2. Prepared by:
Mr. Shubham Gupta
[Work at PAPC]
Student at Alwar Pharmacy College, Alwar
Rajasthan, India

3. INTRODUCTION:
Psychosis is serve psychiatric illness with serious distortion of
thought, behavior, and capacity to recognize reality and of
perception (delusions and hallucination). There is inexplicable
misperception and misevaluation, that patient is unable to meet
the ordinary demands of life.
Psychosis is an abnormal condition of the mind that involves a
“loss of contact with reality”. People experiencing psychosis may
exhibit personality changes and thought disorder. Depending on
its severity, this may be accompanied by unusual or bizarre
behavior, as well as difficulty with social interaction and
impairment in carrying out daily life activities.

4. SITE WHERE PSYCHOSIS OCCURS:

5. SYMPTOMS:
Hallucination (may occur in any of senses and take on almost any
form, which may include simple sensation “such as lights, colors,
tastes, and smell” to experiences such as seeing and interacting
with fully formed animals and people, hearing voices, and having
complex tactile sensations).
Change in behavior: Homicidal, Suicidal, Terroristic,
Impulsive/ Self- Defeating, Alcohol And Drug Abuse, Gang
Participation And Anti Social, Unwanted Pregnancies, Poor
Compliance And Replace Risk, School Difficult, Social And
Vocational Problem, Self- Neglect, Victimization.

6. TYPES OF PSYCHOSIS:
1. Schizophrenia- Characterised by disorders thinking and behavior
(experienced for at least six months).
2. Schizophreniform disorder- Same as schizophrenia but persist
for 1-6 months.
3. Schizoaffective disorder- Prominent mood symptoms occur with
the characteristic symptoms of schizophrenia.
4. Delusional disorder- Involves holding strong, false beliefs
(delusions). Increases day to day.
5. Substances induce psychosis- Drug and alcohol use or
withdrawal can result in psychotic symptoms. Drug-
Methamphetamine.
6. Dementia- Appear with memory disturbances in conditions.
That causes physiological deterioration of the brain, such as head
injury, AIDS, post-encephalitis, brain tumour.

7. 7. Major depressive disorder- Major depression.
8. Postpartum psychosis- Psychosis develops after 6 months of
birth.
9. Delirium- Meningitis, Septicaemia.
10. Brief psychotic episode- Suddenly behavior, stressful life
events, crime scene.
11. Due to general medical conditions- Like- Brain Tumour.
12. Bipolar disorders (manic depression) - Mood disturbances. E.g.
in depression hearing voices.

8. REASONS CAUSE PSYCHOSIS:
There are many of theories are gives such as-
Chemical imbalance theory
Genetic vulnerability theory
Complex disease theory
Stress & vulnerability theory
Other reasons such as disorders- heart, diabetes and asthma can
occur psychosis due to genetic & environmental factor.

9. STUDIES:
Family studies- In children inherit genes that make sensitive to
psychosis. Home environment can occur psychosis in children.
Twin studies- Twins share gene 50% with each other, if, single
gene passed alone can occur psychosis and another fetus have
100% same illness.
Adoption studies- If a child adopted
From family suffering from psychosis in any of related member
then compare of child with his history, tell about psychosis OR
child activities compare with child having psychosis.

11. ANTIPSYCHOTIC DRUGS:
Drugs having a salutary therapeutic effect in psychoses are as:
Classification-
1. Phenothiazines:
Aliphatic side chain:
Chlorpromazine
Triflupromazine
Piperidine side chain:
Thioridazine
Piperazine side chain:
Trifluoperazine
Fluphenazine

12. 2. Butyrophenones:
Haloperidol
Trifluperidol
Penfluridol
3. Thioxanthenes:
Flupenthixol
4. Other hetrocyclics:
Pimozide
Loxapine

13. 5. Atypical antipsychotics:
Clozapine
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Ziprasidone
Amisulpiride
Zotepine

14. MECHANISM OF ACTION:
Except clozapine- like atypical ones, all antipsychotics agents have
potent dopamine D2 receptor blocking action. Phenothiazines and
Thioxanthenes also block D1, D3 and D4 receptors.
Blockade of dopaminergic projection to the
temporal and prefrontal areas related to the “LIMBIC SYSTEM”
and in mesocortical areas is responsible for action of drug.
A ‘DOPAMINE
THEORY OF SCHIZOPHRENIA’ states that DA over activity in limbic
area to be responsible for disorder. Blocking of DA activity produce
antipsychotic effect.
The over activity of DA as well as 5-HT [monoaminergic],
Glutamate [amino-acid] neurotransmitter system may also
affected.

