Pharmacology

Obat Lepra dan TBC Kutis

Dharma Permana, PhD, Apt

 Obat Lepra/ Kusta
(WHO,2000 dan Depkes, 2012)
 Obat Lepra/ Kusta
• Leprosy is a chronic disease caused by a slow multiplying bacillus,
Mycobacterium leprae.
• M. leprae multiplies slowly and the incubation period of the disease is
about 5 years. Symptoms can take as long as 20 years to appear.
• The disease mainly affects the skin, the peripheral nerves, mucosa of the
upper respiratory tract and also the eyes.
• Although not highly infectious, it is transmitted via droplets, from the nose
and mouth, during close and frequent contacts with untreated cases.
• Early diagnosis and treatment with multidrug therapy (MDT) remain key in
eliminating the disease as a public health concern
• Untreated, leprosy can cause progressive and permanent damage to the
skin, nerves, limbs and eyes.
• Official figures from 115 countries show the global registered prevalence
of leprosy at 189 018 at the end of 2012 and during the same year, 232
857 new cases were reported.
 Obat Lepra/ Kusta
• Several drugs are used in combination in multidrug therapy (MDT).
(See table) These drugs must never be used alone as monotherapy
for leprosy.
• Dapsone, which is bacteriostatic or weakly bactericidal against M.
leprae, was the mainstay treatment for leprosy for many years until
widespread resistant strains appeared. Combination therapy has
become essential to slow or prevent the development of resistance.
Rifampicin is now combined with dapsone to treat paucibacillary
leprosy. Rifampicin and clofazimine are now combined with
dapsone to treat multibacillary leprosy.
• A single dose of combination therapy has been used to cure single
lesion paucibacillary leprosy: rifampicin (600 mg), ofloxacin (400
mg), and minocycline (100 mg). The child with a single lesion takes
half the adult dose of the 3 medications.
 Obat Lepra/ Kusta
(WHO,2000 dan Depkes, 2012)
 Single Lesion Paucibacillary (SLPB) Leprosy
(one time dose of 3 medications taken together) RFT
c Not recommended for pregnant women or children less than 5 years

Rifampicin Ofloxacin Minocycline

Adult 600 mg 400 mg 100 mg
50 - 70 kg
Child 300 mg 200 mg 50 mg
5 - 14 yearsc
 DDS (Dapson)
• Singkatan dari Diamino Diphenyl Sulfone
• Bentuk obat berupa tablet putih dengan ukuran 50
mg/tab dan 100 mg/tab
• Sifat bakteriostatik dengan menghambat enzim
dihidrofolat sintetase.
• Dosis dewasa 50-100 mg/hari, anak-anak 1-2 mg/hari
• Obat ini sangat murah, efektif, dan relatif aman.
• Well absorbed orally,widely distributed, Excreted in
urine as acetylated
• Efek samping yang mungkin timbul antara lain: erupsi
obat , anemia hemolitik, leukopenia, insomnia,
neuropatia, methemoglobinemia. Namun efek samping
tersebut jarang dijumpai pada dosis lazim.
 Lamprene / Clofazimine
• Bentuk kapsul warna coklat dengan takaran 50 mg/kapsul dan 100
mg/hari
• Sifat bakteriostatik setara dengan dapson. Bekerja mungkin melalui
gangguan metabolisme radikal oksigen. Disamping itu mempunyai efek
antiinflamasi sehingga berguna untuk pengobatan reaksi kusta.
• Cara pemberian secara oral, diminum setelah makan untuk menghindari
gangguan gastrointestinal
• Absorption from the gut is variable, Stored mainly in reticuloendothelial
tissues and skin, Half-life 2 months, Excreted mainly in feces.
• Dosis untuk kusta adalah 50 mg/hari atau 100 mg tiga kali seminggu dan
untuk anak-anak 1 mg/kgbb/hari. Selain itu dosis bulanan 300 mg juga
diberikan setiap bulan untuk mengurangi reaksi tipe 1 dan tipe 2.
• Dapat menyebabkan pigmentasi kulit yang sering merupakan masalah
pada ketaatan berobat penderita.
• Efek sampingnya hanya terjadi pada dosis tinggi berupa gangguan
gastrointestinal (nyeri abdomen, diare, anoreksia dan vomitus)
 Rifampisin
• Bentuk kapsul atau tablet takaran 150 mg, 300 mg, 450 mg dan 600
mg
• Dewasa : 600 mg/bulan, disupervisi Dilanjutkan dengan 50 mg/hari
• Anak 10 – 14 th : 450 bulan (12 – 15 mg/kg BB/bulan)
• Sifat bakterisidal kuat, bekerja dengan menghambat enzim
polymerase RNA yang berikatan secara irreversible.
• Dosis tunggal 600 mg/hari (atau 5-15 mg/kgbb) mampu membunuh
kuman kirakira 99,9% dalam waktu beberapa hari.
• Cara pemberian obat secara oral, bila diminum setengah jam
sebelum makan maka penyerapan lebih baik
• Efek samping yang harus diperhatikan adalah hepatotoksik,
nefrotoksik, gejala gastrointestinal dan erupsi kulit.
• Efek samping : Urin, tinja, keringat merah.
 Obat TBC Kutis
Epidemiologi
• Terutama di negara berkembang
• Mengenai sosek rendah
• Umumnya mengenai anak-anak & dewasa muda
• RSCM : skrofuloderma (84%),
TBC kutis verukosa (12%)
Etiologi
• Mycobacterium tuberculosis (humanus) 91,5%
• Mycobacterium atipik 8,5%
Obat TBC Kutis
 Obat TBC Kutis
2 tahapan :
1. Tahap awal (intensif) : membunuh kuman
sebanyak & secepat mungkin
bakterisidal
2. Tahap lanjut : membunuh kuman yang
tumbuh lambat
Obat TBC Kutis
Obat TBC Kutis
Obat TBC Kutis
Obat TBC Kutis
 Obat TBC Kutis
. Obat baku (primer, barisan I )
1. INH (H).
• Bakterisidal lengkap
• ES : neuritis perifer, gangguan hepar
• Anak :10 mg/kg BB, dewasa : 5 mg/kg BB

