Antipsychotic Drugs

Question 1

what are antipsychotic drugs also known as?

Answer 1

neuroleptics - used for psychosis, mainly used in the treatment of schizophrenia

Question 2

what are the positive symptoms of schizophrenia?

Answer 2

delusions, hallucinations, and thought disorders

Question 3

what are the negative symptoms of schizophrenia?

Answer 3

social withdrawal, emotional flattening, reduced drive, inability to feel pleasure, and poverty of speech

Question 4

what may antipsychotics also be used for?

Answer 4

agitated depression and severe anxiety

Question 5

what causes schizophrenia?

Answer 5

cause is not clear
environmental factors play a part and there is a significant genetic component in that 10-15% of first-degree relatives share the condition
may be due to abnormalities in the cerebral cortex
alterations in various neurotransmitter systems (eg the dopaminergic pathways)

Question 6

discuss the dopamine theory of schizophrenia

Answer 6

D2 receptor antagonism has antipsychotic effect

Question 7

what do antipsychotic drugs do?

Answer 7

antipsychotic drugs can alleviate the positive symptoms of schizophrenia but have little effect on the negative symptoms - in fact they can produce apathy and decreased initiative

Question 8

discuss the neuronal targets of antipsychotic drug treatments

Answer 8

neuroleptics act by antagonising D2 receptors in mesocorticolimbic pathways. however dopamine releasing neurones are also found in the basal ganglia (nigrostriatal pathway) and in the hypothalamus (tuberoinfundibular pathway)

as a consequence all neuropleptics cause extrapyramidal side effects - pseudo-parkisonism and increase the release of prolactin. unfortunately with the older (typical) neruoleptics the tendency to produce these side effects generally increases with antipsychotic potency and D2 antagonism

Question 9

what are three classes of typical neuroleptics?

Answer 9

phenothiazines
thioxanthines
butyrophenones

Question 10

name the phenothiazines

Answer 10

chlorpromazine, thioridazine

Question 11

name a thioxanthine

Answer 11

flupenthixol

Question 12

name a butyrophenone

Answer 12

haloperidol

Question 13

what are the advantages of these drugs

Answer 13

relieve the positive symptoms

sedative

Question 14

what are prominent disadvantages of these drugs

Answer 14

ineffective against negative symptoms
extrapyramidal symptoms
hyperprolactinaemia leading to galactorrhoea and amenorrhoea
aplastic anaemia

Question 15

discuss the pharmacological profile of the typical neuroleptics

Answer 15

in addition to binding D2 receptors the phenothiazines (eg chlorpromazine) are antagonists of histamine (H1) muscarinic (mACh) and a1 adrenoreceptors,

binding to H1 receptors could explain the marked sedative effects of some neuroleptics while antagonism of a1 adrenoreceptors can cause hypotension. mACh receptor antagonism produces anti-cholinergic effects but can also amerliorate pseudo-parkisonism effects

Question 16

what are the atypical neuroleptics (prototype, clozapine)?

Answer 16

Dibenzazepine derivatives - clozapine, olanzepine, quetiapine

benzisoxazole derivative - risperidone

Question 17

what are the advantages of atypical neuroleptics?

Answer 17

can relieve both positive and negative symptoms
can relieve psychosis resistant to typical neuroleptics
lower incidence and severity of extra-pyramidal symptoms

Question 18

what are the disadvantages of atypical neuroleptics?

Answer 18

marked sialorrhoea (dribbling) 
agranulocytosis (clozapine) 
weight gain (systemic fat)
prolongation of the cardiac QT interval

Question 19

pharmacological profile of atypical neuroleptics

Answer 19

Dibenzazepine derivatives:
partial agonists of D2 receptors
antagonists of 5HT2A/2C receptors
muscarinic and a2 antagonism - less EPS

risperidone:
weak partial 5HT1A agonist - relieves negative symptoms

Question 20

What is the third generation antipsychotic ?

Answer 20

aripiprazole

Question 21

discuss aripiprazole

Answer 21

it is a dopamine receptor D2 antagnsim and 5HT2A receptor antagonist, both of which are likely to underlie its antipsychotic effects, it is also a 5HT1A partial agonist : this action is thought to indirectly increase DA release in the cortex and so relive negative symptpoms

Question 22

side effect profile of aripiprazole

Answer 22

incidence of EPS - no difference from placebo
little weight gain
few CV - (QT) abnormalities
apparently safe in overdose

but is associated with hyperprolactinaemia and hypercholesterolaemia