Beta lactams, Vancomycin, DNA gyrase and DNA strand breakers Flashcards
What target does both beta lactams and Vancomycin attack?
cell wall synthesis which takes place in the membrane
What’s the difference between gram positive and gram negative?
based on the structure of their cell wall, gram positive takes up gram stain and you can’t wash the stain out with acetone , cell wall has lots of peptidoglycan however gram negative also takes up stain but can be washed with acetone, has a thin layer of peptidoglycan, lipid bilayer and lots of proteins
What are norcardiform bacteria?
gram positive bacteria that is difficult to stain because the lipids confer resistance to staining, includes mycobacteria
What is peptidoglycan?
structural component, has repeating disaccharide units of 2 amino sugars (NAGA and NAMA)
What is carboxypeptidase and its function?
enzyme in cell membrane that acts on cell wall synthesis, cleaves of terminal D alanine for any peptide that hasn’t made a crosslink. Can be displaced just by water so not productive
What are some examples of beta lactam antibiotic groups and what do they have in common?
Penicillins, Cephalosporins & carbapenems all contain lactam ring
Why is penicillin difficult to synthesis in lab?
4 membered ring is constrained at 90 degree angle but carbonyl prefers 120 degrees
How does Beta lactam ring react with Transpeptidase or Carboxypeptidase?
when they interact, they take part in nucleophilic substitution at the 4 membered ring carbonyl, beta lactam ring is opened and enzyme forms a covalent bond
What is the activity and usefulness of Penicillin determined by?
ability to penetrate cell wall, resistance to b lactamases, affinity to penicillin binding proteins, resistance to stomach acid, formulation, pharmacokinetics, toxicology
Which amino acids is Penicillin G made from?
cysteine, valine and phenylalanine
What are some examples of Penicillins?
Penicillin G, Amoxicillin, Flucloxacillin, Methicillin, Ampicillin
Describe cephalosporins and give some examples
active against gram negative bacteria, beta lactam antibiotics, cefaclor & ceftriaxone. Second gen given orally, third gen injected IM
What are carbapenems?
another beta lactam active against gram negative bacteria, very broad spectrum and resistant to most beta lactamases
What is Vancomycin?
a non-ribosomal peptide with many unusual amino acids, it’s glycosylated and product of the soil organism Amycolatopsis orientalis
What is the mode of action of Vancomycin and its uses?
interferes with cell well synthesis, used for serious gram positive infection, used orally for C difficile but normally injected
What is an alternative for Vancomycin?
Teicoplanin, another glycopeptide with similar mode of action
What is DNA gyrase and why is it important?
a topoisomerase, it introduces supercoiling into DNA of bacteria using ATP, it maintains the negative helical tension of bacterial chromosome and its needed for DNA to fit into cell
What are quinolones and how do they target DNA gyrase?
broad spectrum antibiotics, active against gram negative bacteria ,they block the A subunit of DNA gyrase and prevent supercoiling by interfering with DNA chain breakage and rejoining
Give an example of a first gen quinolone and its uses
Nalidixic acid used for uncomplicated UTIs
Give some examples of second gen quinolones and their uses
ciprofloxacin used infections of urinary and respiratory tract, gonorrhea, prophylaxis of meningitis and anthrax / ofloxacin & norfloxacin
What are some problems with ciprofloxacin?
reduced absorption with magnesium or aluminium antacids, severe CNS disturbances can occur with NSAIDs, damage to cartilage C/I in pregnancy
Give some examples of third gen quinolones and its uses
levofloxacin indicated in pneumonia and UTIs, broad spectrum and active against streptococci
What is the class of antibacterial DNA strand breakers called and what are some examples of drugs in that class?
Nitrofurans including Nitrofurantoin, used to treat gram positive and negative UTIs
What is another class of antibacterials that act in a similar way to Nitrofurans?
Nitroimidazoles including metronidazole
What are Nitroimidazoles used for?
to treat anaerobic bacterial and protozoal infections including bacterial vaginosis, acute oral infections and C diff, protozoal infections like amoebiasis and trichomoniasis
What is C diff and why do patients acquire it?
C difficile is a type of bacteria already present in some people which can cause a bowel infection, most patients acquire pathogenic strains in hospital, if the patient is treated with a broad spectrum antibiotic it will eliminate normal microflora and promote overgrowth of c difficile
What are some symptoms of C diff?
diarrhoea, abdominal pain, fever and nausea, in severe cases pseudomembranous colitis which can cause fatal peritonitis and perforation of the colon
How would you treat C diff?
stop use of antibiotic, rehydration, first line drug: metronidazole and second line is oral Vancomycin
How is C diff spread?
resistant spores which can persist in hospital rooms for up to 40 days, passed on from person to person, usually due to poor hygiene
Which prescribing measure can prevent infection with C diff?
minimise use of broad spectrum antibiotics, use narrow spectrum, review antibiotic use to minimise microflora damage
What is Fidaxomicin?
a macrolide with an 18 membered ring, very effective against C diff, retained in gut making it narrow spectrum
Which measures are used to prevent cross infection of C diff?
patient suspected to have C diff put in isolation, strict hygiene precautions, daily cleaning of room, linen and equipment, handwashing with soap and water
