Antipsychotics 2017

Psychosis is a loss of contact with reality and having
false belief that some event is taking place
(delusions) & seeing / hearing things that don’t
persist (hallucinations)
Auditory Hallucinations
Visual Hallucinations
Antipsychotics are the drugs used to treat all types of
functional psychoses including schizophrenia
SCHIZOPHRENIA
A chronic psychiatric illness affecting young people

having strong hereditary factor in disease pathogenesis
characterized by abnormal social behavior and failure to
understand what is real
SCHIZOPHRENIA
Common symptoms include:

 False beliefs
 Confused thinking
 Hearing voices that others don't listen
 Reduced Social Engagement
 Reduced Emotional Expression
 Lack Of Motivation
SCHIZOPHRENIA
Positive Symptoms:
Delusions (false beliefs that are unshakable not
accepting any argument)
Hallucinations (esp. in form of voices)
Abnormal behavior (stereotyped & sometimes
aggressive)
SCHIZOPHRENIA
Negative Symptoms:
Withdrawal from Social contacts
Flattening of emotional responses

SCHIZOPHRENIA
Additional symptoms
Deficit in cognitive functions (e.g. attention,
memory)
Anxiety and depression
Suicidal tendencies
Also known as
Neuroleptic drugs
Anti-schizophrenic drugs
Major tranquilizers
These drugs have common property of
blocking dopamine receptors (which are
responsible for neuroleptic and antiemetic
effects)
Broadly classified as
1. Typical or Classical Antipsychotics
Block both D1 & D2 dopamine receptors
2. Atypical
They selectively block D2 dopamine
receptors
Phenothiazines:
Type 1 :
Chlorpromazine, Promazine & Promethazine
Type 2 :
Thioridazine & Piperacetazine
Type 3 :
Trifluroperazine, Fluroperazine &
Prochlorperazine
Butyrophenones
Haloperidol, Droperidol, Penfluridol
Thioxanthenes
Thiothixene, Chlorprothixene, Clopenthixol,

Flufenthixol (also available as IM injection)
Newer Generation / Atypical
(Almost free from extra-pyramidal symptoms)
Cloxapine, Loxapine, Olanzapine,
Risperidone, Ziprasidone,
Pimozide, Sulpiride
Blockade of D1 receptors in brain cause
extra-pyramidal symptoms produced by
typical / classical
antipsychotics
The newer atypical antipsychotics induce
minimal or no extra-pyramidal
dysfunction due to D2 receptors selectivity

CHLORPROMAZINE
Originally tested as antihistamine; this drug

emerged as an effective treatment for psychotic
illness in 1950s
IT IS A PROTOTYPE ANTIPSYCOTIC
CHLORPROMAZINE
Lipophilic & incompletely absorbed as it

undergoes extensive first-pass metabolism
Well absorbed after oral administration (Dose
100-1000mg/day)
 Extensively protein-bound (92-95% hence cross
BBB and placental barrier)

CHLORPROMAZINE
 For rapid symptoms relief IM route is used
 Metabolized in liver by CYP 450 (Only
amisulpride is eliminated by kidneys without
hepatic metabolism)
Depot preparations e.g. flufenazone
decanoate & haloperidol given
intramuscularly can act for 2-4 weeks and
are useful for maintenance therapy

Plasma half lives of different antipsychotics
vary
 12 hours for Clozapine
 18 hrs. for Haloperidol
 33 hrs. for Olanzapine
 35 hrs. for Chlorpromazine
Beneficial effects of antipsychotic drugs are
due to their actions on brain pathways in
which dopamine is neurotransmitter

1. Dopaminergic pathways
2. Tuberoinfundibular (related to prolactin

release)
3. Nigrostriatial (related to motor control &

deficient in parkinsonism)
4. Mesolimbic : It is overactive in psychotic

illness
 Excess release of dopamine in mesolimbic
pathway has been linked to psychotic
experiences
 It is the blockade of dopamine receptors
in this pathway that is thought to control
psychotic experiences
Mechanism of Action
Chlorpromazine & other antipsychotic drugs
cause D2 receptor blockade (in mesolimbic &
mesocortical areas) >> antipsychotic effect
Contd.
Mechanism of Action
D2 receptor blockade (in nigrostriatal pathway)

