antibiotics Flashcards
define antibiotic and what they are broadly used for?
- a chemical produced by a microorganism that kills or inhibits the growth of another microorganism
- antibiotics are used to prevent & treat infectious diseases
define an antimicrobial agent
a chemical (microorganism or synthetic) that kills or inhibits the growth or microorganism
what is chemotherapy?
- involves the use of chemical agents to treat or control disease
- both antibacterial agents & anti fungal agents
define bacteriostatic agents
- chemical agents that prevent bacterial growth by stopping cells from dividing
define bacteriocidal agents
- chemical agents that prevent bacterial growth by killing them
describe the purpose of selective toxicity in antimicrobials
- antimicrobials are selectively toxic for bacteria with minimal harm or side-effects for the patient
- antimicrobials act on structures found in bacteria but not the host
describe the 2 categories of antimicrobials
bacteriostatic agents
- reversibly inhibit growth of bacteria, allowing host immune defences to eliminate infection
- duration of treatment must be sufficient for host defences to eradicate infection
bacteriocidal agents
- cause irreparable damage & bacterial cell death by binding irreversibly to target structures
- used for infections that cannot be controlled or eradicated by host (critical site of infection or immunocompetence)
- most drugs are both bacteriostatic & bacteriocidal depending on the clinical situation
what are broad spectrum antimicrobials and when are they used?
- are effective against a wide range or microorganisms
- used with seriously ill patients or if organism is unidentified
what are narrow spectrum antimicrobials and when are they used?
- are effective against only a small number of microorganisms of a single taxonomic group
- used if organism is identified as it minimises disruption to host microflora
- decreases likelihood of resistance
what are the 6 problems with antimicrobials?
- not selective in their elimination of microbiota, leading to disruption of normal microflora
- toxicity
- resistance
- drug hypersensitivity/allergy reactions
- other adverse reactions
- residues of antimicrobials in animal products for human consumption
which high risk drugs should never be used on horses? what could using these cause?
- lincomycin
- clindamycin
- oral penecillins
-> lead to pseudomembranous colitis due to overgrowth of Clostridium difficile bacteria in hindgut
which drugs are considered risky for horses but can be usefully employed in certain conditions?
- oxytetracycline
- erythromycin
which drugs are fatal in guinea pigs? what could using these drugs cause?
- broad spectrum antimicrobials (gram positive spectrum) -> ampicillin, penicillin, bacitracin, erythromycin, linocmycin, gentamicin, clindamycin, streptomycin, vancomycin & tetracycline are fatal
- reduce normal GI anaerobes & gram positive bacteria -> leading to overgrowth or coliforms & clostridial bacteria
which drugs cannot be used orally on guinea pigs but can be used parentally?
- enrofloxacin
- chloramphenicol
what toxicity problems can aminoglycosides cause?
- nephrotoxic
- ototoxic
what toxicity problem can chloramphenicol cause?
aplastic anaemia
what toxicity problems does fluoroquinolones cause? Which animals should it not be used in?
- inhibits cartilage growth, so it is not to be used in young animals
- causes retinopathy in cats
what toxicity problems do trimethoprim / sulphonamides have?
- keratoconjunctivitis sica (KCS) (dry eye) with prolonged use
- idiosyncratic hepatotoxicity in DOGS
- athropathies, cutaneous reactions & haemolytic anaemia
what toxicity problems does tetracycline have?
- have effect bone growth & stain teeth in young animals
- doxycycline can cause oesophageal strictures (should follow drug with food)
what is antimicrobial resistance?
- occurs when a micro-organism previously susceptible to the action of the antimicrobial is no longer affected by it
- antimicrobial resistance is a serious threat
which drugs are hypersensitivity reactions most common with?
- penicillins
- cephalosporins
- sulphonamides
what can drug hypersensitivity manifest as? (3)
- acute anaphylaxis
- cutaneous reaction
- haematological disturbances
what other adverse reactions can be induced by antimicrobials?
- tissue necrosis at injection site
- impaired host immunity
- hepatic microsome enzyme induction or inhibition
- adverse interactions with other drugs
what is the mechanism of action of B-lactams, glycopeptides, bacitracin drugs?
- inhibit cell wall synthesis
what is the mechanism of action of polymixins (polypeptides)?
- inhibition of cell membrane function
what is the mechanism of action of chloramphenicol, macrolids, tetracyclines, amionglycosides & rifamycins?
