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  2. 2. • from the Greek "psyche", for mind/soul, and "-osis", for abnormal condition or derangement) • Psychotic illnesses are characterized by disordered thought processes WHAT IS PSYCHOSIS
  3. 3. • The psychoses are among the most severe psychiatric disorders • Serious inability to think • Symptoms of false beliefs (delusions) • Abnormal sensations (hallucinations) • Representative syndromes in this category include schizophrenia brief psychoses, and delusional disorders.
  4. 4. • Psychosis results from an overactivity of dopamine function in the brain, particularly in the mesolimbic pathway • Substance induced Pathophysiology
  5. 5. • The purpose of the brain is to collect information from the body (pain, hunger, etc.), and from the outside world, interpret it to a coherent world view, and produce a meaningful response. The information from the senses enter the brain in the primary sensory areas. They process the information and send it to the secondary areas where the information is interpreted. Spontaneous activity in the primary sensory areas may produce hallucinations which are misinterpreted by the secondary areas as information from the real world.
  6. 6. • Tertiary brain cortex collects the interpretations from the secondary cortexes and creates a coherent world view of it. A study investigating structural changes in the brains of people with psychosis showed there was significant grey matter reduction in the right medial temporal, lateral temporal, and inferior frontal gyrus, and in the cingulate cortex bilaterally of people before and after they became psychotic
  7. 7. • sensory deprivation have shown that the brain is dependent on signals from the outer world to function properly. If the spontaneous activity in the brain is not counterbalanced with information from the senses, loss from reality and psychosis may occur after some hours
  9. 9. • dopamine receptor antagonists • 5-hydroxytryptamine (5-HT) receptors antagonists PHARMACOLOGICALLY, THEY ARE CHARACTERISED AS
  10. 10. • Antischizophrenic drugs or major tranquillisers-conventionally refers to those used to treat schizophrenia, one of the most common and debilitating forms of mental illness. ANTISCHIZOPHRENIC:
  11. 11. • Classification of antipsychotic drugs main categories are: – First-generation ('typical') antipsychotics (e.G. Chlorpromazine, haloperidol , fluphenazine, flupenthixol, clopenthixol) – Second-generation ('atypical') antipsychotics (e.G. Clozapine , risperidone , sertindole, quetiapine, amisulpride, aripiprazole , zotepine).
  12. 12. • Distinction between typical and atypical groups is not clearly defined but rests on: – Receptor profile – Incidence of extrapyramidal side effects (less in atypical group) – Efficacy (specifically of clozapine ) in 'treatment-resistant' group of patients – Efficacy against negative symptoms.
  13. 13. • Delusions • Hallucinations- Auditory, Visual, Olfactory, and Tactile • Losing Sense of Reality • Disorganization of Thought • Thought Blocking SYMPTOMS :
  14. 14. • Bipolar Disorder • Shizophrenic disorders • Depression • Personality Disorders DISORDERS WITH PSYCHOSIS:
  15. 15. Two main different types: • Bipolar I • Manic around 1 week • Depressive around 2 weeks • Bipolar II • Depressive • Hypomanic Treatments: Mood Stabilizers: - Lithium Antipsychotics BIPOLAR DISORDER
  16. 16. Symptoms: • Delusions • Hallucinations • Disorganized speech and behavior • Negative Symptoms • Blunted affect (lack of emotional reactivity) • Alogia (poverty of speech) • Avolition ( lack of drive, or motivation to pursue meaningful goals)
  17. 17. • Treatment: – Mood Stabilizers – Antipsychotics
  18. 18. • Phenothiazine antipsychotic drugs TRICYCLIC ANTIPSYCHOTIC AGENTS
  19. 19. • Prominent sedative effect • Adverse autonomic and neurologic effects, severe anxiety and restlessness (akathisia) • The risk of developing advers extrapyramidal effects, including tardive dyskinesia PHARMACOLOGICAL PROPERTIES
  20. 20. • Auditory processing and attention, spatial organization, verbal learning, verbal memory, and executive functions, are impaired in schizophrenia patients. Potent d2-antagonist neuroleptics have very limited beneficial effects on such functions. Some atypical antipsychotic agents with mixed D2/5-HT2A activity (including clozapine, quetiapine, olanzapine, and risperidone), as well as the D2 partial agonist aripiprazole, seem to improve cognitive functioning in psychotic patients. 1-EFFECTS ON COGNITIVE FUNCTION
  21. 21. • Antipsychotic drugs have inconsistent effects on sleep patterns but tend to normalize sleep disturbances characteristic of many psychoses and mania. 2-EFFECTS ON SLEEP
  22. 22. • Actions of antipsychotic agents are based on their ability to antagonize the actions of DA as a neurotransmitter in the basal ganglia and limbic portions of the forebrain. 3-EFFECTS ON SPECIFIC AREAS OF THE NERVOUS SYSTEM
  23. 23. • Antipsychotic drugs interact with dopaminergic projections to the prefrontal and deep-temporal (limbic) regions of the cerebral cortex, with relative sparing of these areas from adaptive changes in DA metabolism 4-CEREBRAL CORTEX
  24. 24. • Many neuroleptic drugs can lower the seizure threshold and induce discharges in the electroencephalogram (EEG) that are associated with epileptic seizure disorders. Clozapine, olanzapine, and aliphatic phenothiazines with low potency (e.g., chlorpromazine) seem particularly able to do this. • while the more potent piperazine phenothiazines and thioxanthenes fluphenazine and thiothixene), risperidone, and quetiapine are much less likely to have this effect. 5-SEIZURE THRESHOLD
  25. 25. • Antagonism of DA-mediated synaptic neurotransmission is an important action of many antipsychotics,this prompted the proposal that many adverse extrapyramidal neurological and neuroendocrinological effects of the neuroleptics are mediated by antidopaminergic effects in the basal ganglia and hypothalamic systems, whereas the antipsychotic effects of neuroleptics are mediated by modification of dopaminergic neurotransmission in the limbic and mesocortical systems
  26. 26. • Many antipsychotic drugs also block the effects of agonists on DA-sensitive adenylyl cyclase associated with D1/D5-receptors in forebrain tissue • Atypical antipsychotic drugs such as clozapine and quetiapine are characterized by low affinity or weak actions in such tests. Initially, the standard antipsychotics increase firing and metabolic activity in dopaminergic neurons. These responses eventually are replaced by diminished presynaptic activity (“depolarization inactivation”) with reduced firing and production of DA, particularly in the extrapyramidal basal ganglia.
