Antibiotics Flashcards
Define bacteriostatic
Prevent bacterial growth
Define bacteriocidal
Kill bacteria
What are the different sites at which antibiotics have an effect?
Bacterial cell wallNucleic acidsProtein synthesisCytoplasmic membrane
Give some antibiotics that act at the peptidoglycan cell wall
PenicillinsCephalosporinsGlycopeptides
Give some antibiotics that have an effect on nucleic acids
AntifolatesQuinolonesRifampicin
Give some antibiotics that have an effect on protein synthesis
Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid
Give some antibiotics that have an effect on the cytoplasmic membrane
Polymixins
When can you give antibiotics as prophylaxis?
Peri-operative
Short term e.g. after meningitis exposure
Long term e.g. asplenic patients
What are some particular characteristics of vancomycin and gentamicin?
Both have ototoxicity and nephrotoxicity at high levels
Give some general methods that bacteria can acquire resistance
Chromosomal gene mutation
Horizontal gene transfer
Describe chromosomal gene mutation
Bacterial gene mutates, giving a trait for resistance. Antibiotic kills bacteria without this resistance, acting as a selection pressure. Gives rise to a population of antibiotic resistant bacteria.
Describe horizontal gene transfer
Made up of three components
- Transformation
- Transduction
- Conjugation
Describe transformation
DNA released from bacterial resistant cell, taken up by recipient cell
Describe transduction
Phage binds to donor cell and is infected. Phage then binds to recipient cell and transfers the DNA to the recipient cell.
Describe conjugation
Connection is made between donor and recipient cell, plasmid is replicated and then transferred between the two.
What are the main methods by which a cell can gain antibiotic resistance?
- Antibiotic inactivation- Adaptations to metabolism- Alteration of drug binding site - Increased efflux mechanisms- Decreased membrane permeability
Describe antibiotic inactivation
Producing an enzyme that inactivate the druge.g. beta lactamase
Describe adaptations to metabolism
Metablic pathways altere.g. changes to dihydrofolate reductase leads to a resistance to trimethorpim
Describe changes to drug binding site
Binding sites change so drug does not have affinity for it
Describe increased efflux
Increased removal of a drug so that it cannot build up the therapeutic levels
Describe decreased permeabiltiy
Cell membrane can change in order to confer resistance.
Describe patterns of emergence of antibiotic resistance
Local selection (hospital) Clonal dissemination (over the country) Global spread
What are the main ways by which we can avoid the spread of antibiotic resistance?
Antibiotic stewardshipInfection control- prevent spread of recognised resistant bacteria- prevent bacterial exposure to antibiotics
Describe time-dependent killing
Need a prolonged presence of the antibiotics but do not need a high concentration
Describe concentration dependent killing
Need a high concentration of the antibiotic but only for a short duration
Describe the minimum inhibitory concentration
Lowest concentration of the antibiotic that will inhibit the visible growth of a microorganism after overnight incubation
Describe the influenza life cycle
Bins to sialic acid sugar via haemaglutinin
EndocytosisH+ in, ATP-dependent, viral membrane contact with endosomal membrane
H+ into virus via M2 ion channel, low pH causes uncoating
Virus released into cytoplasm
Replicates using cells machinery
New virus buds off, bound to sialic acid
Neuraminidase cleaves attachment for viral release
Give some M2 ion channel blockers
AmantidineRimantidine
Why do you use M2 ion channel blockers?
Treatment and prophylaxis for influenza A
Mechanism for M2 ion channel blockers
Prevent H+ entering virus via M2, so it cannot uncoat and be released into the cytoplasm
ADRs for M2 ion channel blockers
DizzinessHypotensionCNS effects - hallucination, confusion, insomniaNephrotoxic at high doses Amantadine gives more pronounced ADRs, so tend to use rimantadine
What is a particular challenge regarding resistance for M2 channel blockers?
Only need a single point mutation in order to have an effect. Changes shape, causing the binding site to change so it does not block the channel when it binds.
Give some neuraminidase inhibitors
ZanamivirOseltamivir
Indications for neuraminidase inhibitors
Treat influenza A and B within 48 hours to have the best effect.
Mechanism for neuraminidase inhibitor
Inhibit neuraminidase enzyme- causes aggregation of virus at the cell surface
ADRs for neuraminidase inhibitors
HeadacheNosebleedBronchospasmResp. depression (rarely)
Describe zanamivir
Low oral bioavailability so given as an inhaled powder. Not used for prophylaxis
Describe oseltamivir
High oral bioavailabliity, given both for treatment and prophylaxis. Should be given within 48 to have best effect on reducing mortality and decreasing duration of illness.
