Antio Flashcards
What are most antibiotics derived from?
→natural products by fermentation
Why are antibiotics chemically modified?
→pharmacological properties ie can they survive in the stomach
→antimicrobial effect
What is an example of totally synthetic antibiotics?
→sulphonamides
What are natural products of fungi and bacteria derived from?
→- soil dwellers natural antagonism and selective advantage
→kill or inhibit the growth of other microorganisms
Why is there selective toxicity?
→Due to the differences in structure and metabolic pathways between host and pathogen
Why is selective toxicity difficult in viruses?
→intracellular
What are the principles of selective toxicity?
→Due to the differences in structure and metabolic pathways between host and pathogen
→Harm microorganisms, not the host
→Target in microbe, not host (if possible)
→Difficult for viruses (intracellular), fungi and parasites
→Variation between microbes
→effect on commensals
What is therapeutic margin?
→active dose (MIC) versus toxic effect
What types of drugs have narrow therapeutic margins?
→toxic drugs
Why is microbial antagonism important?
→Maintains flora
→Limits growth of competitors and pathogens
What happens with loss of flora?
→bacterial or pathogen overgrowth
Example of a disease cause by loss of flora
→Antibiotic Associated Colitis
Which bacteria can cause pseudomembranous colitis?
Clostridioides difficile
Which antibiotics most commonly cause colitis?
→Fluoroquinolones
→clindamycin,
→broad-spectrum lactams
What conditions cause immunosuppression?
→cancer chemotherapy,
→transplantations,
→myeloma,
→leukaemias,
→HIV with low CD4
→Neutropenics,
→asplenics,
→renal disease,
diabetes
How are antibiotics classified?
→Type of activity
→Structure
→ Target site for activity
What are bactericidal antibiotics?
→Kill bacteria
→Used when the host defense mechanisms are impaired
→Required in endocarditis, kidney infection
Describe bacteriostatic antibiotics
→Inhibit bacteria eg tetracyclin
→Used when the host defense mechanisms are intact
→Used in many infectious diseases
What might a bacteriostatic antibiotic become if dose is increased?
→bactericidal if dose is increased
Examples of broad spectrum antibiotics
→Cefotaxime
→
Example of narrow spectrum antibiotics
→Penicillin G
What are cephalosporins now most effective against?
→gram negatives
What are basic penicillin active against?
→streptococci,
→pneumococci,
→meningococci,
→treopnemes
Which bacteria are resistant against basic penicilin?
→Staphylococcus aureus
What type of natural substance does penicilin have?
→Beta-lactams
What are anti-staphylococcal penicillin?
→narrow spectrum,
→G+ves,
→beta-lactamase resistant
Compare Pen G and Pen V?
Pen G
→not acid stable
→i/v or i/m
→good for some G-ves as well as G+ves
Pen V
→oral (more acid stable than penG)
→less active v G-ves,
→ same activity with G+ves as PenG
What are broader spectrum penicillins?
→Spectrum of activity is similar to basic penicillins but also includes some Gram-negative organsims and also enterococci
What are anti-pseudomonal penicillin?
→extended spectrum beta-lactam antibiotic
→also G+ve, G-ve, anaerobes
Example of anti-pseudomonal penicillin
→piperacillin
What are beta-lactam/lactamase inhibitors?
→Spectrum like amoxicillin plus activity against some Gram-negatives and Staph aureus
What are pseudomonal?
→a major cause of lung infections in people with cystic fibrosis.
→thrive in moist environments and equipment
What are the molecular structure classifications of antibiotics?
→nalidixic acid →ciprofloxacin →erythromycin →tetracycline →vancomycin →streptomycin(aminoglycosides)
What are beta lactams?
Structural mimics of natural substrates for enzymes
Why are beta-lactams important?
→Without B lactam there will be no antimicrobial property
→stop bacterial growth by inhibiting PBPs that are indispensable for the cross-linking process during cell wall biosynthesis
Which bacteria have beta lactams?
→penicillin
What are carbepenams?
→effective antibiotic agents commonly used for the treatment of severe or resistant bacteria
What are the modes of actions of bacteria?
→cell wall synthesis →DNA →folic acid →metabolism →cell membrane →protein sythesis- 50S and 30S →DNA and RNA processing- Gyrase, DNA-directed RNA polymerase
Is tetracycline -cidal or static?
→static
How do antibiotics reach membrane of gram negatives?
→porins in outer membrane mediate the passive diffusion of antibiotics
What are the sites of action of inhibitors of bacterial cell wall synthesis?
→cytoplasm- synthesis of cell wall precursors
→cytoplasmic membrane- synthesis of cell wall subunits
→cell wall- new wall unit attachment
What are D-alanines?
→incorporated by PBPs into peptidoglycan
How does cycloserine inhibit bacteria cell wall synthesis?
→inhibits incorporation of alanine into cell wall precursor
How does vancomycin inhibit bacteria cell wall syntesis?
→bind to terminal D-ala D-ala residues to prevent incorporation of subunit into peptidoglycan
How does bacitracin inhibit bacteria cell wall synthesis?
→prevents dephosphorylation of phospholipid carrier which prevents regeneration of carrier to continue synthesis
How do penicillin and cephalosporins inhibit bacteria cell wall synthesis?
→inhibit enzymes which catalyse cross linking
Which bacteria is resistant against penicillin?
→mycoplasma pneumoniae
→have sterol packed cell membrane
What type of antibiotic are folic acid synthesis inhibitors?
→bactericidal
→broad spectrum
What are the targets of folic acid synthesis inhibitors?
→PABA
→dihydrofolate reductase- human DHFR is less inhibited hence selective toxicity
How do aminoglycosides inhibit protein sythesis?
→Binding fmet t-RNA Initiation complex formation
→streptomycin
How does gentamycin inhibit protein synthesis?
→Translocation of fmet t-RNA
to P site
How does tetracycline inhibit protein synthesis?
→Competition with new Aminoacyl t-RNA at the A site
How does chloramphenicol inhibit protein synthesis?
→Blocks formation of peptide bond peptidyl transferase
→Bind to 50S ribosome
How do erythromycin and fusidic acid inhibit protein sythesis?
→Block translocation of peptidyl t-RNA
What 2 infections can antibiotics be used prophylaxis?
→meningitis
→tuberculosis
How is antibiotic given in a meningitis case?
→i/m injection
Which conditions are antibiotics given topically?
→conjunctivitis
→antiseptic creams
→burns
What does minimum inhibition concentration depend on?
→age →weight →renal and liver function →severity of infection →susceptibility of the organism →properties of the antibiotic
What are the two pharmacodynamic properties of antibiotics killing activity?
→time-dependence
→concentration-dependence = max or area above MIC
Why are antibiotic combinations used?
→life-threatening infections e.g. endocarditis, septicaemia
→Polymicrobial infections
→Less toxic doses
→synergy eg. penicillin and gentamicin
→reduce antibiotic resistance e.g. Tuberculosis
