6/7 antibiotics and antimetabolites Flashcards
3 classes of antimicrobial agents
- antiseptics: no selective toxicity, topical/surfaces, chlorhexidine mouthwash
- sulphonamides = antimetabolites
- antibiotics = produced by microorgs to combat each other
perfect antibiotic, 8 traits
- selective toxicity
- bacteriocidal
- long in vivo half life
- good tissue distribution
- low plasma protein binding
- oral and parental admin possible
- limited drug interactions
- eventual elimination
S B L G L O L E
super big large giant lion owns little elephant
pneumoic for 8 perfect traits
super big large giant lion owns little elephant
sel.tox, bacteriocidal, long in vivo, good tissue distrib, low pp binding, oral/parental admin, limited drug ineraction, eventual elim.
empirical therapy uses what tests
- diffusion: biggest zone of inhibition means most bacterial susceptibility
- dilution: clear in medium = MIC; no growth of the clear ones on plate with no abx = MBC
5 big problems with abx use
- side effects
- harm commensal flora and allow pathogenic bacteria space to grow
- resistance
- allergy
- $$$
odontogenic infection
bacteria gains access to pulp
periapical infection
spread of infection from root canals into periapical region of alveolar bone
what was the nasty puffy neck person pic
periapical absess (from root to bone)
all the light areas in the X ray = infection spread throughout alveolar bone
periapical infection 1st line of treatment
-debridement
-endo therapy
-extraction
^^^mechanical
when do you use abx for periapical infection
- when infection has spread beyond alvoelar bone
- use mechanical methods in conjunction
when do you use abx for periodontal infection?
- when mechanical/home care does not resolve
- when immunocompromised
- early onset periodontitis
- systemic disease that predisposes to periodontitis
- severe perio infection (absess etc)
what situations warrant abx prophylaxis? (3)
- immunocompromised (chemo, radiation, immundeficiency disease)
- facial/skull fracture
- patients at risk for IE
infective endocarditis
- platelets adhere to heart valve abnormalities to form sterile thrombus (sterile vegetation)
- bacteria introduced into bloodstream then colonize the thrombus (tooth extraction, perio therapy)
- heart valves scar and thicken (vegetation)
- emboli (clots) form and break off, or just gets so big that CHF
bacteremia can also result from….? (non invasive procedures)
- brushing, flossing
- eating
- perio lesions from poor oral hygiene
5 ways bacteria become resistant
- decreased entry
- efflux pump
- enzymatic inactivation/modification of drug by bacteria
- bypass pathway: drug has non susceptible pathway that does same fxn
- altered target site: bacteria modifies wahtever cell of its own that is the drug target
peptidoglycan composition
- parallel chains of NAM adn NAG that are CROSS LINKED by short amino acid chains
- G pos cells have more of it
cell wall synthesis inhibitors
- B-lactams: binds PBP’s which make cross links
- glycopeptides: bind directly to growing chain
- bacteriocidal because they block peptidoglycan synthesis
- selective toxicity bc we do not have peptidoglycan
beta-lactams
penicillin, amoxocillin, methicillin (**narrow spectrum, insensitive to some b-lactamases)
cephalosporins (1st only Gpos but now G neg as well)
- allergies common
- res = alter PBP, b-lactamases cleave b-lactam ring
- oral, IV, intramuscular admin
beta-lactam resistance and get aroudn it how
- alter PBP’s
- b-lactamases cleave b-lactam ring
**augmentin = potassium clavulanate + amoxicillin
beta-lactamase mechanism
-block action of PBP’s (transpeptidase) which cause cross linking between NAM subunits
glycopeptides
(vancomycin, teicoplanin – Gpos only)
- mech: bind directly to growing peptidoglycan chain
- skin rash, oto/nephrotoxicity (used for IE prophylaxis)
- res: Gneg inherently resistant; alter NAM/NAG terminal aa
how does vancomycin work
bind D-ala-D-ala terminal sequence of peptidoglycan on G pos cells (glycopeptide)
protein synthesis inhibitors (6 groups)
- largest group
- target rRNA: 30S, 50S SU
- aminoglycosides
- tetracyclines
- macrolides
- lincosamides
- chloramphenicol
- fusidic acid
**different drugs target different steps of translation
what is the target for the largest variety of abx?
