Antimicrobials Flashcards
What are the major sites of action for antibiotics? What are examples of each?
DNA synthesis:
Quinolones - ciprofloxacin
Folic acid antagonists - trimethoprim
Protein synthesis:
Aminoglycosides - gentamicin
Macrolide - eryth/clarithromycin
Tetracyclines
Cell wall synthesis:
Beta lacatams: penicillins, cephalosporins, carbapenems
Glycopeptides: vancomycin
What are the uses of antibiotics?
Prophylactic:
You can use antibiotics to prevent infection – for example if people have been exposed to meningitis, or during surgery on the GI tract (and other surgeries) to prevent surgical site infections. Also used in asplenia and immunodeficiency – long term.
Treatment
You can either treat a culture proven infection or empirically treat a suspected infection.
What are common antibiotic ADRs?
GI upset due to killing commensal organisms, can lead to clostridium difficile infection (particularly cerufoxime, ciprofloxacin)
Allergic reactions
DDIs, especially with the COCP
Aminoglycoside antibiotics can damage the eighth cranial nerve (vestibulocochlear) causing deafness and poor balance
Tetracycline and doxycycline stain teeth and bones in children
Linezolid interacts with SSRIs and MAOIs causing hypertension
Vancomycin can lead to pseudoanaphylaxis if administered quickly – leads to histamine release.
Chloramphenicol leads to dose dependent bone marrow suppression and sporadic bone marrow failure
What are ADRs of aminoglycosides?
Gentamicin
Aminoglycoside antibiotics can damage the eighth cranial nerve (vestibulocochlear) causing deafness and poor balance
What are ADRs of tetracyclines?
Tetracycline and doxycycline stain teeth and bones in children
What are ADRs of glycopeptides?
Vancomycin can lead to pseudoanaphylaxis if administered quickly – leads to histamine release.
Describe how antimicrobial resistance occurs genetically
In chromosomal mutation, the bacterial chromosome spontaneously mutates, and the new gene confers resistance to an antibiotic. If the antibiotic is used on the population, only those with the mutation survive to replicate and they then have all the resources they could ask for, so freely proliferate.
In horizontal gene transfer (sad bacteria version of sex) cells exchange replicated plasmids (small DNA loops) via a conjugation tube
What are mechanisms of antibiotic resistance?
• Antibiotic inactivation
o Such as beta-lactamase production which breaks down penicillins and other beta-lactams
• Alteration of target site
o Such as penicillin binding protein
• Alteration of metabolic pathways
o Such as switching from requiring para-aminobenzoic acid to preformed folic acid
• Reducing intracellular antibiotic accumulation
o Active efflux
o Or decreasing permeability – such as losing pores (which is costly to the organism)
What are the main steps to avoid spread of antimicrobial resistance
Infection control is important (prevention is better than cure)
• Isolation of patients
• Hand hygiene
• Decolonise patients (e.g. MRSA screening and treatment)
Antimicrobial stewardship (appropriate prescribing) is also essential. You should give:
• The right antibiotic
• At the right time
• At the right frequency, dose and duration
• Via the right route
What is the minimum inhibitory concentration?
MIC is minimum inhibitory concentration – the minimum concentration needed to have antimicrobial effect.
What is time dependent killing? Concentration dependent killing?
Time dependent killing is when successful treatment requires a prolonged exposure of the pathogen to the antibiotic, but not high concentration.
Concentration dependent killing is when treatment requires high antibiotic concentration at the site of infection, but not necessarily for a long period of time.
What are ADME factors affecting pharmacokinetics?
Absorption is affected by route of administration – often oral or IV, depends on site of infection and whether IV is available to you
Distribution depends on the drug
Metabolism and elimination are features of the drug and the patient and will vary
Why right antibiotics need therapeutic drug monitoring?
This is because they have a narrow therapeutic window and such monitoring produces a better outcome (including reduced length of stay and less toxicity). You need to ensure the dose is adequate and non-toxic
Gentamicin (amino glycoside), vancomycin (glycopeptide)
What is the group and MOA of penicillins?
Beta lacta - cell wall synthesis
What is the group and MOA of ciprofloxacin?
Quinlone - inhibit DNA synthesis
