Efta Triastuti,M.Farm.klin.,Apt
Pharmacy Field of Study
Medicinal Faculty Brawijaya University
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
Consideration
Schizophrenia
clinical syndrome
several disease entities
psychotic symptoms
cognitive impairement
insight & motivation
disorder
loss of emotional
range
poverty of speech
Epidemiology
1% suffer schizophrenia
World’s population
Present in late adolescence & early adulthood
Equally prevalent between gender
Symptoms appear earlier in males
Etiology
Monozigot twin 50% if other diagnosed
Both parents diagnosed 40% risk
1st degree relatives 10% risk
Evidence supports genetic basic
??? (intrauterine viral/bacterial infections; environmental stimuli)
no single “schizophrenic gene”
Pathophysiology
Characteristic symptoms
Two (or more) of the following, each present for asignificant portion of time during a 1-month period:
Delusions
Hallucinations
Disorganized speech
Grossly disorganized behavior
Negative symptoms
Schizophrenia Criteria
Characteristic symptoms
Social/occupational
dysfunction
Continuous signs of disturbance persist
Ruling out other
disorders
Dopaminergic Treatment of Parkinson Disease May Lead Symptoms of Schizophrenia
L-dopa
• increased formation and release of dopamine
MAO inhibitors
• inhibit the breakdown of dopamine and thus increase its availability for release in the synaptic cleft
Cocaine
• stimulates dopamine release in the synaptic cleft
Amphetamine
• inhibits dopamine uptake in presynaptic nerve endings and thus at thesame time raises the transmitter concentration in the synaptic cleft
Antidopaminergic Substance Can Improve Schizophrenia
phenothiazines, haloperidol
• displace dopamine from receptors
Reserpine • Dopamine-depleting agent
at present not used therapeutically
Neuroleptic (Antipsychotic) Role to Dopamine
First-Generation Antipsychotics (FGAs)
Long-Acting Neuroleptics
FGAs Side Effect
Second-Generation Antipsychotics
Comparative Side Effects Among SGAs & Haloperidol
Schizophrenia Algorithm
First-Line Antipsychotic Therapy in Specific Patients
Metabolism and Drug Interactions with Antipsychotics
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
Monitoring Protocol for Patients
Consideration
Mood disorder
1 or more episodes of
mania or hypomania
history of one or more major
depressive episodes
Bipolar disorder
can be mixed
With/without psychosis
Increase suicide risk
Epidemiology
Bipolar disorder
Mean age onset: 20
Bipolar disorder I
one or more manic or mixed mood
episodes
affects men and women equally
Bipolar disorder II
one or more major depressive episodes
and at least one hypomanic episode
more common in women
Etiology
Trauma Environmental factors
Genetic Anatomic
abnormalities
Others Exposure to chemicals or drugs
Remain unclear
Secondary Cause of Bipolar Mania
Pathophysiology Hypothesis
Imbalance of cholinergicand
catecholaminergic neuronal activity
elevation of norepinephrine
(NE) and dopamine (DA) caused mania,
and a
reduction caused depression
mechanisms of
action of lithium and other mood stabilizers
Inositol depletion cause poor neuronal
growth
Bipolar Disorder Clinical Presentation
Gen
eral
hypomanic, manic, depressed or mixed state;
may or may not be in acute distress
Mo
od
an
d a
ffec
t Mood elevation,
Expansive mood,
Irritable mood,
Depression,
Hopelessness,
Suicidality
Ph
ysic
al/b
ehav
iora
l Agitation, Impulsivity, Aggression, Rapid & pressured speech, Decreased need for sleep, Insomnia (sometimes for days or weeks), Hypersexuality, Increased physical energy,
Heightened interest in pleasurable activities with high risk of negativeconsequences, Fatigue, Hypersomnia
Acute Manic Algorithm Therapy
Acute Manic Algorithm Therapy Cont...
Acute Depressive Episode
Acute Depressive Episode Cont...
Pharmacological Therapy of Bipolar Disorder
Pharmacological Therapy of Bipolar Disorder Cont...
Pharmacological Therapy of Bipolar Disorder Cont...
Pharmacological Therapy of Bipolar Disorder Cont...
Bipolar Disorder Medicine Absorption
Bipolar Disorder Medicine Distribution
Bipolar Disorder Medicine Renal Clearance
Bipolar Disorder Medicine Metabolism
Bipolar Disorder Medicine Side Effect
Valproic acid Carbamazepine Lamotrigin Lithium salts
loss of appetite, nausea, dyspepsia,and diarrhea, tremor, and drowsiness. (gastrointestinaldistresscan be reduced by co-administration with food), teratogenic
drowsiness,dizziness, ataxia, lethargy, and confusion, teratogenic
maculopapular rash, occurring in up to 10% ofPatients
gastrointestinal upset,tremor, & polyuria(dose-related).Nausea, dyspepsia, &diarrhea can be minimized bycoadministration with food, use of sustained-release formulations,& giving smaller doses more frequently to reduce theamount of drug in the gastrointestinal tract at a given time
Bipolar Disorder Medicine Drug Interaction
Valproic acid Carbamazepine Lamotrigine Lithium salts
•The risk of a dangerous rash due to lamotrigine is increased when given concurrentlywith divalproex
•The metabolism of divalproex can beincreased by enzyme-inducing drugs such ascarbamazepine &phenytoin
•While divalproexmay simultaneously slow metabolism of the other agents
•Carbamazepine induces the hepatic metabolism of many drugs & also autoinducer
•Antidepressants, macrolide antibiotics including erythromycin and clarithromycin, azole antifungal drugs including ketoconazole & itraconazole, and grapefruit juice may decrease the metabolism of Carbamazepine
•Divalproex slows the rate of eliminationof lamotrigine by about half(necessitating dosage reduction)
•Carbamazepineincreases the rate of lamotriginemetabolism
•The ACEIs increase serum lithium with the potential for acute and fatal toxicity
•Thiazide diuretics & NSAIDs increase Lithium retention
Monitoring Protocol for Patients
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
Thank You Very Much
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?
Cognitive Impairment
Thinking abnormalities
Reasoning abnormalities
Attention abnormalities
Perception abnormalities
Memory abnormalities
Motivation Disorder
10% die by suicide
Loss of motivation
Genes Involved
genes encoding dopamine receptors
Genes encoding serotonin receptors
Genes encoding enzyme that metabolizes dopamine
Genes encoding catechol-O-methyltransferase (COMT)