Antimicrobial Drugs

Prepared by:
Stephanie Lois R. Sanchez, RPh,
MSPh
 The History of Chemotherapy
• Paul Ehrlich in Germany during early part of
20th century
– He speculated about some “magic bullet” that
would selectively find and destroy pathogens but
not harm the host.
• In 1928, Alexander Fleming
– Observed that the growth of the bacterium S.
aureus was inhibited by Penicillium notatum.
 The History of Chemotherapy
• Antibiosis → Antibiotic → a substance
produced by microorganisms that in small
amounts inhibits another microorganism.
• In 1940, Howard Florey and Ernst Chain
– Succeeded in first clinical trials of penicillin

• Sources of Antibiotics: Streptomyces sp.,

genus Bacillus, genera Penicillium and
Cephalosporium
Representative Sources of Antibiotics
MICROORGANISMS
Gram-Positive Rods
Bacillus subtilis
Bacillus polymyxa
Actinomycetes
Streptomyces nodosus
Streptomyces venezuelae
Streptomyces aureofaciens
Streptomyces erythraeus
Streptomyces fradiae
Streptomyces griseus
Micromonospora purpureae
Representative Sources of Antibiotics

MICROORGANISMS

Fungi

Cephalosporium spp.

Penicillium grisofulvum

Penicillium notatum
The Spectrum of Antimicrobial Activity
• Narrow spectrum
• Broad-spectrum
• Superinfection

• Action: bactericidal and bacteriostatic

 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis

• 1. PENICILLINS
• Scientists develop these penicillin's in two
ways:
– 1. they can interrupt synthesis of the
molecule by Penicillium and obtain only the
common penicillin nucleus for use.
– 2. They can remove the side chains that
make them more resistant to penicillinase, or
give them an extended spectrum
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 1. PENICILLINS
• Natural Penicillins
• Penicillin G (Benzylpenicillin) – against gram-
positive bacteria, requires injection
– Procaine/Benzocaine penicillin (IM)
– Benzathine penicillin (IM)
• Penicillin V (Phenoxymethylpenicillin) – against
gram-positive bacteria, oral administration
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 1. PENICILLINS
• Semisynthetic Penicillins
• A. Penicillinase-resistant/Narrow spectrum
– Methicilin
– Nafcillin
– Isoxazoyl Penicillins (Oxacillin, Cloxacillin, Dicloxaciliin)
• B. Aminopenicillins/Antistaphylococcal Penicillin/Broad
Spectrum
– Ampicillin (Parenteral)
• Prodrugs: Hetacillin, Bacampicillin, Cyclacillin
• Combined with sulbactam
– Amoxicillin (PO)
• combined with clavulanic acid
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 1. PENICILLINS
• Semisynthetic Penicillins
• C. Extended Spectrum/Anti-Pseudomonal Penicillin
– Carboxypenicillin (Carbenicillin and ticarcillin)
– Ureidopenecillin (Piperacillin, Azlocillin, Mezlocilllin)
• 2. MONOBACTAM
– Aztreonam – effective for gram-negative bacteria only,
including Pseudomonas spp, E. coli. And Neisseria
• 3. CARBAPENEMS
– Thienamycin, Meropenem, Imipenem –very broad spectrum
• Combined with cilastatin
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 4. CEPHALOSPORINS
1st gen.
• Cephalexin
• Cephapirin
• Cephradine
• Cefazolin
• Cefadroxil

2nd gen.
• Cefaclor
• Cefoxitin
• Loracarbef
• Cefotetan
• Cefprozil
• Cefmetazole
• Cefamandole
• Cefuroxime
• Cefonicid
• Cefpodoxime
• Ceforanide
 3rd gen.
• Cefixime • Ceftizoxime
• Cefoperazone • Ceftriaxone
• Cefotaxime • Ceftazidime
• Ceftibuten • Moxolactam

4th gen. 5th gen.

