Lecture on Dopaminergic Pathways and Antipsychotics

Overview

• Discussion of dopaminergic pathways.
• Exploration of first and second generation antipsychotics (typicals vs atypicals).
• Coverage of extrapyramidal symptoms (EPS) and neuroleptic malignant syndrome.

Dopaminergic Pathways

1. Mesolimbic Pathway

• Originates at the ventral tegmental area (VTA) and projects to the nucleus accumbens.
• Associated with positive symptoms of schizophrenia (hallucinations, delusions).
• Overactivity due to excess dopamine; treated by decreasing dopamine using antipsychotics.

2. Mesocortical Pathway

• Projects from VTA to the cortex.
• Linked to negative symptoms of schizophrenia (anhedonia, flat affect).
• Dysfunction due to decreased dopamine levels.

3. Nigrostriatal Pathway

• Starts in the substantia nigra, projects to the striatum (caudate and putamen).
• Responsible for coordination of movement.
• Decreased dopamine can induce Parkinsonism due to antipsychotics.

4. Tubero-Infundibular Pathway

• Hypothalamus to pituitary gland.
• Dopamine inversely affects prolactin release.
• Decreased dopamine increases prolactin, causing galactorrhea and amenorrhea.

Antipsychotics

First Generation (Typicals)

• Primary drug: Haloperidol.
• Mechanism: D2 receptor inhibition (also blocks H1, alpha, M1 receptors - anti-HAM).
• High incidence of EPS and risk of neuroleptic malignant syndrome.

Second Generation (Atypicals)

• Include risperidone, olanzapine, clozapine, etc.
• Block D2 and serotonin 2A receptors, reducing EPS.
• Side effects: metabolic syndrome, weight gain, hyperprolactinemia (particularly risperidone), agranulocytosis (clozapine).

Extrapyramidal Symptoms (EPS)

Types and Treatments

• Dystonia: Sustained muscle contractions treated with anticholinergics (benztropine or Benadryl).
• Akathisia: Restlessness treated with beta blockers.
• Parkinsonism: Movement disorders identical to Parkinson’s disease; treated with anticholinergics.
• Tardive Dyskinesia: Repetitive movements of lips, tongue, neck; treated by discontinuing antipsychotic, possibly clozapine.

Neuroleptic Malignant Syndrome

• Life-threatening condition from excessive antipsychotic use.
• Symptoms: fever, tachycardia, rigidity, confusion, possible rhabdomyolysis.
• Treatment: Discontinue antipsychotic, administer dantrolene, and dopamine agonist.

Summary

• Know dopaminergic pathways and their relation to dopaminergic activity changes.
• Understand the pharmacological differences and side effects between typical and atypical antipsychotics.
• Identify and manage EPS and neuroleptic malignant syndrome effectively.
• High-yield material essential for USMLE, COMLEX, and clinical practice.