TUJUAN PEMBELAJARAN

• Mengetahui tujuan pengobatan

• Mengetahui kategori obat

• Mengetahui mekanisme kerja obat

• Mengetahui indikasi dan kontraindikasi obat

• Mengetahui efek samping obat

 PENDAHULUAN
• Tuberkulosis adalah suatu penyakit infeksi menular yang disebabkan oleh bakteri
Mycobacterium tuberculosis, yang dapat menyerang berbagai organ, terutama paru-
paru.
• Dapat menimbulkan komplikasi parah hingga kematian
• Perkembangan penyakit dan pengobatannya :
• 1882 : identifikasi bakteri oleh Robert Koch
• 1906 : Vaksin BCG ditemukan
• 1943 : Streptomisin sebagai obat TB pertama yang efektif
• 1951 : INH
• 1952 : Pirazinamid & Sikloserin
• 1956 : Ethionamide
• 1957 : Rifampisin
• 1962 : Ethambutol
• 1980 – 1990an : Epidemi, dilanjutkan dengan kasus resisten terhadap obat
 PENDAHULUAN
EPIDEMIOLOGI
• Dunia : (WHO)
• Kematian : 2 juta / tahun
• 2013 : 8,6 juta, 1% adalah pasien HIV positif.
• 75% adalah penduduk Afrika
• 2012 : sekitar 6% kasus anak
• Indonesia : (BPS 2017)
• 1990 : 443 kasus per 100.000 penduduk
• 2013 : 280 kasus per 100.000 penduduk
257 kasus usia 15 tahun ke atas
 PENDAHULUAN
• Slow-growing bacillus
FAKTOR RISIKO • Mycolic acid wall =>
Agent ; Bakteri Penyebab : gram +/- => Virulency
Mycobacterium tuberculosis factor
• Dormant forms in
macrophages
 PENDAHULUAN
Faktor Risiko
Host ; Pejamu / Inang
Vulnerabilitas terhadap infeksi
sangat dipengaruhi oleh daya tahan
tubuh,
Mis. Pada penderita HIV/AIDS
Environment ; Lingkungan =
Sanitasi :
• Pencahayaan
• Ventilasi
• Kepadatan penghuni rumah
• Kelembaban udara
ANTIBIOTIC CLASSIFICATION AND MECHANISM
Mechanism of action Agents
Cell Wall Synthesis Penicillins
Cephalosporins
Vancomycin
Beta-lactamase Inhibitor
Carbapenems
Aztreonam
Polymycin
Bacitracin
Protein Synthesis Inhibitors Inhibit 30s subunit :
• Aminoglycosides (Gentamicin)
• Tetracyclines
Inhibit 50s subunit
• Macrolides
• Chloramphenicol
• Clindamycin
• Linezolid
• Streptogramins
DNA Synthesis Inhibitors Fluoroquinolones
Metronidazole
RNA Synthesis Inhibitors Rifampin

Mycolic Acid Synthesis Inhibitors Isoniazid

Folic Acid Synthesis Inhibitors Sulfonamides

Trimethoprim
 Anti-Tuberculosis drugs
First-line Second-line
• Isoniazid • Clarithromycin
• Rifampicin • Ciprofloxacin
• Ethambutol • Capreomycin
• Cycloserine
• Pyrazinamide
• Kanamycin
• Streptomycin
• Amikasin
Anti-Tuberculosis
Drugs
FIRST-LINE
ISONIAZID
RIFAMPICIN
ETHAMBUTOL
PYRAZINAMIDE
STREPTOMYCIN
 ISONIAZID (INH)

• Indication : Bactericidal on Mycobacterium

(tuberculosis, bovis, kansasii)
• Mechanism of action :
Interferes with mycolic acid synthesis (unique to
mycobacterial cell wall)
• Pharmacokinetic :
• Absorbsi : via oral administration, reduced with food
• Metabolism : hepatic
• Ekskresi : 50-70% via urine
• Half life : 1- 5 hours
 ISONIAZID (INH)

