Antipsychotics (General)

Question 1

Psychosis

Answer 1

Abnormal condition of the mind

Question 2

Schizophrenia (What is it?)

Answer 2

Psychiatric Illness (Disorder)

Question 3

Schizophrenia (Affects Who?)

Answer 3

Affects young people
Strong hereditary factor

Question 4

Schizophrenia (Positive Symptoms)

Answer 4

Excess/Distortion of normal behaviour:
- Delusions
- Hallucinations
- Thought Disorder: Wild thoughts, delusions

Question 5

Schizophrenia (Negative Symptoms)

Answer 5

Absence/Loss of normal behaviour
- Withdrawal from social contacts
- Flattening of emotional response
- Inability to enjoy pleasure (Anhedonia)

Question 6

Schizophrenia (Other Symptoms)

Answer 6

Deficits in cognitive function
- Attention
- Memory

Question 7

Schizophrenia (Positive Symptoms)
- Neurotransmitters Involved

Answer 7

Under-activity of glutamate
- Receptor hypofunction (Glu/NMDA Receptor)

Dopamine Dysregulation
- Too much/little in some areas

Question 8

Schizophrenia (Positive Symptoms)
- Mechanism

Answer 8

Overactivation of D2 in mesolimbic pathways

NMDA Receptor Hypofunction
- Not enough activation of GABAergic Neurons –> Not enough inhibition of dopaminergic neurons
–> Too much synthesis and release of dopamine

Question 9

Schizophrenia (Negative Symptoms)
- Mechanism

Answer 9

Decreased activity of D1 dopamine receptors in mesocortical pathway
–> Not enough NMDA receptor activity
–> Too little activation of dopaminergic neurons

Question 10

What pathways are responsible positive/negative symptoms
- Mesolimbic
- Mesocortical

Answer 10

Mesolimbic = Positive Symptoms
Mesocortical = Negative Symptoms

Question 11

Schizophrenia (Cognitive Symptoms)
- Mechanism

Answer 11

NMDA Receptor Hypofunction
–> Affects GABAergic Interneurons altering cortical processing and causing cognitive impairment

Question 12

Schizophrenia (Treating Positive vs Negative Symptoms)

Answer 12

Treatments work better on Positive Symptoms
–> They target D2 Receptors

Question 13

Antipsychotics (Mechanism of Treatment)

Answer 13

Antagonism of D2 Receptors
- Also block many other receptors
–> Can cause good/bad side effects

Question 14

First Generation Antipsychotics vs
Second Generation Antipsychotics

Answer 14

1st Gen:
- D1 Selectivity = D2 Selectivity
- Higher Extrapyramidal Disturbances
- Less Effective Against Negative Symptoms

2nd Gen:
- D2 Selectivity > D1 Selectivity
- Lower Extrapyramidal Disturbances
- Effective Against Negative Symptoms
–> 5-HT2A Antagonism

Question 15

Antipsychotics
- Extrapyramidal Side Effects

Answer 15

Motor Disturbances
- Blocks D2 Receptors in Nigrostriatal Pathway

Parkinson’s Disease (Dystonia)
- Involuntary movements

Irreversible Dyskinesia
- Involuntary movement of face, limbs, tongue

Question 16

Antipsychotics (Endocrine Effects)

Answer 16

Enhanced Prolactin secretion and Galactorrhea
- Blocks D2 Receptor in Tuberohypophyseal Pathway

Question 17

Antipsychotics (Pleasure Effects)

Answer 17

Blocks D2 Receptors in Mesolimbic Pathway
- Reduces Pleasure

Question 18

Antipsychotics (Worsening of _ Symptoms)

Answer 18

Blocks D2 Receptors in Cortex
- Worsening of Negative Symptoms

Question 19

Antipsychotics can have an effect on other receptors
- Name some examples?

Answer 19

Antihistamine: Sedation
mAchR Inhibition:
- Blurred Vision
- Constipation / Urinary Retention
- Dry Mouth
Alpha-Adrenoceptor Block: Low Blood Pressure

Question 20

Antipsychotics (Side Effects)
- Clozapine

Answer 20

Leukopenia/Agranulocytosis
- Lowers white blood cell count

Question 21

Antipsychotics (Side Effects)
- Skin

Answer 21

Jaundice
Urticarial (Hives) Skin Reaction

Question 22

Antipsychotic Malignant Syndrome

Answer 22

Muscle Rigidity
Rapid increase in body temperature
Mental Confusion

Question 23

How can Antipsychotic’s Side Effects be useful?

Answer 23

Blocking other unintended receptors can provide beneficial effects

Question 24

Relation between Dopaminergic and Cholinergic Neurons

Answer 24

Dopaminergic Neurons can inhibit Cholinergic Neurons
–> Reduces Motor Side Effects

Question 25

How can Antipsychotic's Side Effects be useful? - Producing Motor Side Effects

Answer 25

Antipsychotic blocks D2 Receptors on Cholinergic Neuron --> No more inhibition --> Enhanced Ach --> Produces Motor Side Effect

Question 26

How can Antipsychotic's Side Effects be useful? - Reducing Motor Side Effects

Answer 26

Antipsychotic blocks mAchR --> Reduces Motor Side Effects Antipsychotic blocks mAchR on Dopaminergic Neurons --> Enhanced Dopamine release --> Activates D2 Receptor on Cholinergic --> Reduced Ach --> Reduced Motor Side Effects

Question 27

How can Antipsychotic's Side Effects be useful? - Nigrostriatal Pathway

Answer 27

Dopamine Needed for Movement Antipsychotic Blocks 5-HT2A Receptor --> Increased Dopamine release --> Reduces Motor Side Effects

Question 28

How can Antipsychotic's Side Effects be useful - Mesocortical Pathway

Answer 28

Too Little Dopamine, need more Antipsychotic Blocks 5-HT2A Receptor --> Increased Dopamine/Glutamate release --> Improve Negative Side Effects

Question 29

How can Antipsychotic's Side Effects be useful? - Mesolimbic Pathway

Answer 29

Too much Dopamine, need less Antipsychotic Blocks 5-HT2A and D2 Receptors --> Decrease dopamine function