SCHIZOPHRENIA

Positive symptoms of schizophrenia

• Delusion

• hallucinations

• disorganised speech

• catatonic behaviour

Negative symptoms of schizophrenia

• decreased emotional expression

• talking less

• lack of initiative and motivation

Describe the Mesolimbic pathway and which symptoms its associated with

Ventral tegmental area to the nucleus accumbens, amygala, and hippocampus

This is associated with positive symptoms 

Mesocortical pathway and which symptoms its associated with

Decresed dopamine activity or dysfunction in this is thought to be responsible for negative and cognitive symptoms

Antipsychotics MOA

Block dopamine D2 receptors - aim to slow down dopamine neurotransmission and correct dysfunction - relief from positive symptoms

Typical antipsychotics

high affinity D2 antagonists - reduce positive symptoms by blocking D2 receptors.

e.g. cholpromazine, halperidol, pluphenazine,fluphentixol, and zuclopenthixol

However, has a diverse side effect profile due to acting as antagonists on histamine H1 receptors, alpha-1 adrenoceptors, and muscarinic M1 receptors.

Atypical antipsychotics

low affinity D2 receptor antagonists and act on other receptors such as serotonin receptors particularly 5-HT2A (antagonist) or 5-HT1A (agonist).

Combination results in an improved side effect profile and potentially better efficacy as both positive and negative symptoms are being treated.

E.g. Clozapine, olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone

Neurotransmitters involved in schizophrenia pathogenesis

• Dopamine

• Serotonin (5-HT)

• Acetylcholine

• GABA

Clozapine

• atypical antipsychotic

• considered the most effective antipsychotic

• treats treatment-resistant schizophrenia

• reduces risk of suicide and aggression

Aripiprazole

• atypical antipsychotic

• D2 partial agonist

• 5-HT1A antagonist

• lower incidence of some side effects due to the unique profile

List the anticholinergic side effects of antipsychotics

• Dry mouth

• blurred vision

• constipation

• urinary retention

List the histamine receptor side effects of antipsychotics

Sedation and drowsiness due to histamine H1 receptor blockade - common with chlorpromazine, clozapine, and olanzapine

List other receptor side effects from antipsychotics

from ATYPICALS

• weight gain

• hyperglycaemia

• diabetes

• dyslipidaemia

• metabolic syndrome

Cardiac effects

• prolong GT interval increasing risk of arrhythmias and sudden cardiac death

List Dopamine D2 receptor blockade side effects

• dystonias

• akathisia

• parkinsonism

• tardive dyskinesia

Typical antipsychotics

• hyperprolactinemia 

• neuroleptic malignant syndrome

Drug interactions

CNS depressants - use of benzodiazepines, opioids, antihistamines or alcohol causes additive sedation and respiratory depression

Parkinson drugs - levadopa are rendered ineffective and can worsen parkinson symptoms

Smoking can increase the metabolism of antipsychotics by inducing CYP1A2 enzymes thus reducing efficacy