2. Rifampisin (R)
• 10 mg/kg BB, pada waktu lambung kosong
• Bakterisidal lengkap
• ES : gangguan hepar
 Obat TBC Kutis
. Pirazinamid (Z)
• 20 -35 mg/kg BB, dosis terbagi
• Selama 2 bulan
• Bakterisidal
• ES : gangguan hepar

4. Etambutol (E)
• Bulan I/II : 25mg/kgBB, berikutnya : 15 mg/kgBB
• Bakteriostatik
• ES dini : ggn penglihatan terhadap warna hijau,
gangguan N 2
 Obat TBC Kutis
Streptomisin
• 25 mg/kg BB per injeksi
• Bakterisid
• ES : gangguan N 8 tu cabang vestibularis
 Obat TBC Kutis
Obat cadangan (sekunder, barisan II )
1. PAS : 200 mg/kg BB, dosis terbagi
2. Etionamid : 15-20 mg/ Kg, dosis tunggal
 Isoniazid (INH)
• Bacteriostatic at low conc. & bacteriocidal at high conc.
Especially against actively growing bacteria.
• Inhibits synthesis of mycolic acid is an essential
components of mycobacterial cell wall
• Readily absorbed from GIT.
• Diffuse into all body fluids and tissues
• Penetrates caseous material and macrophages so it is
effective against intra and extracellular organisms.
• Metabolized in liver by acetylation
• Excreted mainly in urine
• Mycobacterial infections (it is recommended to be
given with pyridoxine to avoid neuropathy)
 Rifampisin
• Bentuk kapsul atau tablet takaran 150 mg, 300 mg, 450 mg dan 600
mg
• Dewasa : 600 mg/bulan, disupervisi Dilanjutkan dengan 50 mg/hari
• Anak 10 – 14 th : 450 bulan (12 – 15 mg/kg BB/bulan)
• Sifat bakterisidal kuat, bekerja dengan menghambat enzim
polymerase RNA yang berikatan secara irreversible.
• Dosis tunggal 600 mg/hari (atau 5-15 mg/kgbb) mampu membunuh
kuman kirakira 99,9% dalam waktu beberapa hari.
• Cara pemberian obat secara oral, bila diminum setengah jam
sebelum makan maka penyerapan lebih baik
• Efek samping yang harus diperhatikan adalah hepatotoksik,
nefrotoksik, gejala gastrointestinal dan erupsi kulit.
• Efek samping : Urin, tinja, keringat merah.
 Etambutol
• Inhibits mycobacterial cell wall synthesis by
inhibiting arabinosyl transferase .
• Bacteriostatic
• Active against intra&extracellular bacilli .
• Well absorbed.
• 20% excreted in feces and 50% in urine in
unchanged form.
• Crosses BBB in meningitis
• Used only in mycobacterial infections
 Pyrazinamide
• Bactericidal
• Acting on intracellular organisms.
• Well absorbed orally ,metabolized in liver
,excreted mainly through kidney
• Prophylaxis of TB in combination with
ciprofloxacin
• Hepatotoxic, Hyperuricemia( provoke acute
gouty arthritis ), Nausea & vomiting, skin rash
 Streptomycin
• Resistant cases (Multidrug resistance
tuberculosis ).
• Amikacin can be used as alternative to
streptomycin.
• Both active mainly against extracellular bacilli.
• Side effects : aminoglycoside side effects
 Aminosalicylic Acid (PAS)
• Similar in structure to sulfonamide and p-aminobenzoic
acid.
• Folate synthesis inhibitor.
• Well absorbed from GIT.
• Widely distributed in tissues except CSF.
• Excreted in urine as active and as metabolic products.
• Causes crystalluria,anorexia,nausea,diarrhea,epigastric
pain.
• Peptic ulcer and haemorrhage can occur.
• Hypersensitivity reactions.
 Ethionamide
• As isoniazid blocks synthesis of mycolic acid .
• Available only in oral form.
• Metabolized by the liver ,excreted by kidney.
• It is poorly tolerated because of :
• -intense gastric irritation
• -neurologic symptoms
• -hepatotoxicity
• Used in TB & leprosy.
 Ref :
• Farina MC, Gegundez MI, Pique E, Esteban J,
Martin L, Requena L, et al. Cutaneous
tuberculosis: A clinical, histopathologic, and
bacteriologic study. J Am Acad Dermatol
1995;33:433‐40
• Zouhair K, Akhdari N, Nejjam F, Ouazzani T,
Lakhdar H. Cutaneous tuberculosis in Morocco.
Int J InfDis 2007;11:209‐12
• Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin
Derm 2007;25:173‐80
TERIMA KASIH