Drugs for Psychosis and Mania

Question 1

What is psychosis?

Answer 1

a mental state in which there is a loss of contact with reality

Question 2

What is mania?

Answer 2

madness or frenzy accompanied by an elevated or irritable mood, increased energy, reduced need to sleep, exaggerated self-importance, reckless behaviour and thought disturbances

Question 3

What is schizophrenia?

Answer 3

a chronic disease with the onset in late adolescence/early adulthood and it is highly disabling to social and vocational functioning

Question 4

What are the 5 domains of schizophrenia symptoms?

Answer 4

• positive symptoms
• negative symptoms
• aggressive symptoms
• cognitive symptoms
• anxiety/depression

Question 5

What are positive symptoms of schizophrenia?

Answer 5

addition of abnormal behaviours interspersed between periods where negative symptoms dominate

Question 6

Give examples of positive symptoms of schizophrenia

Answer 6

• delusions (often paranoid)
• hallucinations e.g. exhortatory voices
• thought disorder including feeling that thoughts are controlled by an outside agency
• abnormal behaviours e.g. stereotypical or aggressive behaviours

Question 7

What are positive symptoms of schizophrenia generally the result of?

Answer 7

increased subcortical release of dopamine, which augments D2 receptor activation and a disturbed cortical pathway through the nucleus accumbens

Question 8

Give examples of negative symptoms of schizophrenia

Answer 8

• withdrawal from social contacts
• flattening of emotional responses

Question 9

What are negative symptoms of schizophrenia?

Answer 9

the subtraction of normal behaviours that become more dominant as the disease progresses

Question 10

What are negative symptoms of schizophrenia generally the result of?

Answer 10

reduced D1 receptor activation in the prefrontal cortex and decreased activity of the nucleus caudatus

Question 11

What is cognitive dysfunction?

Answer 11

the impairment of selective attention and working memory

Question 12

Why are cognitive dysfunction symptoms important in schizophrenia?

Answer 12

they predict the level of social and vocational functioning, and hence treatment outcome, better than positive symptoms

Question 13

What are environmental factors of schizophrenia?

Answer 13

• neurodevelopmental abnormalities
• maternal viral infections during pregnancy
• obstetric complications

Question 14

What is the onset of schizophrenia in late adolescence consist with?

Answer 14

neurodevelopmental abnormality involving myelination of cortico-cortical pathways

Question 15

What are the 3 proposed neurochemical theories of schizophrenia?

Answer 15

• dopamine theory
• 5-HT theory
• glutamate theory

Question 16

What is the dopamine theory?

Answer 16

dysregulation of dopamine activity in the brain plays a central role in the development of symptoms

Question 17

What is the 5-HT theory?

Answer 17

dysregulation of 5-HT system, particularly involving the 5-HT2A receptor, contributes to the development of symptoms

Question 18

What is the glutamate theory?

Answer 18

dysregulation of the glutamate neurotransmitter system, particularly involving NMDA receptors, plays a central role in the development of symptoms

Question 19

What are the 2 key typical antipsychotics?

Answer 19

chlorpromazine and haloperidol

Question 20

What are the 4 key atypical antipsychotics?

Answer 20

amisulpride, clozapine, olanzapine, risperidone

Question 21

What do typical antipsychotics do?

Answer 21

control positive symptoms and produce EPS by blocking D2 receptors

Question 22

What do atypical antipsychotics do?

Answer 22

control positive and negative symptoms and produce less EPS

Question 23

What EPS does blocking of D2 receptors cause?

Answer 23

• dry mouth, constipation, blurred vision via M1 receptors
• sedation, weight gain via H1 receptors
• postural hypotension, dizziness via alpha-adrenergic receptors

Question 24

What is chlorpromazine derived from?

Answer 24

antihistamine drugs

Question 25

What is the most widely used antipyschotic drug and why?

Answer 25

haloperidol since its single selective mechanisms reduce the side effects

Question 26

What are motor EPS?

Answer 26

dystonias and tardive dyskinesia

Question 27

What is the cause of motor EPS?

Answer 27

actions on the extrapyramidal motor pathways

Question 28

What does the extrapyramidal motor pathway involve?

Answer 28

the basal ganglia, including the striatum and substantia nigra

Question 29

What are the pyramidal motor pathways?

Answer 29

the output from the primary motor cortex via the pyramids of the medulla oblongata to the spinal cord

Question 30

What is acute dystonia?

Answer 30

a tremor at rest due to D2 antagonism in the nigrostriatal pathway that occurs within the first few weeks of treatment and is reversible when the drug is stopped

Question 31

What is tardive dyskinesia?

Answer 31

is involuntary movements of the face due to upregulation or super-sensitivity of dopamine receptors

Question 32

What do many atypical antipsychotics have?

Answer 32

- greater affinity at 5-HT2 receptors - greater affinity at D4 receptors - mixed antagonism at α-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors

Question 33

What is the core MOA of most atypical antipsychotics?

Answer 33

serotonin-dopamine antagonism

Question 34

How do atypical antipsychotics reduce the incidence of tardive dyskinesia?

Answer 34

they dissociate more rapidly and so are more readily displaced by competition from endogenous dopamine

Question 35

What are benefits of atypical antipsychotics?

Answer 35

- more effective against negative symptoms e.g. clozapine, olanzapine, risperidone - ameliorate cognitive dysfunction better than typical antipsychotics e.g. clozapine, risperidone - better at mood stabilization e.g. clozapine, olanzapine, risperidone - antagonism at presynaptic 5-HT2 heteroreceptors on dopaminergic terminals may regulate dopamine levels in the PFC

Question 36

What does combination of atypical antipyschotics with antidepressants do?

Answer 36

stabilise mood but also increase range of adverse effects

Question 37

What are adverse effects of atypical antipsychotics?

Answer 37

- same EPS as typical antipsychotics - clozapine-induced agranulocytosis - hyperglaecemia - diabetes - increased prolactin secretion