Antimicrobial Drugs

PHARMACOLOGY AND TOXICOLOGY II

Presented for Department of PharmacyUniversity of Darussalam Gontor - Indonesia

Surya Amal

Antimicrobial DrugsPart I

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.

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

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

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

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

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

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

Mikroba•Bakteri

•Virus

•Fungi

Parasit•Protozoa

•Cacing

Antimicrobial Agent

Antimicrobial Antimicrobial agent : Chemical

that kills or inhibits the growth of

microorganisms

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

AntibioticAntibiotic

• Antibiotic: Chemical produced by a microorganism that kills or inhibits the growth of another inhibits the growth of another microorganism

Microbial Sources of Antibiotics

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.

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.

Chemotherapy

• The use of drugs to treat a disease

• Selective toxicity: A drug that kills harmful microbes without damaging the host.

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

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

Antibiotic Spectrum of ActivityAntibiotic Spectrum of Activity

No antibiotic is effective against all microbes

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

Modes of Antimicrobial Action

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

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)

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)

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

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

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)

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