Antimicrobials and Chemotherapeutic Agents

Antimicrobials and Antineoplastic Agents

• Chemotherapeutic agents selectively act against microbes or malignant cells, without affecting body cells.
• Antimicrobials are used to treat infectious diseases caused by microbes, and antibiotics are a type of antimicrobial produced by microbes to inhibit or kill other microbes.

Terminologies

• Bacteriostatic: stops the growth of bacteria
• Bactericidal: kills bacteria
• Bacteriolytic: destruction or dissolution of bacterial cells

Gram Positive and Gram Negative Bacteria

• Gram positive bacteria have a thick cell wall and peptidoglycan directly accessible from the environment.
• Gram negative bacteria have a thin cell wall, surrounded by an inner and outer membrane, with lipopolysaccharides, phospholipids, and proteins, making it a barrier to antibiotic diffusion.

Historical Perspectives

• 1877: Louis Pasteur discovered the phenomenon of antibiosis.
• 1906: Paul Ehrlich coined the term "chemotherapy" and is considered the father of chemotherapy.
• 1935: Domagk discovered sulfonamides (Prontosil to sulphanilamide).
• 1929, 1939, 1941: Fleming, Chain, and Florey discovered penicillin from penicillium.
• Waksman discovered streptomycin from actinomycetes and coined the term "antibiotic".

Antimicrobial Classification

• Classification by chemical structure (e.g., β-lactams, aminoglycosides)
• Classification by mechanism of action (e.g., inhibitors of cell wall synthesis)
• Classification by activity against organisms (e.g., anti-bacterial, anti-fungal)
• Classification by spectrum of activity (e.g., narrow, broad, extended)
• Classification by origin/source of antimicrobials

Classification by Organism Affected

• Anti-viral
• Anti-bacterial
• Anti-fungal
• Anti-protozoal
• Anthelmintic

Classification by Spectrum

• Narrow spectrum: e.g., penicillin G, streptomycin, erythromycin
• Broad spectrum: e.g., tetracycline, chloramphenicol
• Extended spectrum: e.g., ampicillin, amoxicillin

Classification by Mechanism of Action

• Cell wall synthesis inhibition: e.g., β-lactams, vancomycin, cycloserines
• Cell membrane leakage: e.g., polypeptides, polyenes
• Folate synthesis inhibition: e.g., sulfonamides, pyrimethamine, cotrimaxazole
• DNA gyrase and topoisomerase inhibition: e.g., fluoroquinolones
• RNA polymerase inhibition: e.g., rifampicin
• Protein synthesis inhibition: e.g., aminoglycosides, tetracyclines, chloramphenicol, macrolides

Differences in Human and Bacterial Cell Components

• Human cells lack a cell wall (peptidoglycans = peptides + sugar)
• Human cell membrane is different (bacteria contain hypanoids in place of sterol)
• Human cells take preformed dihydrofolic acid (no need for PABA in humans)
• Dihydrofolic acid reductase enzyme is different (thousand-time affinity)
• Topoisomerase II are different (in bacteria, DNA gyrase)
• DNA-dependent RNA polymerase is different
• Ribosome 60S subunit for human (in bacteria, 50S)
• Ribosome 40S subunit for human (in bacteria, 30S)

Penicillins

• Penicillins are bactericidal and active against a variety of bacteria, with low direct toxicity.
• Examples: ampicillin, amoxicillin, carbenicillin, ticarcillin
• Spectrum: narrow spectrum to broad spectrum
• Pharmacokinetics: vary depending on the specific penicillin

β-Lactamase Resistant Penicillins

• Examples: flucloxacillin, methicillin, nafcillin, oxacillin, dicloxacillin
• Spectrum: very narrow, active against penicillinase-producing staphylococci
• Pharmacokinetics: vary depending on the specific penicillin

Broad-Spectrum Penicillins

• Examples: ampicillin, amoxicillin
• Spectrum: broad spectrum, active against a variety of bacteria
• Pharmacokinetics: vary depending on the specific penicillin

Cephalosporins

• Cephalosporins are beta-lactam antibiotics, similar in structure and actions to penicillins.
• They are bactericidal, often resistant to beta-lactamases, and active against a broad spectrum of pathogens.
• Classification: 1st generation, 2nd generation, 3rd generation
• Examples: cephalexin, cefuroxime, cefamandole

This quiz covers the basics of antimicrobials and chemotherapeutic agents, including their selective action against microbes or malignant cells.