Antipsychotics
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What is Psychosis
Psychosis is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality." People suffering from it are said to be psychotic. ► Patient experience hallucinations or delusional beliefs, and may exhibit personality changes and disorganized thinking.
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► Psychosis:
Positive & negative symptoms
Positive:
(primary manifestation of acute)
Agitation Delusions Disorganized speech Disorganized thinking Hallucinations Insomnia
Negative: (harder to treat/poorer prognosis) Apathy (avolition) Affective flattening Lack of motivation Lack of pleasure (anhedonia) Poverty of speech (alogia) Social isolation
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Antipsychotics Drugs
are also referred to as neuroleptic drugs, neuroleptics ► This term reflects the drugs' ability to make movement more difficult and sluggish, which clinicians previously believed indicated that a dose was high enough ► The lower doses used currently have resulted in reduced incidence of motor side effects and sedation, and the term is less commonly used than in the past.
► Antipsychotics
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Classification of Antipsychotics
Antipsychotics are broadly divided into two groups ► Typical or first-generation antipsychotics (major tranqullizers because some of them can tranquilize and sedate. ) ► Atypical or second-generation antipsychotics. ► Dopamine partial agonists,which are often categorized as atypicals.
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Phenothiazines ► Chlorpromazine (Thorazine) ► Fluphenazine (Prolixin) - Available in decanoate (long-acting) form ► Perphenazine (Trilafon) ► Prochlorperazine (Compazine) ► Thioridazine (Mellaril) ► Trifluoperazine (Stelazine) ► Mesoridazine ► Promazine ► Triflupromazine (Vesprin) ► Levomepromazine (Nozinan) ► Promethazine (Phenergan)
First Generation Antipsychotics
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Butyrophenones ► Haloperidol (Haldol) - Available in decanoate (long-acting) form ► Droperidol ► Pimozide (Orap) - Used to treat Tourette syndrome ► Melperone ► Benperidol ► Triperidol
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Thioxanthenes ► Chlorprothixene ► Flupenthixol (Depixol and Fluanxol) ► Thiothixene (Navane) ► Zuclopenthixol (Clopixol and Acuphase)
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Second Generation Anti-psychotics Other Heterocyclic: ► Pimozide ► Loxapine ► Reserpine Atypical neuroleptics ► Clozapine ► Risperidone ► Olanzepine
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Third Generation Anti-psychotics
Aripiprazole (Abilify) – Mechanism of action is thought to reduce susceptibility to metabolic symptoms seen in some other atypical antipsychotics
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Mode of action of Antipsychotic drugs
Phenothiazines( first generation) ► Cause Blockade mainly of postsynaptic Dopaminergic(d2 receptor) and to smaller extent 5-HT receptor. ► Modify the function of mesolimbic system ► Reduce the incoming sensory stimuli by acting on the brainstem reticular formation.
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TRIFLUOPERAZINE ► Mode of action ► Greater dopamine blocking activity. ► Less antiadrenergic activity. chlorpromazine ► Less anticholinergic activity.
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Adverse effects of Phenothiazines
Extrapyramidal side-effects (i)Acute dystonic reactions. (ii) Akathisia. (iii) Pseudo parkinsonism. (iv) Tardive dyskinesia Hyperprolactinaemia Antiserotonergic side-effect: depression Anticholinergic side-effects Antihistaminergic side-effect Antiadrenergic side-effects
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HALOPERIDOL (Butyrophenones class)
Mode of action ► 1 Greater dopamine blocking activity. ► 2 Less antiadrenergic activity than chlorpromazine ► 3 Less anticholinergic activity
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Adverse effects Less sedation. Less postural hypotension. Fewer anticholinergic side-effects. Danger of severe EPSE with ECG changes at high dose
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PIMOZIDE Second generation drugs
Mode of action ► More specific blocker of D3- and D2receptors ± cf chlorpromazine. Useful in monosymptomatic delusional psychosis ± it is claimed that ► pimozide has success in specically targeting monosymptomatic ► hypochondriacal delusions
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Pimozide Adverse effects
sedation. ► Following reports of sudden unexplained death, An ECG prior to commencing treatment in all patients. ► ECGs at regular intervals in patients taking over 16mg daily. ► A review of the need for pimozide if arrhythmias develop.