- inhibition of protein synthesis
- antimicrobials of this class target the structure of prokaryotic ribosomes which is different to eukaryotic ribosomes
- chloramphenicol & macrolides - inhibit 50S ribosome
- tetracycline & aminoglycosides - inhibit 30S ribosome
- rifamycins - inhibits RNA polymerase
what is the mechanism of action of quinolones & imidazoles?
- inhibition of nuclei acid synthesis
- quinolones inhibit DNA supercoiling
what is the method of action of sulphonamides & trimethoprim
- inhibition of synthesis of essential metabolites
how do B-lactam drugs work?
- B-lactams all have a 4-sided B-lactam ring which bind to penicillin binding proteins
- stops cross-linking of bacteria cell wall
- triggers peptidoglycan breakdown
name the broad spectrum B-lactams in common use
- ampicillin/amoxycilin
- 1st generation cephalosporins
name 3 narrow spectrum B-lactams that target gram positive bacteria (Staphs & Streps)
- methicillin
- cloxacilin
- penicillin
name 3 narrow spectrum B-lactams that target gram negative bacteria (& some gram positives)
- ticarcilin (targets pseudomonas)
- 2nd, 3rd & 4th generation cephalosporins
- carbapenems/monobactam
which B-lactam inhibitor combination can be used against bacteria that produce B-lactamase enzyme?
- clavulanic acid added to amoxillin & ticarcillin
How do glycopeptides (vancomycin) inhibit cell wall synthesis? and what is there importance against S. aureus?
- glycopeptides bind to the end to the peptidoglycan pentapeptide chain to prevent access of the end of the penta-peptide chain to the active site of enzyme that synthesises call wall
- only effective against gram positives
- important last line against antimicrobial resistant S.aureus
how does bacitracin work? what type of applications does it have
- bacitracin interferes with transport of peptidoglycan precursors across the cytoplasmic membrane
- its toxicity limits its use to topical applications
- common in non-prescription first-ad ointments
how does polymyxins inhibit cell membrane function?
- polymyxins contain cationic detergents which bind to phospholipids in the outer membrane of gram NEGATIVES
- cationic detergents increase permeability & disrupt cell
- only used as topical preparations
how does chloramphenicol work? When is it used?
- inhibits protein synthesis by binding to 50S ribosomal subunit & inhibiting peptidyl transferase activity
- prevents peptide bonds from forming, blocking protein synthesis
- good penetration through blood-brain barrier & eyes, so it is effective against a wide range of microorganisms
- drug of last restore for life-threatening infections
- aplastic anaemia is a rare side effect
how does macrolides & lincomycins work?
- reversibly bind to 50S ribosome to prevent continuation of protein synthesis
- effective against gram positives & mycoplasma
- drug of choice for penicillin allergies
how do aminoglycosides work?
- irreversibly bind to 30S ribosomal subunit causing distortion & malfunction of ribosome, blocking initiation of translation
- bactericidal
how do tetracyclines work?
- reversibly bind to 30S ribosomal subunit
- blocks tRNA from attaching to ribosome to prevent continuation of protein synthesis
- effective against certain gram +ves & -ves
- useful against intracellular bacteria
how does Quinolones (Fluoroquniolones) work?
- inhibits the action of topoisomerase DNA gyrase which normally maintains supercoiling of DNA
- prevents supercoiling of DNA
- well tolerated in birds, reptiles & pocket pets
- use for gram +ve & -ve (not anaerobes except new pradofloxacin)
how does Nitromidazoles work?
- binds to DNA & fragments of DNA to inhibit nucleic acid synthesis
- particularly effective in anaerobes
how do sulphonamides & trimethoprim inhibit the synthesis of essential metabolites?
- sulphonamides competitively inhibit the synthesis of folate
- trimethoprim blocks enzyme in folate synthesis
(folate is required for purine synthesis in bacteria)
how do we know whether an antimicrobial agent will work?
- by using disc diffusion susceptibility testing (Kirby-Bauer procedure)
- bacteria isolate is then classified as sensitive, intermediate or resistance
- it is then approximated whether the plasma concentration attained by the antimicrobial is high enough to inhibit the growth of bacteria
define the minimum inhibitory concentration (MIC) used for measuring antimicrobial sensitivity
- the MIC is the lowest concentration if a drug which inhibits bacterial growth
what are the 3 methods for determining MIC of an antimicrobial?
- concentration gradient on a strip
- agar dilution
- broth dilution
what are antimicrobials used for clinically?
- antimicrobial drugs are used to treat or prevent disease produced by infectious bacterial agents
- treatment should be based on clinical diagnosis
- only use prophylactically is risk is real
what is important to remember for antimicrobial use?
- use the most appropriate antimicrobial for the case, at the right dose & only for as long as necessary
