SCHIZOPHRENIA AND ITS

PHARMACOLOGICAL TREATMENT

• Nature of psychosis, schizophrenia

• Etiology and pathogenesis of schizophrenia

• Pharmacodynamic and toxicodynamics of

antipsychotic
SCHIZOPHRENIA – CLINICAL FEATURES

• Positive symptoms – ▪ Delusion and impaired

thinking
▪ Hallucinations
▪ Confusion and impaired
judgement
▪ Anxiety and emotional
dyscontrol
SCHIZOPHRENIA – CLINICAL FEATURES

• Negative symptoms – ▪ Flat blunted affect

▪ Poverty of thought
▪ Anhedonia (no joy)
▪ Psychomotor retardation
▪ Blunting of perception
EVIDENCE FAVORING DOPAMINE HYPOTHESIS

• Dopamine Enhancers – schizophrenic episodes

• Dopamine Depressors – schizophrenic

symptoms

• Dopamine receptors – schizophrenics

• HVA – schizophrenic treatment

 DOPAMINERGIC PATHWAYS
Dopamine Tract Origin Innervation Function

• Nigrostriatal • Substania Nigra • Caudate Nucleus • EPS

• Putamen • Movement

• Mesolimbic • Midbrain ventral • Limbic areas • Arousal

Tegmentum • Memory
• Motivational
behavior

• Mesocortical • Midbrain ventral • Frontal and • Cognition

Tegmentum pre-frontal lobe • Communication
cortex • Social function
• response +
stress

• Tubero-in • Arcuate nucleus • Midian • Prolactin

fundibular eminence release
DOPAMINE RECEPTORS – CLASSIFICATION
• D1 receptor - ▪ Chromosome 5, ↑ cAMP
▪ Putamen, Nucleus accumbens,
Olfactory tubercle
• D5 ▪ Chromosome 5, ↑ cAMP
▪ Hippocampus,Hypothalamus

• D2 receptor - ▪ Chromosome 11, ↓ cAMP

• D3 receptor - ▪ Chromosome 11, ↓ cAMP
▪ Frontal cortex, medulla,
midbrain
• D4
ANTIPSYCHOTICS – CLASSIFICATION

• Conventional – ▪ chlorpromazine
▪ Fluphenazine
▪ thioridazine
▪ Haloperidol
▪ Thiothixene

• Atypical – ▪ Clozapine
▪ Risperidone
▪ Olanzepine
▪ Ziprasidone
TYPICAL Vs ATYPICAL ANTIPSYCHOTICS

• Receptor profile

• Extrapyramidal symptoms

• Efficacy – ▪ Resistant patients

▪ Negative symptoms
 α1
H1

D2

Conventional
 HT2A-5
SDA D2

HT, DA Antagonists-5
RECEPTOR BINDING – POTENCY

• Chlorpromazine – α1 = 5-HT2 > D2 > D1

• Haloperidol – D2 > D1 = D4 > α1 > 5-HT2

• Clozapine – D4 = α1 > 5-HT2 > D2 = D1

• Risperidone – D2 = 5-HT2 > D1 = α1

• Olanzepine – 5-HT2 > D1 = D2 = α1

ANTIPSYCHOTICS – THERAPEUTIC USES
• Schizophrenia
• Schizoaffective disorders
• Mania
• Alzheimer disease
• Emesis – Prochlorperazine
• Sedation – Promethazine
• Neuroleptanesthesia – Droperidol + Fentanyl
• Tourette’s Syndrome
ANTIPSYCHOTICS – ANS SIDE EFFECTS

• Loss of accomodation,
Dry mouth,
Urinary retention,
Constipation

• Orthostatic hypotension,
Failure of ejaculation
ANTIPSYCHOTICS – ENDOCRINE SIDE EFFECTS

• Amenorrhea
Female
• Galactorrhea
• Gynecomastia
Male
• Impotence
• Infertility
• ↓ GH
• Poikilothermic
ANTIPSYCHOTICS – CNS SIDE EFFECTS

• Extrapyramidal Symptoms
▪ Parkinson’s syndrome
▪ Akathesia, Dystonia
▪ Tardive dyskinesia, Choreoathetosis

• Sedation

• Seizure threshold – Clozapine

 ANTIPSYCHOTICS – PHARMACODYNAMIC /
TOXICODYNAMICS

Drug Clinical Extrapyramidal sedative Hypotensive

(conventional) Potency Toxicity Action Action
Chlorpromazine Low Medium High High
Fluphenazine High High Low Very low
Thiothixene High Medium Medium Medium
Haloperidol High Very high Low Very low
ANTIPSYCHOTICS – PHARMACODYNAMIC /
TOXICODYNAMICS

Drug Clinical Extrapyramidal sedative Hypotensive

(atypical) Potency Toxicity Action Action

Clozapine Medium Very low Low Medium

Risperidone High Low Low Low
Olanzapine High Very low Medium Very low
Ziprasidone Medium Very low Low Very low
ANTIPSYCHOTICS – UNIQUE FEATURE

• Chlorpromazine – inexpensive, many side

effects
• Thioridazine – slight , cardiotoxicity
extrapyramidal
syndrome
• Fluphenazine – low autonomic , ↑ tardive
side effects dyskinesia
• Thiothixene – decreased tardive dyskinesia
• Haloperidol – severe extrapyramidal syndrome
ANTIPSYCHOTICS – UNIQUE FEATURE

• Clozapine – little or no , agranulocytocis

extrapyramidal
syndrome

• Risperidone – Broad efficacy , EPS & Hypotension

no EPS (high doses)

• Olanzepine – Effective against , weight gain

negative as well
as positive symptoms,
no EPS