>> parkinsonism
D2 receptor blockade (in CTZ centre in brain &
in stomach) >> antiemetic effect
Contd.
Mechanism of Action
D2 receptor blockade (in tubero-infundibular

region) >> hyperprolactinemia because it
reverses the dopaminergic inhibition of prolactin
in the anterior pituitary
Mechanism of Action
Also block α, muscarinic, H1 and 5HT2

receptors
Newer drugs may have less effects on D2

receptors than other dopamine receptor
subtypes
Mechanism of Action
1.H1 receptor blockade >> sedation
2.Muscarinic receptor blockade >>
 Blurring of vision
Dryness of mouth
Constipation
Urinary retention
3.α1 receptor blockade >> hypotension
4.Serotonin (5-HT) receptor blockade >>

decreased excitement in schizophrenia
INDICATIONS:
Schizophrenia
Non-maniac excited states
Tourette syndrome (repetitive, stereotyped,

involuntary movements)
Paranoid state (anxiety & fear)
Alzheimer’s (neurodegenerative) disease

NON- PSYCHOTIC INDICATIONS:
As anti-emeic
As anti-hiccup
As antipruritic
In neurolept anesthesia (droperidol + fentanyl)

NON- PSYCHOTIC INDICATIONS:
Neurolept anesthesia
An anesthetic process that involves combining a
neuroleptic/antipsychotic (a potent D2
receptor antagonist droperidol) & a potent opioid
analgesic fentanyl to produce a pain-free anesthetic state
CONTRAINDICATIONS:
Alcohol withdrawal
Seizure disorders
Concomitant use with  blockers as they already block

 receptors
Concomitant use with quinidine like drugs as they may
cause cardio toxicity (thioridazine & ziprasidone are
themselves cardio toxic)
ADVERSE EFFECTS:
Pseudo depression
Akinesia (loss or impairment of the power of
voluntary movement)
Neuroleptic malignant syndrome (muscle rigidity,
elevated temperature & raised creatinine kinase level)

ADVERSE EFFECTS:
Parkinsonism
Akathisia (uncontrollable restlessness)
Tardive dyskinesia (involuntary movements of tongue,
lips, jaw & face)

Ocular drug deposits in lens & retina (e.g.
thioridazine)
ADVERSE EFFECTS:
Heart block, arrhythmia
Orthostatic hypotension (leading to syncope)
Urinary retention
Impaired ejaculation
Mouth dryness, increased appetite & weight
Hyperglycemia (insulin resistance due to weight gain)

ADVERSE EFFECTS:
Skin eruptions
Agranulocytosis (with clozapine)
Cholestatic jaundice
Infertility & loss of libido (in both sexes)
Teratogenicity risk
DRUG INTERACTIONS:
Antacids, kaolin & activated charcoal impede absorption of
antipsychotics
Chlorpromazine & impiramine inhibit hydroxylation and
raise serum level of each other

Inhibit phenytoin metabolism
Additive action with sedatives & antimuscarinics

DRUG INTERACTIONS:
Chlorpromazine reverses antihypertensive effect of
sympathetic ganglion blockers/ adrenergic blockers e.g.

methyldopa & clonidine
HALOPERIDOL
Most commonly used antipsychotic drug
Dose: 2-60 mg oral/ parenteral
t ½ 12-38 hrs.
Excretion by kidney (major) & bile (minor portion)
Higher brain selectivity (cerebral concentration 10 times
more than plasma)

HALOPERIDOL
It is a potent drug & blocks dopamine postsynaptic receptors
Effects: calmness, sleep, blocks apomorphine induced
vomiting
Less anticholinergic & alpha blocking properties
Causes hypotension due to  block (although to lesser

extent)
HALOPERIDOL
INDICATIONS:
Schizophrenia / Mania
Delirium (incoherent talk)
Amphetamine poisoning
Vomiting (as antiemetic)

