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Flashcards in Antipsychotics Deck (18)
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1
Q

What is the principal mechanism of action of antipsychotics?

What are they principally used for?

A
  • Common property of antagonising the actions of dopamine in the brain.
  • Mainly used in the treatment of schizophrenia and other psychotic illnesses.
2
Q

What are the clinical features of schizophrenia?

A
  • Positive symptoms:
    • Delusions
    • Hallucinations
    • Thought disorders
  • Negative symptoms:
    • Withdrawl from social contact and flattening of emotional responses.
3
Q

Describe the dopamine theory.

A
  • Amphetamine produces symptoms almost indistinguishable from schizophrenia.
  • D2-receptor agonists produce similar symptoms in animals and exacerbate symptoms in humans.
  • Strong correlation between clinical potency ofantipsychotics and D2 blocking action.
  • ↑ dopamine content in restricted area of the temporal lobe of schizophrenics (amygdala).
  • ↑ dopamine synthesis and release in the striatum of schizophrenics.
4
Q

Describe the glutamate theory.

A
  • NMDA receptor antagonists (e.g. phencyclidine andketamine) produce psychotic symptoms.
  • ↓ glutamate and receptor density reported in post- mortem schizophrenic brains.
  • Transgenic mice with ↓ NMDA receptor expression show stereotypic schizophrenic behaviours and ↓ social interactions.
    • respond to antipsychotics.
  • Glutamate and dopamine exert excitatory and inhibitory effects respectively on GABAergic striatal neurones which project to the thalamus and constitute a sensory ‘gate’.
  • Too little glutamate or too much dopamine disables the ‘gate’ allowing uninhibited sensory input to reach the cortex.
  • Excess dopamine could be responsible for the positive symptoms and reduced glutamate for the negative symptoms.
5
Q

What are the categories of first generation (classical) antipsychotics?

Give an example of each.

A
  • Phenothiazines
    • chlorpromazine
    • fluphenazine
    • pipotiazine
  • Butyrophenones
    • haloperidol
  • Thioxanthines
    • flupentixol
    • zuclopenthixol
6
Q

What are the categories of second generation (atypical) antipsychotics?

Give an example of each.

A
  • Benzamides
    • Amisulpride (selective D2 and D3 receptor antagonists).
  • Dibenzodiazepines
    • Clozapine and Olanzapine (very unselective receptor blocking profile).
  • Others
    • Risperidone, paliperidone (mixture of receptor types blocked)
    • Quetiapine (α adrenoceptor blocker)
    • Aripiprazole (Dopamine and 5-HT antagonist)
7
Q

Describe the action of second generation antipsychotics.

A
  • Overcome some of the problems of the classical

neuroleptics.

  • Show efficacy in treatment-resistant patients.
  • Improve the negative as well as positive symptoms.
  • No real evidence that they are more effective than the first generation classical neuroleptics in controlling symptoms.
8
Q

How is the distinction between typical and atypical groups defined?

A
  • Not clearly defined, but rests on:
    • Receptor profile
    • Incidence of extrapyramidal side-effects
      • Less in atypical group
    • Efficacy in treatment-resistant group of patients
    • Efficacy against negative symptoms
9
Q

Look at the relatice receptor affinity of antipsychotic drugs (don’t memorise).

A
  • α1 receptors - most associated with blood vessels
  • H1 receptors - histamine
  • mACH receptors - muscarinic ACh
  • 5-HT2A - serotonin.
10
Q

What are the behavioural effects of antipsychotics?

A
  • Apathy and reduced initiative
  • Display few emotions, drowsy
    • Can be easily stirred from this
  • Aggressive tendencies inhibited
  • Effects are distinct from those produced by hypnotics and anxiolytics
11
Q

What are the main types of motor disturbances caused by antipsychotics?

A
  • Acute, reversible Parkinson-like symptoms
    • due to block of nigro-striatal dopamine receptors
  • Slowly developing tardive dyskinesia
    • one of the most serious problems with antipsychotics
12
Q

Describe tardive dyskinesia.

A
  • Involuntary movements of face and limbs
  • Appears after months/years of treatment
  • Associated with proliferation of dopamine receptors in the corpus striatum
  • Treatment is generally unsuccessful
  • Less common with newer antipsychotics
13
Q

What are the other unwanted effects of antipsychotics?

A
  • Endocrine actions
    • ↑ prolac􏰀tin secreti􏰀on by blocking D2 receptors in the pituitary.
  • Anti-muscarinic actions
    • Blurring of vision, dry mouth & eyes, constipation.
    • Can help attenuate extrapyramidal actions.
  • α-adrenoreceptor blocking actions
    • Orthostatic hypotension.
  • H1-receptor blocking actions
    • Sedative and anti-emetic actions.
14
Q

Give a summary of the unwanted effects of antipsychotics.

A
  • Postural hypotension
  • Sedation
  • Weight gain
  • Endocrine actions
  • Diabetes

Autonomic actions (atropine-like)

  • Extrapyramidal actions
  • Jaundice
  • Leucopoenia and agranulocytosis
  • Skin reactions (itchy rash)
  • Neuroleptic malignant syndrome
15
Q

Look at the relative adverse effects of antipsychotics (do not memorise).

A
16
Q

Describe the variability in uptake of antipsychotic drugs.

A
  • Very different uptake between individuals - pharmacokinetics is different in each different patient.
17
Q

Describe the treatment algorithm for first-episode schizophrenia.

A
18
Q

What are the different clinical uses of antipsychotic drugs?

A
  • Schizophrenia
    • Both classical and atypical depending on side effects.
  • Acute Behavioural Emergencies and Mania
    • Chlorpromazine
    • Haloperidol
  • Treatment of emesis
    • Prochlorperazine
  • Huntington’s disease
    • e.g. Olanzapine, Risperidone and Quetiapine
  • Occasionally used in depression
    • Flupentixol