Conjunctival administration

Liver Hepatitis was attributed to conjunctival administration of 0.5% chloramphenicol eye drops in a 37-year-old male engineer with conjunctivitis [31" ]. 

Intraconjunclival Administration. Lupine (1931) tried the intra-conjunctival administration of pituitary gonadotropin, in rabbits treated for 20 days, without result. 

This preservative has been used in a dry eye treatment and was shown in a clinical study to have the same biocompatibility as another marketed preparation [152]. Cetrimonium chloride (0.01%) produced the same corneal and conjunctival changes after one-month ocular administration in rats as the effective levels of other major preservatives [153],... 

Although the ocular absorption of peptide as well as nonpeptide drugs is poor [96,196-198], the ocular route is by far the least studied for the usefulness of penetration enhancers. This is in part due to the perceived sensitivity of ocular tissues to irritation and the fear of corneal and conjunctival damage caused by the enhancers. Whereas the rat nasal epithelium may tolerate up to 5% sodium glycocholate [199], ocular administration of sodium glycocholate at a concentration of 2% and beyond induces reddening of the eye and tear production in rabbits (Kompella and Lee, unpublished observation). 

In a toxicity summary submitted by Eastman Kodak Company (1978), ocular administration of di-n-octylphthalate resulted in slight conjunctival irritation and no corneal damage. No further details were provided. 

Ocular complications following local or systemic administration of steroids include glaucoma, cataracts, adverse influence on specific ocular infections, pseudotumor cerebri, ptosis, mydriasis, subjective visual complaints, visual field defects, systemic absorption of the topical medication, conjunctival and palpebral petechiae, epithelial punctate keratitis, and, possibly, corneal and scleromalacia. ... 

Natural alkaloids and most tertiary antimuscarinic drugs are well absorbed from the gut and conjunctival membranes. When applied in a suitable vehicle, some (eg, scopolamine) are even absorbed across the skin (transdermal route). In contrast, only 10-30% of a dose of a quaternary antimuscarinic drug is absorbed after oral administration, reflecting the decreased lipid solubility of the charged molecule. 

An ophthalmic preparation seems to be efficacious for conjunctival inflammation and to reduce pain after traumatic corneal abrasion. Gingival inflammation is reduced after administration of indomethacin oral rinse. Epidural injections produce a degree of pain relief similar to that achieved with methylprednisolone in postlaminectomy syndrome. 

In addition to oral administration for hepatitis C infection in combination with interferon alfa, aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12-18 hours per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and duration of illness. Aerosolized ribavirin has also been used to treat influenza A and infections but has not gained widespread use. Systemic absorption is low (< 1%). Aerosolized ribavirin is generally well tolerated but may cause conjunctival or bronchial irritation. Health care workers should be protected against extended inhalation exposure. The aerosolized drug may precipitate on contact lenses. 

Hastings et al. [55] used this same in vitro technology to assess the enhancement delivery of dexamethasone using the Visulex iontophoretic system. The Visulex applicator and a freshly excised rabbit sclera were positioned between two halves of a side-by-side diffusion cell with the conjunctival side of the sclera facing the applicator (Figure 26.10). The donor drug solution (1 mg of dexamethasone phosphate) was present in the applicator, and diluted vitreous humor was modeled in the receptor cell. One milliampere direct current was applied for 60 min, and samples were collected during different treatment periods. It was demonstrated that the Visulex system produced a twofold increase in the amount of dexamethasone phosphate delivered after 60 min, compared with a standard iontophoretic administration (without the Visulex applicator). 

Studies of omalizumab in asthmatic volunteers showed that its administration over 10 weeks lowered plasma IgE to undetectable levels and significantly reduced the magnitude of both the early and the late bronchospastic responses to antigen challenge. Clinical trials have shown repeated intravenous or subcutaneous injection of anti-IgE MAb to lessen asthma severity and reduce the corticosteroid requirement in patients with moderate to severe disease, especially those with a clear environmental antigen precipitating factor, and to improve nasal and conjunctival symptoms in patients with perennial or seasonal allergic rhinitis. 

Indomethacin enjoys the usual indications for use in rheumatic conditions and is particularly popular for gout and ankylosing spondylitis. In addition, it has been used to treat patent ductus arteriosus. Indomethacin has been tried in numerous small or uncontrolled trials for many conditions, including Sweet s syndrome, juvenile rheumatoid arthritis, pleurisy, nephrotic syndrome, diabetes insipidus, urticarial vasculitis, postepisiotomy pain, and prophylaxis of heterotopic ossification in arthroplasty, and many others. An ophthalmic preparation seems to be efficacious for conjunctival inflammation (alone and in combination with gentamicin) to reduce pain after traumatic corneal abrasion. Gingival inflammation is reduced after administration of indomethacin oral rinse. Epidural injections produce a degree of pain relief similar to that achieved with methylprednisolone in postlaminectomy syndrome. 

As mentioned above, the ability to adsorb to the cornea and an optimal drug release rate have been defined as the two liposomal attributes most responsible for increasing bioavailability after topical ocular administration. A number of factors, including drug encapsulation efficiency, liposome size and charge, distribution of the drug within liposomes, stability of liposomes in the conjunctival sac and ocular tissues, their retention in the conjunctival sac, and most importantly their affinity toward the corneal surface and the rate of release of the encapsulated drug, have... 

For administration, the drug-impregnated paper strip is moistened with a drop of normal saline or extraocular irrigating solution, and the applicator is gently touched to the superior or inferior bulbar conjunctiva or to the inferior conjunctival sac.To avoid the risk of cross-contamination between eyes, practitioners should use separate applicators for dye delivery to eyes with suspected infection. 

Topical application represents the most common route of administration of local anesthetics for procedures involving the eye. Topically applied anesthetics are surface-acting drugs that produce a reversible inhibition of the sensory nerve endings within the corneal and conjunctival epithelium, producing transient local anesthesia of the corneal and conjunctival surfeces. 

Of the two types of bone marrow toxicity that chloramphenicol can cause, it may cause the late type only in genetically predisposed patients. The overall risk of aplastic anemia after oral administration of chloramphenicol is 1 30 000 to 1 50 000, which is 13 times greater than the risk of idiopathic aplastic anemia in the population as a whole. Since topical administration achieves systemic effects by absorption through the conjunctival membrane or through drainage down the lacrimal duct, with eventual absorption from the gastrointestinal tract, the risk may be similar to that after oral administration. However, based on two case-control studies and a cohort study, the incidence of blood dyscrasias due to chloramphenicol eye-drops was estimated to be somewhat lower, namely 1 100 000 treated patients (40,66). 

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