• Cefepime • Ceftaroline
• Cefpirome • Ceftobipole
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 4. CEPHALOSPORINS
Gram (+) Gram (-)
1st gen +++ +
2nd gen +++ ++
3rd gen + +++
4th gen ++ ++++
5th gen ++++ ++++
 The Action of Antibacterial Drugs
• Inhibitors of Cell Wall Synthesis
• 5. POLYPEPTIDE ANTIBIOTICS
• A. Bacitracin
• B. Vancomycin
– A glycopeptide type
– Causes Redman’s syndrome
 The Action of Antibacterial Drugs
• Inhibitors of Protein Synthesis
• Binds to 30s Ribosomes
• 1. AMINOGLYCOSIDES (Streptomycin,
Amikacin, Gentamicin, Netilmicin, Neomycin,
Tobramycin)
– Streptomycin
– Neomycin
– Gentamicin
– Tobramycin .
 The Action of Antibacterial Drugs
• Inhibitors of Protein Synthesis
• Binds to 30s Ribosomes
• 2. TETRACYCLINES
– Tetracycline, oxytetracycline, chlortetracycline,
demeclocycline
– Semisynthetic: doxycycline and minocycline
• AE: Gastric discomfort, deposition in the bones
and primary dentition causing discoloration and
hypoplasia of the teeth and a temporary stunting
of growth, hepatotoxicity, phototoxicity
(demeclocycline), vestibular problems
(minocycline)
 The Action of Antibacterial Drugs
• Inhibitors of Protein Synthesis
• Binds to 50s Ribosomes
• 1. CHLORAMPHENICOL
– Serious AE: suppression of bone marrow activity,
aplastic anemia, gray baby syndrome
 The Action of Antibacterial Drugs
• Inhibitors of Protein Synthesis
• Binds to 50s Ribosomes
• 2. MACROLIDES
– Erythromycin
– Clarithromycin
– Azithromycin
– Telithromycin
• AE: epigastric distress, cholestatic jaundice (estolate form of
erythromycin)
 The Action of Antibacterial Drugs
• Inhibitors of Protein Synthesis
• Binds to 50s Ribosomes
• 3. LINCOSAMIDES
– Clindamycin
• AE: Pseudomembranous colitis and rash
• 4. STREPTOGRAMINS
– Quinupristin and dalfopristin (Synercid)
• 5. Oxazolidinones
– Linezolid
 The Action of Antibacterial Drugs
• Injury to the Plasma Membrane
• 1. POLYMYXIN B
 The Action of Antibacterial Drugs
• Inhibitors of Nucleic Acid Synthesis
• QUINOLONES AND FLUOROQUIONOLONES
– Nalidixic acid
– Norfloxacin, Ciprofloxacin
– Moaxifloxacin and gatifloxacin
• AE: development of cartilage, Diarrhea, nausea,
headache, dizziness, nephrotoxicity, phototoxicity
 The Action of Antibacterial Drugs
• Competitive Inhibitors of the Synthesis of essential
Metabolites
• 1. SULFONAMIDES
• Trimethoprim-sulfamethoxazole
– Effective against Pneumocystic pneumonia
– Very effective in penetrating the brain and
cerebrospinal fluid
 The Action of Antibacterial Drugs
• Competitive Inhibitors of the Synthesis of essential
Metabolites
• 1. SULFONAMIDES
– Silver sulfadiazine and Mafenide (Flammazine®)
– Sodium sulfacetamide
– Quinine + pyrimethamine + sulfadoxime
(Fansidar®)
 The Action of Antibacterial Drugs
• Antimycobacterial antibiotics
• 1. Rifampin
– AE: red-orange coloration of body fluids
• 2. Isoniazid
– AE: hepatoxicty, peripheral neuropathy
• 3. Ethambutol
– AE: optic neuritis
 The Action of Antibacterial Drugs
• Antimycobacterial antibiotics
• 4. Pyrazinamide
– AE: hyperuricemia and hepatotoxicity
• 5. Ethionamide
– AE: Hepatotoxicity, Peripheral neuritis
• 6. Streptomycin
– AE: Ototoxicity, nephrotoxicity
 Antifungal Drugs
• Agents affecting Fungal Sterols
• 1. POLYENES
– Amphotericin B
• Can cause kidney toxicity → drugs are
encapsulated in lipids (liposome)
– Nystatin and Natamycin
 Antifungal Drugs
• Agents affecting Fungal Sterols
• 2. AZOLES
– Imidazole (Clotrimoxazole, miconazole)
– Ketoconazole
– Voriconazole (Fluconazole and itraconazole)
• 3. ALLYAMINES
– Terbinafine, naftifine
 Antifungal Drugs
• Agents affecting Fungal Cell wall
• 1. ECHINOCANDINS
– Caspofungin (Cancidas)

• Agents Inhibiting Nucleic acids

• 1. FLUCYTOCINE
– Cruptococcus neoformans and Candida
– AE: kidney and bone marrow toxicity
 Antifungal Drugs
• Other fungal Drugs
• 1. GRISEOFULVIN
• 2. TOLNAFTATE
• 3. PENTAMIDINE ISETHIONATE
 Antiviral Drugs
• Nucleoside and Nucleotide Analog
• 1. Acyclovir, famiclovir, ganciclovir, ribavirin
• 2. Lamivudine
• 3. Cidofovir

• Other enzyme Inhibitor

• 1. Zanamivir and oseltamivir phosphate
• 2. Amantadine and Zimantadine
 Antiviral Drugs
• Interferons
• 1. Alpha-interferon
• 2. Imiquimod
 Antiviral Drugs
• ANTIRETROVIRALS
• Nucleoside Reverse Transcriptase inhibitors
• Abacavir, didanosine, lamivudine, stavudine,
zalcitabine, zidovudine
• Nucleotide Reverse Transcriptase Inhibitor
• Tenofovir
• Non-nucleoside Reverse Transcriptase Inhibitors
• Delavirdine, elvirenz, nevirapine
• Protease inhibitors
• Amprenavir, nelfinavir, ritonavir, saquinavir,
lopinavir, indinavir, saquinavir
 Antiprozoan drugs

• 1. Quinine
• Chloroquine, mefloquine, primaquine
• 2. Quinacrine
• 3. Diiodohydroxyquin (iodoquinol)
• 4. Metronidazole
 Antihelminthic drugs

• 1. Niclosamide
• 2. Praziquantel
• 3. Mebendazole and albendazole
• 4. Ivermectin
 Drug resistance
• Resistance may due to enzymatic destruction
of a drug, prevention of penetration of the
drug to its target site, or cellular or metabolic
changes at target sites.
• Rapid efflux (ejection)
• Hereditary drug resistance factors are carried
by plasmids and transposons.

• ..\..\..\..\..\Downloads\Animation of
Antimicrobial Resistance.mp4
• Antibiotic safety
• The risk versus the benefit must be
evaluated prior to use of antibiotics

• Effects of combinations of drugs

• Synergistic or antagonistics
• The future of chemotherapeutic Agents
• Many bacterial diseases, previously treatable
with antibiotics, have become resistant to
antibiotics.
• Chemicals produced by plants and animals are
providing new antimicrobial agents called
antimicrobial peptides.
• New antimicrobial drugs include DNA that is
complementary to specific genes in a pathogen;
the DNA will bind to the pathogen’s DNA or
mRNA and inhibit protein synthesis.