眼睛疾病的抗炎症治疗（英文ppt）antibioticand antiinflammatory therapy for ocular

Antibiotic and anti-inflammatory therapy for ocular diseases Mario La Rosa Dipartimento di Pediatria, UO di Broncopneumologia, Allergologia e Fibrosi Cistica, Universit degli Studi di Catania l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases Ocular infections l Eyes are organs with a high probability of contracting infections because of their anatomical position. l Natural ocular mechanisms of defence are not always able to control infectous lesions. l It is really important, for exemple, to diagnose corneal infections, because if they are not appropriately treated they can evolve in corneal opacities, with a deep decrease of sight. Ocular infections Endophtalmithis need an urgent tratement in order to avoid the widespread of the infection in the closer tissues, that in serious cases can cause the loss of function of the ocular bulb Ocular infections Allergic conjunctivities incidence is increasing and it affects a large amount of people, with some problems in its tratement. As a matter of fact therapy is based on the control of symptoms, without a definitely resolution of the disease. Ophthalmic antibiotic therapy In the therapy of bacterial ocular diseases a large number of antibiotics acting locally alone or sistemically are being used. With the introduction of antibiotics in the 1940s, effective tratement of blinding ocular infections finally became a reality. Since that time, to echo a popular slogan: “Weve come a long way”. John P Witcher, West J Med 1994 l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases Ophthalmic antibiotic therapy Antibiotics available for topical use in the eye are: - Chloramphenicol - Fucidic acid - Aminoglicosides - Chlortetracyclines - Fluoroquinolones - Polymixin Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy Cloramphenicol, fusidic acid, the aminoglicosides and chlortetracycline, show a quantitative biochemical selectivity. In differing ways they interact with bacterial ribosomes and inhibit the syntesis of bacterial proteins. Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy Chlortetracycline shows a quantitative selectivity, which is in part biochemical, because of the differences between human and bacterial ribosomes, and in part distributional, as sensitive bacteria are able to accumulate higher concentrations of the drug, either by passive diffusion and by active transport. Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy The aminoglycocides framycetin, gentamicin and neomycin exert a rapid bactericidal effect which cannot be explained only trough inhibition of protein synthesis. As a matter of fact there is some evidence that these drugs cause a disruption of the cytoplasmatic membrane structure. Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy The fluoroquinolones (ciprofloxacin, ofloxacin) are bactericidal through the inhibition of nucleic acid synthesis as a result of their inhibition of the enzyme DNA gyrase. The activity of this enzyme is necessary to initiate DNA and RNA synthesis. Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy The cationic detergent properties of the polymyxins allows them to interact with the phospholipids of the cell membrane. These drugs are then able to enter the membrane and disrupt its structure Vale Janet; Ophtal Physiol Opt 1998 Ophthalmic antibiotic therapy The Penicillins, which are bactericidal and qualitatively selective through their action in disrupting synthesis of bacterial cell walls, are not generally used topically because of widespread resistance and allergy problems. Selected compuonds, such as ticarcillin, carbenicillin, piperacillin are used by other routes for Pseudomonas infections. Vale Janet; Ophtal Physiol Opt 1998 l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases Antibiotics for Specific Ophtalmic Conditions It is well known that the initial therapy for suspected bacterial keratitis should include broad-spectrum antibiotics, considering that this therapy should be altered if the corneal ulcers worsens and microbiological investigations prove that the responsable pathogen is resistant to the initial therapy. Bacterial keratitis Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis With the increase of resistance among infective agents, it is important to know the antibiotic susceptibility of current ocular surface pathogens, in order to optimaze the initial therapy for patients with suspected bacterial keratitis. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis Cameron N. and coll. performed a quantitative susceptibility testing to six antibiotics on all bacteria isolated from 112 patients who presented to the Sydney Eye hospital Emergency Department with presumed bacteria keratitis. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis Bacterial species isolated from corneal scrapings taken from 112 patients with suspected bacterial keratitis. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis Antibiotics used in the study. The initial topical antibiotic treatement is shown in the black bar and the number of successful cases shown in the shaded bar. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis l The mentioned study showed that cephalosporins and aminoglycosides were complementary in their microbial cover. l The Cephalosporin plus aminoglycoside combination therapy has proven an effective initial broad-spectrum treatement of bacterial keratitis in many other studies in London, Sweden and the USA. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis The use of fluoroquinolones has been shown to be an effective alternative for the usual cephalosporine and aminoglycoside combination therapy, as demonstrated in large prospective multicentre studies that supported the use of 0,3% ciprofloxacin topical monotherapy and 0,3% ofloxacin topical monotherapy. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis Ciprofloxacin is also one of a few antibiotics that enters the human eye after oral administration. Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Ophthalmic antibiotic therapy in bacterial keratitis Distribution of ciprofloxacin minimum inhibitory concentration (MIC). Fifty -one out of 53 isolates were likely to respond to ciprofloxacin (MIC /= 4,0) Cameron N Ly MB BS;Clinical and Experimental Ophthalmology 2006 Antibiotics for Specific Ophtalmic Conditions Conjunctivitis l Most cases of conjunctivitis have a viral etiology, with prominent symptoms being itchy, watery, red eyes with lid and conjunctival edema. In this case eyedrop antibiotics are useful to prevent a secondary bacterial infection. l Good choises include: - Polytrim - Tobramycin Richmond Eye Associates; Ophtalmology Update Jul 2001 Antibiotics for Specific Ophtalmic Conditions Conjunc tivitis Antibiotics for Specific Ophtalmic Conditions Conjunctivitis Bacterial conjunctivitis is characterized by a copious purulent discharge. Good antibiotic choises include: - Polytrim - Ocuflox - Gentamycin - Tobramycin - Neosporin Richmond Eye Associates; Ophtalmology Update Jul 2001 Antibiotics for Specific Ophtalmic Conditions Conjunctivitis Chlamydia Trachomatis is a cause of chronic conjunctivitis and appropriate systemic treatement is indicated along with Erythromycin ophthalmic ointment. Richmond Eye Associates; Ophtalmology Update Jul 2001 Antibiotics for Specific Ophtalmic Conditions Prophylaxis of corneal abrasions Antibiotics eyedrops or ointments should be used during the healing period of corneal abrasions to prevent corneal ulcer. Good antibiotic choices include: - Gentamicin, Tobramycin, Polytrim - Cipro, Ocuflox, Quixin (if there are stronger risk factors for infection due to the nature of the injury) - Erythromycin, Bacitracin (for particularly large corneal abrasions) Richmond Eye Associates; Ophtalmology Update Jul 2001 Antibiotics for Specific Ophtalmic Conditions Blepharitis For significant flare-ups of the condition, antibiotic oinments applied at bedtime such as Erytromycin, Bacitracin or Tobramycin can be useful. Yet short courses fo steroid/antibiotic combination oinments such as Maxitrol, Dexacidin and Tobradex may give more rapid relief. Richmond Eye Associates; Ophtalmology Update Jul 2001 Antibiotics for Specific Ophtalmic Conditions Blepha ritis Antibiotics for Specific Ophtalmic Conditions Endophthalmitis John P Witcher, West J Med 1994 Antibiotics for Specific Ophtalmic Conditions Endophthalmitis Antibiotics in ocular tuberculosis The most common manifestation of the ocular involvment in tuberculosis is uveitis, usually presenting as a chronic anterior uveitis, panuveitis or as a choroiditis. In the posterior ocular pole it is possible to find choroidal tubercles, which appear yellow, becoming more pigmented as the time passes. C. Micheal Samson, M.C.; The Ocular Immunology and Uveitis Foundation 1999 Antibiotics in ocular tuberculosis Fundus potographs and corresponding fluorescein angiogram of presumed choroidal tubercle. The patient was strongly PPD reacting and was treated with anti-tuberculous medications. Photos courtesy of Joseph Walsh , M.D., Chairman of Ophthalmology at the New York Eye and Ear Infirmary. Antibiotics in ocular tuberculosis Fundus photo and corresponding fluorescein angiogram of the same patient, after six months of treatement with anti- tuberculous medications. Photos courtesy of Joseph Walsh , M.D., Chairman of Ophthalmology at the New York Eye and Ear Infirmary. l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases Ophthalmic anti-inflammatory therapy Anti-inflammatories drugs used in ophthalmology can be divided in two groups: l Topic and injectable steroidal