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► Less
ZUCLOPENTHIXOL ACETATE
Mode of action
injection administered intramuscularly as an oily injection and rapidly released into the bloodstream. ► Useful for immediate management of acutely disturbed behaviour as an alternative to haloperidol since: ► Zuclopenthixol acetate is more sedative than haloperidol. These injections (maximum of four) are more easily administered.
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► Short-acting
ATYPICAL ANTIPSYCHOTICS RISPERIDONE
Mode of action ► Potent dopamine D2-receptor antagonist; in addition it has a regional preference for blocking D2-receptors in the mesolimbic cortical bundle. ► Low affinity for serotonin 5HT2-receptors. ► Potent a1-adrenergic receptor antagonist. ► No appreciable affnity for muscarinic M1receptors. ► Low affnity for histamine H1-receptors.
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Adverse effects of RISPERIDONE
Dose-dependent elevation in prolactin levels. ► Minimal weight gain due to low affinity for serotonin 5HTreceptors ► Postural hypotension ► Gastrointestinal side-effects:nausea, dyspepsia, abdominal pain.
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►2
OLANZAPINE (Atypical Neuroleptics)
Mode of action ► Potent dopamine D2-receptor antagonist; it preferentially blocks ► D2-receptors in the mesolimbic cortical bundle, of the nigrostriatal pathway. ► Potent serotonin 5HT2A-receptor antagonist. ► High affinity for serotonin 5HT2C-receptors. ► Moderate affinity for a1-adrenergic receptors. ► High affinity for muscarinic M1-receptors. ► High affinity for histamine H1-receptors.
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Adverse effects of OLANZAPINE
signicant prolongation of the QTc interval ► Anticholinergic side-effects: dry mouth may occur ► Associated with an increased risk of stroke in elderly patients with dementia ► elevation in prolactin level.
► Not
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How are Atypical antipsychotics different from Typical antipsychotics?
► The
first generation antipsychotic drugs like Thorazine (Chlorpromazine) and Haldol etc. (Haloperidol), may have been effective but they often caused serious side effects, including Tardive dyskinesia (TD) - a disorder characterized by abnormal movements of the mouth, limbs, or body. Compared to the first antipsychotics, the atypical antipsychotics appear to cause far fewer side effects and yet have the same ability to control psychotic thinking and acute manic episodes as are experienced in Bipolar I disorder. There is also evidence that they may have moodstabilizing, anti-anxiety and antidepressant
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► Typical
antipsychotic drugs have an equal or greater affinity for D2 receptors than for 5HT2 receptors. ► Atypical antipsychotic drugs, have a greater affinity for 5-HT2 receptors than for D2 receptors and some atypical drugs have increased affinity for D3 or D4 receptors
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Case report
►A
20 years unmarried female, referred from civil hospital Thane, was brought to our casualty in an unconscious state with high grade fever and bladder incontinence of 12-16 hours duration. Prior to this, she was admitted at the civil hospital for an acute psychotic episode which, as per her relatives started after a breakup with her boyfriend. She was treated there with intramuscular injection of haloperidol. There was no history of psychiatric illness in the past. There was no history suggestive of seizures, headaches or vomiting.
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► On
examination her temperature was 390C , heart rate was 110 per minute and her blood pressure was 110/70 mm Hg. The patient was diaphoretic. There was no cyanosis, icterus or rash on the body. On CNS examination she was unconscious, not responding to verbal commands or painful stimuli. Pupils were bilaterally normal in size and reacting to light. She had neck stiffness, lead pipe rigidity in all four limbs and plantar response was flexor. Rest of the systemic examination was normal.
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