Antipsychotics Flashcards
What are the 4 key symptoms of a psychotic episode?
- Hallucinations
- Delusions
- Disrupted thought patterns
- Lack of self-awareness
Define schizophrenia.
Defined by the ICD10 as being characterized by distortions of thinking and perception; and of affect (the emotional response to stimuli/situations) inappropriate to the situation or blunted (i.e. reduced)
What is the diagnostic criteria for schizophrenia?
Disturbance lasts for six months or longer, with at least one month of at least two of the classical symptoms:
- Delusions (persecutory nature)
- Hallucinations (any sensory modality but mainly auditory)
- Disorganised/catatonic behaviour
- Negative symptoms
What are the negative symptoms of schizophrenia?
- Affective blunting
- Alogia
- Anhedonia
- Avolition
What are disorganisation syndromes?
Alterations in speech, thought patterning and behaviour commonly including:
- Thought insertion/withdrawal
- Thought echo
- Thought broadcasting
What are the positive symptoms of schizophrenia?
‘Hyper’ types of behaviour e.g. agitation, hallucinations and exaggerated behaviour
What do auditory hallucinations tend to be like in schizophrenic patients?
In the 3rd person like an external voice giving them direction or commenting on their behaviour
What are the classes of antipsychotic drugs?
- 1st generation (classical/typical): DA antagonist
- 2nd generation (atypical): DA antagonist
- 3rd generation: partial DA agonist
What is the only 3rd generation antipsychotic to date?
Aripiprazole
What are the main characteristics of 1st generation anti-psychotics?
Main target = DA D2 receptor
Also = H1, M1 + a1 adrenergic antagonists
Higher risk of neurological side effects
Not as effective at targeting -ve symptoms as +ve
What are the main characteristics of 2nd generation antipsychotics?
Main target = 5HT2 more than D2 receptor
Also = multiple 5HT, DA, M, H + a1 adrenergic receptor subtypes
Higher risk of metabolic (cholinergic) side effects but lower risk of extrapyramidal side effects
Thought to be better at targeting -ve symptoms but no evidence that they are better than 1st generation to date
What are the 4 dopamine (DA) pathways (from inner-outer brain)?
- Tuberohypophyseal
- Nigrostriatal
- Mesolimbic
- Mesocortical
Reduced dopamine (DA) in Parkinson’s disease cause what symptoms?
Reduced movement
Reduced emotions
Dampened personality
What is thought to be the main mechanism for psychosis?
Too much DA in the mesolimbic pathway
What are the main roles of the prefrontal cortex?
Planning Personality \+ve emotions Judgement Reasoning
What are the main roles of the limbic system?
-ve emotions Social recognition Spatial awareness Sensory perception Memory
Give some examples of 1st generation antipsychotic.
4 types:
- Butyrophenones e.g. Haloperidol
- Phenothiazines e.g. Chlorpromazine
- Thioxanthines e.g. Zuclopenthixol
- Dibenzodiazenes e.g. Sulpiride
Give some examples of 2nd generation antipsychotics.
Clozapine
Risperidone
Amisulpride
Aripirazole
What are the side effects of 1st generation antipsychotics?
Dry mouth, constipation + hypotension (M1)
Rigidity, slow movements + prolactin elevation (D2)
Blurred vision + drowsiness (a1)
Weight gain + sedation (H1)`
What are the key features of Haloperidols structure?
‘OH group’ due to ‘-ol’
Halogen so contains F, Cl, Br, I + At
What are the key features of Zuclopenthixol structure?
Thioxanthines (‘thix’) have a classic 3 ring structure with a sulphur in place of the oxygen in the middle ring
What is the main problem when prescribing patients with psychosis or related disorder antipsychotics?
Adherence to prescription regimes which often leads to fluctuating plasma levels and instability of effects so may need to give them via depot
What are the side effects of 2nd generation antipsychotics?
Weight gain, somnolence, dizziness + constipation (5HT)
Tremor, stiffness, slow speech + rigidity (DA)
What is the gold standard antipsychotic?
Clozapine (despite having the highest amount of side effects e.g. CV effects of 2nd generation antipsychotics)
What type of activity does Risperidone show?
Biphasic - acts like a 2nd generation antipsychotic at low doses but like a 1st generation antipsychotic at high doses (used in other disorders e.g. dementia + in child/adolescent use)
What are the side effects called that 75% of antipsychotic users experience? Why?
EPS (e.g. tremor, slow movement, akathisia + sedation) due to altered activity of nigrostriatal pathway
What are the extrapyramidal tracts?
Rubrospinal Reticulospinal Basal ganglia Tectospinal Vestibulospinal
Why might prolactin elevation occur as a side effect?
Altered activity in tuberohypophyseal DA pathway
What are symptoms of hyperprolactinaemia?
Enlargements of breasts + lactation (milk production)
Irregular menstrual cycles
Oestrogen deficiency symptoms (in women)
or testosterone deficiency (in men) leading to erectile dysfunction + infertility
Why do 2nd generation antipsychotics show less extrapyramidal symptoms (EPS) than the 1st generation?
They have a comparatively higher affinity for the mesolimbic and cortical DA pathways than the nigrostriatal DA pathway
What is tardive dyskinesia?
Disabling involuntary movements including tongue protruding, choreiform movements, grimacing + twisting of face + limbs in long-term 1st generation anti-psychotic use which can be irreversible
What is the treatment for tardive dyskinesia?
It can spontaneously remit but otherwise is difficult to treat - change to 2nd generation antipsychotic + remove any anticholinergic drugs in use along with various other drugs/supplements
What is neuroleptic malignant syndrome?
Rapid onset of extreme side effects caused by genetic polymorphism of D2 receptor presenting within the 1st couple of weeks following antipsychotic prescription characterised by high fever, autonomic problems (e.g. tachycardia, incontinence) + altered consciousness
How do you treat neuroleptic malignant syndrome?
Immediate withdrawal of antipsychotic
DA agonists
BZDs
List some hyperkinetic disorders.
HD RLS Sydenham Chorea Choreoathetosis Dystonia
List some hypokinetic disorders.
PD
Dementia with lewy bodies
Multiple systems atrophy
Progressive supranuclear palsy
What dopamine (DA) pathway is involved in movement?
Nigrostriatal projecting from brainstem to basal ganglia
What does Huntington’s Disease (HD) result in degeneration of?
Striatum (caudate nucleus + putamen)
Antipsychotics are antagonists at the D2 receptors. How would this alter movement controlled by the indirect basal ganglia pathway?
DA acting at D2 receptors inhibit indirect pathway in striatum - as this pathway inhibits movement, this will cause a net increase in movement so an antagonist will stop disinhibition reducing movement
What type of inheritance pattern does Huntington’s Disease (HD) have?
Autosomal dominant
What are the 5 domains of symptoms exhibited by schizophrenic patients?
- Positive
- Negative
- Cognitive
- Aggressive
- Anxiety/depression
What anatomical alterations can be seen in schizophrenic patients?
Grey matter degeneration particularly within medial temporal lobes causing enlarged ventricles and sulci apparent on scanning
Cerebral blood flow is reduced in basal ganglia + frontal lobes
Who is most likely to get schizophrenia?
Males more than females
Strong genetic link to certain genes
What is Haloperidol most commonly used for?
Short-term treatment of extreme behaviour for rapid tranquilisation e.g. psychomotor agitation, excitement, violence + impulsivity BUT NOT for long-term management of challenging behaviour
What are the most commonly used antipsychotics?
1st generation: Chlorpromazine + Haloperidol
2nd generation: Amisulpride, Risperidone + Clozapine
