Antimicrobials Flashcards
Week 2
Phase I clinical trial
Test on healthy volunteers for safety and dose-ranging
Phase II clinical trial
Test on patients to assess efficacy, effectiveness and safety
Phase III clinical trial
Assess efficacy, effectiveness and safety
Narrow spectrum antimicrobial
Antimicrobial effective against a limited number of bacterial genera
Broad spectrum antimicrobial
Antimicrobial effective against a large number of bacterial genera
Give some features of the ideal antibiotic
- selective toxicity
- bacterialcidal
- slows emergence of resistance
- narrow spectrum of activity
Why is a narrow spectrum of activity ideal?
Doesn’t encourage resistance developing over many generas
4 ways to classify anti-bacterial agents
- Bacterialcidal or bacteriostatic
- Spectrum of activity
- Chemical structure
- Targets/selective toxicity
Ribosomes of bacteria
70s
Ribosomes of eukaryotes
80s
What can bacteria synthesise on their own which humans need to take in?
Folic acid/folate
Why enzyme involved in folic acid synthesis do humans also have
DHPS
2 kinds of beta-lactam antibiotics
penicillins
chepalosporins
What do beta-lactams inhibit?
The enzymes PBPs (penicillin binding proteins) which are required for transpeptidation of cell wall
Transpeptidation =
the last step in cross-linking of peptidoglycan cell wall
3 antibiotic classes that work on cell wall synthesis =
penicillins
cephalosportins
glycopeptides
broad spectrum penicillin
amoxicillin
most common glycopeptide
vancomycin
Vancomycin is only active against what type of bacteria?
Gr+ (MRSA)
Glycopeptides MoA
Bind to cell wall subunit and prevent incorporation of unit
Classes of antibiotics which inhibit protein synthesis
- macrolides
- aminoglycosides
- tetracyclins
- chloramphenicol
- lincosamides
- puromycin
- fusidic acid
Macrolides
50S inhibitors
Tetracyclins
30S inhibitors
Aminoglycosides
30S inhibitors
Classes which disrupt nucleic acid synthesis
Quinolones
Rifamycins
Quinolones
Inhibit DNA replication
Classes of antimetabolites
Sulfonamides
Trimethoprim
Which pathway do antimetabolites distrupt?
formation of dihydrofolic acid.
Sulfonamides MoA
Inhibit PABA
Trimethoprim MoA
Inhibits DHPS
Which antimetabolite inhibits an enzyme found in humans?
trimethoprim
Class of antibiotics which acts as a detergent on plasma membrane
Polmyxins
Ex narrow spectrum antibiotics
Macrolides
Vancomycin
penG
Ex broad-spectrum antibiotics
Aminoglycosides
2nd and 3rd gen cephalosporins
quinolones
some synthetic penicillin
Narrow spectrum penicillin
benzyl penicillin
suffix of macrolides
- thromycin
Bacteriostatic or bacteriocidal: aminoglycosides
both
What kind of bacteria are aminoglycosides best for?
Gr- aerobes
What can be used with an aminoglycoside to treat Gr+ infections like staph endocarditis
Beta-lactam
Ex of aminoglycodies
gentamicin
neomycin
streptomycin
tobramycin
Side effects of aminoglycodies
ototoxicity
nephrotoxic
inhibit Ach release (contraindicated in MG)
Use of tetracylines
Acne, community acquired pneumonia, intracellular pathogens, MRSA
Side effects of tetracyclines
Phototoxicity
tinnitus
permanent teetch discoloration and delayed bone growth
nephrotoxic and hepatotoxic
Ex of macrolides
erythormycin, azithromycin, clarithromycin
Bacteriostatic or bacteriocidal: macrolides
bacteriostatic
Spectrum of macrolides
Narrow. Gr+ aerobic, Gr- aerobic
Some uses of macrolides
Resp infections, STIs, H.pylori
DOC in pregnancy
amoxicillin
Bacteriostatic or bacteriocidal: cephalosporins
bacteriocidal
name 2 drugs that can have cross-reactivity (hint = they have a similar chemical structure)
penicillins and cephalosporins
DOC for MRSA
Vancomycin
What drug does sulfonamides increase plasma conc of?
Warfarin
2 antibiotics which need to be metabolised by liver first
Sulfonamides
Trimethoprim
Bacteriostatic or bacteriocidal: sulfonamides
Bacteriostatic (cidal when with TMP)
Bacteriostatic or bacteriocidal: trimethoprim
Bacteriostatic (cidal when with smx)
Trimethoprim contraindications
pregnancy and children (teratogenic and bone marrow suppression)
Stages of antibiotic resistance/sensitivity
sensitive
intermediate
resistance
What does ‘intermediate’ mean in terms of antibiotic resistance
higher dose of antibiotic needed
Minimum inhibitory concentration =
Minimum conc below which bacterial growth is not inhibited (need to be above MIC)
innate resistance
bacteria lacks a suitable target or is impermeable to the drug
acquired resistance
resistance acquired via mutation or gene transfer
Major mechanisms of bacterial resistance:
- modify target
- limit access (reduce penetration, increase efflux)
- bypass pathway
- enzymatic inactivation
S.aureus developed resitance to beta-lactams in 2 ways=
beta-lactamases
alter PBP so beta-lactam can’t fit
Ex of mechanisms which can cause multi-drug resistance
efflux pumps