CP1 - Introduction to Antibacterial Agents Flashcards
what are antibiotics?
chemical products of microbes that inhibit or kill other organisms. used interchangeably with antimicrobial agents.
what is an antibiotic spectrum?
the spectrum of organisms that the medicine covers
what are the classes of antimicrobial agents?
- antibiotics
- synthetic compounds
- semi-synthetic compounds (modified antibiotics)
what are the modes of action of antibiotics?
- bacteriostatic - inhibit further bacterial growth eg. protein synthesis inhibitors
- bactericidal - kill bacteria eg. by preventing the formation of the cell wall
what is the minimum inhibitory concentration
the minimum concentration of antibiotic at which visible growth is inhibited
why is the difference between bacteriostatic and bactericidal mode of action only an in vitro concept?
this is because some antibiotics are bacteriostatic at a lower temperature and bactericidal at a higher temperature
what are the types of antimicrobial interactions?
- synergism
- antagonism
- indifference
why are antimicrobial interactions clinically significant?
the synergism between beta-lactam and amino glycoside is used to treat streptococcal endocarditis
why are combined antibiotics given?
- to increase efficacy
- to adequately provide for a broad spectrum
- to reduce resistance, since it would be more difficult for bacteria to develop resistance to multiple antibiotics simutaneously
what are the main characteristics of antimicrobials?
- ability to inhibit critical processes in bacterial cells
- it is selectively toxic
- the antibacterial needs to be able to get into the microbe
what is selective toxicity?
the ability of antimicrobials to target micro-organisms but not human cells
what are the examples of targets of antibiotics?
- cell wall
- protein synthesis
- DNA synthesis
- RNA synthesis
- Plasma Membrane
what is the major component of bacterial cell walls?
peptidoglycan (in both gram positive and gram negative bacteria)
what is peptidoglycan composed of?
a glycopeptide -
N-acetyl muramic acid (NAM)
N-acetyl glucosamine (NAG)
what are the main classes of antibiotics?
- B-lactams
- Glycopeptides
- Aminoglycosides
- Macrolides, Lincosamides, Streptogramins (MLS)
- Tetracyclines
- Oxazolidinones
- Sulphonamides
- Quinolones and fluoroquinolones
what are the examples of B-lactam antibiotics?
- amoxicillin
- flucoxicillin
- Benzylpeneckllin
- Cephalosporins (broad spectrum)
- Carbapenems (very broad spectrum)
what are thecaracteristics of B-lactams?
- contain a 4 membered carbon ring called the beta lactic ring
- structural analogues of D-alanyl-D-alanine
what is the mode of actions of beta lactam?
interferes with the function of penicillin binding proteins (transpeptidase enzymes) involved in cross-linking peptidoglycan to construct the cell wall
what is the mode of administration of beta lactams?
orally and IV
why may this not be the chosen class of antibiotics for treatment?
1-10% of the population have a general rash and 0.01% of patients have anaphylaxis to beta lactams
which type of beta lactams should be avoided in the elderly?
cephalosporins
name some examples of glycopeptides
vancomycin
teicoplanin
what are the characteristics of glycopeptides?
- they are large molecules, which directly bind to the terminal D-alanyl-D-alanine on NAM pentapeptides
- they are unable to penetrate the outer membrane porins on gram negative bacteria
what is the mode of action of glycopeptides?
they inhibit the binding of transpeptidases and thus prevent peptidoglycan cross-linking
what are the examples of aminoglycosides?
gentamycin, amikacin
what is the mode of action of aminoglycosides?
they bind to the 30S ribosomal unit, inhibit protein synthesis
exact mechanism is not fully understood
what are the side effects of aminoglycosides?
- potentially reversible nephrotoxicity
- irreversible ototoxicity
therefore requires therapeutic drug monitoring
what is the full form of MLS?
macrolides, lincosamides, Streptogramins (MLS)
what are the examples of MLS antibiotics?
Erythromycin, clarythromycin (macrolides), clindamycin (lincosamide)
what is the mode of action of MLS?
inhibit protein elongation by binding to the 50S subunit and blocking the exit tunnel
which drug has lesser side effects? clarithromycin or erythromycin?
clarithromycin
which antibiotic is associated with causing c diff infections?
clindamycin
name some examples of tetracyclines
tetracycline, doxytetracycline
what is the mode of action of tetracyclines?
bind to the 30S subunit and inhibit translation of RNA by inhibiting the binding of tRNA to rRNA
examples of oxazolidinones
linezolid
what is the mode of action of oxazolidinone?
inhibits the initiation of protein synthesis by binding to the 50S ribosomal unit and inhibiting the assembly of the initiation complex
what is a side effect of linezolid?
causes bone marrow suppression
what is trimethoprim used for?
UTIs
what is the mode of action of trimethoprim?
inhibits folate synthesis (folic acid is a precursor of purine synthesis) therefore inhibits DNA synthesis
what is a characteristic feature of sulphonamides?
they can be combined as co-trimoxazole
what is the mode of action go sulphonamides?
inhibit DNA synthesis
examples of quinolones and fluoroquinolones?
nalidixic acid
ciprofloxacin
levofloxacin
what is the mode of action of quinines and fluoroquinolones?
they inhibit either or both DNA gyrase and topoisomerase IV, which are involved in remodelling of DNA during replication
what is the mode of action of rifampicin?
inhibits DNA polymerase, therefore preventing the synthesis of mRNA
how is rifampicin used in clinical practice?
always administered in combination with another antibiotic
which bacteria do colistin and daptomycin work against?
gram negatives
what is a structural characteristic of colistin and daptomycin?
they are both cyclic lipopeptides
what is the mode of action of colistin and daptomycin?
destroy PM by targeting a structure*
why is this not used as first line treatment?
bacteria have colistin resistance
which antibiotics are prescribed most commonly?
beta lactams
what are the stages of beta lactic allergy?
- intolerance - nausea, diarrhoea, headache
- minor allergic reaction - non severe skin rash
- severe allergic reaction - anaphylaxis, urticaria, angio-oedema, bronchospasm, severe skin reaction, stevens-johnsons syndrome
which antibiotics can be used in patients penicillin allergy?
cephalosporins and carbapenems (for non severe)
azetreonam (for all stages)
what are the adverse effects of antibiotics on the body?
nausea vomiting headache skin rashes infusion reactions allergic reactions
how are c diff infections caused?
by the destruction of the normal floras resistance to antibiotics, could potentially be a result of antibiotics
how does C diff harm the body?
by production of enterotoxins A and B and spores
what are the common antibiotics used for treatment of c diff?
4 Cs co-amoxiclav cephalosporins ciproflocacin clindamycin
what are the clinical strategies for use of antibiotics?
start broad, then focus (once cultures have been obtained)
only start antibiotics if there is a clinical evidence of bacterial infection
stop and re-evaluate the situation at 48 hours
which drugs have a good in vevo efficacy in CSF and urine?
CSF - Beta lactams
urine - beta lactams and trimethoprim
which drugs have a poor in veto efficacy in CSF and urine?
CSF - ahminoglycosides and vancomycin
urine - MLS