• Adverse effect :
• Rash
• Abnormal liver function
• Hepatitis
• Peripheral neuropathy
• CNS effects
• Food Interactions :
• Avoid aged food, pickled food chocolate
• Avoid alcohol
• Take on empty stomach ; 1-2 hours before meals
• Take with water
 RIFAMPICIN / RIFAMPIN
• Description : Bactericidal, broad spectrum
• Indication : Tuberculosis and Tuberculosis-related
mycobacterial infections
• Mechanism of action :
Inhibition of DNA-dependent RNA polymerase => suppression
of RNA synthesis and cell death
• Pharmacokinetic :
• Absorbsi : well absorbed via GIT, reduced with food
• Metabolism : hepatic
• Ekskresi : 30% via urine
• Half life : 3 hours
 RIFAMPICIN / RIFAMPIN

• Adverse effect :
• Nausea, vomiting
• Unconsciousness
• Orange discoloration of urine, sweat, tears
• Food Interactions :
• Avoid alcohol
• Take on empty stomach ; 1-2 hours before meals
• Take with water
 ETHAMBUTOL

• Description : Bactericidal
• Indication : as adjunct in Pulmonary Tuberculosis
• Mechanism of action :
Inhibits arabinosyl transferases which is involved in cell wall
synthesis => increase in cell wall permeability
• Pharmacokinetic :
• Absorbsi : 75-80% from GIT
• Metabolism : hepatic
• Ekskresi : 50% via urine, 20% via feces
• Half life : 3-4 hours
 ETHAMBUTOL

• Adverse effect :
• GIT upset
• Optic neuropathy/neuritis :
• Red-green color blindness → reduced visual acuity
• Dose-related
• Reversible
• May be unilateral
• Pruritus
• Joint pain
• Food Interactions :
• Take with food to reduce irritation
 PYRAZINAMIDE
• Description : bacteriostatic/bactericidal
• Indication : initial treatment of active tuberculosis
when combination with other anti-TB agents
• Mechanism of action :
Pyrazinamide is converted to pyrazinoic acid by
pyrazinamidase => bind to ribosomal protein => inhibit
translation
• Pharmacokinetic :
• Absorbsi : well absorbed from GIT
• Metabolism : hepatic
• Ekskresi : 70% via urine
• Half life : 9-10 hours
 PYRAZINAMIDE

• Adverse effect :
• Arthralgia : hyperuricemia => Gout
• Anorexia
• Nausea , vomiting
• Malaise
• Hypersensitivity reactions ; urticaria, pruritus, skin
rashes
• Food Interactions :
• Take without regard to meals
 STREPTOMYCIN
• Description : aminoglycoside, as bactericidal
• Indication : Tuberculosis, and as combination to treat
tularemia, plague, brucellosis, enterococcal
endocarditis
• Mechanism of action :
Irreversibly bind to specific 30s-subunit proteins and 16s
rRNA => interfere the initiation complex => misreading of
mRNA => incorrect amino acids => non functional proteins
• Pharmacokinetic :
• Absorbsi : rapidly absorbed after im injection
• Ekskresi : urine, small amounts in milk, saliva, and sweat
• Half life : 5-6 hours
 STREPTOMYCIN
• Adverse effect :
• OTOTOXICITY is caused by accumulation in the
endolymph and perilymph of the inner ear => damage
of hair cells of cochlea
• NEPHROTOXICITY is caused by accumulation of the
drug in the proximal renal tubular cells => damage
• Vestibular toxicity : vertigo, nausea & vomiting, loss of
balance
• USES :
• very ill patients
• Multi- drug resistance
• Not responding to treatment
Anti-Tuberculosis
Drugs
SECOND-LINE
CLARITHROMYCIN
CIPROFLOXACIN
CAPREOMYCIN
CYCLOSERINE
KANAMYCIN
AMIKASIN
 CLARITHROMYCIN
• Description : semisynthetic macrolide,
bacteriostatic/bactericidal depends on organism and
drug concentration
• Indication : TB, alternative to acute otitis media,
pharingitis, tonsilitis, skin infection, H.pylori infection
• Mechanism of action :
Penetrates bacteria cell wall => binds to ribosomal
RNA => blocking translocation & polypeptide synthesis
• Pharmacokinetic :
• Absorbsi : well absorbed with food
• Metabolism : hepatic
• Ekskresi : via urine, 20% via feces
• Half life : 3-4 hours
 CLARITHROMYCIN

