Nurdiana.

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PD-B/ 0810713031

MODUL NEUROPSIKIATRI 1

MODULE TASK

Case:
A college student is brought to the emergency room by friends. The physician is
informed that the student had taken a drug and then "went crazy.'" The patient is agitated
and delirious. Several persons are required to hold him down. His skin is warm and
sweaty, and his pupils are dilate& Bowel sounds are normal. Signs and symptoms include
tachycardia, marked hypertension, hyperthermia, increased muscle tone, and both
horizontal and vertical nystagmus.

1. What is the most likely cause of these signs and symptoms? Explain your answer
Hallucinogens
Phencyclidine : the arylcyclohexylamine drug phencyclidine (PCP; angel dust) is
probably the most dangerous of the currently popular hallucinogenic agents. Psychotic
reactions are common with PCP, and impaired from judgement often leads to reckless
behavior. This drug should be classified as a psychotomimetic. Effects of overdosage
with PCP include nystagmus, marked hypertension and seizures, which may be fatal.
2. What are the management of this patient? Explain your answer.
Parenteral benzodiazepines (eg, diazepam, lorazepam) are used to curb excitation
and protect against seizures
MODUL NEUROPSIKIATRI 2

MODULE TASK 1
Case :
The wife of a 24-year-old computer programmer considers him to be of a "nervous
disposition." He is easily startled, worries about inconsequential matters, and sometimes
complains of stomach cramps. At night he grinds his teeth in his sleep. There is no
current history of drug abuse.
1. Assuming that the symptoms experienced by this young man are not related to a
medical con-
dition, what is the most appropriate drug treatment ? Explain your answer.
Golongan benzodiazepines, eg : chlordiazepoxide, diazepam, temazepam.
Benzodiazepines memiliki kemampuan untuk menginisiasi ikatan antara neurotransmitter
inhibitor g-aminobutyric acid (GABA) dan GABAA, subtipe dari reseptor GABA yang
berupa multisubunit, ligand-gated chloride channels, sehingga memperbanyak aliran
GABA terinduksi inoik yang melalui kanal tersebut.
Efek yang menonjol dari benzodiazepines adalah sedasi, hypnosis, penurunan
kecemasan, relaksasi otot, anterograde amnesia dan anticonvulsant.
Benzodiazepines memiliki kemampuan depresi CNS yang lebih rendah dari barbiturates
dan volatile anesthetics, sehingga benzodiazepines lebih aman digunakan dalam
pemakaian klinis. Bertambahnya dosis benzodiazepine membuat efek sedasi menjadi
hypnosis dan kemudian stupor. Literatus klinis sering menggunakan efek "anesthetic" ini,
tetapi benzodiazepines tidak menimbulkan efek anesthesia sepenuhnya, karena kesadaran
biasanya tetap ada dan relaksasi yang ditimbulkan tidak cukup untuk melakukan prosedur
operasi.
Meskipun pemakaian benzodiazepine dalam dosis tinggi dapat menimbulkan coma, tidak
ada anesthesia surgical atau intoksikasi fatal yang diproduksi benzodiazepines tanpa
adanya obat lain yang berfungsi sebagai depresan CNS. Sebagai pengecualian adalah
midazolam, yang diasosiasikan dengan penurunan volume tidal dan respiratory rate.
Sebagai tambahan, antagonist dari benzodiazepines telah tersedia. Hal-hal tersebut
menjadikan benzodiazepines relative aman digunakan sehingga benzodiazepines telah
secara luas menggantikan agen lain untuk pengobatan insomnia dan kecemasan.

