Lecture 9: Antipsychotics

Question 1

Flow chart of psychotic disorders

Answer 1

See figure

Question 2

What is schizophrenia?

Answer 2

Chronic psychosis with deterioration of functional capacity

Inability to interact mentally and emotionally with other people

Question 3

Diagnosis symptom groups

Answer 3

Positive symptoms

Negative symptoms

Cognitive symptoms

Affective symptoms

Question 4

What are positive symptoms of schizophrenia

Answer 4

Excess cognition

Hallucinations (50%)

Delusions (65%)

Disorganized speech (50%)

Question 5

What are negative symptoms of schizophrenia

Answer 5

Deficits in behaviour

Avolition

Alogia (poverty of speech)

Anhedonia

Blunted affect

Question 6

Cognitive symptoms of schizophrenia

Answer 6

Declines in attention, language, memory, executive function

Probably present from birth

Question 7

Affective symptoms of schizophrenia

Answer 7

Blunted, inappropriate, odd expression

Often lead to social stigmatization

Question 8

Dopamine hypothesis of schizophrenia

Answer 8

Too much mesolimbic dopamine pathway activity leads to positive symptoms

Negative symptoms result from low dopaminergic activity in the mesocortical pathway

Question 9

Dopamine systems and their relation to symptoms

Answer 9

Mesolimbic pathway responsible for positive symptoms

Mesocortical pathway responsible for negative symptoms

See figure

Question 10

Dopaminergic systems

Answer 10

Substantia nigra to stratium

Tegmentum (VTA) to prefrontal cortex

Tegmentum to nucleus accumbent

Hypothalamus

Question 11

Support for dopamine hypothesis?

Answer 11

Drugs that increase dopaminergic activity can produce psychosis

Question 12

Mechanism of typical antipsychotics

Answer 12

Thought to be antagonism of D2 receptors in mesolimbic pathway (decrease positive symptoms)

Also block nigrostriatal (EPS) and tuberoinfundibulnar (hyper-prolactin) pathways

Question 13

Typical antipsychotics (FGAs)

Answer 13

Chlorpromazine (Thorazine)

Fluphenazine (Permitil, Prolixin)

Haloperidol (Haldol)

Thiothixene (Navene)

Question 14

What are the adverse effects of antipsychotics related to?

Answer 14

Receptor non-selectivity

Blokage of non-mesolimbic D2 dopaminergic pathways

Question 15

Drugs targeting nigostriatal pathway - what do they block? Side effects?

Answer 15

Block dopamine D2

Extrapyramidal side effects (EPS)

Parkinson’s syndrome

Akathisia

Acute dystonic reactions

Tardive dyskinesia (no reliable treatment;
can be irreversible)

Question 16

Tuberoinfundibular pathway - what do they block? Side effects?

Answer 16

Block dopamine D2

Increased prolactin production

Women: lactation, amenorrhea, infertility

Men: lactation, impotence, decreased libido, gynecomastia

Question 17

Advantages of atypical antipsychotics

Answer 17

Block D2 in Nucleus accumbens: decreases positive symptoms (also less EPS and prolactin)

Reduced D2 affinity: Nigostriatal = decreased EPS

Block 5HT2 receptors = decreased negative symptoms

Question 18

How do atypical antipsychotics decrease negative symptoms?

Answer 18

They have increased serotonin 5HT2 affinity

5HT2 receptors suppress dopamine in the mesocortical pathway, so if they are blocked, we get increased dopamine activity

Relief of negative symptoms of schizophrenia

Question 19

Comparison of adverse effects of typical and atypical

Answer 19

See figure

Typical are associated with more EPS and hyper-prolactin

Atypical are associated with less WPS and less prolactin, but more weight gain and hyperglycaemia

Question 20

Important enzymes in metabolism of atypical antipsychotics

Answer 20

Cyp3A4, 1A2, 2D6 are common

Inducers and inhibitors can affect these enzymes

Question 21

Drug interactions with antipsychotics

Answer 21

Excess sedation (anxiolytics, alcohol, antidepressants, antihistamines)

Additive antimuscarinic effects

Metoclopramide - D2 antagonist, EPS

SSRI antidepressants - dopamine suppression in NGS and EPS

Question 22

Progression of selection of anti-psychotics

Answer 22

SGA: second generation antipsychotics

FGA: first generation antipsychotics