Professional (AMHP) AND your nearest relative.
 Must be seen within 14 days of making application.
 Must be signed by TWO APPROVED HEALTH PROFESSIONALS + NEAREST RELATIVE/ OTHER APPROVED HEALTH PROFESSIONAL.
 One of the two AMPH must be approved under ‘section 12’.
• Doctors must have seen you within 5 days of each other (if the other health professional is a doctor).
• Admission to hospital must be arranged within 14 days of the last medical examination.

  • The length of detainment is up to 28 days.
  • Section 2 can’t be renewed but the patient may be transferred onto Section 3.
56
Q

what do patients have right to under the Mental Health Act? what can’t patients refuse?

A

 Appeal against detention to a Tribunal during the first 14 days of detainment.
 Appeal to the Mental Health Act managers.
 Ask for the help of an Independent Mental Health Advocate.
 A Patient Rights Leaflet informing them about their legal rights.

  • THE PATIENT CAN’T REFUSE TREATMENT.
  • However, some treatments can’t be given without consent unless certain criteria are met, such as electro-convulsive therapy (ECT).
57
Q

who can patients be discharged by under Section 2 and 3?

A

 Responsible Clinician
 Mental Health Act managers
 Nearest relative (although this can be overruled by the Responsible Clinician)
 Tribunal (court of Justice)

58
Q

aftercare under Section 2?

A
  • Before discharging, a care plan should be made under the Care Programme Approach (CPA) which will look at how the patient’s needs will be met.
  • Many hospitals contact within 7-14 days of discharge.
59
Q

why are patients detained under Section 3?

A
  • You are detained in hospital for treatment.
  • This treatment is necessary for health, safety or protection of other people.

• The patient can be detained under Section 3 for two reasons:

  1. If the patient has a known mental health illness and therefore assessment, under Section 2, is not needed.
  2. If the patient is transferred from Section 2.
60
Q

Section 3

  • what is a Community Treatment Order
  • what is the procedure
  • length of detainment
  • can detention be renewed
A

• A Community Treatment Order allows someone discharged from Section 3 to be readmitted if they don’t obey specific conditions (usually adherence to medication).
• To be detained, the same procedure as in section 2 (above) is followed – application.
 Must be signed by TWO APPROVED HEALTH PROFESSIONALS + NEAREST RELATIVE/ OTHER APPROVED HEALTH PROFESSIONAL.
 One of the two AMPH must be approved under ‘section 12’.

• The length of detainment is up to 6 months.
• Detention can be renewed for a further 6 months
 This can only be done by a responsible doctor, 2 months before due date.
 After that, detention can be renewed for further periods of one year at a time.

61
Q

what rights does the patient have under Section 3? what don’t they have rights to?

A

• The patients have the right to:
 Appeal against detention to a Tribunal once during the first 6 months of detainment.
 Appeal once during the second six months if section 3 renewed.
 Appeal to the Mental Health Act managers for discharge.
 Ask for the help of an Independent Mental Health Advocate.
 A Patient Rights Leaflet informing them about their legal rights.

• THE PATIENT CAN’T REFUSE TREATMENT.
 They can be treated against their will for 3 months after which they have to be seen by a second opinion appointed doctor (SOAP) which then decide on treatments.
 However, some treatments can’t be given without consent unless certain criteria are met such as electro-convulsive therapy (ECT)

62
Q

What is the Mental Capacity Act? does the mental health law mention capacity? justifications for this?

A
  • Under the Mental Capacity Act, a patient without “capacity” can be admitted and treated for general medical or psychiatric illness in order to sustain life or prevent a serious deterioration in their condition; can restrain or threaten to restrain to protect from harm, in proportion to the risk and severity of harm.
  • It must be assumed that the patient has capacity and if in doubt, take all steps to support decision making, act only in best interests of patient but take least restrictive approach.

• The mental health law does not specifically mention lack of decisional competence/capacity.

• Possible justification for this are:
 Use of coercion justified because of risk to self or others:
 Coercion - the practice of forcing another party to act in an involuntary manner by use of intimidation or threats or some other form of pressure or force.
 Use of coercion justified because having a mental disorder (automatically) entails lack of competence to make decisions.
 Mental disorder is qualitatively different from physical disorder.
 Tradition

  • The Mental Capacity Act is an example of case law consolidated into statute
63
Q

what are pharmacological measures to improve compliance? Ley’s model of compliance?

A
  • While atypical antipsychotics have demonstrated improvements in psychotic symptoms, insight and cognition, these may not be enough to ensure compliance with oral daily medication.
  • Long-acting risperidone may therefore bring together the benefits of the atypical antipsychotics with the long-acting injection delivery system required to build a platform for improved outcomes.

memory and understanding -> satisfaction -> compliance

64
Q

Early Intervention Service

  • why developed
  • what is their aim
  • what does it reduce
  • what does it improve
A
  • Early intervention services (EIS) have been developed to address the needs of individuals (aged 14-35 years) with early psychosis.
  • Typically, there is a delay between the onset of the first episode of psychosis and receiving an effective treatment – a period of untreated psychosis.
  • Reducing this duration of untreated psychosis (DUP) for people with schizophrenia may lead to an improved prognosis.

