chapter 6 inhibitors of cell wall synthesis
TRANSCRIPT
Inhibitors of Cell Wall SynthesisPenicillin
Natural penicillinsSemisynthetic penicillinsExtended-spectrum penicillins
PenicillinsLow toxicityEffective 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 PenicillinsAbscessesBeta-hemolytic streptococcusMeningitisOtitis mediaPneumoniaRespiratory infectionsTooth and gum infectionsVenereal diseases (syphilis and gonorrhea)Endocarditis due to streptococci
Penicillins’ Side EffectsDiarrheaAllergies in 7% to 10% of population
Penicillins’ Dispensing IssuesTake on an empty stomach
Food slows absorptionAcids in fruit juices or colas could deactivate
the drug
The Structure of Penicillins
The Structure of Penicillins
Retention of Penicillin G
The Effect of Penicillinase on Penicillins
-b Lactam AntibioticsPenicillin
Penicilinase-resistant penicillins
Penicillins + -lactamase inhibitors
CarbapenemsSubstitute a C for a
S, add a double bond
MonobactamSingle ring
Inhibitors of Cell Wall SynthesisCephalosporins
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 SynthesisPolypeptide 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 SynthesisChloramphenicol
Broad spectrum Binds 50S subunit; inhibits peptide bond formation
Inhibitors of Protein SynthesisAminoglycosides
Streptomycin, neomycin, gentamycin Broad spectrum
Changes shape of 30S subunit
Inhibitors of Protein Synthesis
Inhibitors of Protein SynthesisStreptogramins
Gram-positives Binds 50S subunit; inhibits translation
Inhibitors of Protein Synthesis
Inhibitors of Protein SynthesisOxazolidinones
Linezolid Gram-positives
Binds 50S subunit; prevents formation of 70S ribosome
Inhibitors of Nucleic Acid SynthesisRifamycin
Inhibits RNA synthesisAntituberculosis
Quinolones and fluoroquinolonesNalidixic acid: Urinary infectionsCiprofloxacinInhibits DNA gyraseUrinary tract infections
QuinolonesStrong, rapid bactericidal action against most
gram-negative and many gram-positive bacteriaAntagonize the enzyme responsible for coiling
and replicating DNA, causing DNA breakage and cell death
Quinolones’ Dispensing IssuesNot to be given with theophyllineAntacids interfere with absorptionAvoid exposure to sun
Therapeutic Uses of QuinolonesBone and joint infections caused by gram-
negative organismsInfectious diarrheaOphthalmic infectionsSome sexually transmitted diseasesUpper respiratory infectionsUTIs
Quinolones’ Side EffectsPrimarily gastrointestinal, with nausea and
vomitingDizzinessUnpleasant tasteCan cause joint problems such as swelling
and malformationsPatients taking them have a tendency to
injure tendons
Rifamycinany 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.
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.