Antibiotics Flashcards
What are the 4 mechanisms of drug resistance?
Drug inactivators
Decreased accumulation
Altered binding site
Alternative pathways
How does drug inactivation work?
Bacteria expresses B lactamase - can break down B lactam ring of B lactam type antibiotics (penicillin type drugs)
(B lactam —> penicilloic acid)
How is resistance passed on?
Selection (chromosomal mutation) occurs when antibiotics overprescribed, kill other colonies but resistant one multiplies
Transference - bacteria carry extra DNA within plasmid, can transfer DNA within or outside of strain - multiple resistance within and between strains
Strategies to reduce resistance?
New antibiotics
Correct antibiotic after sensitivity testing
Reduced use as growth promoters
No use in viral infections
Increase compliance
Decrease prescriptions - especially young children (otalgia)
What is gram positive and negative?
Positive - cell wall retains the purple stain
(anthracis, listeria, clostridium, staph, strep, (coccuses))
Negative - doesn’t retain purple (pink)
(enterobacter, gonorrhoea, E coli, salmonella, shigella, H. pylori, meningitidis, haemophilus influenzae)
What factors should be considered when choosing an appropriate antibiotic?
Spectrum - start with broad if don’t know but narrow down if do because broad cause resistance more quickly
Orally active? Bactericidal/static (if bacteria full of toxins, static may be better) Mechanism Adverse effects (penicillin allergy) Resistance Pharmacokinetics
Presumptive treatment (sepsis - if meninges inflammed - some don’t reach there, others only reach there) (simple chest infection - community or hospital?)
Combination therapy Site of action Duration of therapy Chemoprophylaxis Special situation (pregnancy, renal) - e.g. grey baby syndrome with chloramphenicol (now just used for conjunctivitis usually)
Name key antibiotics in each group
1) Nucleic acid
2) Cell wall
3) Protein synthesis
1) Sulfamethoxazole, ciprofloxacin, metronidazole, trimethorpim
2) Flucloxacillin, amoxicillin, (cephalosporins), vancomycin
3) Tetracycline, clarithromycin, chloramphenicol (so toxic used outside body now)
What are types of nucleic acid inhibitors?
Sulphonamides
Trimethoprim
Quinolones
Nitroimidazoles
How do nucleic acid inhibitors work?
Sulphonamides: block dihydropteroate synthase (eventually prevents synthesis of purines and pyrimidines)
Trimethopim: blocks dihydrofolate reductase (has 100x higher affinity for bacterial version)
Quinolones: inhibits DNA gyrase (topoisomerase II) which packages the DNA (coils it for packaging) - so it remains unwound and is easier to shear and break - ATP needed to fix so causes cell exhaustion
Nitroimidazoles: cause strand breaks within the DNA itself - runs out of energy, also can’t replicate DNA for a while
(metronidazole likes low environments of oxygen, gets metabolised by bacteria (to active ingredient) itself so v specific, metabolised enzyme causes the strand breaks
What are sulphonamides?
Sulfadiazine, sulfamethoxazole
Bacteriostatic, orally active
Action prevented by pus (neutrophils provide PABA)
Widespread resistance to hospital acquired infections
Nausea and vomiting
Hypersensitivity reactions (sulphur drug)
Bone marrow suppression (think DMARD - methotrexate inhibits dihydrofolate reductase
Replaced by antimicrobials with less resistance and less toxicity
What is co-trimoxazole?
Sulfamethoxazole and trimethoprim
Using two drugs in linear system:
- Partly because of resistance - (think of alternative pathways) but resistance occurs more when using mono therapy (i.e. nucleic acid only or cell wall only)
- Because not all drugs are 100% effective so increase in effectiveness
- Could use less of each one to reduce side effect profile
Stephen-Johnson syndrome - 1 million per year
Bone marrow suppression
What are the uses of co-trimoxazole?
Used in TB and prophylaxis of TB
- TB associated with HIV
- used if prone to bacterial infections, especially if poor immune system
Otitis media Pneumonia Strepococcus pneumonia and haemophilius influenzae Toxoplasmosis Nocardiasis
What are the uses of trimethoprim?
Invasive salmonella
Respiratory tract
Prostaitis (UTI)
Shigellosis
What are quinolones?
Ciprofloxacin, norfloxacin
-ve > +ve - widely used in some gram -ve organisms
V.broad spectrum - useful in hospital e.g. simple chest infection - don’t get side effects seen with some drugs
Effective against organisms resistant to penicillins and some cephalosporins
Orally active, poorly absorbed by BBB (not used meningitis, avoid in sepsis - good for presumptive treatments but be careful what you try)
Inhibition of P450 enzymes (interaction with theophylline and warfarin - they build up) - ciprofloxacin interactions
What are first line uses of quinolones?
Pyelonephritis (UTI)
Bacillary dysentry
Severe gastroenteritis - normally even bactericidal gastroenteritis is self limiting - travellers diarrhoea
Pseudomonas (opportunistic often in CF or HIV)
What are nitroimidazoles?
Metronidazole, tinidazole
Bactericidal - causes strand breaks in DNA following metabolism by the bacteria
Broad spectrum
Orally active
Important in serious anaerobic infections e.g. sepsis
Anaerobes metabolise the imidazole to its active form
Effective against H. pylori
Interacts with ethanol, warfarin metabolism Bitter taste (goes into breast milk)
What are first line uses of nitroimidazoles?
Pelvic infections Anaerobic sepsis Infected wounds C. difficile colitis Post surgery
How do cell wall synthesis inhibitors work?
Block elongation and division, makes cell wall less rigid
Peptidoglycan on outside of wall - can provide antigenicity (Cag-A, pic-B) and provide sticky surface for getting into blood vessels/sticking in gut
Has to build using variety of enzymes - one is blocked by penicillin-like antibiotics
Peptidoglycan made of polymer chains cross linked by pentapeptide bridges - B lactam antibiotics inhibit enzymes that cross link PG and render wall weak - lose structural integrity of cell, can’t control what enters/leaves - tries to fix but runs out of energy and dies / ‘pops’
