Penicillins: Mechanism and Effects

• Penicillins are antibacterial
• Penicillins can treat Gram-positive and Gram-negative bacteria
• Penicillins can treat Spirochetes, such as treponema pallidum
• Penicillins can treat Actinomyces

The Mechanism of Action

• Penicillins bind to PBPs on the bacterial cell wall
• Penicillins inhibit trans-peptidation reactions, which are essential for bacterial cell wall synthesis
• Penicillins activate intracellular auto-lytic enzymes (autolysins), leading to cell rupture

Adverse Effects

• Hypersensitivity reactions occur in 10% of patients receiving penicillin
• These reactions occur with all types of penicillin
• Hypersensitivity can be caused by a degradation product
• Reactions include a simple rash to acute anaphylaxis and angioedema
• Early hypersensitivity (type I) occurs within 2 minutes of administration
• Delayed hypersensitivity (type II) can occur up to 12 days after administration
• Can also cause Superinfection, Stomatitis, Diarrhea
• Can cause Neurotoxicity: Convulsions, coma, and death, following intrathecal injections
• Can cause Cation toxicity
• Can cause Agranulocytosis associated with methicillin and cloxacillin
• Methicillin causes interstitial nephritis, hence it is no longer used
• Can cause Masking of infection (syphilis and gonorrhea)

Metronidazole

• It Is a 5-nitroimidazole compound
• Targets Anaerobic protozoa & bacteria that lack mitochondria, they generate ATP using ferredoxin oxidoreductase enzyme in the cytoplasm
• The enzyme system transfers an electron to the 5-nitro groups, which produces a cytotoxic product
• This product causes DNA damage and inhibits DNA repair
• Active against anaerobic organisms including anaerobic bacteria like Bacteroids, C. difficile, E. histolytica, G. lamblia, T. vaginalis, B. coli.

Therapeutic uses

• Kills trophozoites but not cysts in Amebiasis
• A treatment for Urogenital trichomoniasis is 250 mg t.d.s. for 7 days and the partner should be treated simultaneously
• A treatment for Giardiasis is 250 mg t.d.s. for 5 days
• A treatment for Balantidiasis is 750 mg t.d.s. for 5 days
• Treats Severe anaerobic infections like puerperal sepsis, peritonitis, acute ulcerative gingivitis

Adverse effects

• Can cause Nausea, vomiting & metallic taste (GIT)
• Can cause insomnia, headache, vertigo, parasthesia, ataxia, & seizures (CNS)
• Can cause bone marrow depression, leukopenia & thrombocytopenia (Blood)
• Can cause Disulfiram-like reaction accumulation of acetaldehyde if alcohol is consumed which leads to nausea & vomiting
• Can cause Dark brown urine

Macrolides

• Includes Erythromycin, azithromycin, clarithromycin
• Bind reversibly to the 50S ribosomal subunit
• Are bacteriostatic in low concentrations
• Are bactericidal in high concentrations
• Treats Gram-positive bacteria like pneumococci, staphylococci, streptococcus species, C. diphtheria
• Treats Gram-negative bacteria, such as Neisseria and H. influenza
• Treats Intracellular microorganisms like Mycoplasma species legionella and Chlamydia.

Aminoglycosides

• Includes streptomycin, Gentamicin, tobramycin, amikacin, kanamycin, and neomycin
• Are usually transported across the inner cell membrane by active transport in Gram-negative aerobic spp.
• Bind to the 30S ribosomal subunit
• Are bactericidal
• Giving a single large dose daily is better
• The drugs have a post-antibiotic effect
• Treats Gram negative bacilli, few Gram positive cocci, and Mycobacteria TB.

Tetracyclines

• Includes Oxytetracycline (prototype), doxycycline and tigecycline
• Bind reversibly to the 30S ribosomal subunit which inhibits bacterial protein synthesis
• Are bacteriostatic
• Treats Most gram-positive, many gram-negative bacteria, and Brucella
• Treats Rickettsia, Coxiella, Mycoplasma and Chlamydia (intracellular organisms)
• Treats Spirochetes, Actinomycines, Protozoa
• Treats Helicobacter pylori