Schizophrenia A chronic mental disorder involving a breakdown in the relation between thought, emotion, and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. Antipsychotic Agents Antipsychotic drugs are able to reduce psychotic symptoms in a wide variety of conditions, including schizophrenia, bipolar disorder, psychotic depression and drug induced psychosis. They have also been termed neuroleptics, because they suppress motor activity and emotionalityClinical Efficacy of Antipsychotic Drugs Antipsychotic drugs are effective in controlling symptoms of acute schizophrenia, when large doses may be needed. Long-term antipsychotic treatment is often effective in preventing recurrence of schizophrenic attacks, and is a major factor in allowing schizophrenic patients to lead normal lives. Classification of Antipsychotic Drugs Typical antipsychotics Phenothiazines (Chlorpromazine, Perphenazine, Fluphenazine, Thioridazine) Thioxanthenes (Flupenthixol, Clopenthixol) Butyrophenones (Haloperidol, Droperidol) Atypical antipsychotics (Clozapine, Risperidone, Sulpiride, Olanzapine, Aripiprazole) Depot preparations are often used for maintenance therapy. Approximately 40% of chronic schizophrenic patients are poorly controlled by antipsychotic drugs; clozapine may be effective in some of these ‘antipsychotic-resistant’ cases.

1. PHARMACOLOGICAL BASIS AND
SIDE EFFECTS OF DRUGS USED IN
SCHIZOPHRENIA

2. ◦ Schizophrenia A chronic mental disorder involving a breakdown in the relation between
thought, emotion, and behaviour, leading to faulty perception, inappropriate actions and
feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a
sense of mental fragmentation. The disorder is characterized by a divorcement from reality in
the mind of the person (psychosis).

3. 1.Etiology DOPAMENERGIC SYSTEM:
2.There are four major pathways for the dopaminergic system in brain :
3.I. The Nigro-Striatal Pathway.
4.II. The Mesolimbic Pathway.
5. III. The Mesocortical Pathway.
6. IV. The Tuberoinfundibular Pathway.
• The Dopamine Hypothesis - Schizophrenia results from excess activity of dopamine neurotransmission in
Mesolimbic and Mesocortical Pathways because: All antipsychotic drugs block dopamine receptors.
Higher levels of dopamine receptors measured in brains of schizophrenics by PET. Stimulant drugs which
act through dopamine can produce schizophrenic-like behaviours (eg.amphetamines).
1.SYMPTOMS POSITIVE SYMPTOMS: Delusions Hallucinations Combativeness Insomnia
2.SYMPTOMS NEGATIVE SYMPTOMS: Affective Flattening (blunt) Alogia Avolition Amotivation
Apathy Asocial Behaviour
3.SYMPTOMS DISORGANIZED SYMPTOMS: Disorganized thought, speech, behaviour. Poor Attention.

4. • Antipsychotic Agents Antipsychotic drugs are able to reduce psychotic symptoms in a wide variety of
conditions, including schizophrenia, bipolar disorder, psychotic depression and drug induced psychosis. They
have also been termed neuroleptics, because they suppress motor activity and emotionality
• Classification of Antipsychotic Drugs Typical antipsychotics Phenothiazines (Chlorpromazine, Perphenazine,
Fluphenazine, Thioridazine) Thioxanthenes (Flupenthixol, Clopenthixol) Butyrophenones (Haloperidol,
Droperidol)
• Atypical antipsychotics (Clozapine, Risperidone, Sulpiride, Olanzapine, Aripiprazole)
• Distinction between ‘typical’ and ‘atypical’ groups is not clearly defined, but rests on: Incidence of
extrapyramidal side-effects (less in ‘atypical’ group) Efficacy in treatment-resistant group of patients
Efficacy against negative symptoms.

5. 1.Drug Targets Dopamine receptors: D1, D2, D3, D4, D5 Serotonin receptors: 5-HT-1A, 2A, 3, 6, 7
Norepinephrine: Alpha-1 & Alpha-2 Muscarinic Acetylcholine: M1 & M4 Dopamine, Norepinephrine &
Serotonin transporters NMDA-glutamate receptor
• Typical Antipsychotics
• MECHANISM OF ACTION There are many type of DA-receptors.
• The antipsychotic drugs probably owe their therapeutic effects mainly to blockade of D2 receptors.
• The main groups, phenothiazines, thioxanthines and butyrophenones, show preference for D2 over D1
receptors; whereas clozapine is relatively non-selective between D1 and D2, but has high affinity for D4.
• Therapeutic Uses Treatment of psychotic disorders: schizophrenia, mania, paranoid states.
• Treatment of nausea and vomiting of certain causes.
• Anaesthesia in hypothermia and artificial hibernation (used with pethidine and promethazine).