• Early Intervention Services (EIS) for psychosis aim to:
 Detect emergent symptoms
 Reduce the duration of untreated psychosis (DUP)
 Improve access to effective treatments, particularly in the ‘critical period’ (first 3-5 years following onset).

•	Early Intervention Services reduce:
	Hospital admission
	Relapse rates 
	Symptom severity
•	Early Intervention Services improve:
	Access to treatment
	Engagement with treatment
65
Q

what components are there to the EIS?

A

Components other than medication:
 CBT – target negative cognitions.
 Family Intervention
 Psychotherapy (Milieu Therapy) – patients join a support group.
 Assertive Community Treatment - aims to help mentally ill patients who suffer from areas of life such as work, social relationships and physical health.
 Cognitive Remediation (Behavioural intervention) - training activities that aim to improve cognitive skills, social cognition, memory, attention and processing speed in everyday life

66
Q

which health professionals are involved in EIS?

A

Care coordinator: responsible for making sure that everyone is working together to identify patient needs and investigate resources available to meet those needs.
 Likely to be a community psychiatric Nurse (CPN), an occupational therapist (OT) or a social worker.
 OT: help people with mental, physical or social disabilities to independently carry out everyday tasks or occupations.
 CPN: experienced, trained mental health nurses who work with people affected in the community and their families.

Approved Mental Health Practitioners:
 Trained and experienced in mental health.
 Makes decisions about whether a person should be compulsorily admitted to hospital for assessment and treatment.

Psychiatrists:
 A doctor who specialises in the diagnosis and treatment of people who are mentally ill.
 May diagnose illness, prescribe medication.

Psychologists:
 They have special training in psychology (study of human behaviour and mind) and in mental health.
 They are not medical doctors.
 Use their specialist skills to assess mental health problems and can provide talking therapies, psychotherapy and counselling.

Support Time Recovery Workers:
 They provide support and time to you the service user to help in patients recovery process.

67
Q

what is the time line of different symptoms?

A

Prodromal (withdrawn) -> active (severe symptoms) -> residual (cognitive symptoms)

68
Q

what are the following:

  • CMHTs
  • CPA
  • CRT?
A

Most people with schizophrenia are treated by community mental health teams (CMHTs)
- Goal of the CMHT is to provide day-to-day support and treatment while ensuring you have as much independence as possible
After your fist episode of schizophrenia, you should initially be referred to an early intervention team

Care programme approach (CPA):

  • People with complex mental health conditions are usually entered into a treatment process known as a care programme approach (CPA)
  • Essentially a way of ensuring you receive the right treatment for your needs
  • Four stages: assessment, care plan, key worker appointed, reviews

Crisis resolution teams (CRT)

  • Treat people with serious mental health conditions who are currently experiencing an acute and severe psychiatric crisis
  • Without the involvement of the CRT, these people would require treatment in hospital
69
Q

when does increased DA develop? what is this stage?

A
  • 18F-DOPA is an analogue of the DA precursor DOPA
  • Uptake provides an index of presynaptic DA function
  • 18F-DOPA uptake directly correlated with severity of prodromal symptoms and neuropsych impairment
  • ‘at risk mental state’ (ARMS) = prodromal, mild symptoms – AKA ultra-high risk (UHR)
  • DA function elevated in patients with prodromal signs of schizophrenia, although they did not yet have the disorder
  • This elevation approached that seen in patients with established schizophrenia
70
Q

where is there elevated DA?

A
  • Elevated DA function in associative, not limbic or sensorimotor subdivision
  • Dopamine significantly elevated in the sensorimotor striatum and particularly in the associative striatum (i.e. nigrostriatal pathway), but normal in ventral striatum (found after two studies)
71
Q

what is dysregulating associative striatum DA function?

A

Most likely explanation is abnormal DLPFC function, possibly secondary to abnormal glutamate NMDA receptors affecting GABA and glutamate function

72
Q

what’s the Glu-DA interaction hypothesis?

A
  1. Neurodevelopmentally hypofunctional NMDA receptor mediated synapse on parvalbumin-containing GABA interneurons
  2. GABA release is low and doesn’t adequately suppress cortico-brainstem glutamate outflow
  3. Excessive direct glutamate stimulation of SNc DA neuron cell bodies leads to increase DA in AST and SMST
  4. Excessive indirect glu stimulation of mesocortical DA neuron cell bodies in VTA
  5. Decrease cortical DA release
73
Q

what causes cognitive and negative symptoms? why does this happen?

