FARMAKOLOGI OBAT

ANTIBIOTIK
Rina Wijayanti, M. Sc., Apt
 Ideal Antimicrobial Agent

 Soluble in body
 Stable in body
 Selectively toxic
 Consistent Toxicity
 Non-allergic
 Bacterial resistance difficult to develop
 Long shelf life
 Reasonable cost
Terms/Concepts of Antimicrobial Agent
• Selective Toxicity
• Spectrum of Activity
• Mode of Action
• Side Effects
• Resistance
 Selective Toxicity
• Concentration that eliminates pathogen
– Therapeutic dosage level
• Concentration that causes damage to host
– Toxic dosage level
• Chemotherapeutic index =
Maximum tolerable dose (per Kg body weight)
Minimum therapeutic dose (per Kg body weight)
 PENGGOLONGAN ANTIBIOTIK
BERDASARKAN DAYA KERJANYA

• ZAT BAKTERISIDA, pada dosis biasa berkhasiat mematikan

kuman
1. Zat yang bekerja pada fase tumbuh (penisilin, sefalosporin,
polipeptida, rifampisin, asam nalidiksat, kuinolon)
2. Zat yang berkerja terhadap fase istirahat (aminoglikosida,
nitrofurantoin, INH, klotrimoksazol)
• ZAT BAKTERIOSTATIK, pada dosis biasa terutama
berkhasiat menghentikan pertumbuhan dan perbanyakan
kuman (Sulfonamida, kloramfenikol, tetrasiklin, makrolida,
linkomisin)
 PENGGOLONGAN ANTIBIOTIK
BERDASARKAN Spectrum of Activity
• Range of microorganisms that are affected by agent
– Broad spectrum
• Wide range, e.g. both gram-pos & gram-neg
• Used when infective bacterial agent on is not precisely
identified
– Narrow spectrum
• Limited number, or specific group of bacteria
• Used to prevent development of resistance
• Less of an affect on normal bacterial flora
Antibiotic Spectrum

Obligate intracellular microorganisms

Chlamydia – tiny, non-motile, spherical bacteria
Rickettsia – small, non-motile, gram-negative bacteria
 PENGGOLONGAN ANTIBIOTIK
BERDASARKAN MEKANISME AKSI

1. Cell Wall
2. Cell membrane
3. Protein synthesis
4. Nucleic Acid Synthesis
5. Antimetabolites
 Some clinically important antibiotics
Site or mode of
Antibiotic Producer organism Activity
action
Penicillin Penicillium chrysogenum Gram-positive bacteria Wall synthesis

Bacitracin Bacillus subtilis Gram-positive bacteria Wall synthesis

Polymyxin B Bacillus polymyxa Gram-negative bacteria Cell membrane

Amphotericin B Streptomyces nodosus Fungi Cell membrane

Erythromycin Streptomyces erythreus Gram-positive bacteria Protein synthesis

Neomycin Streptomyces fradiae Broad spectrum Protein synthesis

Streptomycin Streptomyces griseus Gram-negative bacteria Protein synthesis

Tetracycline Streptomyces rimosus Broad spectrum Protein synthesis

Vancomycin Streptomyces orientalis Gram-positive bacteria Protein synthesis

Rifamycin Streptomyces mediterranei Tuberculosis Protein synthesis

 Cell Wall Disruption - Antibacterial

• Bacteria have a high internal osmotic pressure

• Without a sturdy cell wall, this pressure will cause
membrane to burst
• Antibiotics can interfere with formation of the cell wall
• Results in cell death by cell bursting open
• Sintesa dinding sel terganggu sehingga dinding menjadi
kurang sempurna dan tidak tahan terhadap tekanan
osmotis dari plasma dengan akibat pecah
- DISRUPTION: GANGGUAN -STURDY: KOKOH – BURST: PECAH -INTERFERE:
MENCAMPURI
 Cell Wall

penicillin

• Penicillin has a 4-member ring

• “looks like” part of the cell wall to the cross-linking enzyme
• Penicillin competes with the normal cell wall component for the
cross-linking enzyme, i.e. competitive inhibition
• Prevents this enzyme from cross-linking cell wall
Penicillin structure
 Penicillin
• Penicillin G is the natural penicillin
– Produced by Penicillium notatum
• Administered by injection
– because is degraded by stomach acids
• Rapidly absorbed into blood & rapidly excreted
• Used against: streptococcus, meningococcus,
pneumonococcus, spirochetes, clostridia, aerobic gram-
positive rods, some staphylococcus and gonococcus
• Active in urine; so used for urinary tract infections
• Generally nontoxic
• Problems
– Allergic reaction (~5% in adults)
– Bacterial resistance
 Semi-synthetic Penicillins
• Add a side-chain to the penicillin structure
• Alters: mengubah

