Anti Infective Drugs - antibacterials, antivirals and anti protozoals Flashcards
differences between bacteria and human cells
- several diff between bac and human cells
- bac cells have a unique cell wall
- diffs in cell membrane
- ba cells show diffs in mechanism of dna and protein synthesis
- bac cells have diff biosynthetic pathways
- these diffs form the basis for the selective toxicity of anti bac drugs
pharmacology of antibacterial agents
1) drugs affecting cell wall synthesis - penicillins, cephalosporins
2) drugs affecting the bac cell membrane - polymyxin b, promamidine
3) drugs affecting bac protein synthesis - aminoglycosides, tetracylines, chloramphenicol, fusidic acid
4) drugs affecting bac dna synthesis - fluoroquinolones
5) drugs affecting bac metabolism - sulphonamides
antibiotics- general considerations
- spectrum of cover - narrow v broad, single v combination
- penetration into appropriate tissue - depends on how deep infection is
- route of administration
- side effects - tolerability, pregnancy/lactation
antibiotic sensitivity testing
- tends to be done when antibiotic prescribed is not having required effect
- Kirby-bauer antibiotic sensitivity tests can be conducted on bac once isolated
- a colony is picked off the agar plates, emulsified in a small volume of saline and spread on a sensitivity test agar plate
- a paper disc which has been impregnated with various antibiotics is placed on top of the culture which is then incubated at 37C for 18 hours
- measure areas of bac inhibition of growth around each disc to identify the most appropriate antibiotic
anti infectives available to optoms
all registered optoms:
- chloramphenicol
- fusidic acid
- propamidine
additional supply
- polymyxin b - discontinued in uk
independent prescribers
- all anti infectives available for the treatment of diseases of eye and surrounding tissues
key features of Chloramphenicol - POM
- bacteriostatic (may be bacteriocidal for some species at high conc)
- broad spectrum (not effective against pseudomonas)
- good safety profile - aplastic anaemia (bone marrow suppression) and ‘grey baby syndrome’ linked with systemic use but extremely unlikely following application
- resistance fairly low
what is POM chloramphenical licensed for, preparations and dose
- treatment of superficial infections of the eye eg bac conj, inf bleph and prophylaxis following trauma
- formulations available are 0.5% eye drops, 1% ointment and minims 0.5% unit dose eye drops
- dose (drops): 1 drop every 2 hrs for 48 hours then every 4 hrs for 5 days
OTC chloramphenicol
- 2005 - reclassified eyedrops from POM to P for treatment of bac conj eg optrex infected eyes 0.5% eyed drops
- ointment reclassified in 2007 eg optrex bac conj eye ointment, 1% chloramphenicol
chloramphenicol: mode of action
the binding of chloramphenicol to peptidyl transferase on the 50S ribosomal subunit prevents the incorporation of new amino acids to the growing peptide chain
name 5 isolates associated with bacterial conjunctivitis
- stapha = staph aureus
- staphe = staph epidermis
- haemop = haemophilus species - tend to be more common in children
- pseudo = pseudomonas
- strep = streptococcus species
key feautures of fusidic acid POM
- effective against a broad spectrum of gram +ve organisms (particularly staph aureus)
- bacteriostatic (slows bac growth) - maybe bacteriocidal - at high temps
- licensed for the treatment of bac conj
- not the most appropriate agent for acute bac conj in children as its ineffective against gram -ve H influenze, most common causative pathogen in the pop
off license uses of fusidic acid
- prophylaxis following corneal abrasion
- blepharitis
fusidic acid formulation
- one formulation available - fusidic acid 1% modified release eye drops POM
- viscous gel, high contact time to eye so only needs to be applied 2x daily
fusidic acid pharmacokinetics
doesnt penetrate into ocular surface readily - good as its used to treat ocular surface conditions
- not used often anymore because of price, but better for pregnant women for above reason
polymyxin b POM
- attaches to and interferes with the functioning of the cell membrane of aerobic gram -ve bacteria, and bacitracin inhibits the synthesis of the cell wall of gram +ve bacteria
