1. بسم الله الرحمن الرحيم Dr: Samah Gaafar Hassan Al-shaygi

2. Schezophrenia represents a heterogeneous syndrome of disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning.

4. E.g:FGAs: Phenoyhiazines, thiozanthines & butyrophenones. SGAs: clozapine, rispridone, sulpride Advantages of “second generation antipsychotics” over FGAs: 1.with few or no acutely occurring extrapyramidal side effects. 2.Enhanced efficacy, for negative & positive symptoms. 3.Lower incidence of tardive dyskinesia. 4.lack of effect on serum prolactin. 5.Different pharmacological profile from the classical drugs.

5. Mechanism of action: 1.Dopamine receptor blocking activity in the brain. The antipsychotic effect is mainly due to the action on D2 receptors(80% block) in the mesolimbic system. The effect on the nigrostriatal system correlates with the S.E. 2.The effect on Serotonin receptor blocking activity in the brain. 3. Action on cholinergic, adrenergic & histaminergic receptors.

6. Pharmacokinetics: Highly lipophilic & plasma protein bound. The relationship between the plasma conc. & the clinical effect is variable & the dose has to be adjusted on a trial & error basis. Most drugs metabolized by CYP450. Most are given orally.

7. A.E: Extrapyramidal motor disturbances: 1.Acute dystonia: reversible involuntary movement, occuring in the first few weeks, due to block of dopaminergic nigrostriatal pathway. 2.Tardive dyskinesia: irreversible, involuntary movements develops months to years, depending on the type of the drug, dose & age, increase in the D2 receptors in the striatum.

8. 3. Seizures. Antipsychotics lower the seizure threshold through 1.GABA depletion. 2.changes in CNS permeability leading to enhanced conduction of a discharge. 3.disruption of DA-acetylcholine balance. 4.the activation of a latent seizure focus. There is an increased risk of drug- induced seizures in all patients treated with antipsychotics.

9. 4. Poikilothermia, All patients receiving antipsychotics should be educated about these potential problems. Thermoregulatory problems are reportedly more common with the use of low-potency FGAs and may occur with the more anticholinergic SGAs. Anticholinergic, antihistaminergic, adrenergic blocking effects.

11. Initial treatment in the acute state: The goals during the first 7 days should be decreased agitation, hostility, anxiety, tension and aggression, and normalization of sleep and eating patterns. If absolutely no improvement after 3 to 4 weeks at therapeutic doses, then an alternative antipsychotic should be considered. in a severely agitated patient (loud, physically or verbally threatening behavior, motor hyperactivity, or physical aggression), we can use (e.g., olanzapine 2.5 to 10 mg IM, or haloperidol 2 to 5 mg IM).

12. Stablization therapy: If no decrease in positive and negative symptoms within 8 to 12 weeks at adequate doses, then an alternate monotherapy antipsychotic is used. Before changing medications in a poorly responding patient, the following should be considered: 1. different diagnosis. 2. long-standing behavioral problem. 3. substance abuse disorder. 4.general medical condition? 5.Is the patient adherent with pharmacotherapy? 6.Are the persistent symptoms poorly responsive to antipsychotics (e.g., impaired insight or judgment, or fixed delusions)? 7.How does the patient’s current status compare with response during previous exacerbations? 8.Would this patient potentially benefit from a change to a different treatment stage? 9.Does this patient have a treatment-refractory schizophrenic illness?

13. MAINTENANCE TREATMENT: After treatment of the first psychotic episode in a schizophrenic patient, medication should be continued for at least 12 months after remission. In patients with multiple acute episodes is more difficult to define, good medication responders should be treated for at least 5 years.

14. Antipsychotics should be tapered slowly before discontinuation. Abrupt discontinuation of antipsychotics, especially low-potency FGAs and clozapine, can result in withdrawal symptoms, as rebound cholinergic outflow. Insomnia, nightmares, headaches, gastrointestinal symptoms (e.g., abdominal cramps, stomach pain, nausea, vomiting, and diarrhea), restlessness, increased salivation, and sweating.

15. Management of treatment resistant schizophrenia: 1.Two treatment failures, including both FGAs and SGAs. 2.those patients who cannot tolerate even conservative doses of other antipsychotics. Clozapine is the drug of choice.