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Anti-psychotics

Anti-psychotics . “ psychosis” = loss of contact with reality . Psychotic disorders. MAJOR PSYCHOTIC DISORDERS Schizophrenia Manic episode Bipolar Persistent delusional disorders Acute and transient psychotic disorders Schizoaffective disorders

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Anti-psychotics

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  1. Anti-psychotics

  2. “psychosis” = loss of contact with reality

  3. Psychotic disorders MAJOR PSYCHOTIC DISORDERS • Schizophrenia • Manic episode • Bipolar • Persistent delusional disorders • Acute and transient psychotic disorders • Schizoaffective disorders • + organic disease caused by metabolic disturbances, toxic substances, psychoactive drugs

  4. Schizophrenia Positive symptoms Negative symptoms

  5. All anti-psychotics work on dopamine pathways So lets have a look at these first…….

  6. Dopamine = Neurotransmitter • Changes in the amount of neurotransmitter released by the presynaptic terminal as well as the number and sensitivity of receptors at the postsynaptic terminal lead to varying activity levels of the neurons. • This modulation in activity on a cellular level can lead to outward changes, or behaviour differences • DOPAMINE

  7. Precursor of Norepinephrine And Epinephrine

  8. Dopamine • Novel stimuli • Reward • Stressful stimuli

  9. Dopamine in the Brain • Dopaminergic neurons form a neurotransmitter system • Originates in: • Substantia nigra (SN), • Ventral tegmental area (VTA) • Hypothalamus • 5 types of dopamine receptors D1. – D5

  10. 4 pathways • Mesolimbic • Transmits dopamine from VTA  nucleus accumbens • SCHIZOPHRENIA • Mesocortical • Transmits dopamine from VTA  frontal cortex • SCHIZOPHRENIA • Nigrostrial • Transmits dopamine from SN  striatum • PARKINSONS , CHOREA • Tuberoinfundibular • Transmits dopamine from the Hypothalamus  piturity • Regulates the secretion of prolactin from anterior piturity

  11. Mesocortical Pathway Nigrostrial Pathway Mesolimbic Pathway

  12. Anti-psychotic drugs • Typical and Atypical

  13. Atypical Risperidone Olanzapine Quetiapine Aripiprazole Clozapine Typical Chlorpromazine Trifluoperazine Haloperidol Clozapine  risk of agranulocyosis – 1%) Check FBC Effective against positive and negative symptoms Shows efficacy in treatment-resistant patients

  14. Anti-psychotic DRUGSSS • 65% D2 receptor occupancy is required for clinical benefit during long-term treatment • HOWEVER, 80% or more blockade in the striatum will produce extrapyramidal unwanted effects. • Ach is often used to control the extra – pyramidal side effects

  15. Cautions • Use in caution with pts with • Cardiovascular disease • Parkinson’s disease • Epilepsy • Myasthenia gravis • BPH

  16. Contraindications • Comatose states • CNS depression • Phaechromocytoma

  17. Monitoring • FBC, U and E, LFT monitored at the start of treatment and then annually • Blood lipids and weight should be measured at baseline, at 3 months and then yearly • ECG should check for any cardiovascular risks

  18. Antipsychotic malignant Syndrome • Muscle rigidity is accompanied by a rapid rise in body temperature and mental confusion • Usually presents when the drug has just been commenced – within 10 days • Usually reversible • Death from renal or cardiovascular failure occurs in 10 – 20% of cases • RHABDO!

  19. Clinical use • Behavioural emergencies • Typical antipsychotics • Haloperidol, chlorpromazine • Depo injections maybe used when oral treatment is a problem • Flupentixol decanoate – typical • Atypical antipsychotic drugs are used if extrapyramidal symptoms are troublesome, if symptom control is inadequate, or for newly diagnosed pts

  20. A 46-year-old man with schizophrenia is brought to the surgery by one of his carers. His current medication includes clozapine and procyclidine (anti-cloingeric drug). His carer reports that he is more tired than usual and generally unwell. She also thinks he may have put on weight. What is the most important test to perform? A: Blood sugar B: FBC C: U and E’s D: Urine dipstick for protein E: LFT’s Answer: B - FBC to exclude agranulocytosis

  21. Which one of the following side-effects is more common with atypical than conventional anti-psychotics? Answer B: weight gain

  22. A 35-year-old man with a history of schizophrenia is brought to the Emergency Department by worried friends due to drowsiness. On examination he is generally rigid. A diagnosis of neuroleptic malignant syndrome is suspected. Each one of the following is a feature of neuroleptic malignant syndrome, except: Answer: D – usually occurs within 10 days

  23. A 45-year-old man taking chlorpromazine for schizophrenia develops involuntary pouting of the mouth. What side-effect of antipsychotic medication is this an example of? C: Tardive Dyskinesia

  24. Summary • Antipsychotics work on DOPAMINE pathways • Mesolimbic and Mesocortical pathways in the brain • Typical and Atypical anti-psychotics • Typical SE – extra pyramidal • Atypical SE – weight gain and diabetes

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