• Adverse effect :
• Diarrhea, nausea, abnormal tastes, dyspepsia, and
abdominal discomfort
• Transient hearing loss => high doses
• Tooth discoloration
• Fetal abnormalities
• Food Interactions :
• Take without regard to meals
 CIPROFLOXACIN
• Description : broad spectrum, bactericidal
• Indication : UTI, lower respiratory tract infection, acute
sinusistis, skin infections, bone & joint infections
• Mechanism of action :
Inhibition of enzymes topoisomerase II(DNA gyrase) and
IV => DNA replication, transcription, repair, recombination
• Pharmacokinetic :
• Absorbsi : well absorbed from GIT
• Metabolism : hepatic
• Ekskresi : 40-50% via urine
• Half life : 4 hours
 CIPROFLOXACIN

• Adverse effect :
• GI irritation
• Food Interactions :
• Avoid caffeine, milk,
• 2 hours before or 6 hours after antacids
• Take with water
 CAPREOMYCIN

• Description : similar to viomycin, produced by

Streptomyces capreolus
• Indication : UTI, lower respiratory tract infection,
acute sinusistis, skin infections, bone & joint
infections
• Mechanism of action :
Inhibition of enzymes topoisomerase II(DNA gyrase)
and IV => DNA replication, transcription, repair,
recombination
 CAPREOMYCIN

• Pharmacokinetic :
• Absorbsi : must be administrated parenterally
• Ekskresi : 52% via urine
• Adverse effect :
• Electrolyte disturbance ; Hypokalemia, hypocalcemia,
hypomagnesemia
 CYCLOSERINE

• Description : broad spectrum,

bactericidal/bacteriostatic, produced by
Streptomyces garyphalus
• Indication : treatment for Mycobacterium avium
complex (MAC) and TB
• Mechanism of action :
Interfere with an early step in bacterial cell wall
synthesis in the cytoplasm
 CYCLOSERINE

• Pharmacokinetic :
• Absorbsi : 70 – 90% from GIT
• Half-life : 10 hours
• Adverse effect :
• Drowsiness
• Confusion, headache, dizziness
• Irritability
• Numbness
 KANAMYCIN

• Description : aminoglycoside group, bactericidal,

from bacterium Streptomyces kanamyceticus
• Indication : treatment for E.coli infections
• Mechanism of action :
Irreversibly bind to specific 30s-subunit proteins and
16s rRNA => interfere the initiation complex =>
misreading of mRNA => incorrect amino acids => non
functional proteins
 KANAMYCIN

• Pharmacokinetic :
• Absorbsi : rapidly absorbed after im injection, poor oral
and topical absorption
• Half-life : 2,5 hours
• Adverse effect :
• Mild nephrotoxicity
 AMIKACIN

• Description : semi-synthetic aminoglycoside group,

• Indication : treatment for gram-negative and gram-
positive bacteria
• Mechanism of action :
Bind to bacteria => misreading of t-RNA => unable to
synthesize proteins
 AMIKACIN

• Pharmacokinetic :
• Absorbsi : rapidly absorbed after im injection, poor oral
and topical absorption
• Metabolism : hepatic
• Ekskresi : urine
• Half-life : 2 – 3 hours
• Adverse effect :
• Nephrotoxicity
• Ototoxicity, irreversible
• Neuromuscular blockage :
ANTI-TUBERCULOSIS ; MECHANISM OF ACTION
Managing Side effects of Anti-TB
Drugs
Managing Side effects of Anti-TB
Drugs
MULTI-DRUG
RESISTENCE(MDR)
TUBERCULOSIS
 DEFINITION
MDR-TB
• TB Resisten Obat adalah keadaan dimana bakteri
M.tuberculosis sudah tidak dapat lagi dibunuh dengan
salah satu atau lebih obat anti-TB (OAT).
• 2013 : 6800 kasus, 5% belum terdiagnosis
General
Principles
For
MDR-TB
Treatment
(Taken from
TREATMENT
OF
TUBERCULOSIS
GUIDELINESS,
WHO, 2010)
GROUPS
OF
DRUGS
For
MDR-TB
(Taken from
TREATMENT
OF
TUBERCULOSIS
GUIDELINESS,
WHO, 2010)
 DAFTAR REFERENSI
• Basic and Clinical Pharmacology by Katzung
• Treatment of Tuberculosis Guideliness by WHO
• InfoDATIN by Kementerian Kesehatan RI
• Website :
• www.drugbank.ca
• www.medscape.com
• www.rxlist.com