2. Regarding the characteristic properties of the drug prescribed for this young man,
what is the physician should be inform to the patient ? Explain your answer.
Disfungsi psikomotor : gangguan kognitif, penurunan kemampuan psikomotor, dan
efek sedasi di siang hari yang tidak diinginkan. Efek ini lebih umum ditemukan pada
benzodiazepines yang memiliki watu paruh yang panjang (eg, diazepam, flurazepam).
Flurazepam meninggkatkan kejadian mimpi buruk terutama minggu pertama
penggunaan dan terkadang menyebabkan garrulousness, anxiety, irritability,
tachycardia, and sweating. Amnesia, euphoria, restlessness, hallucinations, dan
perilaku hypomanic telah dilaporkan terjadi dalam penggunaan berbagai macam
benzodiazepines.
Penggunaan yang salah dari flunitrazepam (ROHYPNOL) dapat menimbulkan "date-
rape drug".
 Gejala withdrawal termasuk bertambahnya intensitas masalah yang menyebabkan
mereka menggunakan obat tersebut (eg. Insomnia atau kecemasan). Gejala lain
adalah dysphoria, irritability, sweating, unpleasant dreams, tremors, anorexia,
faintness, dan dizziness terutama bila penghentian yang tiba-tina dari penggunaan
benzodiazepine.

MODULE TASK 2
Case :
An 18-year-old woman was admitted for evaluation of therapy for frequent epileptic
absence attacks associated with minor automatisms. The patient had a history of
unsuccessful treatment with ethosuximide. The EEG showed generalized 3/s spike-and-
wave complexes and intermittent left temporal discharges. Therapy was restarted using
sodium valproate and carbamazepine. A 24-hour electroencephalographic study revealed
71 absence attacks. Increasing the valproate dosage from 1200 mg/d to 2400 mg/d was
associated with a significant but transient decline in absence frequency. Mean serum
levels of valproic acid at that time were 81 mg/L (109 mg/L peak, 36 mg/L trough) on a
twice-daily dosage regimen. Slow withdrawal of carbamazepine resulted in a decrease in
the number of clinical or electroencephalographic attacks. The addition of ethosuximide,
1000 ragC, resulted in disappearance of all seizure activity. The mean serum
ethosuximide level was 70 mg/L.
Six months later, an attempt was made to reduce the dosage of valproate. On a twice-
daily dose of 300 mg (600 mg/d total), mean serum levels dropped to 34 mg/L. There was
a prompt recurrence of
seizures, but they declined again when valproate dosage was returned to 2400 mg/d. A
follow-up study 8 months later demonstrated a continuing favorable response.

1. What was the rationale for the initial treatment with carbamazepine? Why was the
drug subsequently withdrawn, and why did the frequency of the seizures
decrease?
Carbamazepin menginduksi formasi dari enzim yang memetabolisme obat di liver
sehingga meningkatkan metabolisme carbamazepine sendiri serta dapat
 meningkatkan clearence dari banyak obat anticonvulsant lain. Pada pasien terdapat
riwayat pengobatan yang tidak sukses dengan etosuximide. Penggunaan
carbamazepin dalam kasus tersebut dapat sekaligus meningkatkan clearance dari
etosuximide.
Withdrawal dari semua obat antiseizure harus dilakukan secara bertahap. Hal ini
untuk menghindari peningkatan intensitas dan frekuensi dari seizure itu sendiri.
Efek dari carbamazepine adalah mengambat kanal sodium di membran neuron. Aksi
ini rate-dependent dan menghasilkan perpanjangan dari masa inactif dari kanal Na+
dan periode refractory di neuron
2. Why were blood levels of the drugs measured several times during the day?
Untuk mengetahui kadar anticonvulsant yang telah diberikan di dalam darah.
3. What are the hazards of therapy with ethosuximide? With sodium valproate?
Ethosuximide : GI distress, lethargy, headache
Valproic acid : GI distress, hepatotoxicity (jarang tetapi fatal), inhibisi
metabolisme obat, teratogen ( neural tube defects, eg. spina bifida)
4. What alternative drugs are possible for the management of absence seizures?
What are the side effects of such backup drugs?
Clonazepam efektif sebagai obat alternative dari absence seizures, tetapi clonazepam
memiliki efek sedasi dan tolerance.