antiinflammatories l Non steroidal antiinflammatories Steroidal anti-inflammatory drugs These kind of drugs are lack of specificity, and they have been used for several years as treatement of inflammation and immunological ophthalmic diseases. Genevieuve N; Clinical and Experimental Optometry 2006 Steroidal anti-inflammatory drugs: mechanisms of action Their antiinflammatory and immunosuppressive action can be related to the following actions: l Inhibition of lymphocites proliferation, above all lymphocytes T, with a decrease of the cell- mediated immunity l Suppression of lymphokines action, of macrophage migration and of the production of some growth factors Steroidal anti-inflammatory drugs: mechanisms of action l Inhibition of the degranulation of neutrophil granulocytes, macrophages, mastcells and basophil granulocytes. l Decrease of vascular permeability l Decrease of Prostaglandines production as consequence of the suppression of arachidonic acid synthesis. Genevieuve N; Clinical and Experimental Optometry 2006 Steroidal anti-inflammatory drugs Genevieuve N; Clinical and Experimental Optometry 2006 Steroidal anti-inflammatory drugs Prednisolone Studies shows that Prednisolone has the greatest anti- inflammatory efficacy of all topical ophthalmic steroids. Prednisolone acetate 1% is the most effective of the topical ophthalmic steroids for the treatement of uveitis and corneal inflammations.it is well suited for treating severe forms of ocular inflammation such as episcleritis, iritis, chemical/termal burns of the cornea. Reveiw of optamometry; June 2006 Steroidal anti-inflammatory drugs Dexamethasone In its approved concentration, Dexamethasone is less clinically effective than prednisolone and has a greater tendency to raise intraocular pressure, making it a drug of second choise. Reveiw of optamometry; June 2006 Steroidal anti-inflammatory drugs Fluorometholones They possesses good to excellent anti- inflammatory properties , while having a diminished propensity to cause secondary IOP increase. There are two formulations of fluorometholone, the alchool and the acetate. Reveiw of optamometry; June 2006 Steroidal anti-inflammatory drugs Fluorometholone alchool It is used very commonly to treat a host of mild to moderate ocular scurface inflammatory conditions, requiring long-term (beypnd three to four week) therapy such as low-grade chronic iridocyclitis and some cases of ocular allergy. Its usefulness in chronic care lies in its reduced tendency to cause secondary IOP increase. Reveiw of optamometry; June 2006 Steroidal anti-inflammatory drugs Fluorometholone acetate This is the more clinically active form of the more familiar FML. The acetate formulation confers to fluorometholone greater clinical efficacy. The indications for this product are essentially the sae for the other corticosteroids. Reveiw of optamometry; June 2006 Steroidal anti-inflammatory drugs Rimexolone It is a potent, relatively safe preparation, and it is close to, but not as effcacious as 1% prednisolone acetate; yet its decreased propensity to raise intraocular pressure is very similar to that of the fluorometholones. Reveiw of optamometry; June 2006 l Introduction l Antibiotic therapy l Antibiotics for Specific Ophtalmic Conditions l Steroidal anti-inflammatory drugs l Non-steroidal anti-inflammatory drugs (NSAIDs) l Conclusions Antibiotic and anti-inflammatory therapy for ocular diseases Non-steroidal anti-inflammatory drugs (NSAIDs) They are inhibitors of prostaglandines synthesis with an anti-inflammatoey and analgesic activity. The advantage of using them than steroidal agents is related to the fact that they do not induce a decrease of immunosystem activity. Moreover they do not interact with the ocular hydrodynamic. Ophthalmic non-steroidal anti- inflammatory drugs Most current NSAIDs inhibit both forms of the cyclo- oxygenase (COX) enzyme. Inhibition of the synthetic pathway from arachidonic acid to the prostaglandines may result in increased production of leukotrienes which are also inflammatory. This may have serious consequances for some patients, e.g asthmatics, as the leukotrienes cause bronchoconstriction. Genevieuve N; Clinical and Experimental Optometry 2006 Ophthalmic non-steroidal anti- inflammatory drugs Currently they are used in intra- and/or post- operative situations to reduce miosis during surgery and inflammation following cataract surgery, laser trabeculoplasty and PRK. They are also used in the prevention and treatment of cystoid macular oedema and for the treatment of allergic conjunctivitis. Vale J; Ophthalm Physiol Opt 1998 Ophthalmic non-steroidal anti- inflammatory drugs Other therapeutics indications of NSAIDs in ocular diseases are: - Inflammations of the anterior segment of the eye, which do not recognize a viral o bacterial etiology, s