Schizophrenia & gangguan bipolar

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  • 1. Efta Triastuti,M.Farm.klin.,Apt Pharmacy Field of StudyMedicinal Faculty Brawijaya University
  • 2. Competence Target Able to recognize schizophrenia symptoms Able to make therapeutic plan for acute psychosis Able to manage antipsychotic agent side effect Able to recognize altered mental status in bipolar disorder Able to prrovide appropriate pharmacological therapy in acute mania Able to determine monitoring strategy for anticonvulsion therapy in bipolar disorder
  • 3. Consideration clinical syndrome several poverty of disease speech entities Schizophrenia loss of psychotic emotional symptoms range insight & cognitive motivation impairement disorder
  • 4. Epidemiology Present in late adolescence & early adulthood 1% suffer Equally prevalent between schizophrenia gender Symptoms appear earlier in males World’s population
  • 5. Etiology Monozigot twin  50% if other diagnosed Both parents diagnosed  40% risk 1st degree relatives  10% risk Evidence supports genetic basic no single “schizophrenic gene” ??? (intrauterine viral/bacterial infections; environmental stimuli)
  • 6. Pathophysiology
  • 7. Characteristic symptoms Two (or more) of the following, each present for a significant portion of time during a 1-month period: Delusions Hallucinations Disorganized speech Grossly disorganized behavior Negative symptoms
  • 8. Schizophrenia Criteria Characteristic symptoms Ruling out Social/occu other pational disorders dysfunction Continuous signs of disturbance persist
  • 9. Dopaminergic Treatment of Parkinson DiseaseMay Lead Symptoms of Schizophrenia • increased formation and release of dopamine L-dopa • inhibit the breakdown of dopamine and thus increase its availability for MAO release in the synaptic cleft inhibitors • stimulates dopamine release in the synaptic cleft Cocaine • inhibits dopamine uptake in presynaptic nerve endings and thus at theAmphetamine same time raises the transmitter concentration in the synaptic cleft
  • 10. Antidopaminergic Substance CanImprove Schizophreniaphenothiazines, • displace dopamine from receptors haloperidol Reserpine • Dopamine-depleting agentat present not used therapeutically
  • 11. Neuroleptic (Antipsychotic) Roleto Dopamine
  • 12. First-Generation Antipsychotics(FGAs)
  • 13. Long-Acting Neuroleptics
  • 14. FGAs Side Effect
  • 15. Second-GenerationAntipsychotics
  • 16. Comparative Side Effects AmongSGAs & Haloperidol
  • 17. SchizophreniaAlgorithm
  • 18. First-Line Antipsychotic Therapyin Specific Patients
  • 19. Metabolism and DrugInteractions with Antipsychotics
  • 20. Desired Outcomes to receive comprehensive treatment designed to achieve functional outcomes to decrease positive symptoms and the associated hostile and aggressive behaviors to not only reduce symptomatology and psychotic relapses, but also to improve functional and social outcomes
  • 21. Monitoring Protocol for Patients
  • 22. Consideration 1 or more history of one Mood episodes of or more major Bipolardisorder mania or depressive disorder hypomania episodes can be mixed Increase suicide With/without risk psychosis
  • 23. Epidemiology Bipolar disorder Mean age onset: 20 Bipolar disorder I Bipolar disorder II one or more major one or more manic affects men and depressive episodes more common in or mixed mood women equally and at least one women episodes hypomanic episode
  • 24. Etiology Environmental Trauma factors Anatomic Genetic abnormalities Exposure to Others chemicals or drugs Remain unclear
  • 25. Secondary Cause of BipolarMania
  • 26. Pathophysiology Hypothesis elevation of norepinephrine Imbalance of mechanisms of (NE) and dopamine Inositol depletion cholinergicand (DA) caused mania, action of lithium and cause poor neuronalcatecholaminergic and a other mood stabilizers growth neuronal activity reduction caused depression
  • 27. Bipolar Disorder ClinicalPresentation hypomanic, Mood elevation, Agitation, Impulsivity, Physical/behavioralGeneral Mood and affect Aggression, Rapid & manic, depressed Expansive mood, pressured speech, or mixed state; Decreased need for Irritable mood, sleep, Insomnia may or may not (sometimes for days be in acute Depression, or weeks), distress Hopelessness, Hypersexuality, Increased physical Suicidality energy, Heightened interest in pleasurable activities with high risk of negative consequences, Fatigue, Hypersomnia
  • 28. Acute Manic Algorithm Therapy
  • 29. Acute Manic Algorithm TherapyCont...
