S3C8 (2.0) Flashcards
How do you treat acute psychotic episodes?
Short acting antipsychotics (e.g. Olanzapine)
Mood stabiliser for acute mania (e.g. Lithium, valproate, carbamazepine)
What is the first-line treatment for schizophrenia?
Second-generation antipsychotics (e.g. Olanzapine, risperidone, quetiapine)
Good at treating positive symptoms
What is the treatment for schizophrenia for patients with poor adherence?
First-generation antipsychotics in depot form (e.g. Fluphenazine, haloperidol, chlorpromazine)
When should clozapine be given to patients?
For treatment resistant schizophrenia
Persistent positive symptoms despite trials lasting over 6 weeks of 2 different antipsychotics at their maximum doses
What are all antipsychotics?
Reversible antagonists at D2 dopamine receptors
What is the threshold for antipsychotic efficacy?
65% D2 receptor occupancy
What is the D2R occupancy patterns for resperidone and olanzapine?
Relatively sustained over 24 hours.
What are the adverse effects of D2 antagonism?
Nigrostriatal motor pathway – Extrapyramidal side effects (EPSE) – Parkinsonism.
Mesolimbic pathway – excessive blockade leads to worsening of the negative symptoms.
Mesocortical pathway – may exacerbate low dopamine, leading to deterioration in cognitive function.
Tuberoinfundibular pathway – hyperprolactinaemia secondary to antipsychotics.
At what efficacy to D2 antagonism side effects occur?
> 72% D2 receptor occupancy
What does 5-HT2A receptor blockade result in? (schizophrenia)
Decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract
What is the MOA for risperidone?
Blockade of D2 receptors in the ventral striatum, alleviating positive symptoms of schizophrenia.
Blockade of 5-HT2receptors in the mesocortical tract, causes an excess of dopamine, resulting in an increase in dopamine transmission, and an elimination of core negative symptoms.
What are the side effects of risperidone?
Hypotension Weight gain Rash Vomiting Constipation
What is clozapine?
Atypical antipsychotic
What are the side effects of clozapine?
Sedation
Hunger
Hypersalivation
Diabetes
What is the main psychoactive substance in cannabis?
Δ-9-tetrahydrocannabinol (THC)
What does smoking cannabis lead to?
Decreased BP
Bloodshot eyes
Feeling dizzy
Increased appetite
What are the types of cannabinoid receptors?
CB1 receptors – mediate most effects of cannabinoids on the CNS (also in the lungs, liver and kidneys).
CB2 receptors – found in the PERIPHERY and are expressed mainly in the immune system and in hematopoietic cells.
What is the role of CB1 receptors?
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.
What are cannabinoid receptors activated by?
Plantcannabinoids – THC – through the production of an endocannabinoid (a ligand known as anadamide)
Endocannabinoids (produced by humans)
What is the MOA of THC?
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.
What is the role of endocannabinoids?
Used in retrograde signalling between neurons, in to temporarily reduce the amount of conventional neurotransmitter released
Where are endocannabinoids produced?
Post-synaptic GABA neurons
Their production is Ca2+ dependent
What is the anticonvulsive MOA of endocannabinoids
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.
What is patient compliance?
The extent to which a person’s behavior coincides with the medical advice he/she has received
adhering to < 70% of prescribed medication during the last week
What amount of schizophrenic patients are fully complaint with therapy
A third are fully compliant with therapy.
Another third are partially compliant, meaning that they will either reduce the dose of the drug prescribed or fail to take drugs from time to time
The final third of patients do not follow prescription instructions at all.
What does partial compliance in schizophrenia increase?
Psychotic symptoms
The risk of relapse and rehospitalisation
Suicide.
What 3 things lead to compliance in Ley’s model of compliance?
Understanding
Satisfaction
Memory
What does section 5(2) of the MHA allow?
A consultant or their “nominated deputy” to detain an inpatient for 72h until further assessed
What does section 5(4) of the MHA allow?
A nurse to detain an inpatient for 6h
What does section 2 of the MHA allow?
2 doctors (either both trained as prescribed in Section 12 of the Act, or one “section 12 approved” psychiatrist and the patient’s GP) and an “Approved Mental Health Professional” (usually a social worker) to detain anyone in hospital for 28 days for assessment (including assessing response to treatment) if they believe they might have a mental illness of “sufficient nature and degree” and are at risk of harming themselves or others
What does section 3 of the MHA allow?
