2. PSYCHOSIS
Psychosis (Greek)
Psyche- "mind/soul", and
-osis "abnormal condition or derangement"
refers to an abnormal condition of the mind.
A syndrome of chronic disordered thinking and disturbed behavior
(schizophrenia, mania, depression)
The most important types of psychosis are:
Schizophrenia
Affective disorders (e.g. depression, mania)
Organic psychoses (mental disturbances caused by head injury, alcoholism, or
other kinds of organic disease).
3. Schizophrenia
A chronic mental disorder involving a
breakdown in the relation between
thought, emotion, and behavior,
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).
5. Etiology
DOPAMENERGIC SYSTEM:
There are four major pathways for the
dopaminergic system in brain :
I. The Nigro-Striatal Pathway.
II. The Mesolimbic Pathway.
III. The Mesocortical Pathway.
IV. The Tuberoinfundibular Pathway.
6. The Dopamine Hypothesis
Schizophrenia results from excess
activity of dopamine neurotransmission
in Mesolimbic and Mesocortical Pathways.
Antipsychotic drugs block dopamine receptors.
Higher levels of dopamine receptors measured
in brains of schizophrenics.
Stimulant drugs which act through dopamine can
produce schizophrenic-like behaviors (eg.
amphetamines).
12. 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
emotion.
** These drugs are not a cure **
Psychotic diseases are life long and it is preferable
to prevent the psychotic episodes than to
treat them.
15. 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.
18. MECHANISM OF ACTION
There are many type of DA-receptors.
The antipsychotic drugs 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.
19. Therapeutic Uses
Treatment of psychotic disorders:
schizophrenia, mania, paranoid states.
Treatment of nausea and vomiting of certain
causes.
Anesthesia in hypothermia and artificial
hibernation (used with pethidine and
promethazine).
20. Adverse Effects
Extrapyramidal motor disturbances:
Parkinson-like symptoms
Neuroleptic Malignant Syndrome
Tardive dyskinesia (involuntary movements of
face, tongue and limbs , appearing after months
or years of antipsychotic treatment).
Acute dystonias.
Seizures
Cardiac toxicity Produce hypotension (primarily
postural) by α-adrenergic blockade.
21. Endocrine effects: Increase prolactin :
which may result in gynecomastia. They
reduce gonadotropin secretion but
infertility occur only occasionally.
ACTH release in response to stress
diminishes.
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.
22. Other side-effects (dry mouth,
constipation, blurred vision, hypotension,
etc.) are due to blockade of other
receptors, particularly α–adrenoceptors
and muscarinic ACh receptors.
Contact dermatitis, blood dyscrasias,
obstructive jaundice sometimes occurs
with phenothiazines.
23.
24.
25. Limitations Of
Conventional/
Typical Antipsychotics
Approximately one-third of patients with
schizophrenia fail to respond
Limited efficacy against Negative
symptoms
High proportion of patient relapse
Side effects and compliance issues
Therefore, Atypical/New generation
Antipsychotics are preferred for the
treatment of various psychotic disorders.
27. 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.
28. 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.
29. 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.
30. Therapeutic uses
Treatment of schizophrenia
Prevention of severe nausea and vomiting
Other uses: Treatment of mania, organic
brain syndromes, anxiety.
Chlorpromazine is used to treat intractable
hiccups. Risperidone and haloperidol are
also commonly prescribed for this tic
disorder.
31. 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.
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.
32. 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.
33. Depot preparations are often used for
maintenance therapy.
Antipsychotic drugs are not generally
effective in improving negative schizophrenic
symptoms.
Approximately 40% of chronic schizophrenic
patients are poorly controlled by
antipsychotic drugs; clozapine may be
effective in some of these ‘antipsychotic-
resistant’ cases.
34. 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.
36. Gene Thearpy???
In February, 2011, Jonathan Sebat, at the University
of California, and his colleagues, published research
identifying a gene which holds particular promise in
the treatment of schizophrenia. According to Dr.
Sebat’s research, Vasoactive Intestinal Peptide
Receptor 2 or VIPR2 is much more likely to be
found in those with schizophrenia. Because VIPR2
responds to synthetic peptides, already available,
targeting this gene is a promising treatment strategy.