Antipsychotic Drugs

Schizophrenia
Split Mind

Describe the fragmented thinking of people

with the disorder

Is a serious brain illness which are characterized by severe problems with a

person’s
- thoughts,
- feelings,
- behavior,
- and use of words and language.
 Neuroleptic drugs

Typical Atypical
)classic drug( )newer agent(

Phenothiazines Thioxanthenes Butyrophenones Heterocyclic

class class class structure

Clozapine
Chlorpromazine
Thioridazine Thiothixene Haloperidol Olanzapine
Fluphenazine Quetiapine
Risperidone
Ziprasidone
What do all antipsychotic in
? have common

They reduce dopaminergic neurotransmission

Dopaminergic pathway in CNS
We will discuss only two pathways

❖ Mesolimbic pathway

❖ Mesocortical pathway
 Mesocortical pathway
Mesolimbic pathway
Diminished activity implicated in :
Excess activity implicated in: - Negative symptoms of
- Positive symptom schizophrenia schizophrenia e.g.
e.g. Restrictions in
- hallucinations - emotion,
- delusions - thought,
- speech,
- pleasure and attention.
What do all antipsychotic in
? have common

They reduce dopaminergic neurotransmission

Typical is D2 antagonist Atypical is serotonin-dopamine antagonist

high affinity to D2 Low affinity to D2 high affinity to 5-HT2A

Typical Atypical Atypical

- - -
D2 receptor D2 receptor HT2A receptor-5

Binding to D2 receptor Binding to D2 receptor

(tight) (loose)

Atypical dissociate rapidly from D2 receptor

Atypical dissociate rapidly from D2 receptor

Dopamine

Atypical

ing
-
d
bin D2 receptor
o se
Lo
 High occupancy for D2 High EPS risk

Antipsychotic efficacy

78%
D2 occupancy

60% 75%

EPS

Which has more EPS risk typical or atypical neuroleptic? And Why?
 Summary

Atypical neuroleptic Typical neuroleptic

• 5-HT2A antagonist
• D2 antagonist D2 antagonist MOA
• Rapid D2 Dissociate
Antagonism of H1,
Antagonism of H1, M1,
M1, alpha-1
5-HT2c, alpha 1 Other effect
receptor , among
receptor , among other
other
 Why to give Antipsychotics?
• Treatment of 1st episode psychosis:
– 80 % better first antipsychotic
– 5% better with different antipsychotic
– 15% treatment resistant
• ¾ of these better on clozapine
• Recurrence common
• Important to prevent exacerbations given major life
tasks of young adulthood
 Side Effects of Antipsychotic Medications

• Extrapyramidal Symptoms (EPS)

• Neuroleptic Malignant Syndrome (NMS)
• Sedation
• Weight gain
• Metabolic syndrome
• Endocrinological
• Haematological
• Seizures
• Cardiovascular
 Side Effects of Antipsychotic Medications
Neuroleptic Malignant Syndrome (NMS)
• Hyperthermia, muscular rigidity, tachycardia, hyper or
hypotension, autonomic instability, rhabdomyolysis,
confusion
• Increased creatine phosphokinase and leukocytes
• More common in first weeks of treatment
• Increased risk with higher doses, multiple drugs, male, and
young
• Can lead to loss of consciousness and death
• Misdiagnosis: catatonia, EPS, serotonin syndrome,
infectious diseases
 Side Effects of Antipsychotic Medications

• Weight gain is most common long term adverse effect of

atypical antipsychotics
• 5% weight gain in 1st 3 months or 0.5 increase in BMI .
• Dyslipidemia, metabolic syndrome, diabetes mellitus,
hypertension, polycystic ovary.
• Amenorrhea, menstrual cycle disorders, breast enlargement,
galactorrhea, sexual effects
– children and adolescents>adults
– esp post-pubertal girls
Cardiovascular: Orthostatic hypotension, increased heart
rate, dizziness