Antipsychotics (General) Flashcards
Psychosis
Abnormal condition of the mind
Schizophrenia (What is it?)
Psychiatric Illness (Disorder)
Schizophrenia (Affects Who?)
Affects young people
Strong hereditary factor
Schizophrenia (Positive Symptoms)
Excess/Distortion of normal behaviour:
- Delusions
- Hallucinations
- Thought Disorder: Wild thoughts, delusions
Schizophrenia (Negative Symptoms)
Absence/Loss of normal behaviour
- Withdrawal from social contacts
- Flattening of emotional response
- Inability to enjoy pleasure (Anhedonia)
Schizophrenia (Other Symptoms)
Deficits in cognitive function
- Attention
- Memory
Schizophrenia (Positive Symptoms)
- Neurotransmitters Involved
Under-activity of glutamate
- Receptor hypofunction (Glu/NMDA Receptor)
Dopamine Dysregulation
- Too much/little in some areas
Schizophrenia (Positive Symptoms)
- Mechanism
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
Schizophrenia (Negative Symptoms)
- Mechanism
Decreased activity of D1 dopamine receptors in mesocortical pathway
–> Not enough NMDA receptor activity
–> Too little activation of dopaminergic neurons
What pathways are responsible positive/negative symptoms
- Mesolimbic
- Mesocortical
Mesolimbic = Positive Symptoms
Mesocortical = Negative Symptoms
Schizophrenia (Cognitive Symptoms)
- Mechanism
NMDA Receptor Hypofunction
–> Affects GABAergic Interneurons altering cortical processing and causing cognitive impairment
Schizophrenia (Treating Positive vs Negative Symptoms)
Treatments work better on Positive Symptoms
–> They target D2 Receptors
Antipsychotics (Mechanism of Treatment)
Antagonism of D2 Receptors
- Also block many other receptors
–> Can cause good/bad side effects
First Generation Antipsychotics vs
Second Generation Antipsychotics
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
Antipsychotics
- Extrapyramidal Side Effects
Motor Disturbances
- Blocks D2 Receptors in Nigrostriatal Pathway
Parkinson’s Disease (Dystonia)
- Involuntary movements
Irreversible Dyskinesia
- Involuntary movement of face, limbs, tongue
Antipsychotics (Endocrine Effects)
Enhanced Prolactin secretion and Galactorrhea
- Blocks D2 Receptor in Tuberohypophyseal Pathway
Antipsychotics (Pleasure Effects)
Blocks D2 Receptors in Mesolimbic Pathway
- Reduces Pleasure
Antipsychotics (Worsening of _ Symptoms)
Blocks D2 Receptors in Cortex
- Worsening of Negative Symptoms
Antipsychotics can have an effect on other receptors
- Name some examples?
Antihistamine: Sedation
mAchR Inhibition:
- Blurred Vision
- Constipation / Urinary Retention
- Dry Mouth
Alpha-Adrenoceptor Block: Low Blood Pressure
Antipsychotics (Side Effects)
- Clozapine
Leukopenia/Agranulocytosis
- Lowers white blood cell count
Antipsychotics (Side Effects)
- Skin
Jaundice
Urticarial (Hives) Skin Reaction
Antipsychotic Malignant Syndrome
Muscle Rigidity
Rapid increase in body temperature
Mental Confusion
How can Antipsychotic’s Side Effects be useful?
Blocking other unintended receptors can provide beneficial effects
Relation between Dopaminergic and Cholinergic Neurons
Dopaminergic Neurons can inhibit Cholinergic Neurons
–> Reduces Motor Side Effects
How can Antipsychotic’s Side Effects be useful?
- Producing Motor Side Effects
Antipsychotic blocks D2 Receptors on Cholinergic Neuron
–> No more inhibition –> Enhanced Ach
–> Produces Motor Side Effect
How can Antipsychotic’s Side Effects be useful?
- Reducing Motor Side Effects
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
How can Antipsychotic’s Side Effects be useful?
- Nigrostriatal Pathway
Dopamine Needed for Movement
Antipsychotic Blocks 5-HT2A Receptor
–> Increased Dopamine release
–> Reduces Motor Side Effects
How can Antipsychotic’s Side Effects be useful
- Mesocortical Pathway
Too Little Dopamine, need more
Antipsychotic Blocks 5-HT2A Receptor
–> Increased Dopamine/Glutamate release
–> Improve Negative Side Effects
How can Antipsychotic’s Side Effects be useful?
- Mesolimbic Pathway
Too much Dopamine, need less
Antipsychotic Blocks 5-HT2A and D2 Receptors
–> Decrease dopamine function
