Mania

The experience of mania is often quite unpleasant and sometimes disturbing, if not frightening, for the
person involved and may lead to impulsive behavior that may later be regretted.

Understanding Mania

Mania is a medical condition characterized by severely elevated mood People who experience a manic
state often describe themselves as feeling high and superior. Generally, mania also provokes racing
thoughts and creative ideas. However, it also pushes sufferers into agitation and poor decisions. Mania is
most usually associated with bipolar disorder, where episodes of mania may alternate with episodes
ofdepression. Not all mania can be classified as bipolar disorder, as mania may result from other diseases
or causes. However, bipolar disorder is the classic manic disease.
Manic patients are frequently grandiose, irritable, belligerent, and frequently deny anything is wrong with
them. Because mania frequently encourages high energy and decreased perception of need or ability to
sleep, within a few days of a manic cycle, sleep-deprived psychosis may appear, further complicating the
ability to think clearly. Racing thoughts and misperceptions lead to frustration and decreased ability to
communicate with others.
Other manic symptoms include irritability, hyper-sexuality, hyper-religiosity, hyperactivity, talkativeness,
and grandiose ideas and plans. In manic and less severe hypomanic cases, the afflicted person may
engage in out of character behavior such as questionable business transactions, wasteful expenditures of
money, risky sexual activity or highly vocal arguments uncharacteristic of previous behaviors. These
behaviors increase stress in personal relationships, problems at work and increases the risk of
altercations with law enforcement as well as being at high risk of impulsively taking part in activities
potentially harmful to self and others.
Additional possible symptoms of mania include elation, extreme optimism, rapid unstoppable flow of
speech, racing thoughts/flights of ideas, agitation, poor judgment, recklessness, inordinate capacity for
activity, tendency to be easily distracted, inability to concentrate, exuberant and flamboyant or colorful
dress, authoritative manner, and tendency to believe they are in their best mental state.
More severe symptoms include hallucinations (hearing, seeing, or otherwise sensing the presence of
stimuli that are not there) and delusions (false personal beliefs that are not subject to reason or
contradictory evidence and are not explained by a person's cultural concepts). Feelings of paranoia,
during which the patient believes he or she is being persecuted or monitored by the government or a
hostile force, may be present. Intense and unusual religious beliefs may also be present, such as a
patient's strong insistence that they have a God-given role to play in the world, a great and historic
mission to accomplish, or even that they possess supernatural powers.

Understanding Hypomania

Hypomania is a less severe form of mania, without progression to psychosis (hallucinations and

delusions). Many of the symptoms of mania are present, but to a lesser degree than in overt mania.
People with hypomania are generally perceived as being energetic, euphoric, overflowing with new ideas,
and sometimes highly confident and charismatic, and unlike full-blown mania, they are sufficiently capable
of coherent thought and action to participate in everyday activities.
Mixed state
In the context of bipolar disorder, a mixed state is a condition during which symptoms of mania (or
hypomania) and clinical depression occur simultaneously (for example, agitation, anxiety, fatigue, guilt,
impulsiveness, insomnia, disturbances in appetite, irritability, morbid and/or suicidal ideation, panic,
paranoia, psychosis, pressured speech, indecisiveness and rage). Mixed states can be the most
dangerous period of mood disorders, during which panic attacks, substance abuse, and suicide attempts
increase greatly.
Cycling
Rapid cycling, defined as having four or more episodes per year, is found in a significant fraction of
patients with bipolar disorder. Ultradian or 'Ultra-Ultra-Rapid' cycling, in which mood cycling can also
occur daily or even hourly, is less common.

Causes of Mania and Bi-Polar Disorder

According to the US government's National Institute of Mental Health (NIMH), there is no single cause for
bipolar disorder, rather, many factors act together to produce the illness. Since bipolar disorder tends to
run in families, researchers have been searching for specific genes passed down through generations
that may increase a person's chance of developing the illness.
It is well established that bipolar disorder is a genetically influenced condition which can respond very well
to medication. Psychological factors also play a strong role in both the psychopathology of the disorder
and the psychotherapeutic factors aimed at alleviating core symptoms, recognizing episode triggers,
reducing negative expressed emotion in relationships, recognizing prodromal symptoms before full-blown
recurrence, and practicing the factors that lead to maintenance of remission.

