General information about Psychosis sign and symptoms Antipsychotic Drugs

1. VANDANA SHARMA
M.PHARM
INDIPENDENT PHARMA TUTOR
(8 YEARS)
OM NAMAH SHIVAYA SHREE KRISHAN SHARNAM MAMAH
STUDY MATERIAL FOR PHARMACY STUDENTS

2. Psychotic Disorder
 Psychotic disorder refer to a group of conditions wherein individuals deviate
from or lose touch with reality or, in the sense that they may see or hear things
that aren’t there or harbor rigid beliefs that contradict reality. Such individuals
also usually do not feel as though they suffer from any psychiatric condition.
 Over activity of dopamine/Increase dopamine level in Mesolimbic area of
brain= Psychosis and Schizophrenia.
Types of Psychosis
Schizophrenia:
 It is a psychotic disorder that affects more than 21 million people worldwide.
 This disorder is a long-term involving behavioural changes, hallucinations and
delusions, which usually lasts for 6 months or more.
Brief psychotic disorder:
 This type of psychosis lasts for a short period of time, with symptoms lasting
for less than a month.

3. Type of Psychosis
Delusional disorder:
 A person suffering from this type of disorder believes false things based on self-
made assumptions despite the clear evidence to the contrary.
Schizoaffective disorder:
 This disorder is a mixture of several mental health conditions, wherein the
person begins to hallucinate and becomes delusional.
 Symptoms like mania and depression may also be seen in a few cases.
Schizophrenic form disorder:
 A person suffering from this disorder shows symptoms of schizophrenia but
unlike schizophrenia, the symptoms last for one month or lesser than six
months.
Shared psychotic disorder:
 This disorder is caused when a person becomes delusional after being in a
relationship with or being in close proximity with a person who is delusional.

4. Causes of Psychosis
 Genetic factors:
 In most of the cases, psychotic disorders run in families. Genes can play a
predisposing role, making some people more susceptible to such disorders.
There’s a 10% chance that a child having a parent suffering from psychotic
disorder will suffer from the same illness, while the risk is even greater in
identical twins.
 Environmental factors:
 Factors like stress, drug abuse, drinking problem, domestic violence, abusive
childhoods and major life events can also trigger psychosis.
 Psychosocial factors:
 Those already suffering from other mental health issues
like anxiety disorder, depression or bipolar disorder have an increased risk of
suffering from psychosis.
The experience of hearing voices (hallucinations).
Ideas that distress you and don't seem to be based in reality (delusions).
Note

5. Sign and Symptoms of Psychosis
GENERALIZE SYMPTOM
 Delusions
 Hallucinations
 Disorganized thought and speech
 Behavioral disturbances
 Disturbed motor movements
 loss of motivation,
 loss of interest in activities and
social withdrawal.
Behavioural changes in people suffering
from psychotic disorder-
 Hallucinations and delusional behavior
at times lead to a heightened sense of
fear in some patients.
 In some cases, the condition affects
their thoughts to such an extent that
they are unable to speak or express their
thoughts in the right manner.
 They may withdraw from their friends and family, preferring to stay alone.
 Their personal hygiene may suffer as well.
 Such disorders tend to affect both one’s social life as well as one’s professional
functioning.
 Individuals suffering from mental illness are additionally straddled with stigma
and discrimination, thus making recovery that much more difficult.

6. Antipsychotic/Neuroleptic/Major tranquilizer
 Antipsychotics are a class of psychiatric medication primarily used to
manage psychosis (including delusions, hallucinations, paranoia or disordered
thought), principally in schizophrenia and bipolar disorder. They are
increasingly being used in the management of non-psychotic disorders.
Antipsychotics are usually effective in relieving symptoms of psychosis.
However, their long term use is associated with significant side effects such
as involuntary movement disorders and metabolic syndrome.
First-generation antipsychotics,
known as typical antipsychotics
Second-generation drugs, known
as atypical antipsychotics
Antipsychotic

7. NOTE:
Eg: of first atypical antipsychotic, clozapine
 The terms neuroleptic and major tranquilizer were used
for older antipsychotic drugs but are gradually dropping
from use.
 Neuroleptic, which originates from the Greek
word neuron ("nerve") and lepsis ("seizure" or "fit)
 Both generations of medication tend to block receptors
in the brain's dopamine pathways, but atypicals tend to
act on serotonin receptors as well.

