Antibacterials - Part II Flashcards
What are the classifications of antimicrobials?
Inhibitors of cell synthesis
Inhibitors of protein synthesis
Inhibitors of folic acid synthesis
Inhibitors of DNA synthesis and structure
What are the examples of inhibitors of protein synthesis?
Aminoglycosides, Chloramphenicol, Tetracyclines, Macrolides, and Lincosamides
What are aminoglycosides?
Two amino sugars joined by a glycoside linkage to a central hexose nucleus
Where are aminoglycosides derived from?
Streptomycins (have a -mycin ending)
Micromonospora (have a -micin ending)
What is the spectrum for aminoglycosides?
Broad gram negative
What is the pharmacokinetics of aminoglycosides?
Mostly given intravenously
Mostly excreted unchanged in the urine
What is the exception of aminoglycosides regarding pharmacokinetics?
Neomycin - because of nephrotoxicity
It is used topically
Why should plasma drug levels be monitored while on aminoglycosides?
They have a low therapeutic index so monitoring is important in order to prevent a toxic effect
What characteristics do aminoglycosides exert?
Concentration-dependent bactericidal activity and post-antibiotic effect.
What is the mechanism of aminoglycosides?
Inhibit bacterial protein synthesis
How do aminoglycosides inhibit bacterial protein synthesis?
Diffuse through porin channels in the outer membrane; use the oxygen-dependent system to move across the cytoplasmic membrane
Where do aminoglycosides bind in the ribosome?
They bind to the 30s subunit
What effect does the binding of aminoglycosides to the 30s subunits have?
Distorts the structure and causes misreading of the mRNA
What is the therapeutic use of aminoglycosides?
Effective for the majority of aerobic gram (-) bacilli
Often combined with a β-lactam for synergistic effect
Treatment of serious infections due to aerobic gram (-) bacilli, serious toxicity limits their clinical utility.
What multidrug-resistant pathogens are sensitive aminoglycosides?
Pseudomonas aeruginosa,
Klebsiella pneumoniae,
Enterobacter sp.
What is the resistance of aminoglycosides?
Efflux pumps, decreased uptake, and/or modification and inactivation by plasmid-associated synthesis of enzymes
What are the adverse effects of aminoglycosides?
Ototoxicity
Nephrotoxicity
Neuromuscular paralysis & allergic reaction
What kind of allergic reactions can happen with aminoglycosides?
Contact dermatitis
What is ototoxicity?
Toxic to neuroepithelium of inner ear & destroy hair cells
Why are anaerobic bacteria not susceptible to aminoglycosides?
Due to a lack of an oxygen-dependent active transport mechanism for amino glycoside uptake.
What are examples of tetracyclines?
Tetracycline
Doxycycline
Minocycline
What are tetracyclines?
Bacteriostatic
What is the mechanism of tetracyclines?
Bind reversibly to 30s ribosomal subunit
Prevent binding of tRNA to m-RNA ribosome complex
Inhibit bacterial protein synthesis
What is the coverage of tetracyclines?
Broad-spectrum, effective against gram (+) and gram (-) bacteria
What are tetracyclines usually used for?
Acne and chlamydia infections
What is the resistance of tetracyclines?
Mainly efflux pumps
Enzymatic inactivation and by proteins that prevent binding to ribosomes
What is the pharmacokinetics of tetracyclines?
They are usually given orally
Also available as IV
Widely distributed into body fluids, including CSF, can cross placenta
Eliminated via kidney
Why are tetracyclines not given to pregnant women?
Can travel through the placenta so unsafe for embryo, also cause tatragenicity
What are the adverse effects of tetracyclines?
Diarrhea, nausea, abdominal pain, anorexia
Deposition of the drug in the bones and teeth
Vestibular dysfunction
Pseudomotor cerebi
Teratogenicity
What is pseudomotor cerebi?
Benign, intracranial hypertension characterized by headache and blurred vision.
What are the contraindications of tetracyclines?
Pregnancy
Age below 8
What is an example of glycylcyckines?
Tigecycline
What are glycylcyclines structurally similar to?
Tetracyclines
What is the spectrum of the glycylcyclines?
Broad spectrum for both gram (+) and gram (-)
Extended-spectrum β-lactamase; producing gram (-) bacteria and anaerobes
What re some examples of pathogens that are sensitive to glycylclines?
MRSA, VRE
Which pathogen do not get affected by glycylcyclines?
Pseudomonas spp.
Proteus spp.
What is the mechanism of glycylcyclines?
Inhibits protein synthesis by interfering with bacterial 30s ribosomal units.
What is the pharmacokinetics of glycylcyclines?
Given by slow IV infusion, penetrates tissue.
Biliary/fecal elimation
What is the resistance of the glycylclines?
Developed to tackle the resistance of tetracyclines but over-expression of efflux pumps can cause resistance
What are common side effects of glycylclines?
Diarrhea, nausea, vomiting
Complicated skin and soft tissue infections are indications of which antibacterial?
Glycylclines
What are examples of macrolides?
Erythromycin, Azithromycin and Clarithromycin
What is bacteriostatic?
May be bactericidal in high concentrations
Where do erythromycin and clindamycin attach?
They bind to the 50s subunits, they inhibit translocation.
