Inhibitors of Cell Wall Synthesis Penicillin Natural penicillins Semisynthetic penicillins Extended-spectrum penicillins

Penicillins Low toxicity Effective derivatives created from manipulating drug’s basic molecular structure Kills bacteria by preventing them from forming the rigid cell wall Because human cells do not have cell walls, they are not affected

Therapeutic Uses of Penicillins Abscesses Beta-hemolytic streptococcus Meningitis Otitis media Pneumonia Respiratory infections Tooth and gum infections Venereal diseases (syphilis and gonorrhea) Endocarditis due to streptococci

Penicillins’ Side Effects Diarrhea Allergies in 7% to 10% of population Penicillins’ Dispensing Issues Take on an empty stomach Food slows absorption Acids in fruit juices or colas could deactivate the drug

The Structure of Penicillins

Retention of Penicillin G

The Effect of Penicillinase on Penicillins

 Lactam Antibiotics Penicillin Penicilinase-resistant penicillins Penicillins +  - lactamase inhibitors Carbapenems Substitute a C for a S, add a double bond Monobactam Single ring

Inhibitors of Cell Wall Synthesis Cephalosporins First-generation: Narrow spectrum, gram- positive Second-generation: Extended spectrum includes gram-negative Third-generation: Includes pseudomonads; injected Fourth-generation: Oral

First-generation Similar to penicillinase-resistant penicillins with greater gram-negative coverage Used for community-acquired infections mild to moderate infections Second-generation Increased activity, especially against Haemophilus influenzae Used for Otitis media in children Respiratory infections UTIs Third-generation Active against a wide spectrum of gram-negative organisms Long half-life, so once-a-day dosing for some Used for Ambulatory patients Children (dosing before or after school)

Inhibitors of Cell Wall Synthesis Polypeptide antibiotics Bacitracin Topical application Against gram-positives Vancomycin Glycopeptide Important "last line" against antibiotic-resistant S. aureus

Comparison of Cephalosporin and Penicillin

The Inhibition of Protein Synthesis by Antibiotics

Inhibitors of Protein Synthesis Chloramphenicol Broad spectrum Binds 50S subunit; inhibits peptide bond formation

Inhibitors of Protein Synthesis Aminoglycosides Streptomycin, neomycin, gentamycin Broad spectrum Changes shape of 30S subunit

Inhibitors of Protein Synthesis

Streptogramins Gram-positives Binds 50S subunit; inhibits translation

Inhibitors of Protein Synthesis

Oxazolidinones Linezolid Gram-positives Binds 50S subunit; prevents formation of 70S ribosome

Inhibitors of Nucleic Acid Synthesis Rifamycin Inhibits RNA synthesis Antituberculosis Quinolones and fluoroquinolones Nalidixic acid: Urinary infections Ciprofloxacin Inhibits DNA gyrase Urinary tract infections

Quinolones Strong, rapid bactericidal action against most gram- negative and many gram-positive bacteria Antagonize the enzyme responsible for coiling and replicating DNA, causing DNA breakage and cell death Quinolones’ Dispensing Issues Not to be given with theophylline Antacids interfere with absorption Avoid exposure to sun

Therapeutic Uses of Quinolones Bone and joint infections caused by gram-negative organisms Infectious diarrhea Ophthalmic infections Some sexually transmitted diseases Upper respiratory infections UTIs

Quinolones’ Side Effects Primarily gastrointestinal, with nausea and vomiting Dizziness Unpleasant taste Can cause joint problems such as swelling and malformations Patients taking them have a tendency to injure tendons

Rifamycin any of a family of antibiotics biosynthesized by a strain of Streptomyces mediterranei, effective against a broad spectrum of bacteria, including gram-positive cocci, some gram-negative bacilli, and Mycobacterium tuberculosis and certain other mycobacteria; used for the treatment of tuberculosis and the prophylaxis of meningococcal infections.Streptomyces mediterraneiMycobacterium tuberculosis

Adverse reactions CNS: ataxia, confusion, drowsiness, fatigue, headache, asthenia, psychosis, generalized numbness EENT: conjunctivitis; discolored tears, saliva, and sputum GI: nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, epigastric distress, flatulence, discolored feces, anorexia, sore mouth and tongue, pseudomembranous colitis GU: discolored urine Hematologic: eosinophilia, transient leukopenia, hemolytic anemia, hemolysis, disseminated intravascular coagulation (DIC), thrombocytopenia Hepatic: jaundice Metabolic: hyperuricemia Musculoskeletal: myalgia, joint pain Respiratory: dyspnea, wheezing Skin: flushing, rash, pruritus, discolored sweat, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome Other: flulike symptoms, hypersensitivity reactions including vasculitis

prophylaxis refers to medical or public health measures taken in order to prevent disease or health problems, rather than to treat or cure an existing condition. Prophylaxis is also a way to stem an outbreak of disease, or minimize the symptoms of someone who has been exposed to a disease or virus.