8. First-generation antipsychotics or typical
antipsychotics
 Typical antipsychotics (sometimes referred to as first generation
antipsychotics, conventional antipsychotics, classical
neuroleptics, traditional antipsychotics, or major tranquilizers) are a
class of antipsychotic drugs and used to treat psychosis (in
particular, schizophrenia).
 Typical antipsychotics may also be used for the treatment of acute mania,
agitation, and other conditions.
 The first typical antipsychotics to enter clinical use were the phenothiazines.
 Second-generation antipsychotics are known as atypical antipsychotics.
Use of Typical Antipsychotics
 Only control Positive Symptom of Psychosis like- Hallucination,
Delusion

9.  Typical antipsychotic drugs block receptors in the brain's dopamine pathways
in mesolimbic area
 Mostly Typical antipsychoyic drugs are D2 Receptor blocker.
MOA of Typical Antipsychotics
Dopamine Release from vesicle and act on
Dopaminergic receptors

11. Common Side Effects of Typical Antipsychotics
1. Extra pyramidal disorder (EPD)-
 It’s a motor nerve defect
 Side effects comes when dopamine level decrease below normal level (Over
activity of acetylecholine --- Contraction in motor nerve).
Types of EPD
 Parkinsonism
 Ekthesia
 Acute muscle dystopia-
 This side effect most common when patient on Triflupromazine therapy.
 Spasm in joint and neck joint. Most common in children.
 Drug of choice for acute muscle dystopian are Trihexyphenidyl (Centrally acting
Anticholinergic) and Promethazine (H1 Antihistaminic)
 Malignent neuroleptic Syndrome
 Spasm in muscle, fever etc
 Drug of Choice is Dentroline (Skelatal muscle relaxant)
 Tardive dyskinasis-
 Repeatative movement or action
 Its is most commom side effect come even after discontineoution of drug

12. 2. Alfa adrinergic inhibition-
 Cause postural hypotension
3. Anti cholinergic activity-
 Costipation
 Urinary retaintion (Contraindicated in BPH)
 Dryness of eye, mouth, skin etc, Tachycardia
4. Increase prolectin secretion (Hyperprolectemia) due to
decrease concentration of Dopamine
 Increased prolectin secretion cause increased in milk secretion
(Gynecomestia- Enlargement of Breast)
Note- All mentioned four side effects are most common with Typical
Antipsychotics

13. Classification of Typical Antipsychotics
Use
 At low dose antiemetic because block D2 receptors of chemo-
trigger zone
 At high dose use as Antipsychotic
10H-phenothiazine
1. Phenothazine dvt (trycyclic antipsychotics)

14. o Promazine
o Chlorpromazine
o Use-
 As Antipsychotic
 As Antihistaminics
 Used to control nausea, vommiting and hiccough
o Triflupromazine
 S/E- Acute musscle dystonia most common in Children [Drug of Choice-
Trihexypenidyl( Anti cholinergic), Promethazine (Antihistaminic)]
Sub class of Phenothazine Dvt
A. Di methyl amino propyl side chain containing Phenothazines
 Also known as Alphabetic side chain containing Phenothazines
 These are also have additional antihistaminic activity
Eg: promazine, Chlorpromazine, Triflupromazine

15. Triflupromazine IUPAC Name-
N,N-dimethyl-3-[2-(trifluoromethyl)-10H-
phenothiazin-10-yl]propan-1-amine
Promazine IUPAC Name-
N,N-dimethyl-3-(10H-phenothiazin-
10-yl)-propan-1-amine
Chlor Promazine IUPAC Name-
3-(2-chloro-10H-phenothiazin-10-yl)-
N,N-dimethyl-propan-1-amine

16. B. Ethyl piperidine side chain containing Phenothaizine
 Advantage- Least EPD side effect-inhibit Acetylcholine due
to their potent anti cholinergic activity or
Anti muscarinic activity
 Disadvantage:
 Due to their potent Anti cholinergic activity s/e comes eg:
urinary retention, Dryness of eye, skin, mouth etc, constipation
 This sub class drugs are contraindicated in Binine prostate hypertrophy (BPH)
in male old age patient specially
 Eg: Thioridazine, Mesoridazine
 Mesoridazine is a metabolite of Thioridazine
 Side effect-
 of Thioridazine is white spot in eye (Pigmentary Retinopathy) at high dose but
mesoridazine have no such type of Side effect

17. Thioridazine IUPAC Name-
10-{2-[(RS)-1-Methylpiperidin-2-yl]ethyl}-
2-methylsulfanylphenothiazine
Mesoridazine IUPAC Name-
10-[2-(1-methylpiperidin-2-yl)ethyl]-2-
methylsulfinylphenothiazine

