Ophthalmic toxicity

Infrequent reactions to interferon therapy include proteinuria, renal toxicity, autoimmune disease, thyroid disease, ophthalmic toxicity, pulmonary dysfunction (pulmonary infiltrates, pneumonitis, and pneumonia), and cardiovascular effects (tachycardia, arrhythmia, hypotension, cardiomyopathy, and myocardial infarction). Rarely, the body may develop antibodies against interferons that inhibit their effectiveness. 

Bartlett JD. Ophthalmic toxicity by systemic drugs. In Chiou GCY, ed. Ophthalmic toxicology, ed. 2. Philadelphia Taylor Francis, 1999. 

Ophthalmic-toxic and rhinal-toxic - it appears with lacrimation, sneezing strongly expressed conjunctivitis and rhinitis symptoms ... 

In an investigation of the ophthalmic toxicity of CS,17 rabbit eyes were contaminated with CS in solution (0.5%—10% in polyethylene glycol), as a solid, and as a pyrotechnically generated smoke (15 minutes at 6,000 mg/m3). The effects were most severe... 

FIGURE 38.3 Autonomic nervous system inputs to the pupil and the lens. Diagram depicting the balance between sympathetic and parasympathetic signaling to the pupil (A) and lens (B), and summarizing how agents causing neuro-ophthalmic toxicity can alter this balance (C). 

Safety/Toxicity Genotoxicity membrane toxicity ophthalmic toxicity pulmonary toxicity " ... 

Safety/Toxicity Acute toxicity C5dotoxicity mutagenicity " ophthalmic toxicity ... 

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... 

Although tyrothricia is too toxic for parenteral therapy, it was formerly sold in the United States as oral lo2enges. Modem tyrothricin formulations are composed of 70—80% tyrocidines and 30—20% linear gramicidins. Tyrocidines are not as active as linear gramicidins and are too toxic for any therapeutic use by themselves. The bactericidal linear gramicidins are used in the United States solely as an ophthalmic solution in combination with polymyxin B sulfate and neomycin sulfate. The linear gramicidin is used in this aqueous product as a substitute for bacitracin, which lacks stabiUty under such conditions. 

One can see by the complexity of these types of manufacturing procedures that much care and attention to detail must be maintained by the manufacturer. This sterile manufacturing procedure must then be validated to prove that no more than 3 containers in a lot of 3000 containers (0.1%) are nonsterile. Ultimately, it is the manufacturer s responsibility to ensure the safety and efficacy of the manufacturing process and the absence of any adverse effect on the product, such as the possible formation of substances toxic to the eye, an ever-present possibility with gas sterilization or when using ionizing radiation. For ophthalmic products sterilized by terminal sterilization (sterilization in the final sealed container, e.g., steam under pressure), the sterilization cycle must be validated to ensure sterility at a probability of 106 or greater. 

Albino rabbits have been the primary species used to test ocular toxicity and irritation of ophthalmic... 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

This preservative is comparatively new to ophthalmic preparations and is a polymeric quaternary ammonium germicide. Its advantage over other quaternary ammonium seems to be its inability to penetrate ocular tissues, especially the cornea. It has been used at concentrations of 0.001-0.01% in contact lens solutions as well as dry eye products. At clinically effective levels of preservative, POLYQUAD is approximately 10 times less toxic than benzalkonium chloride [87,137], Various in vitro tests and in vivo evaluations substantiate the safety of this compound [137,141,142], This preservative has been extremely useful for soft contact lens solutions because it has the least propensity to adsorb onto or absorb into these lenses, and it has a practically nonexistent potential for sensitization. Its ad-sorption/absorption with high water and high ionic lenses can be resolved by carefully balancing formulation components [143],... 

This preservative is also comparatively new to ophthalmic formulations and has been used as a disinfectant in contact lens solutions. Polyaminopropyl biguanide (polyhexamethyl biguanide) also is a polymeric compound that has a low toxicity potential at the concentrations generally used in these solutions [141, 149, 150]. 

Surfactants. The use of surfactants is greatly restricted in formulating ophthalmic solutions. The order of surfactant toxicity is anionic > cationic >> nonionic. Several nonionic surfactants are used in relatively low concentrations to aid in dispersing steroids in suspensions and to achieve or to improve solution clarity. Those principally used are the sorbitan ether esters of oleic acid (Polysorbate or Tween 20 and 80), polymers of oxyethylated octyl phenol (Tyloxapol), and polyoxyl 40 stearate. The lowest concentration possible is used to perform the desired function. Their effect on preservative efficacy and their possible binding by macromolecules must be taken into account, as well as their effect on ocular irritation. The use of surfactants as cosolvents for an ophthalmic solution of chloramphenicol has been described [271]. This com-... 

Immunocompetent patients 800 mg q4h (Stimesa day) for7days Severely immunosuppressed or ophthalmic zoster 10 mg/kg IV over 1 hour q8h keep patient vyell-hydrated lethargy, confusion, tremor. May cause meperidine toxicity. 

Q74 Prilocaine should be avoided in patients receiving co-amoxiclav. Prilocaine may cause ocular toxicity v/hen used for ophthalmic procedures. 

Prilocaine is a local anaesthetic of low toxicity, which should be avoided in severe or untreated hypertension, severe heart disease and in patients using drugs that may cause methaemoglobinaemia. Prilocaine may cause ocular toxicity, which has been reported with the use of the product in excessively high doses during ophthalmic procedures. 

Targeting a drug to its site of action is useful to enhance its effectiveness and reduce toxicity. If accessible this can be achieved by direct local application, e.g. eye drops to treat ophthalmic conditions, inhalers to treat respiratory conditions, but currently strategies such as the development of targeting agents such as monoclonal antibodies or the use of the more permeable nature of tumour capillaries to allow accumulation of macromolecular carriers have also been employed. 

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