Download - ANTIMICROBIAL DRUGS (part I)
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Antimicrobial Drugs
PHARMACOLOGY AND TOXICOLOGY II
Presented for Department of PharmacyUniversity of Darussalam Gontor - Indonesia
Surya Amal
Antimicrobial DrugsPart I
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Learning ObjectivesLearning Objectives
1. Memahami pengertian, penyebab, mekanisme terjadinya, penyebaran, dan akibat yang ditimbulkan oleh penyakit infeksi serta prinsip ditimbulkan oleh penyakit infeksi serta prinsip pengobatan dengan kemoterapi.
2. Penggolongan Obat-Obat Antiinfeksi.
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Background Background
• Before antimicrobials discovered, large number of people died from common illnesses
• Now many illnesses easily treated with antimicrobials
• However, many antimicrobial drugs are becoming less useful
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Paul Erlich (1909) found the first pharmaceutical effective for treatment of syphilis: Salvarsan
• Arsphenamine highly toxic
History and Development of Antimicrobial Drugs
• Arsphenamine highly toxic
Ehrlich’s Magic Bullets
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History and Development of Antimicrobial Drugs
Sulfonamide was the first sulfa drug• In vitro derivative of
Prontosil dye Prontosil dye • effective against
streptococcal infections• Nobel prize in
Medicine, 1939Gerhard Domagk
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Penicillin discovered by Alexander Fleming (1928)
• Identified mold Penicillium that produced a bactericidal substance that was effective against a wide
History and Development of Antimicrobial Drugs
that was effective against a wide range of gram + microbes
• Inhibits cell wall synthesis• Mass production of penicillin during
WWII
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History and Development of Antimicrobial Drugs
Streptomycin (1943) isolated from soil bacterium Streptomyces griseus by Selman griseus by Selman Waksman • Bacteriostatic • Inhibits protein
synthesis by binding to ribosome
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History and Development of Antimicrobial Drugs
• Development of new generation of drugs– In 1960s scientists
alteration of drug structure gave structure gave them new properties• Penicillin G altered
to create ampicillin– Broadened
spectrum of antimicrobial killing
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Mikroba•Bakteri
•Virus
•Fungi
Parasit•Protozoa
•Cacing
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Antimicrobial Agent
Antimicrobial Antimicrobial agent : Chemical
that kills or inhibits the growth of
microorganisms
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Features of Antimicrobial Drugs
• Most modern antibiotics come from organisms living in the soil– Includes bacterial species Streptomyces and Bacillus
as well as fungi Penicillium and Cephalosporium
• To commercially produce antibiotics• To commercially produce antibiotics– Strain is grown until maximum antibiotic
concentration is reached
– Drug is extracted from broth medium
– Extensively purified
– May be chemically altered• Termed semi-synthetic
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AntibioticAntibiotic
• Antibiotic: Chemical produced by a microorganism that kills or inhibits the growth of another inhibits the growth of another microorganism
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Microbial Sources of Antibiotics
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Prinsip Terapi Antimikrobial
1. Suatu antimikroba/antibiotika seharusnyamembunuh atau menghambat pertumbuhanbakteri tanpa berbahaya terhadap tubuhbakteri tanpa berbahaya terhadap tubuhmanusia sebagai inangnya.
2. Obat berpenetrasi ke jaringan tubuh yang dituju, dan menuju ke mikroorganisme target secara spesifik.
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o Bakteriostatis penghambatan pertumbuhan ataumultiplikasi suatu bakteri
o Bakterisidal bersifat destruktif (membunuh) bakteritertentu.
o Desinfektan = bahan kimia yang digunakan untukmembunuh organisme patogen dilakukan terhadapbenda mati.
Terms that relate to antimicrobial medications
benda mati.
KHM (Kadar Hambat Minimum) = kadar minimum obatyang diperlukan untuk menghambat pertumbuhanmikroba/bakteri.
KBM (Kadar Bunuh Minimum) = kadar minimum obatyang diperlukan untuk membunuh mikroba atau bakteri.
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Chemotherapy
• The use of drugs to treat a disease
• Selective toxicity: A drug that kills harmful microbes without damaging the host.
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Infeksi adalah proses masuknya organisme di dalam tubuh.