HALOPERIDOL
ADVERSE EFFECTS:
More potent. More toxic and less hypotensive however it

causes extrapyramidal signs and depression
HALOPERIDOL
ADVERSE EFFECTS:
Causes hyperthermia in sensitive cases Neuroleptic
malignant syndrome: (a life-threatening idiosyncratic
reaction to antipsychotics characterized by fever, altered
mental status, muscle rigidity, and autonomic
dysfunction)
dysfunction
HALOPERIDOL
ADVERSE EFFECTS:
Leucopenia & agranulocytosis
Orthostatic hypotension
Jaundice
ATYPICAL ANTIPSYCHOTICS
Generally more effective for treating negative

symptoms and have lower risk of extrapyramidal
symptoms
These cause weight gain & raised serum lipids (also
Hyperglycemia / DM)
CLOZAPINE
Dose: 50-600mg/day
A prototype atypical antipsychotic drug
Used for schizophrenia refractory to other drugs
Only drug indicated for suicidal tendencies
Can cause agranulocytosis, epileptic fits
Sometimes it causes myocarditis

OLANZAPINE
Given in dose: 5-30mg /day
Effective for both positive & negative symptoms of

schizophrenia
Causes weight gain & seizures but free from
extrapyramidal symptoms
LOXAPINE
Does not cause weight gain
QUETIAPINE
Has short t1/2 hence given twice daily

RISPERIDONE
Highly efficacious but may cause seizures & hypotension
ZIPRASIDONE
Given in dose: 40-160mg /day (also parenterally)
Can cause raised QT interval

SULPRIDE
Not used nowadays due to too many side effects
Sometimes used to increase milk production

(hyperprolactinemia)

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Psychosis is a loss of contact with reality and having

false belief that some event is taking place

(delusions) & seeing / hearing things that don’t

A chronic psychiatric illness affecting young people

Common symptoms include:

Withdrawal from Social contacts

Flattening of emotional responses

blocking dopamine receptors (which are

responsible for neuroleptic and antiemetic

1. Typical or Classical Antipsychotics

Block both D1 & D2 dopamine receptors

They selectively block D2 dopamine

Haloperidol, Droperidol, Penfluridol

Thiothixene, Chlorprothixene, Clopenthixol,

Cloxapine, Loxapine, Olanzapine,

extra-pyramidal symptoms produced by

dysfunction due to D2 receptors selectivity

Originally tested as antihistamine; this drug

Lipophilic & incompletely absorbed as it

 Extensively protein-bound (92-95% hence cross

BBB and placental barrier)

 For rapid symptoms relief IM route is used

 Metabolized in liver by CYP 450 (Only

amisulpride is eliminated by kidneys without

decanoate & haloperidol given

intramuscularly can act for 2-4 weeks and

are useful for maintenance therapy

due to their actions on brain pathways in

which dopamine is neurotransmitter

2. Tuberoinfundibular (related to prolactin

3. Nigrostriatial (related to motor control &

4. Mesolimbic : It is overactive in psychotic

Chlorpromazine & other antipsychotic drugs

cause D2 receptor blockade (in mesolimbic &

mesocortical areas) >> antipsychotic effect

D2 receptor blockade (in nigrostriatal pathway)

D2 receptor blockade (in tubero-infundibular

Also block α, muscarinic, H1 and 5HT2

Newer drugs may have less effects on D2

4.Serotonin (5-HT) receptor blockade >>

Non-maniac excited states

Tourette syndrome (repetitive, stereotyped,

Alzheimer’s (neurodegenerative) disease

In neurolept anesthesia (droperidol + fentanyl)

Concomitant use with  blockers as they already block

Akinesia (loss or impairment of the power of

elevated temperature & raised creatinine kinase level)

Akathisia (uncontrollable restlessness)

Tardive dyskinesia (involuntary movements of tongue,

lips, jaw & face)

Heart block, arrhythmia

Orthostatic hypotension (leading to syncope)

Mouth dryness, increased appetite & weight

Hyperglycemia (insulin resistance due to weight gain)

Agranulocytosis (with clozapine)

Infertility & loss of libido (in both sexes)

raise serum level of each other

Additive action with sedatives & antimuscarinics

Chlorpromazine reverses antihypertensive effect of

sympathetic ganglion blockers/ adrenergic blockers e.g.