– Chemical characteristics
– Spectrum of activity
– Development of bacterial resistance
• Methicillin
– Penicillinase resistant
– resistance by an different mechanism developed
• Ampicillin
– broad spectrum ( gram-neg & gram-pos)
– acid resistant, i.e. oral administration
 β-lactam Antibiotics
Cephalosporins
• Produced by fungi, Cephalosporium
• ring similar to penicillins
– so action similar to penicillins
• Originally for gram-positive cocci
• Used when
– infecting bacterial strain is reistant due to penicillinase
– when allergy or toxicity to penicillin present
• Broader spectrum
• few serious side effects
– Local irritation at injection site
– Nausea, vomiting, diarrhea
– Penicillin allergic persons can also be sensitive (~15%)
 Cell Wall - Polypeptide Antibiotics
• Bacitracin
– Produced by Bacillus licheniformis
– Small polypeptide
– Inhibits cell wall formation Luka tembak
– Used on lesions & wounds because:
• Poorly absorbed in body luka

• Toxic to kidneys
• Vancomycin
– Streptomyces
– Very narrow spectrum
– Used against Staphylococcus that is resistant to penicillin
– Vancomycin resistance is now developing
dihasilkan
 Cell Wall - Antimycobacterial

• Isoniazid (INH)
– Inhibits synthesis of mycolic acid in cell wall of Mycobacteria
• Tuberculosis
– Administered with other antibiotics to prevent development of
resistance mencegah

• Ethambutanol
– Inhibits incorporation of mycolic acid into cell wall
• Rifampin (inhibits mRNA synthesis)
– Hits alternative target in cell
• Isoniazid Complications

– Competitive inhibitor of niacin & Vitamin B6

– Prevents enzymes from converting niacin or Vitamin B6
to useful molecules
– Often supplement patient’s diet with extra Niacin &
Vitamin B6 during treatment
 MEMBRAN SEL

• Molekul lipoprotein dari membran plasma ( di

dalam dinding sel) dikacaukan sintesanya
sehingga menjadi lebih permeabel.
• Hasilnya zat-zat penting dari isi sel dapat
merembes keluar.
• Contoh : polipeptida dan polyen (nistatin,
amfoterisin) dan imidazol (mikonazol,
ketokonazol)
 Aminoglikosida

• Streptomisin, neomisin
• Menghambat sintesis protein
• Berikatan dengan ribosom sub unit 30S dan
mengubah bentuknya sehingga terjadi
misreading informasi yang dibawa oleh
mRNA
• Penghambatan terjadi pada tahap elongasi
 Makrolid

• Eritromisin, spiramisin
• Mengikat molekul sub unit 23S rRNA
• Menghambat tahap
translokasi
 Quinolon

• Ciprofloxacin
• Menghambat DNA girase (topoisomerase II)
Golongan Sulfa
• Analog PABA
• Menghambat terbentuknya THF (carrier
karbon yang digunakan dalam sintesis A, G,
T dan M)
 3. SELEKSI ANTIBIOTIK
ANTIBIOTIKA APAKAH YANG PALING TEPAT ?

FAKTOR ORGANISME FAKTOR PASIEN FAKTOR ANTIBIOTIK

 TERAPI EMPIRIK  BERATNYA INFEKSI  SPEKTRUM
SEBELUM HASIL AKTIVITAS
TES MIKROBIOLOGI,  STATUS IMUN ANTIBIOTIK
KULTUR &
SENSTIVITAS  FAKTOR  DOSIS, RUTE,
FARMAKOKINETIK FREKUENSI
 TEMPAT INFEKSI PEMBERIAN
DITEMUKAN  RIWAYAT PENYAKIT
 FARMAKOKINETIK
 EFEK OBAT PADA  STATUS ALERGI
ORGANISME  EFEK SINERGISTIK
 FAKTOR
 MIC, MBC FARMAKOGENETIK  INTERAKSI OBAT

 RESISTENSI  EFEK SAMPING

ANTIBIOTIK
 HARGA/BIAYA
13/10/2017 27