MODUL NEUROPSIKIATRI 3

MODULE TASK 1
1. A schizophrenic patient developed bradykinesia, rigidity, and tremor during treatment
with haloperidol. His drug therapy was changed to thioridazine, which was just as
 effective in reducing his psychiatric symptoms. However, thioridazine did not cause
extrapyramidal dysfunction in this patient. What is the most likely explanation of
this?
Reversibel neurologic effect:
Dose dependent extrapiramidal effect (brady kenesia, rigidity, tremor) keracunan ini
dapat dibalik prosesnya dengan menurunkan dosi dan mungkin proses concomitant
penggunaan muscarinic agent keracunan ini biasanya disebabkan haloperidol.
Thioridazine has a wide therapeutic margin. At low and medium doses it relieves tension
and anxiety, and acts against multiple symptoms 9e.g. agitation depresion sleep
disturbance anxiety, tension, mixed states of anxiety and depression, agitation ) of non-
psychotic mental disorders.

2. A 30-year-old male patient is on drug therapy for a psychiatric problem. He

complains that he feels "flat" and that he gets confused at times. He has been gaining
weight and has lost his sex drive. As he moves his hands, you notice a slight tremor.
He tells you that since he has been on medication he is always thirsty and frequently
has to urinate. What is the drug he is most likely to be taking? Explain your answer.
Thioridazine dan phenotiazine ( chlorpazamine)
Karena memiliki autonomic effect muscarinic receptor blockade, obat ini susah di
management pada pasien berumur tua, karena toleransi pada autonomic effect muncul
dengan therapy yang berkelanjutan
Ciri: mulut kering, konstipasi, urin retensi, visual problem. Anti muscarinic yang ada
terkadang dapat menyebabkan keracunan sehingga pasien mengalami kebingungan

3. A young male patient diagnosed as schizophrenic develops severe muscle cramps

with torticollis a short time after drug therapy is initiated with haloperidol. What
would be the best course of action? Explain your answer.
Dystonic reaction have been reported in 10%-60% of patient treted with neuroleptic
medication, most commonly when patient just start or increase the dose of the drug. The
highest frequency of dystonic reaction has occured in patients receiving high-potency
neuroleptics. It has also been suggested that haloperidol-induced dystonic reaction are a
result of the toxic metabolites of the agent.
GC and torticollis reaction may occur 12-24 hours after treatment with a high potency
neuroleptic, even in the absence of symptoms of extrapyramidal side effect (EPSEs). The
delayed dystonic reaction may begin suddenly (no early EPSE symptomatology).

4. The effective treatment of a bipolar patient has necessitated doses of lithium that
result in plasma levels of 1.4 to 1.5 meq/L. Lately he has begun to suffer from
increased motor activity, aphasia, mental confusion, and social withdrawal. What
would be the best course of action? Explain your answer.
Lithium diserap secara cepat dari GIT. Obat ini didistribusikan melalui cairan tubuh dan
dikeluarkan oleh ginjal. Plasma level harus diperhatikan terutama pada minggu awal
pemberian. Trepai , plasma concentrasi dikeluarkan melalui cairan tubuh. Dehidrasi +
thiazide menyebabkan kenaikan lithium dalam darah ketahap keracunan theopilin
meningkatkan renal clearence dari lithium.

5. Within days of starting haloperidol treatment for a psychiatric disorder, a young male
patient developed severe generalized muscle rigidity and a high fever. In the
emergency room he was incoherent, with increased heart rate, hypotension, and
diaphoresis. Laboratory studies indicated acidosis, leukocytosis, and increased
creatine kinase. The most likely reason for these symptoms is that the patient was
suffering from what condition? Why is this happened? How is the management of
this condition?
Neyroleptic malignan syndrom, pasien yang sensitive terhadap extrapyramidal effect
dari antiphsycotic dapat menyebabkan malignant hypertermic syndrome. Symptom
termasuk kekakuan otot, berkeringat, hyperpyrexia, autonomic instability yang mungkin
life threatening. Obat: datrolene dan dopamine agonis

