Intraocular administration

Intraocular administration only for miosis during surgery carbachol also available as a topical Also available as a gel and an insert the duration of these doseforms is longer (18 to 24 hour week, respectively) than the solution. 

Peinado-Ramon, P., Salvador, M., Villegas-Perez, M. P, and Vidal-Sanz, M., Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study, Invest. Ophthalmol. Visual Sci., 37,489, 1996. 

Prior studies have demonstrated the promise of growth factors, neurotrophic factors, and cytokines given by intravitreal injection in short-term animal experiments as potential therapy for RP (15,27,28,30). Among these, ciliary neurotrophic factor (CNTF) is effective (15). Unfortunately, the chronic nature of the disease and the adverse effects associated with repeated short-duration intraocular administration mitigates the use of CNTF by this delivery method. 

Adapted from Nursing94, line, Intraocular Drug Administration, pp. 44-45, which was adapted trom Giving drugs by advanced techniques [1993], Springhouse, PA Springhouse Corp.)... 

However, for certain routes of injection, such as intrathecal, intraocular, or into any part of the brain, isotonicity and physiological pH are critical in order to minimize potential nerve damage. Absence of preservatives is also critical for these routes of administration for the same reason. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

Only the first three are discussed in any detail here. Most of these routes of administration place a drug directly or indirectly into systemic circulation. There are a number of these routes, however, by which the drug exerts a local effect, in which case most of the drug does not enter systemic circulation (e.g., intrathecal, intraventricular, intraocular, intraracistemal). Certain routes of administration may exert both local and systemic effects depending on the characteristics of the drug and excipients (e.g., subcutaneous). 

An oximine (i.e., a substituted oxime) analogue of alprenoxime was examined in an attempt to overcome the problem of low stability in aqueous solution. To this end, the methoxime analogue of alprenolol (11.74, R = Me) was prepared and evaluated [109]. Stability in solution was greatly improved at neutral pH. Topical administration to rabbits produced a decrease in intraocular pressure that had the same onset and intensity as that produced by alprenolol, but that lasted longer. Alprenolol was, indeed, formed in eye tissues as a metabolite, with the peak concentration reached 30 min after topical administration of the methoxime. 

The most common side-effects to nasal administration of fluticasone are local reactions, including irritation of the nose and throat and epistaxis. Steroids may cause a raised intraocular pressure or glaucoma. Hypersensitivity reactions, including occurrence of bronchospasms, have been reported. 

Carbachol is a powerful cholinic ester that stimulates both muscarinic and nicotinic receptors, as well as exhibits all of the pharmacological properties of acetylcholine while in addition resulting in vasodilation, a decrease in heart rate, an increase in tone and con-tractability of smooth muscle, stimulation of salivary, ocular, and sweat glands as well as autonomic ganglia and skeletal muscle. For this reason, use of carbachol, like acetylcholine, is limited. The exception is that it is used in ophthalmological practice and post-operational intestines and bladder atony. Upon administration in the eye, the pupil constricts and the intraocular pressure is reduced. It is used for severe chronic glaucoma. Synonyms of this drag are doryl and miostat. 

Pharmacokinetics Topical administration appears to produce effective concentrations within the corneal stroma, but not in intraocular fluid. Absorption from the Gl tract is very poor. Systemic absorption should not occur after topical administration. 

Epinephrine also has been used to lower intraocular pressure in open-angle glaucoma. Its use promotes an increase in the outflow of aqueous humor. Because epinephrine administration will decrease the filtration angle formed by the cornea and the iris, its use is contraindicated in angle-closure glaucoma under these conditions the outflow of aqueous humor via the filtration angle and into the venous system is hindered, and intraocular pressure may rise abruptly. 

Iritis, which affects up to 25% of patients undergoing fomivirsen therapy, can be managed with topical corticosteroids. Vitreitis and increased intraocular pressure may also result from fomivirsen administration. Fomivirsen is contraindicated in patients who have been treated with cidofovtr within the previous 2 to 4 weeks because cidofovir increases the risk of ocular inflammation. 

The most frequent adverse reactions to trifluridine administration are transient burning or stinging and palpebral edema. Other adverse reactions include superficial punctate keratopathy, epithelial keratopathy, hypersensitivity, stromal edema, irritation, keratitis sicca, hyperemia, and increased intraocular pressure. 

Glucocorticoids induce cataract formation, particularly in patients with rheumatoid arthritis. An increase in intraocular pressure related to a decreased outflow of aqueous humor is also a frequent side effect of periocular, topical, or systemic administration. Induction of ocular hypertension, which occurs in about 35% of the general population after glucocorticoid administration, depends on the specific drug, the dose, the frequency of administration, and the glucocorticoid responsiveness of the patient. 

The pharmacological actions of physostigmine are similar to those of cholinergic drugs. Topical instillation into the eye produces miosis, spasm of accommodation and decrease in intraocular pressure. Physostigmine is well absorbed after oral as well as parenteral administration and also produces central cholinergic actions because of penetration into blood brain barrier. 

Systemic administration of 3-blocking drugs for other indications was found serendipitously to reduce intraocular pressure in patients with glaucoma. Subsequently, it was found that topical administration also reduces intraocular pressure. The mechanism appears to involve reduced production of aqueous humor by the ciliary body, which is physiologically activated by... 

Mannitol Physical osmotic effect on tissue water distribution because it is retained in the vascular compartment Marked increase in urine flow, reduced brain volume, decreased intraocular pressure, initial hyponatremia, then hypernatremia Renal failure due to increased solute load (rhabdomyolysis, chemotherapy), increased intracranial pressure, glaucoma IV administration Toxicity Nausea, vomiting, headache... 

Administration of succinylcholine may be associated with the rapid onset of an increase in intraocular pressure (< 60 seconds), peaking at 2-4 minutes, and declining after 5 minutes. The mechanism may involve tonic contraction of myofibrils or transient dilation of ocular choroidal blood vessels. Despite the increase in intraocular pressure, the use of succinylcholine for ophthalmologic operations is not contraindicated unless the anterior chamber is open ("open globe") due to trauma. 

A 0.1% ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery. A topical gel containing 3% diclofenac is effective for solar keratoses. Diclofenac in rectal suppository form can be considered for preemptive analgesia and postoperative nausea. In Europe, diclofenac is also available as an oral mouthwash and for intramuscular administration. 

An 11-year-old boy with iridocyclitis developed Cushing s syndrome, a posterior subcapsular cataract, and increased intraocular pressure in both eyes after the topical administration of prednisolone acetate 1% eye-drops bilaterally for 6 months. The Cushing s syndrome was aggravated when periocular methylpredni-solone acetate was started while bilateral posterior subtenon injections of 80 mg of suspension were continued every 6 weeks for 6 months. He had not used systemic glucocorticoids before. 

Nevertheless, very limited research has been carried out to develop DDS for the posterior segment of the eye in the last decades. Whereas new antiangiogenic compounds and neurotrophic factors can open new therapeutic avenues in the treatment of AMD, retinal dystrophies and ocular manifestations of diabetes, the frequent intraocular injections of these compounds remain a problem and are associated with complications and discomfort for the patient. Thus, the need for efficient noninvasive DDS for the administration of drugs to the back of the eye is awaiting a ground-breaking multidiscipline advancement. 

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