Sensivitas individu terhadap mikroorganisme
Sensitivity
Sensivitas individu terhadap mikroorganismetergantung : Jumlah mikroba atau organisme patogen Tingkat Keganasan Daya tahan tubuh
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Antibiotic Spectrum of Activity
SPEKTRUM = luas aktivitas obat antimikrobialterhadap suatu jenis bakteri
Narrow spectrumWork on narrow range of organismsWork on narrow range of organismsGram-positive only OR Gram-negative onlyAdvantage: effects pathogen onlyDisadvantage: requires identification of pathogen
Broad spectrumAdvantage: Work on broad range of organismsDisadvantage : disruption of normal flora
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Antibiotic Spectrum of ActivityAntibiotic Spectrum of Activity
No antibiotic is effective against all microbes
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Mechanisms of Antimicrobial Action
• Bacteria have their own enzymes for– Cell wall formation– Protein synthesis– DNA replication– RNA synthesis– Synthesis of essential metabolites
Viruses use host enzymes inside host cellsSynthesis of essential metabolites
• Viruses use host enzymes inside host cells• Fungi and protozoa have own eukaryotic enzymes
• The more similar the pathogen and host enzymes, the more side effects the antimicrobials will have
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Modes of Antimicrobial Action
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Classification of Antimicrobials
• Inhibit cell wall synthesis
– Penicillins
– Cephalosporins
– Carbapenems
– Monobactams (aztreonam)
– Vancomycin
• Alter nucleic acid metabolism
– Rifamycins
– Quinolones
• Inhibit folate metabolism
– Trimethoprim
• Inhibit protein synthesis
– Chloramphenicol
– Tetracyclines
– Macrolides
– Clindamycin
– Streptogramins(quinupristin/dalfopristin)
– Oxazolidinones (linezolid)
– Aminoglycosides
– Trimethoprim
– Sulfamethoxazole
• Miscellaneous
– Metronidazole
– Daptomycin
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Antifungal Drugs
• Fungi are eukaryotes
• Have unique sterols in their cell walls
• Pathogenic fungi are • Pathogenic fungi are often outside the body
Contoh obat : Golongan poliena (amfoterisin B, nistatin); Golongan azol (klortrimazol, mikonazol, ketokonazol, dll);
Golongan lainnya (flusitosin, griseovulvin, terbinafin)
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Antiviral Drugs
• Viruses are composed of nucleic acid, protein capsid, and host membrane containing virus proteins
• Viruses live inside host cells and use many host enzymes
• Some viruses have unique • Some viruses have unique enzymes for DNA/RNA synthesis or protein cutting in virus assembly
Contoh obat : Obat antiinfluenza (amantadin, tromantadin); Obatantiherpes (asiklovir, valasiklovir, brivudin, famsiklovir); Penghambat
transkriptase-balik (zidovudin, zalsitabin, lamivudin. nevirapin, stavudin); Penghambat protease (indinavir, ritonavir, sakuinavir,
nelvinavir)
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Adverse Effects of Antimicrobial DrugsAdverse Effects of Antimicrobial Drugs
1. Allergic Reactions: some people develop hypersensitivities to antimicrobials
2. Toxic Effects: some antimicrobials toxic 2. Toxic Effects: some antimicrobials toxic at high concentrations or cause adverse effects
3. Suppression of normal flora: when normal flora killed, other pathogens may be able to grow to high numbers
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Selecting an Antimicrobial
• Confirm the presence of infection
– History and physical
– Signs and symptoms
– Predisposing factors
• Selection of presumptive therapy• Drug factors• Host factors
• Monitor therapeutic response– Predisposing factors
• Identification of pathogen
– Collection of infected material
– Stains
– Serologies
– Culture and sensitivity
response• Clinical
assessment• Lab tests• Assessment of
therapeutic failure
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Antiprotozoan Drugs
• Protozoa are eukaryotic cells
• Many drugs are experimental and experimental and their mode of action is unknown
Contoh : Obat malaria (primaquin, kuinin, klorokuin, dll); Obatamoebisidal (metronidazol, tinidazol, diloksanid, dll)
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Antihelminthic Drugs
• Helminths are macroscopic multicellular eukaryotic organisms: tapeworms, roundworms, tapeworms, roundworms, pinworms, hookworms (cacing pita, cacing gelang, cacing kremi, cacing tambang)
Contoh Obat : praziquantel, mebendazol, dan pirantel
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