Management and neurobiology of schizophrenia Flashcards
What was the first discovered anti-psychotic?
Chlorpromazine
What are the 2 types of classifications of anti-psychotics?
Typical vs atypical
1st vs 2nd vs 3rd generation
What is the main theory of schizophrenia pathophysiology?
Dopamine theory
What are the 5 main dopamine pathways?
- Mesocortical pathway
- Mesolimbic pathways
- Nigrostriatal pathway
- Hypothalamic pathway
- Tuberoinfundibular pathway
What is the role of the mesocortical and mesolimbic pathways in schizophrenia?
The mesocortical and mesolimbic run through the higher cortical regions pathways and seem to be involved in positive symptoms of schizophrenia such as hallucinations, delusions and thought disorders
Function of the nigrostraital pathway
Movement
Function of the tuberoinfundibulnar pathway?
Hormone secretion from the pituitary gland (Especially prolactin)
Function of the hypothalamic pathway
Runs from movement centres into the spinal tract
What is the MOA of the ideal anti-psychotic?
D2 dopamine receptor antagonist of the mesolimbic pathway
What are some other neurotransmitters thought to be associated with schizophrenia?
Glutamine (NMDA receptor)
Serotonin
Examples of 1st generation, typical anti-psychotics?
Haloperidol
Prochlorperazine
Fluphenazine
Chlorpromazine
Trifluperazine
MOA of 1st generation, typical anti-psychotics?
- Non-selectively block D2 and other receptors
- Reduce positive symptoms
Examples of 2nd generation, atypical anti-psychotics
Olanzapine
Rispiridone
Quetiapine
Aripiprazole
Clozapine
Amisulpride
Lurasidone
MOA of 2nd generation, atypical anti-psychotics
- Work on D2 and 5HT-3 (serotonin) to reduce side effect profile
- Also work on H1, alpha and cholinergic
- Reduce positive symptoms with no worsening of negative symptoms
What are some side effects of anti-psychotics on the nigrostriatal pathway (Extra-pyramidal)
Acute dystonic reaction
Parkinsonism
Tardive dyskinesia
What are some effects of acute dystonic reaction?
- Onset in minutes
- Increasing muscle tone
- Energetic
- Torticolis
- Oculogyric crisis
- Tongue protrusion
What is Parkinsonism?
- Bradykinesia
- Cogwheeling rigidity
- Resting tremor
- Shuffling gait
What is tardive dyskinesia?
- Long-term and often permanent
- Involuntray, repetetive orofacial movements
- Blinking, grimacing, pouting, lip-sacking
Side effects of anti-psychotics affecting the tuberoinfundibular pathway
Neuroleptic malignant syndrome
Hyperprolactinaemia
What are some side effects of anti-psychotics affecting the hypothalamic pathway
Akathesia (Restless legs)
What causes extra-pyramidal pathway symptoms to occur with anti-psychotics?
caused by an imbalance of acetylcholine and dopamine signalling
How can extra-pyramidal symptoms be managed in anti-psychotic use?
symptoms can be treated by depleting the levels of acetylcholine signalling to match the depleted levels of dopamine signalling, therefore anticholinergics can be given
What are some examples of anti-cholinergics given to reduce extra-pyramidal symptoms of anti-psychotics
- Procyclidine 5mg PO or IM
- Trihexyphenidyl
- Orphenadrine
What is neuroleptic malignant syndrome
A triad of:
- Autonomic instability (E.g. heart rate, temperature control)
- malignant hyperpyrexia
- Increasing muscle tone
It is potentially fatal
How is neuroleptic malignant syndrome managed?
- Stop antipsychotic
- Rapid cooling, renal support
- Muscle relaxants
- Dopamine agonists
How does hyperprolactinaemia present in women?
- Galactorrhoea
- Low libido, low arousal, anorgasmia
- Amenorrhoea
- Anovulation
How does hyperprolactinaemia present in men?
- Gynaecomastia
- Erectile dysfunction
- oligospermia
- Low libido
How does hyperprolactinaemia present in both men and women?
- Decreased bone mineralisation
- Low bone density → Osteoporosis
- Falls → Fractures
How do antipsychotics cause hyperprolactinaemia?
Dopamine inhibits prolactin, so decreasing dopamine transmission increases prolactin
What is akathisia?
The inability to sit at peace (Restlessness)
How does akathisia present?
- Pacing
- Rocking foot to foot
- Unable to sit or stand still
- Poor sleep
How is akathisia managed?
ß-blocker used to treat (E.g. propranolol) or benzodiazepines (2nd line)
What is the most effective antipsychotic?
Clozapine
What are the advantages of clozapine
Good for -ve syndromes and anti-suicidal properties
What are some of the side effects of clozapine?
- Agranulocytosis → Neutropenic sepsis
- Myocarditis
- Constipation → Gastric paresis → Obstruction → Perforation
- Weight gain (10kg in 3 months average)
- Sedation
- Sialorrhoea
What are some other symptoms of anti-psychotics?
- Orthostatic hypotension
- Anticholinergic side effects
- Weight gain
- Sedation
- Haloperidol linked with prolonged QT
What monitoring is required for clozapine use?
- ECG and FBC before starting
- FBC every week for 18 weeks then every 2 weeks thereafter
- Patient must notify if started or stopping smoking
- Weight calculated on each visit to ensure dose remains in therapeutic range
What is an adverse effect of risperidone
Most likely to cause EPSE and increased PRL side effects (e.g. galactorrhoea)
Side effects of olanzapine
metabolic syndrome
Side effects of quetiapine
sedation and weight gain
Prognosis of schizophrenia
People with schizophrenia die 10-20 years before the rest of the population
Why is life expectancy reduced in schizophrenia?
- Poverty
- Poor diet
- Lack of support
- Chronic health conditions
- Poor access to transport
- Amotivation → Reduced exercise
- Poor concentration → Missed appointments, prescriptions, scans
- Higher rates of smoking
- Co-morbid drug use
What are some brain changes seen in schizophrenia?
Enlarged ventricles
Reduced fronton-temporal volume
Reduced activation of prefrontal areas on specific tasks