15. PHARMACOLOGICAL ACTIONS:
1. CNS- Neuroleptic selectively inhibit conditioned avoidance
response without blocking the unconditioned response to a
noxious stimulants. This action has shown good co-relation with
the antipsychotic potency of different compounds. In animals, a
state of rigidity and immobility is produced which resembles the
bradykinesia seen clinically.
2. ANS- Neuroleptic have different degree of ᾴ adrenergic
blocking activity.
CPZ= Triflupromazine= Thioridazine> Clozapine> Fluphenazine>
Haloperidol> Trifluperazine> Pimozide Weak dgree may-
Thioridazine> CPZ> Triflupromizine> Trifluperazine= Haloperidol
3. Local Anaesthetic- CPZ is a potent local anaesthetic as procaine.
But not use as well because irritant action.

16. 4. CVS- Drug formed hypotension by a central as well as peripheral
action on sympathetic tone. Action is more increased as drug is
given by parentral root.
5. Skeletal Muscle- Drug has no any effect on muscle fiber or on
muscle transmission.
6. Endocrine- Increase the secretion of prolactin by blocking the
inhibitory action of DA on pituitary lactotropes. This may result-
Galactorrhoea and Gynaecomastia. Reduce the secretion of
Gonadotropin. Blood sugar level is not affected by drugs.

17. PHARMACOKINETIC:
Metabolized by liver mainly by CYP2D6 metabolites. Therapeutic
effect seen at dose 30-200 ng/ml. The value of t1/2 variable but
commonly t1/2 = 18-30 hours. The metabolites are excreted in
urine and bile for months after discounting the drug.

18. DISTINCTIVE FEATURES OF NEUROLEPTICS:
Triflupromazine- More potent than CPZ. Used mainly as antiemetic. It
frequently produces acute muscle dystonias in children, especially when
injected.
Thioridazine- A low potency phenothiazine having central anticholinergic
action. Extrapyramidal side effects is very low. Risk of eye damage limits
long term use.
Trifluoperazine, Fluphenazine- These are high potency phenothiazines.
Minimum autonomic actions. Hypotension, sedation and lowering of
seizure thresholds are not significant. Cause jaundice and
hypersensitivity actions.
Haloperidol- Potent drug, produce few autonomic effects, is less
epileptogenic, dose not cause weight gain, jaundice is rare. Preferred
drug for schizophrenia, metabolised by CYP3A4 and 2D6 both. The t1/2=
24 hours.

19. Trifluperidol- Similar to haloperidol but more potent.
Penfluridol- Long acting drug, for chronic schizophrenia and social
maladusment.
Flupenthixol- This thioxanthine is less sedating than CPZ .
Pimozide- Selective DA agonist with little α adrenergic or
cholinergic blocking activity. Because of long duration of action of
action. But it tends to prolonged myocardial ADP and carries risk
of arrhythmias.
Loxapine- Dibenzoxazepine having CPZ like DA blocking and
antipsychotic activity. The action are quick and short lasting (t1/2=
8hours).

20. ATYPICAL (SECOND GENERATION) ANTIPSYCHOTICS:
The newer antipsychotic that have weak D2 blocking but potent 5-
HT2 antagonistic activity.
Clozapine- First atypical drug has only weak D2 blocking action,
produces few/no extrapyramidal symptoms. It is quite sedating,
moderately potent anticholinergic, induces hypersalivation. H1
blocking properties is present. Clozapine is metabolised by
CYP1A2, CYP2C19 and CYP3A4. T1/2 is 12 hours.
Rispridone- It is in combination with D2 + 5-HT2 receptor blocade.
B.P. can rise if it is used with SSRI. It is more potent than clozapine.
It cause agitation.