Diagnosis of Mania and Bi-Polar Disorder

The DSM-IV-TR details four categories of bipolar disorder, Bipolar I, Bipolar II, Cyclothymia, and Bipolar
Disorder NOS (Not Otherwise Specified). There are many problems with symptom accuracy, relevance,
and reliability in making a diagnosis of bipolar disorder using the DSM-IV-TR. These problems all too
often lead to misdiagnosis. If misdiagnosed with depression, patients are usually prescribed
antidepressants, and the person with bipolar depression can become agitated, angry, hostile, suicidal,
and even homicidal (these are all symptoms of hypomania, mania, and mixed states).

Treatment of Mania and Bi-Polar Disorder

Currently, mania and bipolar disorder cannot be cured, but psychiatrists and psychologists believe that it
can be managed. Before beginning treatment for mania, careful differential diagnosis must be performed
to rule out non-psychiatric causes.
Acute mania in bipolar disorder is typically treated with mood stabilizers and/or antipsychotic medication.
When the symptoms of mania have gone, long-term treatment then focuses on prophylactic treatment to
try to stabilize the patient's mood, typically through a combination of pharmacotherapy
and psychotherapy.
The emphasis of treatment is on effective management of the long-term course of the illness, which
usually involves treatment of emergent symptoms. Treatment methods include pharmacological and
psychotherapeutic techniques. The goals of long-term optimal treatment are to help the individual
achieve the highest level of functioning while avoiding relapse.
Bipolar disorder is a severely disabling medical condition. In fact, it is the 6th leading cause of disability in
the world, according to the World Health Organization. However, with appropriate treatment, many
individuals with bipolar disorder can live full and satisfying lives. Persons with bipolar disorder are likely to
have periods of normal or near normal functioning between episodes.
Ultimately one's prognosis depends on many factors including the right medicines and the right dose of
each, an informed patient, a good working relationship with a competent medical doctor, a competent,
supportive, and warm therapist, and a balanced lifestyle including a regulated stress level, regular
exercise and regular sleep and wake times.
There are obviously other factors that lead to a good prognosis, as well, such as being very aware of
small changes in one's energy, mood, sleep and eating behaviors, as well as having a plan in conjunction
with one's doctor for how to manage subtle changes that might indicate the beginning of a mood swing.

Wikipedia: Bipolar Disorder in Children

The following 4 paragraphs briefly presents information on mania and manic-depressive illness in
children. This material has been adapted from Wikipedia.
Children with bipolar disorder tend to have rapid-cycling or mixed-cycling. Rapid cycling occurs when the
cycles between depression and mania occur quickly, sometimes within the same day or the same hour.
When the symptoms of both mania and depression occur simultaneously, mixed cycling occurs.
Often other psychiatric disorders are diagnosed in bipolar children. These other diagnoses may be
concurrent problems, or they may be misdiagnosed as bipolar disorder.
Depression, ADD, ADHD, OCD,schizophrenia, and Tourette syndrome are common comorbid conditions.
Misdiagnosis can lead to incorrect medication. Incorrect medications can trigger mania and/or suicidal
ideation and attempts.
During severe episodes of mania and mixed states, a child may suffer from symptoms of psychosis.
These episodes can be negative (such as thinking their poster on the wall is staring at them angrily) or
positive (such as telling people that a rock band is coming to his or her birthday party).
There are many medications which can help calm the symptoms of bipolarity, including in children and
adolescents. However, finding the right medicine or combination of medicines is not easy. An exact
scientific means of choosing medication for bipolar treatment does not exist. With children this problem is
made worse by the fact that as children grow, their weight, metabolism, hormones, brain structure, etc.

changes. These changes often require adjustments in the medication(s), significantly more often than
adults.

Etiology
A number of factors contribute to bipolar affective disorder, or manic-depressive illness (MDI), including
genetic, biochemical, psychodynamic, and environmental factors.

Genetic factors
Bipolar disorder, especially bipolar type I (BPI) disorder, has a major genetic component, with the
involvement of the ANK3,CACNA1C, and CLOCK genes.[18, 19, 20, 16, 17, 25, 43] The evidence indicating a genetic
role in bipolar disorder takes several forms.
First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the
general population. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having
another major psychiatric disorder. One logitudinal study found that subthreshold manic or hypomanic
episodes were a diagnostic risk factor for the development of subsequent manic, mixed, or hypomanic
episodes in the offspring of parents with bipolar disorder. High-risk offspring, compared with offspring of
parents without bipolar disorder, also had higher rates of ADHD, disruptive behavior disorders, anxiety
disorders, and substance use disorders.[44]
Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. As identical twins share
100% of their DNA, these studies also show that environmental factors are involved, and there is no
guarantee that a person will develop bipolar disorder, even if they carry susceptibility genes.
Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur
in families. Children whose biologic parents have either BPI or a major depressive disorder remain at
increased risk of developing an affective disorder, even if they are reared in a home with adopted parents
who are not affected. Frey and colleagues work supports the genetic contributions in bipolar affective
disorder.[45, 46]
Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that
schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability
was the same for schizoaffective disorder as for the other 2 syndromes.[47] This finding suggests an
independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders, as
Berrettini[48] previously speculated and that has been confirmed in the recent large-scale GWAS studies
mentioned above.[17]
Gene expression studies also demonstrate that persons with bipolar disorder, major depression, and
schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and
abnormalities of white matter in various brain regions.

Biochemical factors
Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular
abnormality is difficult. A number of neurotransmitters have been linked to this disorder, largely based on
patients responses to psychoactive agents as in the following examples.

The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted
incidentally to cause depression. This led to the catecholamine hypothesis, which holds that an increase in
epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes
depression.
Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines,
including serotonin, norepinephrine, or dopamine, can all potentially trigger mania, implicating all of these
neurotransmitters in its etiology. Other agents that exacerbate mania include L-dopa, which implicates
dopamine and serotonin-reuptake inhibitors, which in turn implicate serotonin.
Evidence is mounting of the contribution of glutamate to both bipolar disorder and major depression. A
postmortem study of the frontal lobes of individuals with these disorders revealed that the glutamate levels
were increased.[49]
Calcium channel blockers have been used to treat mania, which may also result from a disruption of
intracellular calcium regulation in neurons as suggested by experimental and genetic data. The proposed
disruption of calcium regulation may be caused by various neurologic insults, such as excessive
glutaminergic transmission or ischemia. Interestingly, valproate specifically upregulates expression of a
calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.
Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis
and the stress response may also contribute to the clinical picture of bipolar disorder.

Neurophysiologic factors
In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of
brain activity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical
networks, that are either hypoactive or hyperactive in a particular illness. For example a meta-analysis by
Houenou et al found decreased activation and diminution of gray matter in a cortical-cognitive brain
network, which has been associated with the regulation of emotions in patients with bipolar disorder.[50] An
increased activation in ventral limbic brain regions that mediate the experience of emotions and generation
of emotional responses was also discovered. This provides evidence for functional and anatomic
alterations in bipolar disorder in brain networks associated with the experience and regulation of emotions.
[50]

Psychodynamic factors
Many practitioners see the dynamics of manic-depressive illness as being linked through a single common
pathway. They see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense
of worthlessness). Therefore, the mania serves as a defense against the feelings of depression. Melanie
Klein was one of the major proponents of this formulation.
A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are
often noted in patients with bipolar disorder and may be enduring characteristics. [51]

Environmental factors
In some instances, the cycle may be directly linked to external stresses or the external pressures may
serve to exacerbate some underlying genetic or biochemical predisposition. For example, pregnancy is a
particular stress for women with a manic-depressive illness history and increases the possibility of
postpartum psychosis.[52]

Because of the nature of their work, certain individuals have periods of high demands followed by periods
of few requirements. For example, a landscaper and gardener who was busy in the spring, summer, and
fall became relatively inactive during the winter, except for plowing snow. Consequently, he appeared manic
for a good part of the year, and then he would crash and hibernate during the cold months.

Pharmacological factors
There is the risk that antidepressant treatment may propel the patient into a manic episode. Researchers
investigated the association between antidepressant therapy and the later onset of mania/bipolar
disorder. They analyzed the electronic records of 21,012 adults presenting to South London and Maudsley
National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental
healthcare in the United Kingdom, between April 1, 2006 and March 31, 2013 with unipolar depression. The
overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of
mania/bipolar disorder was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years).
Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder
ranging from 13.1 to 19.1 per 1000 person-years. Results suggest that in people with unipolar depression,
antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These
findings highlight the importance of considering risk factors for mania when treating people with depression.
[53]

Medications
A number of medications are used to treat bipolar disorder. The types and doses of
medications prescribed are based on your particular symptoms.
Medications may include:

Mood stabilizers. Whether you have bipolar I or II disorder, you'll typically need
mood-stabilizing medication to control manic or hypomanic episodes. Examples of mood
stabilizers include lithium (Lithobid), valproic acid (Depakene), divalproex sodium
(Depakote), carbamazepine (Tegretol, Equetro, others) and lamotrigine (Lamictal).

Antipsychotics. If symptoms of depression or mania persist in spite of treatment

with other medications, adding an antipsychotic medication such as olanzapine
(Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify),
ziprasidone (Geodon), lurasidone (Latuda) or asenapine (Saphris) may help. Your doctor
may prescribe some of these medications alone or along with a mood stabilizer.

Antidepressants. Your doctor may add an antidepressant to help manage

depression. Because an antidepressant can sometimes trigger a manic episode, it's
usually prescribed along with a mood stabilizer or antipsychotic.

Antidepressant-antipsychotic. The medication Symbyax combines the

antidepressant fluoxetine and the antipsychotic olanzapine. It works as a depression
treatment and a mood stabilizer. Symbyax is approved by the Food and Drug
Administration specifically for the treatment of depressive episodes associated with
bipolar I disorder.

Anti-anxiety medications. Benzodiazepines may help with anxiety and improve

sleep. Benzodiazepines are generally used for relieving anxiety only on a short-term
basis.

Mood stabilitator adalah kelompok obat yang secara primer digunakan untuk penanganan
penyakit manik-depresif , efektif untk mania akut, tdk utk depresi akut. Terdiri atas Lithium dan
Antikonvulsan yaitu Valproat dan Carbamazepin. Obat antikonvulsan terbaru dan antipsikotik
atypical seperti closapine juga menjanjikan sebagai mood stabilitator pada sbg kecil percobaan
klinis. Obat lainnya seperti verapamil Ca chanel Bloker juga bersifat mood stabilitator sama
baiknya dengan Clonasepan yg merupakan Benzodiasepin potensi tinggi yang juga bersifat mood
stabilitator .
Penggunaan kombinasi mood stabilizator diperimbangkan jika penggunaan tunggal tidak
memberikan respon yang optimal, kombinasi harus di beri perhatian pada timbulnya toksititas,
dgn memonitor level darah obat kombinasi tersebut. Suatu kesalahan yg umum pd polifarmasi
pada bipolar adalah memberikan ps AD yg terlalu lama,yg bresiko minduksi atau pemeliharaan
keadaan mania.
1. LITHIUM
Lithium adalah zat padat yang paling ringan pada table periodik, zat aktif psikofarmakologik
dalam bentuk kation. Ditemukan scr tak sengaja oleh Code pd thn 1949 saat di gunakan sbg efek
penenang pd binatang dan kemudian dicobakan pada 10 pasien mania. 1970 digunakan di AS
setelah tertunda akibat timbulnya keracunan Li pd 1940 an pd penggunan sbg pengganti garam.
Farmakologi
Tablet dan kapsul Li tersedia sebagai garam karbonat yang sedikit mengiritasi traktus GI
daripada Klorida, tiap 300 mg tablet berisi 8 mmol Li. Karena ion tunggal maka sama dgn 8
mEq. Tersedia sebagai sirup lithium sitrat.
Ekskresi di ginjal maksimal pd bbrp jam pertama setelah kadar puncak dicapai bekerja
lebihlambat beberapa hari kemudian. Pada orang dewasa sehat eliminasi waktu paruh Li 24 +8
jam, pd ps tua eliminasi waktu paruh mungkin memanjang , juga mungkin meningkat pada
disfungsi renal, kehamilan meningkatkan klirens Li.
Mekanisme Kerja
Li memiliki efek akut dan kronik pd pelepasan serotonin dan norepinefrin dari ujung saraf,
pada konsentrasi yng lebih tinggi memiliki efek pada pompa ion transmembran.Mekanisme kerja
Li yg terbaru saat ini adalah hipotesis deplesi inosital dan kerja Li pd jalur kecil wnt.
Indikasi
Li efektif pada pengobatan gangguan bipolar baik untuk mania akut maupun untuk
pencegahan kambuhnya mania.
Gangguan Bipolar
Li adalah pengobatan yang paling baik dan efektif utk gangguan bipolar. Li tidak secara
penuh pada semua fase , efektif untuk mania akut dan mencegah kekambuhan mania, efektif
sedang pada pencegahan kekambuhan depresi dan tidak adekuat untuk pengobatan depresi akut.
Untuk episode depresif Li di kombinasi dengan obt lain. Selama mania akut kombinasi dgn AP
dan BZ sering bermanfaat. Selama episode depresi akut penggunaan AD sering di indikasikan,
karena kekompleksitasnya maka gangguan bipolar diobatai secara terpisah spt di bawah ini :
Mania Akut
Li adalah pengobatan yg efektif pd episode mania lebih efektif dari pd AP yg di pakai untuk
terapi tunggal untuk mengobati mania akut.Li digunakan tunggal jika gjl mania tdk terlalu berat,
jika mania berat/hebat respon terapeutik Li melambat.Jadi awalnya pd pengobatan mania akut ,
AP sering digunakan sbg tambahan , efektif diberikan dlm dosis penuh AP (8-10 mg hlp), BZ
digunakan jika sedasi tambahan diperlukan dalam pegobatan awal mania akut (lorazepam 1-2
mg atau klonazepam 0,5 mg tiap 2 jam). Verapamil Ca chabel bloker dpt digunakan utk mania

akut, baik sbg obat tunggal, kombinasi dngn Li atau AP dan dipakai utk pengobatan propilaksis
serangan spt valproat, CBZ, gabapentin
Mania refrakter terhadap pengobatan
Kombinasi Valproat CBZ pd ps refrakter Li atau intoleransi Li telah dilaporkan sukses,
Biasanya dosis valproat ditingkatkan tau dosis CBZ di turunkan jika kombinasi ini digunakan.
Episode yg sgt berat dari mania yg tdk berespon terhadap pengobatan dapat berespo thdp
therapy ECT , remisi sering terjadi setelah 6 kali pengobatan, krn gg bipolar memerlukan
profilaksis jangka pjng yg tdk dapat di berikan pd ECT . ECT aman dan efektif pd ps yg menerima
Li atau AP, valproat atau CBZ akan meningkatkan ambang serangan.
Depresi bipolar akut
Pengobatan AD pd ps bipolar memberikan pencetus timbulnya mania atau hipomania atau
mempengaruhi siklus cepat, jadi aturannya bhw pengobatan depresi bipolar dgn AD digunakan
bersama antimania berbeda dngn ps uniplar.Jika psikosis ada selama episode depresif suatu
obat AP atau ECT dpt dipertimbangkan.
2. PENGGUNAAN ANTIKONVULSAN
Ada dua macam AK yg terbukti berhasil untuk terapi keluhan afektif bipolar, yg lain msh
diteliti. CBZ adakah AK yg pertama digunakan untuk mania, tapi saat ini dokter lebih menyukai
as valproat dan lebih diterima utk pengobatan gangguan bipolar.
Sepert Li baik as valproat dan CBZ lebih efektif mengobati dan mencegah episode mania
daripada episode depresif. Phenitoin dan barbiturate tidak memiliki efek sbg mood stabilizeryg
dipakai utk penanganan gg bipolar, antikonvulsan lainnya masih dlm penelitian utk dipakai di
psikiatri. Clonazepan efektif pada gg panik dan dipakai sbg terapi adjuvan pd ps gg bipolar dan
psikotik yg membutuhkan ansiolitik dan sedasi sbg terpi tambahan.
VALPROAT
Valproat sama efektifnya dgn Li dalam pengobatan gangguan bipolar.Awalnya di pakai sbg
antikonvuksan dan efektif utk mengontrol petit mal, mioklonik dan kejang tonik-klonik umum.
Kurang efektif untuk kejang fokal dgn atau tanpa keluhan Kompleks. Obat ini diakui oleh FDA
pd thn 1995 utk pengobatan mania akut. Valproat Lebih superior dari Li siklus cepat dan
disphorik mania. di pilih sebagi lini pertama terapi mania oleh banyak dokter.
Farmakologi
Sediaan btk kapsul atau sirup, divalproat sodium sbg btk enteric-coated yg mengandung as
valproit dan natrium valproit.baik as valproit dan valproeks dlm btk ion valproat.
As valproat diserap cepat stlh penberian oral, mencapai puncaknya 1 2 jam jika perut kosong, 4
5 jam jika bersamaan dgn makanan.Divalproat sodium diabsorbsi lbh lambat puncak dlm
serum 3 8 jam. Di plasma VA 80 -95 % terikat protein, cepat dimetabolisme di hati , metabolit
aktif blm diketahui.Dpt berinteraksi dengan obat lainya yang terikat dgn protein dan di
metabolisme di hati.VA eliminasi singkat dgn wkt paruh 8 jam yg dipakai 3 kali sehari pd
epilepsi, di berikan dosis terbagi pd gg bipolar. Sedikit hubungan antara level serum dgn efek
anti manik , tp level 50 150 ug/mL dianjurkan, level serum di ukur dgn immunoassay atau
khromatografi gas.
Mekanisme kerja pd gg bipolar dan epilepsi tidak diketahui, tp VA meningkatka level sinaps dr
GABA yg bekerja menghambat neurotrasmiter di otak.
Interaksi Obat
Interaksi farmakodinamik dgn obt psikotropik, spt CBZ, Li, dan AP yang bspt toksi pd SSP.
Interaksi farmakokinetik dgn menghambat metabolisme obat yg dioksidasi di hati , shg terjadi
peningkatan obt AD siklik dan mungkin jg SSRI, phenitoin, phenobarbital dan obt lainnya.
Konsentasi VA menurun oleh obt yg menginduksi enzim mikrosomal hepatik spt CBZ, meningkat
oleh obt yg menghambat enzim mikrosomal hepatik spt SSRI.
Krn sebagian di eliminasi mllui urine sbg ketometabolit, dpt slh interpretasi pd tes ketone urine.
CARBAMAZEPIN

Antikonvulsan imunostabiizer yg scr struktu mirip dgn imipramine AD trisiklik.

Drug of choice utk epilepsi patial dgn atau tanpa gejala kompleks, juga efektif utk kejang umum
primer. Juga utk neuralgia trigeminal dan juga gejala nyeri neuropati lainnya.
Efektif utk mania akut, sama efektif dgn LI, juga utk propilaksis jangka panjang ps
bipolar.meskipun refrakter thd LI.
Farmakologi
Sediaan oral 100 dan 200 mg tablet dan sirup, btk perenteral tdk tersedia.
Diabsorbsi lambat, level puncak dicapai 4 8 jam atau lebih lambat, btk slow-release lbh stabil
dlm konsentrasi serum disbanding btk tablet.
Kurang larut dlm cairan lambung , 15 25 % dieksresikan melalui faces btk utuh.efek makanan
thdp absorbs kurang berarti, 65 -85 % terikat protein dlm darah.
Level terapi utk epilepsy 4 12 ug/ml , batas bawah efektif utk kjg tonik klonik, batas atas efektif
utk kejang partial dgn atau tanpa kjg tonik klonik.
Untuk bipolar level darah 8 12 mg/ml merpkan efikasi terapi.
CBZ dimetabolisme di hati, 10-,11-epoxide adalah hasil metabolit yg mrpkn suatu antikonvulsan,
tdk diketahui sbg zat antimanik.
Waktu paruh pd dosis tgl dgn org normal 18 -55 jam, dosis ulangan menurun 5 20 jam (lbh pjg
pd org tua), penurunan ini terjadi krn induksi obat dr metabolitme sendiri olh enzim P450 hepar
(efek aotoinduksi).
Iduksi jg oleh obt antikonvulsan; phenytoin, phenobarbital dan primidone yg mengakibatkan kdr
serum lbh rendah.
Mekanisme Kerja
Ada dua meknisme yg di kenal; pembukaan chanel sodium sensitiv-voltase adlh pusat dari
mekanisme potensial aksi neuron.Chanel menjadi tdk aktif sementara stlh digunakan , CBZ
terikat pd keadan inaktif dr chanel natrium, menghambat scr berulang aksi potensial; CBZ
mempengaruhi didaerah chanel natrium pd badan sel neuron. Jg memblok chanel nNa di
presinaps shg depolarisasi terhambat pd ujung presinap . Akibat efek depolarisasi darii
potensial aksi Na di hambat, Ca chanel di hambat scr sekunder, hasilnya berkurang masuknya
Ca ke ujng presinap. Mekanisme ini dpt menjelaskan pengobatan epilepsi, untuk gg mood tidak
diketahui.