6. • Adverse Effects Extrapyramidal motor disturbances:
• 1.Parkinson-like symptoms
• 2.Neuroleptic Malignant Syndrome
• 3.Tardive dyskinesia (involuntary movements of face, tongue and limbs , appearing after months or years
of antipsychotic treatment).
• 4.Acute dystonias.
• 5. Seizures ,Cardiac toxicity ,Produce hypotension (primarily postural) by α-adrenergic blocked.
• 2.Endocrine effects: Increase prolactin : which may result in gynecomastia.
• They reduce gonadotropin secretion but infertility occur only occasionally.
• ACTH release in response to stress is diminish. Decreased release of ADH may result in an increase in
urine volume.
• Urticarial skin reactions are common but usually mild. Excessive sensitivity to ultraviolet light may also
occur.
• Other side-effects (dry mouth, constipation, blurred vision, hypotension, etc.) are due to block of other
receptors, particularly α– adrenoceptors and muscarinic ACh receptors.
• Contact dermatitis, blood dyscrasias, obstructive jaundice sometimes occurs with phenothiazines.
• Limitations Of Conventional/Typical Antipsychotics Approximately one-third of patients with
schizophrenia fail to respond Limited efficacy against Negative symptoms High proportion of patients
relapse Side effects and compliance issues Atypical/New generation Antipsychotics are preffered for
the treatment of various psychotic disorders.

7. • Atypical Antipsychotics
• Clozapine Effective in treating some patients with psychosis unresponsive to standard neuroleptic drug.
Blocks D4 receptor and have low affinity for D1 and D2 dopamine receptors.
• Relative high selectivity for D4 and 5-HT2 receptors
• Lacks extrapyramidal side effects.
• Must monitor the granulocyte counts due to higher incidence of agranulocytosis and other blood dyscrasias.
• Risperidone Combination of D2 + 5-HT2 receptor blockade.
• In addition it has high affinity for α1, α2 and H1 receptors; blockade of these may contribute to efficacy as
well as side effects like postural hypotension.
• Risperidone is more potent D2 blocker than clozapine; extrapyramidal side effects are less. Prolactin levels
rise during risperidone therapy, but it is less epileptogenic than typical agents.
• Caution: increased risk of stroke in the elderly.

8. • Olanzapine Broader spectrum of efficacy covering schizo-affective disorders.
• Resembles clozapine in blocking multiple monoaminergic (D2, 5- HT2, α1, α2) as well as muscarinic and
H1 receptors. Both positive and negative symptoms of schizophrenia appear to be benefited.
• Monotherapy with olanzapine may be as effective as a combination of lithium/valproate +
benzodiazepines. Incidence of stroke may be increased in the elderly.
• Agranulocytosis has not been reported with olanzapine.
• Therapeutic uses Treatment of schizophrenia Prevention of severe nausea and vomiting Other uses:
Treatment of mania, organic brain syndromes.
• Adverse events Parkinson-like symptoms of bradykinesia, rigidity, and tremor usually occur within weeks
to months of initiating treatment.
• Tardive dyskinesia
• Hypersensitivity reaction: Cholestatic jaundice, myocarditis, agranulocytosis.
• Miscellaneous: Weight gain (not with haloperidol), blood sugar and lipids may tend to rise. Risk of
worsening of diabetes and blue pigmentation on skin and retinal degeneration may increases.
• Second generation antipsychotics have weak D2 blocking but potent 5-HT2 antagonistic activity.
Extrapyramidal side effects are minimal, and they may improve the impaired cognitive function in
psychotics

9. 1.Clinical Efficacy of Antipsychotic Drugs
Antipsychotic drugs are effective in controlling symptoms of acute schizophrenia, when large doses may be
needed.
Long-term antipsychotic treatment is often effective in preventing recurrence of schizophrenic attacks, and is a
major factor in allowing schizophrenic patients to lead normal lives.
Depot preparations are often used for maintenance therapy.
Approximately 40% of chronic schizophrenic patients are poorly controlled by antipsychotic drugs; clozapine
may be effective in some of these ‘antipsychotic-resistant’ cases.

10. THANK YOU