The document discusses psychosis, detailing its definition, classification, and the pharmacological profiles of typical and atypical antipsychotics. It emphasizes the roles of dopamine in schizophrenia, the side effects of antipsychotics such as extrapyramidal symptoms, metabolic effects, and the importance of careful dosing, especially in the elderly and during pregnancy. The document concludes by highlighting the need for personalized treatment and ongoing monitoring of adverse effects in the management of psychotic disorders.

1. Name:- Bhadani Smit Ramjibhai
Roll No.:- 17BPH095
Program:- B.Pharm
Sem.:- IV
Subject:- Pharmacology

2. 1. Definition :- Psychosis:-
2. Dopamine Hypothesis:-
3. Classification of Antipsychotics:-
4. Pharmacological Profile of Each Category:-
5. Clinical Usage:-

3. • A Symptom Of Mental illnesses.
• Characterised by Distorted or Non-Existent sense of Reality:-
- Hallucination.
- Delusions.
- Disorganised Speech.
- Disorganised or Agitated Behaviour.

4.  Mood Disorder (Major Depression or Mania With Psychotic Features).
 Substance Induced Psychosis.
 Dementia with Psychotic features.
 Delirium with Psychotic features.
 Schizophrenia.

5.  Put Forward by Arvid Carlsson.
 “The Clinical features Of Schizophrenia (Sometimes extended to
psychosis in General) is related to over activity of dopaminergic
function within the brain.”

6.  Typical/First Generation Antipsychotics:-
I. Phenothiazine Ex. :- Chlorpromazine
II. Butyraphenones Ex. :- Haloperidol
III. Thioxanthenes Ex. :-Flupentixol
 Atypical/Second Generation Antipsychotics:-
Ex. :- Clozapine , Risperidone , Olanzapine , Quetiapine , Aripiprazole.

7.  Mode Of Action :-
- Predominantly Act as antagonists at brain dopamine D2 receptors.
- Also Blocks
Muscarinic acetylcholine receptors
Antihistamine receptors
α adrenoceptors

9.  High rapid oral absorption.
 Highly lipophilic with high apparent volumes of distribution.
 Undergo extensive phase 1 metabolism by CYPs and
subsequent phase 2 conjugations.
 Excreted in the urine and to some extent in the bile.

10.  Extrapyramidal Motor Effects:-
 Due to dopamine D2 receptor blockade in the nigrostriatal
pathway (except tardive dyskinesia).
A. Acute dystonia
B. Akathisia
C. Parkinsonism
D. Tardive Dyskinesia

11.  Spasm of muscles of tongue, face, neck, back.
 High risk in- first few weeks, young, antipsychotic naive.

12.  Develops after months or years.
 In 20-40% of patients treated with first-
generation antipsychotic drugs.
 Often irreversible, often gets worse when
antipsychotic therapy is stopped.
 Elderly at 5-fold greater risk.

13.  Endocrine effects:-
Due to blockage of dopamine D2 receptors in tuberohypophyseal
pathway     Increased prolactin.:-
 Gynaecomastia.
 Agalactorrhea.
 amenorrhea in women.
 sexual dysfunction or infertility in men.

14.  Central antagonism of H1 receptors:-
a) Sedation.
b) Weight gain via appetite stimulation.
 Muscarinic antagonism -anticholinergic effects.
 1 Adrenergic antagonism - orthostatic hypotension.

15.  Adverse Cardiac Effects:-
Blockage of cardiac K+ channels
Prolong QT in ECG
Ventricular arrhythmia & sudden cardiac death.

16.  Increased risk for cerebrovascular events and all- cause
mortality in dementia patients.
 Lowers seizure threshold.
 Increased triglycerides.
 Hyperglycaemia.

17.  A fatal idiosyncratic ADR of antipsychotics.
 Characterized by,
1. Mental status changes.
2. Muscle rigidity.
3. Hyperthermia.
4. Autonomic dysfunction.

18. A. Typical/First Generation Antipsychotics:-
A. Phenothiazine e.g. chlorpromazine.
B. Butyraphenones e.g. haloperidol.
C. Thioxanthenes e.g. flupentixol.
B. Atypical/Second Generation Antipsychotics:-
e.g. Clozapine, Risperidone, Olanzapine, Quetiapine,
Aripiprazole.

19.  Mode of Action:-
Predominant antagonism of 5-HT2A receptors with a lesser
degree antagonism of dopamine D2 receptors.
 Has efficacy against negative symptoms esp. Clozapine.

21.  Extrapyramidal Motor Effects:-
 Considerably less compared to typical antipsychotics.
 Blockage of 5-HT2A receptors increase dopamine in striatum preventing
extrapyramidal effects.
 Cardiotoxicity:-
 Less associated with QT prolongation at therapeutic doses.

22.  High risk of new onset diabetes and diabetes ketoacidosis esp.
with clozapine and olanzapine.
 Agranulocytosis common with clozapine esp. in first 6 months
 regular FBC monitoring essential.

26.  Various disorders treated with antipsychotics in the elderly –
psychosis, bipolar affective disorder, delirium & dementia.
 Use extreme caution because of side effect profile.
 ‘Start low & go slow’ (Malone et al 2007) & titrate over longer periods
of time to reach the required dose.
 Avoid polypharmacy wherever possible.

27.  Avoid antipsychotics if possible.
 Use the lowest effective dose.
 Neonatal adverse effects observed include generalized hypertonicity
and dystonic reactions.

28.  The safety of atypical agents is yet to be established but preliminary reports
there to be no deleterious effects to the fetus.
 Isolated cases of congenital abnormalities with the use of Clozapine.
 No increased risk has emerged with the use of Olanzapine.
 The conventional agents are generally preferred.
 Supervised dose reduction and cessation 7-10 days prior to delivery should
be considered.

29.  Remember that antidepressant medication is only part of the
treatment for antenatal depression and anxiety. Also consider:-
 Psychological therapies.
 Exclude organic illness as a cause of mental health symptoms.
 Address any alcohol and/or illicit substance abuse.
 Assess the social situation.
 General lifestyle measures: adequate rest/sleep, balanced diet, exercise.
 The decision to treat should be made on an individual case basis.

30.  Conventional and atypical antipsychotics are used as the foundation for pharmacological
management of schizophrenia and related psychosis.
 All have equal efficacy, exception Clozapine.
 Atypical generally better tolerated & have less EPSE.
 Atypical first line treatment.
 Start lowest effective possible dose & titrate upwards.
 Ongoing monitoring & management of adverse effects.
 Caution numerous drug interaction & potential for neuroleptic malignant syndrome.