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)