Antipsychotics Flashcards
What are the key characteristics of a psychotic episode?
- Delusion
- Hallucinations
- Lack of self awareness
- Disrupted thought patterns
What is schizophrenia?
Distortions of thinking and perception
Distortions of affect (inappropriate to situation)
Disturbance lasting 6+ months
At least one month of 2+ classical symptoms (delusions, hallucinations, disorganised behaviour, negative symptoms)
What are the 4 A’s (negative symptoms) of schizophrenia?
Anhedonia (lack of joy)
Affective blunting (reduction in mood)
Alogia (lack of speech)
Avolition (lack of motivation)
What characterises disorganisation syndromes?
Alterations in speech, thought patterning and behaviour (thought pattern changes commonly involve thought insertion or withdrawal, thought echo and thought broadcasting)
What are the classes of antipsychotic drugs?
First generation (classical/ typical) Second generation (atypical) Third generation (new)
What is the main target of first generation antipsychotics?
Dopamine (D2) receptors
What is the main target of second generation antipsychotics?
Serotonin (5HT) receptors
[and Dopamine receptors]
Which class of antipsychotics has a higher risk of neurological side effects?
First generation antipsychotics
Which class of antipsychotics has a higher risk of metabolic side effects?
Second generation antipsychotics
Which class of antipsychotics has a higher risk of extrapyramidal side effects?
First generation antipsychotics
What are the 4 main dopamine pathways within the CNS?
Mesocortical
Mesolimbic
Nigrostriatal
Tuberohypophyseal
What behaviours are associated with the prefrontal cortex?
Judgement Personality Reasoning Positive emotions Planning
What behaviours are associated with the limbic system?
Negative emotions Sensory perception Spatial awareness Memory Social recognition
Which antipsychotic drugs are first generation?
Haloperidol
Chlorpromazine
Which antipsychotic drugs are second generation?
Aripirazole
Clozapine
Amisulpride
Risperidone
What other receptors (aside from D2) can first generation antipsychotics act as antagonists on?
Histamine (H1)
Muscarinic (M1)
Alpha-1 Adrenergic
What side effects are associated with 5HT antagonists?
Constipation
Dizziness
Weight gain
Drowsiness
What side effects are associated with D2 antagonists?
Rigidity
Tremor
Slow speech
Stiffness
What is the ‘gold standard’ antipsychotic?
Clozapine
What is the nigrostriatal pathway?
One of the major dopamine pathways in the brain
Efferent connection between the substantia nigra and corpus striatum
What is the extrapyramidal system?
Part of the motor system causing involuntary movements.
Includes the rubrospinal, reticulospinal, tectospinal and vestibulospinal tracts as well as the basal ganglia.
What symptoms characterise Tardive Dyskinesia?
Involuntary movement
Protruding tongue
Grimacing
Twisting of the face and limbs
What symptoms characterise Neuroleptic Malignant Syndrome?
High fever
Autonomic dysfunction
Altered consciousness
What are the 5 domains of symptoms exhibited by people with schizophrenia?
- Positive symptoms
- Negative symptoms
- Anxiety/ depression
- Cognition symptoms
- Aggressive symptoms
What side effects can you get from 1st gen antipsychotics due to their antagonist effects on Muscarinic (M1) receptors?
Constipation
Blurred vision
Dry mouth
What side effects can you get from 1st gen antipsychotics due to their antagonist effects on Histamine (H1) receptors?
Weight gain
Sedation
What side effects can you get from 1st gen antipsychotics due to their antagonist effects on Dopaminergic (D2) receptors?
Prolactin elevation
Rigidity
Slow movements
What side effects can you get from 1st gen antipsychotics due to their antagonist effects on alpha1 andrenergic receptors?
Hypotension
Drowsiness
Changes in which dopamine pathway can result in elevation of prolactin levels?
Tuberohypophyseal
How might an increase prolactin level present in patients?
Enlargement of breasts
Increased lactation
Irregular menstrual cycle (due to oestrogen deficiency)
Erectile dysfunction and infertility (due to testosterone deficiency)
Which group of side effects are more apparent in 2nd gen antipsychotics?
Cholinergic effects
Which symptoms are classed as extrapyramidal side effects?
Slowed movement
Tremor
Akathisia (restlessness/ inability to stay still)
Sedation
Which hyperkinetic disorders can be treated with antipsychotics?
Huntingdon's Disease Dystonia Restless leg syndrome Choreoathetosis Sydenham Chorea
Why do antipsychotics cause Tardive Dyskinesia?
Down-regulation of dopamine system and increased glutamatergic transmission resulting in oxidative neurodegeneration
Which dopamine pathway is involved in controlling movement?
Nigrostriatal
Which 2 basal ganglia nuclei form the striatum?
Putamen
Caudate nucleus
What is the dopamine hypothesis of schizophrenia?
Caused by excessive DA release in the mesolimbic pathway (causes positive symptoms)
Hypoactivity of DA in mesocortical responsible for negative/ cognitive/ affective symptoms)
What anatomical changes are seen in patients with schizophrenia?
Degeneration of grey matter (esp. medial temporal lobes)
Enlarged ventricles and sulci (esp. medial temporal lobes)
Reduced blood flow in basal ganglia and frontal lobes
How can Tardive Dyskinesia be managed?
Decrease symptoms through supplement use (Vit E and Vit B6), Benzodiazepines and Beta-Blockers
[Nb. no definitive cure for TD, can spontaneously remit]
What causes Neuroleptic Malignant Syndrome?
Genetic polymorphism of D2 receptor gene present in approx. 15% of schizophrenic patients
Onset of syndrome after starting antipsychotic treatment
