1. Efta Triastuti,M.Farm.klin.,Apt
Pharmacy Field of Study
Medicinal 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

4. Consideration
clinical
syndrome
several
poverty of
disease
speech
entities
Schizophrenia
loss of
psychotic
emotional
symptoms
range
insight &
cognitive
motivation impairement
disorder

5. Epidemiology
Present in late adolescence &
early adulthood
1% suffer Equally prevalent between
schizophrenia gender
Symptoms appear earlier in
males
World’s
population

6. 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)

7. Pathophysiology

8. 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

9. Schizophrenia Criteria
Characteristic
symptoms
Ruling out Social/occu
other pational
disorders dysfunction
Continuous signs of
disturbance persist

11. Dopaminergic Treatment of Parkinson Disease
May 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 the
Amphetamine
same time raises the transmitter concentration in the synaptic cleft

12. Antidopaminergic Substance Can
Improve Schizophrenia
phenothiazines,
• displace dopamine from receptors
haloperidol
Reserpine • Dopamine-depleting agent
at present not used therapeutically

13. Neuroleptic (Antipsychotic) Role
to Dopamine

14. First-Generation Antipsychotics
(FGAs)

15. Long-Acting Neuroleptics

16. FGAs Side Effect

17. Second-Generation
Antipsychotics

18. Comparative Side Effects Among
SGAs & Haloperidol

19. Schizophrenia
Algorithm

20. First-Line Antipsychotic Therapy
in Specific Patients

21. Metabolism and Drug
Interactions with Antipsychotics

22. 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

23. Monitoring Protocol for Patients

25. Consideration
1 or more history of one
Mood episodes of or more major Bipolar
disorder mania or depressive disorder
hypomania episodes
can be mixed
Increase suicide With/without
risk psychosis

26. 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

27. Etiology
Environmental
Trauma
factors
Anatomic
Genetic
abnormalities
Exposure to
Others chemicals or
drugs
Remain unclear

28. Secondary Cause of Bipolar
Mania

29. Pathophysiology Hypothesis
elevation of
norepinephrine
Imbalance of mechanisms of
(NE) and dopamine Inositol depletion
cholinergicand
(DA) caused mania, action of lithium and cause poor neuronal
catecholaminergic
and a other mood stabilizers growth
neuronal activity
reduction caused
depression

30. Bipolar Disorder Clinical
Presentation
hypomanic, Mood elevation, Agitation, Impulsivity,
Physical/behavioral
General
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

32. Acute Manic Algorithm Therapy

33. Acute Manic Algorithm Therapy
Cont...

34. Acute Depressive Episode

35. Acute Depressive Episode Cont...

36. Pharmacological Therapy of
Bipolar Disorder

37. Pharmacological Therapy of
Bipolar Disorder Cont...

38. Pharmacological Therapy of
Bipolar Disorder Cont...

39. Pharmacological Therapy of
Bipolar Disorder Cont...

40. Bipolar Disorder Medicine
Absorption

41. Bipolar Disorder Medicine
Distribution

42. Bipolar Disorder Medicine Renal
Clearance

43. Bipolar Disorder Medicine
Metabolism

44. Bipolar Disorder Medicine Side
Effect
Valproic acid Carbamazepine Lamotrigin Lithium salts
loss of appetite, drowsiness, maculopapular rash, gastrointestinal upset,
nausea, dyspepsia, dizziness, ataxia, occurring in up to 10% tremor, & polyuria
and diarrhea, tremor, lethargy, and of (dose-related).
and drowsiness. confusion, teratogenic Patients Nausea, dyspepsia, &
(gastrointestinal diarrhea can be
distress minimized by
can be reduced by co- coadministration with
administration with food, use of
food), teratogenic sustained-release
formulations,
& giving smaller doses
more frequently to
reduce the
amount of drug in the
gastrointestinal tract
at a given time

45. Bipolar Disorder Medicine Drug
Interaction
Valproic 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

46. Monitoring Protocol for Patients

47. 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

48. Thank You Very Much

49. Post Test
1. 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?

50. Cognitive Impairment
Thinking abnormalities
Reasoning abnormalities
Attention abnormalities
Perception abnormalities
Memory abnormalities

51. Motivation Disorder
10% die by
suicide
Loss of
motivation

52. Genes Involved
genes encoding dopamine receptors
Genes encoding serotonin receptors
Genes encoding enzyme that metabolizes dopamine
Genes encoding catechol-O-methyltransferase (COMT)