Anti Infective Drugs - antibacterials, antivirals and anti protozoals Flashcards

1
Q

differences between bacteria and human cells

A
  • 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
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2
Q

pharmacology of antibacterial agents

A

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

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3
Q

antibiotics- general considerations

A
  • 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
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4
Q

antibiotic sensitivity testing

A
  • 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
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5
Q

anti infectives available to optoms

A

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

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6
Q

key features of Chloramphenicol - POM

A
  • 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
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7
Q

what is POM chloramphenical licensed for, preparations and dose

A
  • 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
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8
Q

OTC chloramphenicol

A
  • 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
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9
Q

chloramphenicol: mode of action

A

the binding of chloramphenicol to peptidyl transferase on the 50S ribosomal subunit prevents the incorporation of new amino acids to the growing peptide chain

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10
Q

name 5 isolates associated with bacterial conjunctivitis

A
  • stapha = staph aureus
  • staphe = staph epidermis
  • haemop = haemophilus species - tend to be more common in children
  • pseudo = pseudomonas
  • strep = streptococcus species
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11
Q

key feautures of fusidic acid POM

A
  • 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
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12
Q

off license uses of fusidic acid

A
  • prophylaxis following corneal abrasion

- blepharitis

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13
Q

fusidic acid formulation

A
  • 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
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14
Q

fusidic acid pharmacokinetics

A

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

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15
Q

polymyxin b POM

A
  • 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
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16
Q

propamidine OTC

A
  • 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
17
Q

propamidine P formulations and dose

A

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
18
Q

other antibacterials used in opthalmology

A
  • fluoroquinilones
  • aminoglycosides
  • tetracylines
  • azithromycin
19
Q

fluoroquinolones

A
  • 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
20
Q

aminoglycosides

A
  • broad spectrum
  • inhibits protein synthesis
  • bacteriacidal
  • epithelial toxicity - gentamycin, neomycin, tobramycin
  • effective against gram -ve and +ve
21
Q

tetracylines

A
  • 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
22
Q

azithromycin

A
  • 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
23
Q

herpes virus

A
  • 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
24
Q

viral keratitis

A

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
25
Q

cytomegalovirus

A
  • infections with cmv can occur in immunocompromised individuals eg AIDS, post transplant
  • in the eye, CMV most commonly presents as a viral nectrotising retinitis
26
Q

anti viral drugs: acyclovir

A
  • 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
27
Q

antiviral drugs: ganciclovir

A
  • 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
28
Q

acanthamoeba

A
  • 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
29
Q

treatment for acanthamoeba keratitis

A
  • 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