- this combination was marketed as polyfax eye ointment which has a broad range of antibiotic activity, includin p aeruginosa
- was discontinued in oct 2012
propamidine OTC
- aromatic diamidine disinfectant which is active against gram +ve but less active against gram -ve
- also has antifungal and anti amoebic properties
- may be used topically for treatment of minor eye infections such as conj and bleph
propamidine P formulations and dose
formulations available: brolene and golden eye ointment
- licensed for the treatment of superficial infections of the eye eg bac conj, inf bleph
- 1-2 drops up to 4x daily
- was used more commonly before reclassification of chloramphenicol
other antibacterials used in opthalmology
- fluoroquinilones
- aminoglycosides
- tetracylines
- azithromycin
fluoroquinolones
- main indication is the treatment of bac keratitis
- inhibit dna gyrase
- effective against gram -ve bac eg pseudomonas
- broad spectrum - ofloxacin, ciprofloxacin, levofloxacin , moxifloxacin
- cl wearers more susceptible to bac keratitis, and most likely bac is gram -ve
- work by inhibiting dna synthesis of bac
- levofloxacin and moxifloxacin more commonly used as less bac resistance to these newer agents
aminoglycosides
- broad spectrum
- inhibits protein synthesis
- bacteriacidal
- epithelial toxicity - gentamycin, neomycin, tobramycin
- effective against gram -ve and +ve
tetracylines
- administered systemically
- broad spectrum
- inhibit bac protein synthesis by blocking the attachment of the transfer rna-amino acid to the ribosome
- main indication is in the treatment of meibomian disease
- used effectively to reduce bac load on lid margins
- eg doxycycline and minocycline
- tend to be used more for anti inflam than anti inf properties - its thought inflam on lid margins is caused by staph bac releasing toxins so by reducing load you reduce inflam
azithromycin
- licensed for trachomatous conj caused by chlamydia trahomatis
- also licensed for acte bac conj
- off license used in bleph
- formulated as unit dose, preservative free
- comes in a pack - weeks unit dose supply
herpes virus
- dna viruses
- establish latent infection
- reactivation in immunocompromised - taken up by sensory neurone eg trigeminal or spinal ganglion
- eg herpes simplex, varicella zoster and cytomegalovirus
- can get a primary infection, virus lies dormant and then gets reactivated for second infection
- varicella zoster = first chicken pox, can lie dormant and reactivate as shingles in adult life - shingles more prevalent in elderly
viral keratitis
HSV
- primary/recurrent/congenital
- most hsv-1 (cold sores)
- 60% children have hsv by 5yrs
- recurrent - thin dendritic ulcers, contain live virus
VZV
- opthalmic shingles common - risk of corneal involvement which is potentially sight threatening if opthalmic nerve involved
- should be obvious
cytomegalovirus
- infections with cmv can occur in immunocompromised individuals eg AIDS, post transplant
- in the eye, CMV most commonly presents as a viral nectrotising retinitis
anti viral drugs: acyclovir
- enters the cell and is converted to aciclovir monophosphate by the HSV enzyme thymidine kinase (TK)
- enzymes add 2 more phosphates to form the active aciclovir triphosphate
- the aciclovir triphosphate completes with 2-deoxyguanosine triphosphate (dGTP) as a substrate for viral DNA polymerase
- opthalmic version discontinued in 2018
- still available as treatment for cold sores as a topical formulation
antiviral drugs: ganciclovir
- eye gel (virgan) available for treatment of HSK
- slow release ocular implants of ganciclovir are available on a named px basis that are inserted into the ye surgically to treat sight threatening CMV retinitis
acanthamoeba
- epidemiology = free living amoeba, water/soil
- life cycle = mobile trophoziotes and dormant cysts
- culture = specialised, non nutrient agar/ e coli
- can be misdiagnosed as a HSV - only when it fails to respond to acyclovir is it suspected
treatment for acanthamoeba keratitis
- propamidine 0.1% and polyhexamethylene biguanide (PHMB) 0.02% are currently the drugs of choice
- administered hourly day and night for 2 days then reduce as condition improves
- PHMB and chlorhexidine have shown to have activity against the cyst form