21. Olanzapine- Resembles clozapine in blocking multiple monoaminergic
(D2, 5-HT2, α -1 & 2) as well as muscarinic and H1 receptors. It causes
weight gain and higher risk of impairing glucose tolerance. It is
metabolised by CYP1A2 and t1/2= 24-30 hours.
Quetiapine- It blocks 5-HT1α, 5-HT2, D2, Α 1&2 and H1 receptors. D2
blocking activity is very low. Can cause blood glucose level increase and
UTI infection. Also can cause weight gain. Metabolised by- CYP3A4 and
t1/2= 6 hours.
Aripiprazole- It is quite long acting. It can be used in mania and bipolar
disorder illness. Metabolised by- CYP2D6 and t1/2 = 3 days.
Ziprasidone- Combined with D2 + 5-HT2Α/2C + H1 + α1 blocking activity.
Nausea vomiting are common side effect. The t1/2 = 8 hours.
Amisulpiride- It produce extrapyradimal side effects and improve many
negative effects of schizophrenia. Absorbed orally and t1/2 = 12 hours.
Zotepine- It having D2+D1, 5-HT2, α1 blocking activities.weight gain,
hyperglycemia and dyslipidemia are likely with clozapine. Absorption is
faster after meal, first pass metabolism is extensive and t1/2 = 14 hours.

22. ADVERSE EFFECTS:
BASED ON PHARMACOLOGICAL ACTIONS-
CNS- Drowsiness, lethargy, mental, confusion, tolerance sedative effect
and weight gain.
CVS- Postural hypotension, palpitation and inhibition of ejacuation.
Anticholinergic- Dry mouth, burring of vision, constipation, UIT in males.
Endocrine- Hyperprolactinemia, lower amenrrhoea, infertility,
galactorrhoea.
Metabolic effect- Clozapine having risk of precipitating diabetes.
Accentuation of insulin resistance.
Extrapyramidal disturbance- (a) Parkinsonism (b) Acute muscular
dystonias (c) Akathisia (d) Malignant neuroleptic syndrome (e) Tardive
dyskinesia
Miscellaneous- Weight gain, sugar and lipids may rise. Blue pigments of
exposed skin, corneal and lenticular opacities: retinal degeneration.

23. HYPERSENSITIVITY REACTIONS-
Cholestatic jaundice
Skin rashes
Agranulocytosis
Myocardiac

24. INTERACTIONS:
Alcohol, opioids, hypnotics must be avoided can cause overdose.
Block the action of levadopa and direct DA agonist in
parkinsonism.
Clonidine and methyldopa action reduces.
Barbiturates, anticonvulsants can reduce the level of neuroleptic
in blood.

25. USES:
Psychoses
Anxiety
As antiemetic
To potentiate hypnotic
Intractable hiccough
Tetanus
Alcoholic hallucinosis

26. DRUG PRESENT IN MARKET :
HALOPERIDOL INJECTION
It (brand name- Ksychosis) is a sterile solution of haloperidol in
lactic acid diluted with water for injection. It contains not less
than 90.0% and not more than 110%.
Molecular Formula– C21H23CIFNO2
Dose- 5mg

27. PIMOZOIDE
Molecular Formula- C28H29F2N3O
IUPAC Name- 1-[1-[4, 4- bis (4-
Flurophenyl) butyl] piperidin- 4- yl]- 1,3 – dihydro- 24- benzimidazol- 2-
one. It contains not less than 99% and not more than 101.0%.
Dose- 10mg

28. REFERENCES:
www.goggle.com/images/psychosis
Vanheule Stijn, “The Subject Of Psychosis: A Lacanian
Perspective”, Pagrave Macmillan Publications, Belgium, 2011, 1-
27.
m.health24.com/health24/Mental-Health/Brain/NNeurological-
conditions/12-types-of-psychosis-20130711
www.earlypsychosis.ca
Tripathi K.D. “Essential of MEDICAL PHARMACOLOGY”. Jaypee
Brothers Medical Publishers (P) LTD. Seventh edition-2013. 435 -
447.
INDIAN PHARMACOPIEA 2014. Volume- II- 1884 and Volume- III-
2494.