Management and neurobiology of schizophrenia

Question 1

What was the first discovered anti-psychotic?

Answer 1

Chlorpromazine

Question 2

What are the 2 types of classifications of anti-psychotics?

Answer 2

Typical vs atypical
1st vs 2nd vs 3rd generation

Question 3

What is the main theory of schizophrenia pathophysiology?

Answer 3

Dopamine theory

Question 4

What are the 5 main dopamine pathways?

Answer 4

• Mesocortical pathway
• Mesolimbic pathways
• Nigrostriatal pathway
• Hypothalamic pathway
• Tuberoinfundibular pathway

Question 5

What is the role of the mesocortical and mesolimbic pathways in schizophrenia?

Answer 5

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

Question 6

Function of the nigrostraital pathway

Answer 6

Movement

Question 7

Function of the tuberoinfundibulnar pathway?

Answer 7

Hormone secretion from the pituitary gland (Especially prolactin)

Question 8

Function of the hypothalamic pathway

Answer 8

Runs from movement centres into the spinal tract

Question 9

What is the MOA of the ideal anti-psychotic?

Answer 9

D2 dopamine receptor antagonist of the mesolimbic pathway

Question 10

What are some other neurotransmitters thought to be associated with schizophrenia?

Answer 10

Glutamine (NMDA receptor)
Serotonin

Question 11

Examples of 1st generation, typical anti-psychotics?

Answer 11

Haloperidol
Prochlorperazine
Fluphenazine
Chlorpromazine
Trifluperazine

Question 12

MOA of 1st generation, typical anti-psychotics?

Answer 12

• Non-selectively block D2 and other receptors
• Reduce positive symptoms

Question 13

Examples of 2nd generation, atypical anti-psychotics

Answer 13

Olanzapine
Rispiridone
Quetiapine
Aripiprazole
Clozapine
Amisulpride
Lurasidone

Question 14

MOA of 2nd generation, atypical anti-psychotics

Answer 14

• 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

Question 15

What are some side effects of anti-psychotics on the nigrostriatal pathway (Extra-pyramidal)

Answer 15

Acute dystonic reaction
Parkinsonism
Tardive dyskinesia

Question 16

What are some effects of acute dystonic reaction?

Answer 16

• Onset in minutes
• Increasing muscle tone
• Energetic
• Torticolis
• Oculogyric crisis
• Tongue protrusion

Question 17

What is Parkinsonism?

Answer 17

• Bradykinesia
• Cogwheeling rigidity
• Resting tremor
• Shuffling gait

Question 18

What is tardive dyskinesia?

Answer 18

• Long-term and often permanent
• Involuntray, repetetive orofacial movements
• Blinking, grimacing, pouting, lip-sacking

Question 19

Side effects of anti-psychotics affecting the tuberoinfundibular pathway

Answer 19

Neuroleptic malignant syndrome
Hyperprolactinaemia

Question 20

What are some side effects of anti-psychotics affecting the hypothalamic pathway

Answer 20

Akathesia (Restless legs)

Question 21

What causes extra-pyramidal pathway symptoms to occur with anti-psychotics?

Answer 21

caused by an imbalance of acetylcholine and dopamine signalling

Question 22

How can extra-pyramidal symptoms be managed in anti-psychotic use?

Answer 22

symptoms can be treated by depleting the levels of acetylcholine signalling to match the depleted levels of dopamine signalling, therefore anticholinergics can be given

Question 23

What are some examples of anti-cholinergics given to reduce extra-pyramidal symptoms of anti-psychotics

Answer 23

• Procyclidine 5mg PO or IM
• Trihexyphenidyl
• Orphenadrine

Question 24

What is neuroleptic malignant syndrome

Answer 24

A triad of:
- Autonomic instability (E.g. heart rate, temperature control)
- malignant hyperpyrexia
- Increasing muscle tone

It is potentially fatal

Question 25

How is neuroleptic malignant syndrome managed?

Answer 25

- Stop antipsychotic - Rapid cooling, renal support - Muscle relaxants - Dopamine agonists

Question 26

How does hyperprolactinaemia present in women?

Answer 26

- Galactorrhoea - Low libido, low arousal, anorgasmia - Amenorrhoea - Anovulation

Question 27

How does hyperprolactinaemia present in men?

Answer 27

- Gynaecomastia - Erectile dysfunction - oligospermia - Low libido

Question 28

How does hyperprolactinaemia present in both men and women?

Answer 28

- Decreased bone mineralisation - Low bone density → Osteoporosis - Falls → Fractures

Question 29

How do antipsychotics cause hyperprolactinaemia?

Answer 29

Dopamine inhibits prolactin, so decreasing dopamine transmission increases prolactin

Question 30

What is akathisia?

Answer 30

The inability to sit at peace (Restlessness)

Question 31

How does akathisia present?

Answer 31

- Pacing - Rocking foot to foot - Unable to sit or stand still - Poor sleep

Question 32

How is akathisia managed?

Answer 32

ß-blocker used to treat (E.g. propranolol) or benzodiazepines (2nd line)

Question 33

What is the most effective antipsychotic?

Answer 33

Clozapine

Question 34

What are the advantages of clozapine

Answer 34

Good for -ve syndromes and anti-suicidal properties

Question 35

What are some of the side effects of clozapine?

Answer 35

- Agranulocytosis → Neutropenic sepsis - Myocarditis - Constipation → Gastric paresis → Obstruction → Perforation - Weight gain (10kg in 3 months average) - Sedation - Sialorrhoea

Question 36

What are some other symptoms of anti-psychotics?

Answer 36

- Orthostatic hypotension - Anticholinergic side effects - Weight gain - Sedation - Haloperidol linked with prolonged QT

Question 37

What monitoring is required for clozapine use?

Answer 37

- 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

Question 38

What is an adverse effect of risperidone

Answer 38

Most likely to cause EPSE and increased PRL side effects (e.g. galactorrhoea)

Question 39

Side effects of olanzapine

Answer 39

metabolic syndrome

Question 40

Side effects of quetiapine

Answer 40

sedation and weight gain

Question 41

Prognosis of schizophrenia

Answer 41

People with schizophrenia die 10-20 years before the rest of the population

Question 42

Why is life expectancy reduced in schizophrenia?

Answer 42

- 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

Question 43

What are some brain changes seen in schizophrenia?

Answer 43

Enlarged ventricles Reduced fronton-temporal volume Reduced activation of prefrontal areas on specific tasks