A

Inadequate release of DA in the VTA is what gives you negative symptoms

Inadequate release of DA in the cortex in mesocortical system which gives you your cognitive symptoms

All of this happens because the NMDA receptors on the GABA interneuron aren’t working adequately

74
Q

summarise the dopamine abnormalities in schizophrenia

A
  • Psychosis is strongly associated with overactivity of presynaptic DA function (synthesis and synaptic release) in nigrostriatal pathway, particularly associative division
  • opposite of PD
  • what would we like? To selectively attenuate this pre-synaptically
  • what do we have? The ability to block the action of the increased DA post-synaptically at D2 receptors
  • Cognitive impairment is associated with decreased DA release in PFC (mesocortical system)
  • Negative symptoms not well explained by DA, but some evidence they may be worse if DA release is decreased in limbic (ventral) striatum (i.e. mesolimbic pathway) (VTA)
75
Q

what is hyperprolactinaemia? symptoms?

A
  • Abnormally high levels of prolactin in blood
Sexual dysfunction: 
-	Diminished libido 
-	Decreased arousal 
-	Orgasmic dysfunction 
Breast pathology:
-	Galactorrhoea 
-	Breast enlargement 
-	Slight increased risk of breast cancer 
Reproductive dysfunction:
-	Anovulation 
-	Oligomenorrhoea 
-	Amenorrhoea 
-	Subfertility 
-	False pregnancy tests 
Hypogonadism:
-	Decreased BMD 
-	Hip fracture 
Miscellaneous:
-	Acne and hirsutism
76
Q

what is the path generally followed to developing schizophrenia? signs?

A

People that go on to develop schizophrenia generally develop later – they walk and talk later, potty train later, perform less well at school, perform less well on IQ tests – starting to get onset of negative symptoms

  • Then start to develop anxiety, depression
  • Then start full psychotic symptoms (not everyone)
77
Q

what is easier to improve positive or negative symptoms?

A

positive

78
Q

where percentage do you want occupancy between?

A
  • > 60% occupancy of D2 in associative striatum has an antipsychotic effect
  • > 75% occupancy of other D2 causes motor SE & hyperprolactinaemia
79
Q

which locus of control is more likely to stop taking medication?

A

internal

80
Q

describe what is meant by capacity?

A
  • Legal and not medical concept
  • Ability to make a decision
  • Related to a particular decision
  • Relates to a particular time
  • Person may be able to make some decisions but not others
  • Can vary over time
81
Q

What is the mental capacity act? what are the principles of it?

A
  • The Mental Capacity Act 2005 provides the legal framework for acting and making decisions on behalf of individuals who lack the mental capacity to make particular decisions for themselves
  • Everyone working with and/or caring for a person over the age of 16 who may lack capacity to make specific decisions must comply with this Act when making or acing for that person
  • The same rules apply whether the decisions are life changing events or everyday matters

THE PRINCIPLES

  • A person must be assumed to have capacity unless it is established that he lacks capacity
  • A person is not to be treated as unable to make a decision unless all practicable steps to help fim to do so have been taken without success
  • A person is not to be treated as unable to make a decision merely because he makes an unwise decision
  • An act done, or decision made, under this Act for or on behalf of a person who lacks capacity must be done, or made, in his best interests
  • Before the act is done, or the decision is made, regard must be had to whether the purpose for which it is needed can be as effectively achieved in a way that is less restrictive of the person’s rights and freedom of action
82
Q

what is the capacity test?

A
  • Understand information related to the decision
  • Retain information related to the decision
  • Use or weigh that information as part of the process of making the decision
  • Communicate the decision (whether by talking, using sign language or any other means)
83
Q

what is the stance on alcohol, drugs, learning disabilities and autism under the MHA?

A
  • Section 1(3) of the Act states that dependence on alcohol or drugs is not considered to be a disorder or disability of the mind for the purposes of the definition of mental disorder in the Act
  • Alcohol or drug dependence may be accompanied by, or associated with, a mental disorder which does fall within the Act’s definition
  • Learning disabilities and autistic spectrum disorders are forms of mental disorder as defined in the Act
  • But a person with learning disability shall not be considered by reason of that disability to be:
    a) Suffering from a mental disorder…for the purposes of the provisions Act
    b) Requiring treatment in hospital for a mental disorder…unless that disability is associated with abnormally aggressive or seriously irresponsible conduct on his part
84
Q

summarise the different sections under the MHA

A
  • Section 2 = assessment, lasts for up to 28 days
  • Section 3 = treatment, lasts for up to 6 months, renewable for another 6 months and then 12 months
  • Section 4 = emergencies, lasts for up to 72 hours
  • Section 5(2) = doctors holding power, lasts for up to 72 hours
  • Section 5(4) = nurses holding power, lasts for up to 6 hours
  • Community Treatment Orders

Medicine Sem 3 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions