Epilepsi Kuliah.pptx

FARMAKOTERAPI I

Epilepsi Presented By :

Ekanita Desiani Program Studi S1 Farmasi Universitas Pekalongan

Definition 

Epilepsi (WHO) : kelainan otak kronik dgn berbagai causa serangan epilepsi (seizure) berulang ok bangkitan neuron berlebihan  Gb klinis  kejang  perubahan tingkah laku  perubahan kesadaran

Definition  Seizure : – Manifestasi klinik dari bangkitan hipersinkron, berlebihan dan abnormal yang bersifat mendadak (paroxysmal) dari populasi neuron kortek

 Epilepsi : – Suatu kelainan neurologik yg bersifat kronik dan ditandai seizure berulang (recurrent seizure)

Definition  Status Epilepticus :  Keadaan dimana serangan epilepsi berlangsung lama ( > 30 menit )  serangan epilepsi (seizure)  berkali kali, serangan berlangsung rata-rata + 2 menit  kesadaran diantaranya tak pulih

Etiology Primary - Idiopathic Cerebrovascular

Symptomatic or Cryptogenic (23%) 5%

4%

4%

4%

CNS Neoplasma 3% 2% 1%

Congenital CNS Malformation Trauma CNS Infection

77%

Primary – Idiopathic (77%)

Other known Birth asphyxia

Causes of Seizures as a Function of a Age at Onset

Simon, et al., Clinical Neurology 7th ed

Mekanisme Dasar Epilepsi  1. Altered neurotransmitter balance • Increased glutamate ( excitatory ) • Decreased GABA ( inhibitory ) • Altered neuromodulator activity  2. Altered ionic homeostasis – K, Ca, Chloride  3. Rearranged neuronal circuits • loss of inhibitory synapses • Overgrowrth of excitatory synapses • Simplified circuits that improved neuronal synchronization

Klasifikasi epilepsi ILAE 1989

 Partial epilepsy

– Idiopathic – Symptomatic – Uncertain etiology

• simple partial • complex partial • secondary generalized

 Generalized epilepsy – Idiopathic – Symptomatic - West sy, Lennox gastaut  Epilepsies undertemined focal or generalized

 Special syndromes – Febrile convulsion – Acute metabolic dearengement 8

International Classification of Epileptic Seizures

Dipiro, et al. 2008. Pharmacotherapy A Pathophysiology Approach 7th Ed.

Partial (focal) Seizures I.  



Simple Partial Seizures Focal motor, gangguan sensory /speech Terbatas pada single limb /grup otot. Seizuresymptoms tdk berubah selama seizure. Tak kehilangan kesadaran II. Complex Partial Seizures (Temporal Lobe epilepsy or Psychomotor Seizures) • Confusion, gangguan perilaku. • Motor activity merupakan non-reflex actions. • Manifestasi klinik bervariasi. • Kehilangan kesadaran. EEG: Bizarre generalized EEG activity with evidence of anterior temporal lobe focal abnormalities.

General Seizures I.  

 



Absence Seizures (Petite Mal)

Kehilangan kesadaran singkat dan tiba tiba . Umumnya symmetrical clonic motor activity (occasional eyelid flutter to jerking of the entire body). Biasanya tidak ada manifestasi motorik. Serangan sangat singkat (5-10 detik), tetapi dapat berkali kali dalam sehari . Seringkali dimulai masak kanak kanak (daydreaming attitude, no participation, lack of concentration).

EEG: Bilaterally synchronous, high voltage, 3-per-second alternating spike and wave pattern.

II.

Generalized Tonic-Clonic Seizures

Major convulsions, biasanya dengan 2 fase:

Fase Tonic: - sustained powerful muscle contraction (meliputi seluruh otot tubuh ) yang menghentikan pernafasan . Fase Clonic : - ada fase alternatif antara contraction dan relaxation, dapat berupa pergerakan bilaterally symmetrical atau “running” movements. EEG: Recruitment of neurons throughout the cerebrum. Tonic (HF, HV, SA), clonic (SF, HV), and post-ictal phases.

III. Atonic Seizures (atypical)  Kehilangan postur tonus tubuh, dgn kehilangan kekuatan menyanggah kepala (head falling). IV. Tonic Seizures  Opisthotonus, kehilangan kesadaran, dan perubahan manifestasi autonomic

V. Clonic Seizures Kontraksi klonik yang rhythmic dari seluruh otot tubuh, kehilangan kesadaran, adanya tanda tanda perubahan manifestasi otonomik . VI.Myoclonic Seizures Isolated clonic jerks yang berkaitan dengan loncatan yang singkat (brief bursts) dari multiple spikes pada gambaran EEG. VI.Infantile Spasms Suatu epileptic syndrome, serangan dalam bentuk fragmentary atau kadang kadang bilateral. Ditandai oleh adanya brief recurrent myoclonic jerks dari seluruh bagian tubuh dengan adanya flexi atau extensi yang tiba tiba dari tubuh atau ekstrimitas .

Ultimate Goal Of Therapy For Epilepsy complete elimination of seizures

 Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: A guideline for discontinuing antiepileptic drugs in seizure free patients [summary statement]. Neurology 1996;47:600–602.  Brodie MJ, French JA. Management of epilepsy in adolescents and adults. Lancet 2000;356:323–328.  Garnett WR. Antiepileptic drug treatment: Outcomes and adherence. Pharmacotherapy 2000;20:191S–199S.

Oral Anti Epilepsi

Generalized seizure • Tonic clonic seizure – Lini I : CBZ, OxCBZ, Valproate – Lini II : Bensodiazepin drugs – ADD : DPH, Lum, primidone

• Absence seizure – Lini I : Valproate – Lini II : Ethosuximide,Bensodiazepin – ADD : Acetazolamide

 Partial seizure – Lini I – Lini II – Add

: CBZ. OxCBZ, Valproate : Bensodiazepn, Vigabatrin : DPH, Lum, primidone

Status Epileptikus harus segera distop ok  Semakin lama seizure – semakin sulit dikontrol &

kerusakan otak >  Kerusakan sel otak ok bangkitan eksitasi yg terus menerus  Faktor sistemik --- kerusakan sel otak  Ok itu status harus distop dlm 30 menit

Algoritma Status Epileptikus   



0 - 10 menit Amankan jalan nafas Monitor tanda vital Ambil darah utk ph, O2, CO2, glukosa, elektrolit, kadar OAE Infus 0.5 saline  Beri vit B1 dan B6 25-50 cc dlm 50 % glukosa

10 - 20 menit (4 pilihan)  Pilihan A : – IV DPH 15-20 mg / kg --- 50 mg /menit dlm 0.5 saline.  Pilihan B : – Diasepam 0.1-0.2 mg / kg --2-3 mg/menit IV – + IV DPH 15-20 mg /kg,-- 50 mg / menit dlm 0.5 saline – ulangi diasepam ssdh 20 menit KP  Pilihan C : Lorasepam IV 0.15 mg/kg, 2-3 ‘

 Pilihan D : – Luminal 15-20 mg/kg -- 100 mg/menit dlm 0.5 saline

> 30 menit  Pindahkan ke ICU  Intubasi dan ventilasi  Monitor EEG, EKG, tekanan darah  Burst supression EEG pattern – Thiopental bolus 20-30 mg/kg diikuti drip 0.5 mg/kg permenit – Phenobarbital bolus 0.05 mg/kg diikuti drip 0.1 mg/kg 27

CASE STUDY

Patient Profile Nama

: Tn. ES

Patient Profile Diagnosa KRS Epilepsi Dx utama : Post stroke infark Komplikasi: S.epileptikus Dx Sekunder: HT + AKI

Terapi KRS Fenitoin 3x100 mg Amlodipin 5mg-0-0 ASA 0-1 tab-0

No

Data Klinik

1

Suhu tubuh (T)

2 3 4

Tekanan darah (TD) Nadi (N) Sesak

5

GCS

6

Kejang

7

Defekasi

8

PU

No

Tanggal (Oktober 2012) 18 (IRD) 36,7 140/ 100 84 +

19 (S-B) 37 150/ 100 92 +

36,5 140/ 100 84 -

315

315

+

+ 600

20

21

23

24

25

26

27

36,6

36,5

37

37

37

84 -

92 -

36 170/ 100 84 -

456

456

456

-

1300

2300

Data Klinik

36,5

22

140/80 160/80

140/80 140/80 150/90 150/90 87 -

86 -

87 -

87 -

456

456

456

456

456

-

-

-

-

-

-

+ 1700

+

+

+

+

+

Tanggal (Oktober 2012) 28

29

30

31

37 140/ 90 84

36 160/ 120 84

36 140/ 80 85

37 140/80

-

-

-

-

456

456

456

456

1

Suhu tubuh (T)

2 3 4

Tekanan darah (TD) Nadi (N) Sesak

5

GCS

6

Kejang

-

-

-

-

7

Defekasi

+

8

PU

+ 600

+ 2300

+ 1300

92

Data

Nilai Normal

GDA GDP BUN Creatinin AST ALT Albumin Na K Cl Ca RBC Hb WBC HCT MCV MCH MCHC

< 200 mg/dl <100 mg/dl 5-23 mg/dl <1,2 mg/dl 0 – 2x 38 u/L 0 – 2x 41 u/L 3,8-4,4 g/dl 135 –145 mmol/L 3,8 – 5,0 mmol/L 97-103 mmol/L 8,5-10,1 mmol/L

PLT Bil. direct Bil.tot Tot. Prot Tot. Kol TG HDL LDL

4,00 – 6,00.10 /μL 6

11,0 – 18,0 g/dL 4,5–10,5x 10³ /mm³ 35-60% 80,0-99,9 mm3 27-31 pg 33-37 g/dl 150-450 x 103/mm3 < 0,20 g/dl 0,3-1,0 mg/dl 00-200 30-150 40-60 00-99

18 137

19

Tanggal (Oktober 2012) 20 23 25 112

28

30

13 1,6

12 1,7

12 1,6

77 11,7 1,4 19 25 4,79 146 3,6 101 18,8 4,79 14,5 11,9 41,4 86,8 30,4 35,0

139 3,4 105 5,48 16,0 11,7 46,9 85,6 29,1 34,0

133

238 0,23 1,12 6,3 154 66 47 93

13 1,7

D A T A L A B O R A T O R I U M

Data Konsul Tgl 19/10/12

Tgl 27/10/12

Konsul Cardio

Konsul IPD

Px dg stroke 3th attack + GTCS + HT

Px dg stroke infark trombotik + HT + pe↑ an serum kreatinin (1,7) mohon evaluasi

Jawaban: Didapatkan px dg HT st. I JNC VII tanpa tanda-tanda gagal jantung akut Saran: Tx amlodipin 5mg-0-0 diteruskan

Jawaban Saran: Lakukan pemeriksaan ulang SK → Hasil dikonsul ulang ke IPD

Data BGA Nilai Normal

Tanggal (Oktober 2012) 18

Ph PCO2

7,35-7,45 25-45

7,16 70

PO2

35-45

248

BE ecf

(-)3,5 – (+) 2

HCO3

22-26

-3,7 25,0

TCO2 SO2

15-22 vol % 95-100%

27,1 100

Pemeriksaan Urine Lengkap Data Urine

Nilai Normal

Tanggal (Oktober 2012) 30 24

SG PH Leu Nit Prot Glu Ket UBG Bil Ery Colour Clarity Ery (Mikr.) Leu (Mikr.) Epitel (Mikr.) Kristal (Mikr.) Lain-lain

1,010-1,015 5-8 Norm Norm 0-2 0-5 Sedikit -

1,004 6 Norm Norm 10 Yellow Clear 1-2 Banyak 2-3 -

1,006 5 Norm Norm Yellow Clear 0-1 0-1 -

Pemeriksaan Lain Foto Thorax AP

Tgl Tgl 18/10/12 18/10/12

Cor : besar & bentuk kesan normal Pulmo: tdk tampak infiltrat Sinus phrenicocostalis kanan & kiri tajam Kesan : saat ini cor & pulmo tdk tampak kelainan CT Scan Axial tanpa kontras Kesimpulan : Chronic ischemic cerebral infarction pada kapsula externa kiri

PROFIL TERAPI

N o 1 2 3

4

5 6 7 8 9 10 11

Jenis Obat Regimen Nama 18 Dosis Dagang/ (IRD) Generik O2 masker 6 lpm v Inf. NS 0,9% 1500 cc/hr v Inj. Prn kejang v Diazepam 1 amp (rect) Loading (15-18 v mg/Kg BB) Fenitoin i.v → 1200mg Maintenance (3x100 mg) Inj. 3x1 amp v Metamizole 5mg-0-0 Amlodipin v (p.o) 1x100 mg ASA (p.o) Inj. Ranitidin 2x1 amp Inj. 3 gr Piracetam Inj. CDP 3x250 mg Cholin Inf. PZ

Tanggal (Oktober 2012) 19

20

21

22

v

v

v

//

v

v

v

v

v

v

v

v

v

v

v

//

v

v

v

v

v

v

v

v

v

//

v

v

23

24

25

26

27

28

29

30

v (p.o)

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

v

//

v

v

v

v

v

v

v

v

v

v

DISCUSSION

AntiepilepticDrugs Drugs Antiepileptic

Neuronal Sites of Action of Antiepilepti cs

Luellmann, 2005. Color Atlas of Pharmacology

Start

drugs

dose

administration

stop

19/11

Phenytoin

3x100mg

Injection to a large vein,max rate is 2050mg/min, an in line 0,225 micron filter is recommended for IVPB solution due to high potential for precipitation of solution. Avoid extravasation, following i.v administration PZ should be injected trough the same needle or i.v catheter to prevent irriitation

-

Max rate 5mg/min by direct i.v injection into large vein, avoid extravasation

23/11

18/10

No

diazepam

1amp (Prn seizure)

Data Klinik

1

GCS

2

Kejang

indication

monitoring plasma level, blood, liver function, sign of toxicity (confusion, loss of motor coordination, nystagmus)

Seizure management

Respiratory, cardiovascular , mental status

Tanggal (Oktober 2012) 18 (IRD)

19 (S-B)

20

315

315

456

+

+

-

21

22

23

24

25

26

27-31

456

456

456

456

456

456

456

-

-

-

-

-

-

-

Summary of Anticonvulsant Drug Therapy Drug

Usual Preparation

Loading or initial Dose

Maintenance Dose

Therapeutics Serum Levels

Phenytoin

100-mg capsule. Also 30-mg capsule, 50-mg tablet

Oral loading: 1000 mg in two to four divided doses over 12-24 hours

300-400 mg/day in a single dose or divided doses

10-20 µg/ml

Intravenous loading: 1000-1500 mg (15-18 mg/kg) not exceeding 50 mg/min Fosphenytoin is prodrug form for intramuscular or intravenous use

Simon, et al., Clinical Neurology 7th ed

Antiepileptic Drug Pharmacokinetic Data

Dipiro, et al. 2008. Pharmacotherapy A Pathophysiology Approach 7th Ed.

Disease States and Conditions that Alter Phenytoin Plasma Protein Binding

McGrawHill, 2008. CLINICAL USEFULNESS OF UNBOUND PHENYTOIN CONCENTRATIONS

Diagnosis & Management of Epilepsy in Adults (A National Clinical Guidelines 2003)

Generalised Tonic Clonic Status Epilepticus

Antihypertensive Antihypertensive Drugs Drugs

ALGORITHM FOR TREATMENT OF HYPERTENSION

JNC 7, 2003

Saseen, JJ & Maclaughlin, EJ 2008, 'Hypertension' in Pharmacotherapy a pathophysiologic approach , 7th Ed., eds D Joseph, T Robert, Y Gary, M Gary, W Barbara & P Michael, The McGraw-Hill Companies, Inc., New York

Algoritma Terapi Hipertensi Akut pada Pasien dengan Stroke

Qureshi, AI 2008, 'Acute hypertensive response in patients with stroke: pathophysiology and management',

Clinical Trial and Guideline Basis For Compelling Indications For Individual Drug Classes

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 2004

Calcium Channe l Blocker ’s Mecha nism of Action

Pharmacokinetics Of Calcium Channel Blocker Drugs

T1/2 (hrs)

OOA (route)

Excretion

Disposition

Dyhidropyridines Amlodipin

30-50

30-50 mnts

Urine (10% as parent; 60% as metabolite)

> 90% bound to plasma proteins; extensively metabolized

Nifedipin

4

< 1 minute (IV), 5–20 minutes (sublingual or oral)

80% of the drug and metabolites excreted in urine.

About 90% bound to plasma protein; metabolized to an acid lactate.

Nicardipine

2-4

20 mnts (oral)

Urine, feces

95% bound; extensively metabolized in the liver.

Nimodipine

1-2

0.5-2 hrs (oral); 10 mnts (IV)

Urine (50%); Extensively metabolized. feces (32%) Katzung, 2007; Lacy, et al., 2010

Tgl

18/10/ 12 KRS

Terapi

Do Regimen

Amlodipin

5mg-0-0 (p.o)

Do literatur

Keterangan

2.5-10 mg once daily

Amlodipin digunakan sebagai terapi antihipertensi pada pasien dengan stroke dimana bekerja dengan menghambat influks Ca. Namun berdasarkan JNC-7, terapi antihipertensi pada pasien dengan stroke & kidney disease lebih direkomendasikan penggunaan ACEI

Data Klinik

Tekanan darah (TD) Data Klinik Tekanan darah (TD)

Monitoring

Tekanan darah

Tanggal (Oktober 2012) 18 (IRD)

19 (S-B)

20

140/ 100

150/ 100

140/ 100

21

140/80 160/80

Tanggal (Oktober 2012) 28 140/ 90

29 160/ 120

30 140/ 80

22

31 140/80

23 170/ 100

24

25

26

27

140/80 140/80 150/90 150/90

Antiplatelet Antiplatelet

Obat ASA

Regime n Dosis 1X100 mg (p.o)

Dosis Literatur Stroke/TIA (noncardioembolic; secondary prevention): Oral: 50-325 mg once daily (Adams, 2008) or 50-100 mg once daily

Tgl Mulai

Tgl Stop

Monitorin g

23/10/12

-

PLT , nyeri epigastrik

Acute ischemic stroke: Oral: 150-325 mg once daily

Data Lab PLT

Normal

18

20

150-450 x 103/mm3

133

238

Sacco et al. 2006, 'Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack', Stroke, vol. 37, pp. 577-617; Adams et al. 2007, 'Guidelines for the early management of adults with ischemic stroke', Stroke, vol. 38, pp. 1655-1711

Sacco et al. 2011. Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack. Stroke, Vol. 42, p. 227-276.

TreatmentFor For Treatment Neuroprotectant Neuroprotectant

THE ROLE OF VARIOUS NEUROPROTECTIVE AGENTS ON THE ISCHEMIC CASCADE

Fisher, M & Schaebitz, W 2000, 'An overview of acute stroke therapy', Archives of Internal Medicine, vol. 160, pp. 3196-3206

Tanggal

Terapi

Mekanisme Kerja

Monitoring

2029/10/12

CDP Cholin

• Citicoline adalah molekul organik yg berfungsi sbg intermediet dlm biosintesis fosfolipid membran sel • Citicoline dikenal sbg nukleotida yg berperan penting dlm metabolisme seluler • Citicoline mampu memperbaiki membran neuronal melalui pe↑ sintesis fosfatidilkolin • Citicoline mampu memperbaiki kerusakan neuron kolinergik melalui potensiasi produksi asetilkolin • Citicoline mampu menurunkan asam lemak bebas pada area stroke yg diinduksi oleh kerusakan saraf

Fungsi Kognitif

Richard Conant, MAc, CN, and Alexander G. Schauss Therapeutic Applications of Citicoline for Stroke and Cognitive Dysfunction in the Elderly: A Review of the Literature Altern Med Rev 2004;9(1):17-31

Interaksi Obat Obat

Level Signifikan

Keterangan

Phenytoin + Diazepam

Significant → Monitor Closely

Phenytoin will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolis. Significant interaction possible, monitor closely

Phenytoin + Amlodipine

Minor

Phenytoin will decrease the level or effect of amlodipin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor or non-significant interaction

Ranitidine + Phenytoin

Minor

Ranitidine increase levels of phenytoin by decreasing metabolism. Minor or non-significant interaction

Kesimpulan & Saran

 Pemilihan terapi antiepilepsi pada pasien sudah sesuai dengan guideline. Hanya saja perlu dipertimbangkan untuk pemilihan Lorazepam karena berdasarkan penelitian & guideline yang sudah ada penggunaan Lorazepam pada pasien dengan status epilepticus dianggap lebih efektif dibandingkan penggunaan diazepam/fenitoin tungal maupun kombinasi  Pasien mendapatkan terapi anti kejang feniton dimana penggunaannya jangka panjang yang dapat menginduksi terjadinya defisiensi folat, maka sebaiknya pasien diberi terapi tambahan asam folat  Pemilihan terapi antihipertensi amlodipin berdasarkan JNC-7 dimana dengan compailling indication stroke & kidney injuri lebih disarankan penggunaan golongan ACEI

TERIMA KASIH

PROPOSED MAJOR PATHWAY OF CITICOLINE NEUROPROTECTION

ArAc, arachidonic acid; GSH, glutathione; nSMase, neutral sphingomyelinase; PLA2 phospholipase A2; PtdCho, phosphatidylcholine; ROS, reactive oxygen species

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of Neurochemistry, vol. 80, pp. 12-23

Biosynthesis of Acetylcholine, Phosphatidylcholine (PtdCho), S-adenosyl-L-methionine (AdoMet), and Glutathione (GSH)

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of Neurochemistry, vol. 80, pp. 12-23

Recent Studies (since 1995) Investigating the Action of Citicoline in Neuropathological Conditions

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of Neurochemistry, vol. 80, pp. 12-23

Mechanism Action Of Citicholin

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of Neurochemistry, vol. 80, pp. 12-23

Indication For Antiepileptics

Luellmann, 2005. Color Atlas of Pharmacology

Simplified Synopsis of Drug Interaction Properties of Common AEDs

Schmidt , 2009. Drug Treatmen of Epilepsy : Option and Limitations

Luellmann, 2005. Color Atlas of Pharmacology

Steady State Concentration

Desired Cp~ fraction (%)

Cp~ Fraction Constant

90 95 99

3,32 4,32 6,65

e.g to achieve 90% steady state concentration of phenytoin we need Css = 3,32 x t ½ = 3,32 x 22h = 73,04h or 3 days • Css is the steady state concentration of pheytoin • T ½ is the average half life of phenytoin Bauer, LA 2008, Applied Clinical Pharmacokinetics 2nd ed, McGrawHill New York

Phenytoin Maintenance Dose Calculation

Bauer, LA 2008, Applied Clinical Pharmacokinetics 2nd ed, McGrawHill New York

 Vmax is the maximum rate of metabolism in mg/d  S is the fraction of the phenytoin salt form that is active phenytoin (0.92 for phenytoin sodium injection and capsules; 0.92 for fosphenytoin because doses are prescribed as a phenytoin sodium equivalent or PE, 1.0 for phenytoin acid suspensions and tablets)  MD is the maintenance dose of the phenytoin salt contained in the dosage form in mg/d  Css is the phenytoin concentration in mg/L (which equals μg/mL)

Phenytoin Maintenance Dose Calculation • Km is the substrate concentration in mg/L (which equals μg/mL) where the rate of metabolism = Vmax/2

Michaelis Manten parameter: • Adult with normal kidney and liver function Vm = 7 mg/kg/day Km = 4 µg/ml • 6 m.o-6 y.o Vm = 12 mg/kg/day Km = 6 µg/ml • 7-16 y.o Vm = 9 mg/kg/day Km = 6 µg/ml

Bauer, LA 2008, Applied Clinical Pharmacokinetics 2nd ed, McGrawHill New York

Dosages and effective plasma concentrations of often used AEDs for adults

Schmidt , 2009. Drug Treatmen of Epilepsy : Option and Limitations

Klirens Kreatinin Kreatinin

18

23

25

28

30

1,4

1,6

1,7

1,7

1,6

52,29

55,56

CrCl : (140-umur) x BB 72 x kreatinin CrCl

63,5

55,56

52,29