18. C. Propyl piperazine side chain containing phenothazine
 These are most potent potent phenothazines that why they have more EPD side
effects
 Eg: Prochlorperazine, Trifluperazine, Perphenazine,
Fluphenazine
 Prochlorperazine-
 Has high prevalence of EPD that why it is used as antiemetic not used as
antipsychotic
 Less Sedative
 Perphenazine –
 An effective Antipsychotic as well as Antiemetic
 Fluphenazine-
 Eg of most potent Antipsychotic Phenothazine

19. Prochlorperazine IUPAC Name-
2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl]-
10H-phenothiazine
Perphenazine IUPAC Name-
2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)
propyl]piperazin-1-yl]ethanol
Fluphenazine IUPAC Name-
2-[4-[3-[2-(trifluoromethyl)-10H-
phenothiazin-10-yl]propyl]piperazin-1-
yl]ethanol

20. 2. 4- floro butyrophenone dvt
 Most potent class of antipsychotic drugs
 Drug of choice of acute schizophrenia.
 Side effect- Most EPD side effect specially
Tar dative dyskinesia
4 fluoro butyrophenoneEg:
 Haloperidol
 Droperidol
 Risperidone
 Trifluperidol
Haloperidol

21.  Most potent 4 fluorobutyrophenone dvt in antipsychotic
drugs
 Drug of choice of
 Schizophrenia
 Psychosis associated with brain damage
 Frequently used to terminate acute mania
 Used in therapy for Gilles de le Tourette’s Syndrome
 Huntington’s syndrome
Haloperidol

22.  Droperidol [combination
with fentanyl] is
an antidopaminergic drug used
as
 an antiemetic and
 antipsychotic.
 Droperidol is also often used
for
 neuroleptanalgesic anesthes
ia and
 sedation in intensive-care
treatment.
Droperidol
Droperidol IUPAC Name-
3-[1-[4-(4-fluorophenyl)-4-oxobutyl]-3,6-
dihydro-2H-pyridin-4-yl]-1H-
benzimidazol-2-one

23. 3. Diphenyl butyl piperidine dvt
 Longest acting class of Antipsychotic
Eg:
 Pimozide
 Penfluridol
 Penfluridol-
 Longest acting Di phenyl butyl piperidine dvt
4. 3-beta 20-alfa yohimbine dvt
E.g.: Reserpine
 It is an as e.g. of Rauwolfia
(R. Serpentine) Alkaloid
 S/E- Suicidal thoughts come
Reserpine IUPAC Name-
methyl (3β,16β,17α,18β,20α)-11,17-dimethoxy-18-
[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-
carboxylate

24. Eg: Loxapine
 Loxapine is a typical
antipsychotic medication, used primarily in
the treatment of schizophrenia.
 The drug is a member of
the dibenzoxazepine class and structurally
related to clozapine (which belongs to the
chemically akin class of dibenzodiazepines).
 Several researchers have argued that
loxapine may behave as an atypical
antipsychotic. That why most time it placed
in separate category.
 Loxapine may be metabolized by N-
demethylation to amoxapine, a tetracyclic
antidepressant.
5. Dibenzoxazepine
Loxapine IUPAC Name-
8-chloro-6-(4-methylpiperazin-1-
yl) benzo [b] [1,4] benzoxazepine
MOA of loxapine
 It blocks D2 recepter
 Means it cometitive
antagonist of Dopamine

25. Second-generation drugs or Atypical
antipsychotics
 The atypical antipsychotics (AAP; also known as second generation
antipsychotics (SGAs)) are a group of antipsychotic drugs (antipsychotic
drugs in general are also known as major tranquilisers and neuroleptics,
although the latter is usually reserved for the typical antipsychotics) used to
treat psychiatric conditions.
 Some atypical antipsychotics have received regulatory approval
for schizophrenia, bipolar disorder, autism, and as an adjunct in major
depressive disorder.
 Both generations of medication tend to block receptors in the brain's dopamine
pathways. Atypicals are less likely – than the most widely used typical
antipsychotic haloperidol – to cause extrapyramidal motor
control disabilities in patients such as unsteady Parkinson's disease-type
movements, body rigidity, and involuntary tremors. However, only a few of the
atypicals have been demonstrated to be superior to lesser-used, low-potency
first-generation antipsychotics in this regard.