  27. 27. • Initially in antipsychotic treatment, DA neurons activate and release more DA, but following repeated treatment, they enter a state of physiological depolarization inactivation, with diminished production and release of DA, in addition to continued receptor blockade. ER, endoplasmic reticulum.
  28. 28. 6-CHEMORECEPTOR TRIGGER ZONE • Most antipsychotics protect against the nausea- and emesis-inducing effects of apomorphine and certain ergot alkaloids, all of which can interact with central dopaminergic receptors in the chemoreceptor trigger zone (CTZ) of the medulla
  29. 29. 7-AUTONOMIC NERVOUS SYSTEM • Chlorpromazine, clozapine, and thioridazine have particularly significant a-adrenergic antagonistic activity. The potent piperazine tricyclic neuroleptics (e.g., fluphenazine, trifluoperazine, haloperidol, and risperidone) have antipsychotic effects even when used in low doses and show little antiadrenergic activity.
  30. 30. 8-KIDNEY AND ELECTROLYTE BALANCE • Chlorpromazine may have weak diuretic effects because of a depressant action on the secretion of vasopressin
  31. 31. • Chlorpromazine and less potent antipsychotic agents, as well as reserpine, risperidone, and olanzapine, can cause orthostatic hypotension, usually with rapid development of tolerance. Thioridazine, mesoridazine, and other phenothiazines with low potency, as well as ziprasidone, droperidol, and perhaps high doses of haloperidol, have a potentially clinically significant direct negative inotropic action and a quinidine-like effect on the heart (prolongation of the QTc and PR intervals, blunting of T waves, and depression of the ST segment) 9-CARDIOVASCULAR SYSTEM
  32. 32. • Many antipsychotics enhance the turnover of acetylcholine Chlorpromazine and low-potency antipsychotic agents, including clozapine and quetiapine, have antagonistic actions at histamine receptors that probably contribute to their sedative effects. 10-MISCELLANEOUS PHARMACOLOGICAL EFFECTS
  33. 33. • The most important are those on the cardiovascular, • central and autonomic nervous systems, and endocrine system. Other dangerous • effects are seizures, agranulocytosis, cardiac toxicity, and pigmentary degeneration of the retina, all • of which are rare TOXIC REACTIONS AND ADVERSE EFFECTS
  34. 34. • Orthostatic hypotension, which may result in syncope, falls, and injuries. Hypotension is most likely to occur with administration of the phenothiazine depress cardiac repolarization, as reflected in the QT interval corrected for heart rate (QTc) Clozapine has rarely been associated with myocarditis and cardiomyopathy. risk of stroke among elderly patients treated with risperidone and olanzapine 1-ADVERSE CARDIOVASCULAR AND CEREBROVASCULAR EFFECTS
  35. 35. • Extrapyramidal motor system, occur by high-potency D2-receptor antagonists (tricyclic piperazines and butyrophenones) 2-ADVERSE NEUROLOGICAL EFFECTS
  36. 36. • Clozapine and olanzapine; somewhat less with quetiapine; even less with fluphenazine, haloperidol, and risperidone 3-WEIGHT GAIN AND METABOLIC EFFECTS
  37. 37. • Mild leukocytosis, leukopenia, and eosinophilia occurs with clozapine and less often with phenothiazines 4-BLOOD DYSCRASIAS4-
  38. 38. • Phenothiazines, including urticaria or dermatitis. 5-SKIN REACTIONS
  39. 39. • Jaundice, typically occurs with chlorpromazine 6-GI AND HEPATIC EFFECTS
  40. 40. • Chlorpromazine increases the miotic and sedative effects of morphine and may increase its analgesic actions. • The antimuscarinic action of clozapine and thioridazine can cause tachycardia and enhance the peripheral and central effects (confusion, delirium) of other anticholinergic agents, such as the tricyclic antidepressants and antiparkinson agents. 7-INTERACTIONS WITH OTHER DRUGS
  41. 41. • Potentiate the effect of medically prescribed sedatives and analgesics, alcohol, nonprescription sedatives and hypnotics, antihistamines, and cold remedies.
  42. 42. • Goodman and Gillman’s manual of Pharmacology and Therapeutics REFERENCES :