The same professionals to detain someone in hospital for 6 months for treatment if they definitely have a specific mental illness that causes a risk to others or their own “health or safety” and there is appropriate treatment available.
What are the functional subdivisions of the striatum?
Sensorimotor - Putamen
Associative - Globus Pallidus
Limbic/Ventral - Ventral Tegmental Area
What are the 4 dopamine pathways?
Tuberoinfundibular
Mesolimbic
Mesocortical
Nigrostriatal
What is the tuberoinfundibular pathway?
From the arcuate nucleus to the median eminence
Dopamine release inhibits prolactin secretion from the anterior pituitary
What is the mesolimbic pathway?
the VTA to the nucleus accumbens and olfactory tubercle
Controls the reward system on the brains (i.e. Pleasure, positive reinforcement)
What is the mesocortical pathway?
VTA to the prefrontal cortex
Controls executive function
What is the nigrostrital pathway?
From substantia nigra to striatum
Controls movement
What dopamine pathway is responsible for the negative symptoms of schizophrenia?
Mesocortical
What dopamine pathway is responsible for the positive symptoms of schizophrenia?
Nigrostriatal - associative striatum
What are the 2 dopamine receptor family?
D1 - activate adenylyl cyclase
D2 - inhibit formation of cAMP by inhibiting adenylyl cyclase
Where are the D1 receptors located?
Motor striatum
Associative striatum
Ventral striatum
Cerebral cortex
Where are the D5 receptors located?
Hippocampus
Hypothalamus
Where are the D2 receptors located?
Motor striatum
Associative striatum
Ventral striatum
Where are the D3 receptors located?
Hippocampus
Associative striatum
Ventral striatum
Amygdala
Where are the D4 receptors located?
Frontal Cortex
Medulla
Midbrain
Amygdala
What is glutamates role in schizophrenia?
NMDA receptor hypofunction is a model for symptoms of schizophrenia.
Hypoactivity of NMDA receptor function → excessive glutamate release which leads to glutamate excitotoxicity → impaired neuronal development → worsening of schizophrenia and progression.
What is the UK prevalence of schizophrenia?
0.4%
What is the age of onset for schizophrenia?
Men: typically early 20s
Women: typically late 20s
Can get very late onset (>60) - make up 25% of total incidence but hard to distinguish from organic disorders and dementia
What are the environmental risk factors of schizophrenia?
Child sexual abuse Taken into care Migration Peri-natal oxygen deprivation Maternal starvation while in utero Urban living, over crowding Parental separations General deprivation as a child Stress Cannabis use
What are the 3 groups of genes linked to schizophrenia?
Connected to glutamate, dopamine or GABA neurotransmitter function
Connected to neuronal structure (often at synapses), plasticity or general synaptic function
Connected to inflammatory/immune response
What are the % increase of risk of schizophrenia depending on family relations also having schizophrenia?
First-degree relative - 7% Second-degree relative - 2-3% Dizygotic twins - 10% Monozygotic twins - 45% Both parents - 40%
What % of schizophrenic patients present with psychosocial dysfunction?
> 30%
What are the predictive factors for an unfavourable course of schizophrenia?
FH Early onset Poor network of social support Male Slow onset of illness More negative symptoms Concomitant substance use disorder
What are the predictive factors for a favourable course of schizophrenia?
Late onset Female Mood symptoms Good network of social support Acute onset of illness More positive symptoms
What % of schizophrenic patients with attempt suicide?
50%
What are the positive symptoms of schizophrenia?
Hallucinations
Delusions
Illusions
Disorganised thought and speech
What are hallucinations?
A perceptual abnormality, in which sensory experiences occur in the absence of external stimuli
What are delusions?
Fixed, false beliefs that are not amenable to reason, despite evidence to the contrary
What are illusions?
A perceptual abnormality, in which real external stimuli are misinterpreted
What is the diagnostic criteria for schizophrenia?
>=2 for atleast 1 month Delusions Hallucinations Disorganised speech Grossly disorganised or catatonic behaviour Negative symptoms
What is the aim of the EIS
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).
What is catatonia?
A behavioural syndrome characterised by abnormal movements and reactivity to the environment