MODULE TASK 2
Case:
A 47-year-old man visited an outpatient clinic with initial complaints of chronic
tiredness, frequent bouts of stomach upset, and weight loss. Physical examination and
laboratory studies were within normal limits. A psychiatric evaluation revealed that the
patient had come to the clinic at the request of his wife, who thought that he was
"depressed." He had been waking during the early morning hours and could not get back
to sleep. The patient acknowledged that over the past year he had lost interest in his work
and had started to wort3" about providing for his family. He admitted to having also lost
interest in sex.
A diagnosis of major depression was made. Amitriptyline, 50 mg daily, was prescribed,
to be taken at bedtime for 3 nights, and 100 mg daily thereafter, also taken at bedtime.
Two weeks later, an interview indicated that the patient was sleeping better but that his
appetite remained poor and his mood was unimproved. The dose of Amitriptyline was
increased to 200 mg/d.
Eight weeks after the initial visit, the patient had regained most of his lost weight and no
longer had insomnia. However, he was not feeling much better. The side effects of the
drug were bothersome, and he was becoming increasingly worried about his job and his
family life. His feelings of inadequacy seemed to be increasing, and he had begun
questioning what use he was to anybody. The psychiatrist initiated dose-tapering of
amitriptyline and prescribed paroxetine (5 mg daily), with weekly increments of 5 mg up
to a maximum dose of 20 mg/d.
Evaluation of the patient after 4 weeks of treatment with paroxetine revealed a major
improvement in his mood. He had a renewed interest in his job and in the activities of his
family. His sex life had improved overall, though he was occasionally anorgasmic. Dry
mouth, constipation, and occasional 'jitteriness' were his only complaints about the drug
he was taking.
Questions:
1. What drug groups are available for the treatment of major depression?
a. Tricyclics (TCAs) imipramine, amitriptyline
b. Heterocyclics second generation : amoxapine, bnpropion, maprotiline,
trazodone. Third generation : mirtazapine, nefazadone, venlafaxine.
 c. Selective serotonin reuptake inhibitors (SSRIs)  Fluoxetine, sertraline,
citaloparm, paroxetine.
d. MAO inhibitors (MAOISs) phenelzine, tranylcypromine, isocarboxazid

2. What reasons would support the initial choice of amitriptyline in this patient?
Sedative adalah efek yang umun dr TCA dan digunakan jika sleeplessness sudah menjadi
suatu masalah. Efek sedative dari TCA dari aktivitas anti cholinergik dan anti
histaminergik. Amitryptilin, trimipramine, dan doxepine adalah agen sedative yang
paling kuat.
3. What reasons can you offer for the change in drug treatment to paroxetine?
TCA memiliki efek samping yang luas dan bisa mematikan apabila dosisnya terlalu
tinggi. Contoh efek samping :
 Efek psikiatrik dapat menyebabkan eksaserbasi dari kelainan psikosis pada
orang yang rentan. Pada konsentrasi plasma yang tinggi efek anti
cholinergik dari TCA dapat menyebabkan konvusion atau delirium.
 Efek antikolinergik : dry mouth, konstipasi, pandangan kabur, delirium,
retensi urin.
 Cardiac effect : tachycardia.
 Autonomic effects : orthostatic hypotension yang merupakan alasan utama
mengapa pemakaian TCA tidak dilanjutkan.

4. What side effects and potential drug interactions are troublesome during treatment of
depression with SSRIs?
SSRI merupakan inhibitor dari isozyme P450 sitokrom hepatic, suatu mekanisme yang
menyebabkan peningkatan aktivitas obat lain termasuk antidepresan trisiklik dan
warfarin. Fluvoxamine menghambat metabolism cisapride, astemizole, dan terfenadine,
dan resultan radiotoksisitas menyebabkan withdrawal dari 2 obat terakhir. Citalopram
menyebabkan interaksi obat yang lebih sedikit daripada SSRI lain. Ketika SSRI
digunakan pada kombinasi dengan obat lain yang meningkatkan fungsi serotonergic,
interaksi berbahaya mungkin terjadi. Sindroma serotonin telah dideskripsikan pertama
kali untuk interaksi antara fiuoxetine dan inhibitor MAO. Sindroma yang mengancam
jiwa meliputi kekakuan otot berat, myoclonus, hyperthermia, instabilitas kardiovaskular,
dan efek stimulasi CNS (kejang). Obat yang terlibat termasuk inhibitor MAO,
antidepresan trisiklik, meperidine, dan mungkin obat rekreasional haram seperti MDMA
(ekstasi). Obat antikejang, relaksan otot, dan reseptor 5-HT bloker (cyproheptadine) telah
digunakan dalam manajemen sindrom.