  • 30. Acute Depressive Episode
  • 31. Acute Depressive Episode Cont...
  • 32. Pharmacological Therapy ofBipolar Disorder
  • 33. Pharmacological Therapy ofBipolar Disorder Cont...
  • 34. Pharmacological Therapy ofBipolar Disorder Cont...
  • 35. Pharmacological Therapy ofBipolar Disorder Cont...
  • 36. Bipolar Disorder MedicineAbsorption
  • 37. Bipolar Disorder MedicineDistribution
  • 38. Bipolar Disorder Medicine RenalClearance
  • 39. Bipolar Disorder MedicineMetabolism
  • 40. Bipolar Disorder Medicine Side EffectValproic acid Carbamazepine Lamotrigin Lithium saltsloss of appetite, drowsiness, maculopapular rash, gastrointestinal upset,nausea, dyspepsia, dizziness, ataxia, occurring in up to 10% tremor, & polyuriaand diarrhea, tremor, lethargy, and of (dose-related).and drowsiness. confusion, teratogenic Patients Nausea, dyspepsia, &(gastrointestinal diarrhea can bedistress minimized bycan be reduced by co- coadministration withadministration with food, use offood), teratogenic sustained-release formulations, & giving smaller doses more frequently to reduce the amount of drug in the gastrointestinal tract at a given time
  • 41. Bipolar Disorder Medicine Drug InteractionValproic acid Carbamazepine Lamotrigine Lithium salts•The risk of a •Carbamazepine •Divalproex slows the •The ACEIs increase dangerous rash due induces the hepatic rate of elimination serum lithium with to lamotrigine is metabolism of many of lamotrigine by the potential for increased when drugs & also about half acute and fatal given concurrently autoinducer (necessitating toxicity with divalproex •Antidepressants, dosage reduction) •Thiazide diuretics &•The metabolism of macrolide antibiotics •Carbamazepine NSAIDs increase divalproex can be including increases the rate of Lithium retention increased by erythromycin and lamotrigine enzyme-inducing clarithromycin, azole metabolism drugs such as antifungal drugs carbamazepine & including phenytoin ketoconazole &•While divalproex itraconazole, and may simultaneously grapefruit juice may slow metabolism of decrease the the other agents metabolism of Carbamazepine
  • 42. Monitoring Protocol for Patients
  • 43. Primary References Wells, B., Dipiro, J.T., Schwinghammer, T.L., Dipiro, C.V., 2009. Pharmacotherapy Handbook. 7th Ed. Mc Graw Hill Companies. Inc. New York Schwinghammer, T.L. & Koehler, J.M. 2009. Pharmacotherapy Casebook: A Patient-Focused Approach. 7th Ed. Mc Graw Hill Companies. Inc. New York Fletcher, A.J., Edwards, L.D., Fox, A.W., Stonier, P. 2002. Principles and Practice of Pharmaceutical Medicine. John Wiley & Sons, Ltd. UK
  • 44. Thank You Very Much
  • 45. Post Test1. Jelaskan peranan dopamin dalam pembentukan schizophrenia!2. Sebutkan sekurangnya 2 penggunaan lain dari antagonis reseptor D2!3. Bagaimanakah efek pemberian clozapine bersamaan dengan penggunaan antibiotik ciprofloksasin? Bagaimana mekanisme terjadinya efek tersebut?4. Bagaimanakah efek pemberian asam valproat bersamaan dengan pemberian lamotrigin? Bagaimanakah mekanisme terjadinya efek tersebut?5. Bagaimanakah cara meminimalisasi efek samping terapi Lithium terhadap saluran cerna?
  • 46. Cognitive Impairment Thinking abnormalities Reasoning abnormalities Attention abnormalities Perception abnormalities Memory abnormalities
  • 47. Motivation Disorder 10% die by suicide Loss of motivation
  • 48. Genes Involved genes encoding dopamine receptors Genes encoding serotonin receptors Genes encoding enzyme that metabolizes dopamine Genes encoding catechol-O-methyltransferase (COMT)