26.  Although atypical antipsychotics are thought to be safer than typical
antipsychotics, they still have severe side effects, including
 Tardive dyskinesia (a serious movement disorder),
 Neuroleptic malignant syndrome, and
 Increased risk of stroke, sudden cardiac death, blood clots, and
 Diabetes.
 Significant weight gain may also occur.
MOA of Atypical Antipsychotics
 Atypical Antipsychotic inhibit D2 receptor in brain
 Additionally inhibit 5HT2 receptor (Serotonin Pathway)

28. Classification of Atypical Antipsychotic
 Ziprasidone
 Dibenzodiazepine- e.g. Clozapine
 Dibenzothiazepine- e.g. Quetiapine
 Thienobenzodiazepine- e.g. Olanzapine
Note-
Control Negative and Positive symptoms of Psychosis
Least EPD side effect

29. Dibenzodiazepine
Clozapine
 Clozapine, is an atypical antipsychotic medication. It is mainly used for
schizophrenia that does not improve following the use of other antipsychotic
medications.
 In those with schizophrenia and schizoaffective disorder it may decrease the
rate of suicidal behavior.
 It is possibly more effective than typical antipsychotics. It is taken by mouth.
MOA of Clozapine
 It inhibit D4 receptor in brain
 Additionally inhibit 5HT2 receptor

30. Adverse Effects of Clozapine
 Clozapine is associated with a relatively high risk of low white blood
cells which may result in death. To decrease this risk it is recommended that
the blood be regularly monitored.
 Other serious risks include
 seizures,
 inflammation of the heart,
 high blood sugar levels, and
 in older people with psychosis as a result of dementia an increased risk of
death.
 Common side effects include
 drowsiness,
 dry mouth,
 low blood pressure,
 trouble seeing, and
 dizziness.
 The potentially permanent movement disorder tardive dyskinesia occurs in
about 5% of people.

31. Summary for Clozapine
 Potent Anticholinergic so less EPD
 Due to its Anticholinergic property it should decrease salivation but
Paradoxically clozapine increase salivation
 Clozapine control both Positive and Negative symptoms of Schizophrenia
 There is legal restriction on its use because it decrease WBC count so not used
commonly.
 Used only in case of Resistant Schizophrenia or Multi drug resistant
Schizophrenia or Refractory psychosis (Not respond to other drugs
 Monitor WBC count during clozapine therapy
Clozapine IUPAC Name-
8-chloro-11-(4-methylpiperazin-1-yl)-5H-
dibenzo [b,e][1,4]diazepine

32. Dibenzothiazepine
 Quetiapine is an atypical
antipsychotic approved for the
treatment of
 schizophrenia,
 bipolar disorder, and
 along with an antidepressant to
treat major depressive disorder.
 It is also sometimes used as a
sleep aid because of its sedating
effect but this use is not
recommended.
Quetiapine
Quetiapine IUPAC Name-
2-(2-(4-dibenzo[b,f][1,4]thiazepine- 11-yl- 1-
piperazinyl)ethoxy)ethanol

33. Thienobenzodiazepine
Olanzapine
Olanzapine IUPAC Name-
2-Methyl-4-(4-methyl-1-piperazinyl)-
10H-thieno[2,3-b][1,5]benzodiazepine
 Olanzapine is an atypical
antipsychotic. It is approved by the
U.S. Food and Drug
Administration (FDA) for the
treatment of
 schizophrenia and
 bipolar disorder.
 Olanzapine is structurally similar
to clozapine and quetiapine.
 It is a dopamine antagonist and is
classified as a thienobenzodiazepine.

34. Ziprasidone
Ziprasidone IUPAC Name-
5-{2-[4-(1,2-benzisothiazol-3-yl)-1-
piperazinyl]ethyl} -6-chloro-1,3-dihydro-2H-
indol-2-one
 Ziprasidone atypical antipsychotic to gain approval in the United States.
 It is approved by the U.S. Food and Drug Administration (FDA) for the
treatment of
 schizophrenia, and
 acute mania and
 mixed states associated with bipolar disorder.

35.  Its intramuscular injection form is approved for acute agitation in
schizophrenic patients for whom treatment with just ziprasidone is
appropriate.
 Ziprasidone is also used off-label for
 depression,
 bipolar maintenance, and
 PTSD.
 The oral form of ziprasidone is the hydrochloride salt, ziprasidone
hydrochloride. The intramuscular form, on the other hand, is the mesylate salt,
ziprasidone mesylate trihydrate, and is provided as a lyophilized powder.
Adverse Effect
Main adverse effect is
 Ziprasidone increase QT interval ----- Cardiac arrhythmia