Antipsychotic Drugs In Antipsychotic Drugs In SchizophreniaSchizophrenia

Vinod Mamraj Saini 309 A

What is 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.

What’s going on in Brain ?• The Dopamine HypothesisThe Dopamine Hypothesis

Schizophrenia results from excess activity of dopamine neurotransmission in Mesolimbic and Mesocortical Pathways because:

a) All antipsychotic drugs block dopamine receptors.b) Higher levels of dopamine receptors measured in brains

of schizophrenics by PET.c) Stimulant drugs which act through dopamine can

produce schizophrenic-like behaviors (eg.amphetamines).

How to cure it ?Psychotic diseases are life long and it is

preferable to prevent the psychotic episodes than to treat them.

* * There is NO CURE * *

Therefore , Antipsychotic DrugsAntipsychotic Drugs drugs are of 1st choice !!

Classification of Antipsychotic Classification of Antipsychotic DrugsDrugs

(A)Typical antipsychotics 1. Phenothiazines ( Chlorpromazine, Perphenazine,

Fluphenazine, Thioridazine) 2. Thioxanthenes ( Flupenthixol, Clopenthixol) 3. Butyrophenones ( Haloperidol, Droperidol)

(B) Atypical antipsychotics 1. Clozapine , 2. Risperidone , 3. Amisulpiride , 4. Olanzapine, 5. Aripiprazole

Which Type of Drug to Choose ?

• According to high-quality studies that have compared newer and older drugs have generally found that newer atypical antipsychotics are not any more effective than older typical antipsychotics (such as haloperidol), at least for initial treatment of first-episode schizophrenia.

• Similarly, for treatment of children and adolescents with schizophrenia, atypical and typical antipsychotics appear to be equally effective, but atypical antipsychotics, particularly clozapine and olanzapine, carry a higher risk for metabolic side effects.

• Side effect profiles between typical and atypical antipsychotics are different. Both groups cause extrapyramidal side effects (including muscle stiffness, tremors, and abnormal movements), but the newer atypical drugs do not seem to cause them as often.

• However, the atypical antipsychotics pose a higher risk for weight gain, which can lead to diabetes as well as heart disease.

• Most antipsychotic medications are approved only for adult patients.

• Some atypical antipsychotics (such as risperidone, aripiprazole, olanzapine, and quetapine) are approved for treatment of schizophrenia in adolescents (ages 13 - 17 years).

What Indian Psychiatrists Think ?

• Although anti-psychotic medications are available in India since a long time, little is known about the prescription patterns of Indian psychiatrists. 1. An email survey of 168 psychiatrists,.2. The three most commonly prescribed anti-psychotics were risperidone, olanzapine, and haloperidol.

It was also found that typical anti-psychotics comprise of 25.15% of all prescriptions

In about 22.36% of the cases the psychiatrists were using more than one anti-psychotic in the same patient.

Haloperidol !! But Y ?• Haloperidol, the most-studied antipsychotic in delirium

treatment, often is the drug of choice because :-1. high potency, 2. low sedative effect, 3. few anticholinergic side effects, 4. minimal cardiovascular side effects, 5. no active metabolites, and 6. multiple administration routes.

How it works ?• It can bind to dopamine D1 and D2 , 5-HT2, histamine

H1 and α2 adrenergic receptors in the brain. • The efficacy of neuroleptics is thought to be due to

antagonism of dopamine receptors in the mesolimbic and mesofrontal systems.

• The adverse effects of typical neuroleptics include tachycardia, impotence and dizziness, and these unwanted effects are caused by non-selective interaction at the α adrenoreceptor.

• Other adverse effects include and sedation and weight gain, which is due to

histamine H1 receptor blockade.• Haloperidol's negligible affinity for histamine H1

receptors and muscarinic M1 acetylcholine receptors.

Haloperidol

Haloperidol

• Pharmacokinetics:-1. The bioavailability of oral haloperidol ranges from 60–

70%.However, there is a wide variance in reported mean Tmax and T1/2 in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively.

RisperidoneRisperidone 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.

OlanzapineOlanzapine 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.

Do you Know ?? , What ?

Vatslav Fomich Nizhinsky 

Russian-born ballet dancer of almost legendary fame, celebrated for his spectacular leaps and sensitive interpretations.

!! спасибо за внимание !!