protein synthesis – so many steps and so much involved
aminoglycosides
strepto, genta, kana, neo, turboMYCIN
- mech: irreversibly bind 30S SU, prevent initiation
- broad spec, bacteriocidal (only target aerobes, not intracellular/anaerobic bacteria)
- topical
- SE: nephro/ototoxic–do not administer sysmetically, adn monitor if you do
- res: efflux, decreased perm, alter 30S
aminoglycosides mechanism
(kana, strepto, ganta, neo, turbo MYCIN)
- irreversibly bind 30S to prevent inititiaon of translation
- bacteriocidal
- does not work on anaerobic/intracellular bacteria
aminoglycosides admin/SE
- topical usually
- SE = nephro/ototoxicity
- so do not administrer systemically (except to kill G(-) intestinal flora pre surgery or prophylaxis for IE)
- if systemic, MONITOR blood levels
tetracyclines
tetra/doxyclycline
- REVERSIBLY binds 30S to prevent tRNA docking
- bacteriostatic, broad spectrum
- oral admin
- used in mouthwash
- SE: GI distress adn discolors teeth in kids (do not give to them)
- Res = high; efflux adn altered 30S
tetracyline mech
bind reversibly to 30S to prevent tRNA docking, b.static and broad
(tetra and doxyclycine)
Macrolides and Lincosamides
- reversibly bind 50S to prevent elongation
- bacteriostatic, but b.cidal in high doses
- broad spec, so good alternative if penicllin allergy
- oral, very safe
- nausea
- res = alter 50S, efflux, decrease perm, inactiveate drug
macrolides
- erythro/azythromycin
- reversibly binds 50S to block elongation by blocking ribosomal translocation
- b.static (unless high dose) and broad, good penicllin alternative
- erythromycin is one of safest drugs ever
lincosamides
- clindamycin
- reversibly binds 50S to prevent elongation by preventing peptide bond formation
- ANAEROBIC INFECTION drug of choice
- broad
- bstat (unless high dose)
lincosamide vs macorlide
both reversibly bind 50S to prevent elongation
- lincosamide = clindamycin; prevents peptide bond formation **anaerobe
- macrolide = erythro/azythromycin; prevent ribosomal translocation
macrolide mech
block ribosomal translocation (bind 50S)
last resort drugs
- chloramphenicol
2. fusidic acid — not avilable in USA
chloramphenicol
- irreversibly binds 50S, broad spectrum
- potentially fatal, use only when infection is life threatening
- fatal aplastic anemia adn gray baby syndrome
fusidic acid
binds elongation factor
toxic to mamalian ribosomes? not available in USA
3 types of abx that inhibit nucleic acid synthesis
- nucleotide synthesis (sulfonamide and trimethoprim)
- DNA rep (quinolones)
- mRNA synthesis (rifamycins)
sulfonamide & trimethoprim
ANTIMETABOLITES - inhibit synthesis of THF (tetrahydrofolate) which is needed for purine (AA) synthesis
admin = oral SE = allergy, nausea, vomit, headache, depression, dizzy
pathway of sulf/trimeth
- PABA, glutamate, pteridine-H2 convert to DHF (folic acid), catalyzed by DIHYDROPTEROATE SYNTHETASE
^^microorgs only - DHF/folic acid is catalyzed by DIHYDROFOLATE REDUCTASE to make THF
- THF then made into purine
sulfonamide
- synthetic structural analogs of PABA, competitively inhibit dihydropteroate synthetase to block DHF (folic acid) synthesis
- we dont make folic acid (eat it) so not toxic to us
- bstatic
- broad (protozoa, intracellular)
- res = overproduce PABA or alter dihydrop.synthetase target
trimethoprim
- synthetic pyridine analog (analog of pteridine portion of DHF)
- competitively inhibits bacterial DHF reductase (50000-100000x higher affinity for bacterial enzyme than human)
- broad
- res = altered DHF reductase (overproduce, mutate, 2nd enxyme) or decreased perm
when are trimethoprim adn sulfonamide most effective (bacteriocidal)
in combo. synergistic.
BACTERIOCIDAL when in combo
sulfamethoxazole + trimethoprim = bactrim-spectra = co-trimoxazole = SXT
quinolones
nalidixic acid, ciprofloxacin
- inhibit DNA gyrase, so the bacteria cannot supercoil its DNA and DNA rep cannot happen
- bacteriocidal
- moderate spectrum, mostly Gneg
- oral admin
- SE = GI, rare…neurotoxicity or photosensitivity
- res = DNA gyrase mutation or decreased perm
quinolone example
nalidixic acid
ciprofloxacin
rifamycins
- bind RNA polymerase to prevent transcription initiation
- bbacteriocidal, broad
- oral admin
- minimal SE
- res = mutant RNA pol beta subunit
names of b-lactams
penicillin amoxilccin ampicillin nafcillin methicillin
and cephalosporins
aminoglycosides, names
streptomycin kanamycin neomycin tobramycin gentamycin
macrolides and lincosamides, names
macrolide = erythromycin and azythromycin
lincosamide = clindamycin (**anaerobic killer)
quinolone names
levofloxin
ciprofloxixin
nalidixic acid
