Ophthalmic medications

Discuss the product differences that direct the selection of ophthalmic medications. 

Because the official compendia require all topically administered ophthalmic medications to be sterile, manufacturers of such medications must weigh numerous alternative approaches as they design manufacturing procedures. Ideally, as preferred by some regulators, especially in Europe, all ophthalmic pro-... 

Discontinue the ophthalmic medication and not ify t he physician if acute redness of eyes, floating spots, severe eye pain or pain on exposure to light, a rapid change in vision (side and straight ahead), or headache occurs... 

Sustained delivery of ophthalmic medications is a novel approach in treating chronic intraocular infections in conditions where systemic administration is accompanied by undesirable side-effects and repeated intravitreal injections carry the risk of infection. The administration of medications by implants or depot devices is a very rapidly developing technology in ocular therapeutics. The various types of implant and mechanisms of drug release have been discussed in general in Chapter 4. 

Due to the accessibility of the eye surface, topical administration of ophthalmic medications is the most common method for treating conditions affecting the exterior eye surface. However, the unique anatomy and physiology of the eye renders it difficult to achieve an effective drug concentration at the target site. Therefore, efficient delivery of a drug past the protective ocular barriers accompanied with minimization of its systemic side effects remains a major challenge. 

Lama, P.J. (2005). Systemic reactions associated with ophthalmic medications. Ophthalmol. Clin. North Am. 18 569-84. 

Studies have investigated the pharmacoeconomics of drug therapy. The drug price may reflect only part of the medication cost. Other costs, such as those associated with adverse drug effects, additional laboratory tests, and office visits, may more realistically reflect the pharmacoeconomics of therapy. For ophthalmic medications, the daily cost of medications also depends on the volmne of the medication, the drop size, dosing regimen, compU-ance, and other fectors. PubUcations have reviewed glaucoma and topical corticosteroid therapy and described more cost-effective treatment options not based solely on the actual medication cost. 

Affective and Mental Disorders. Anxiety and emotional instability can be associated with psychogenic reactions, such as vasovagal syncope, that may appear to be drug related. Medications used to treat these disorders may potentiate the activity of ophthalmic medications. The use of monoamine oxidase inhibitors or tricyclic antidepressants can enhance the systemic effects of topically applied phenylephrine and a2-adrenergic agonists. 

Modified from Wilson FM. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmol 1979 24(2) 57-88. 

For yoimg children, ophthalmic medications in ointment form are often preferred because they are less likely to be diluted and washed out by tears, and the drop... 

Hypersensitivity to benzalkonium chloride has been reported in association with the use of ophthalmic medications. Because several of the commonly used topical ocular anesthetics contain benzalkonium as a preservative (see Table 6-2), it is reasonable to assume that some of the local allergic reactions to anesthetics may be due to this preservative. 

Combination therapy of topical and systemic drugs is also an important treatment consideration. When symptoms are isolated to the eye, topical treatment is rapid and most efficient. However, in cases of rhinoconjunctivitis, when nasal symptoms are also present, optimum management includes combining topical ophthalmic medications, olopatadine or ketotifen, for example, with a nasal spray or systemic treatment, such as the oral antihistamine desloratadine. For rhinitis, nasal steroids provide a good treatment option. The above approach targets particular areas of involvement by utilizing the most efficacious route of treatment. 

Low lOP after cataract surgery can be due to a variety of reasons, including woimd leak, cihochoroidal effusion, cyclodialysis cleft, retinal detachment, or aqueous suppression from ophthalmic medication. 

Unique to ophthalmic medical management, self-medicating with ophthalmic drops is a learned skill that does not come naturally. In fact, the natural defense systems of the eye (corneal reflex, blepharospasm) must be overcome to be successful. It is not uncommon, even for a patient who believes he or she is faring well, to complain that his or her 2.5-ml bottle of topical prostaglandin is lasting only 3 weeks. 

Certain insurers have a preferred ophthalmic medication formulary. These select drugs typically represent the result of a negotiated price between a pharmaceutical company and an insurance provider. These costsaving measures are an integral part of the health care industry and serve to keep costs manageable for the... 

Elderly people are particularly likely to make errors in the administration of ophthalmic medications, resulting in overdosage and adverse toxic effects or underdosage with inadequately controlled glaucoma (12). This may reflect impaired memory, mental confusion, impaired vision, hearing, and mobility, or a combination of these factors. It is wise to assess both adherence to therapy and administration technique to ensure the safe and effective use of... 

Flach AJ. Systemic toxicity. Associated with topical ophthalmic medications. J Fla Med Assoc 1994 81(4) 256-260. 

Gohen EM, Grim WM, Harwood RJ, Mehta GN. Solid state ophthalmic medication. United States Patent No. 4,179,497 1979. Harwood RJ, Schwartz JB. Drug release from compression molded films preliminary studies with pilocarpine. Drug Dev Ind Pharm 1982 8 663-682. 

Topically administered ophthalmic medications are potentially epitheliotoxic and may delay comeal repair. The clinician must balance the therapeutic benefits achieved by their use against any possible injurious effects... 

Excipients are not foods, but many are identical to chemicals used as food additives, leading to multiple sources and increasing doses when foods, prescription drugs, and/or over-the-counter medications containing them are ingested at the same time. Though excipients are extensively used in inhalational, parenteral, and ophthalmic medications, the consideration here is limited to ingestion. Effects of toxic inhalational, parenteral, and ophthalmic excipients are considered in the Chapters 18, 23, and 28. 

An ophthalmic medication should be at room temperature prior to administration. If the eye drops are in a suspension, the container should be gently shaken before administration. A child old enough to follow directions should tilt his or her head slightly backward and to the side so that the eye drops will not drain into the tear ducts near the nose. The eyelids should be separated and the patient should be asked to look up. The appropriate amount of medication is instilled into the lower eyelid, using the medication dropper, which should be accomplished without touching the eyelids. The patient should look downward for a few seconds after drug administration. The eye(s) should then be closed for several minutes... 

Because the official compendia require all topically administered ophthalmic medications to be sterile, manufacturers of such medications must weigh numerous alternative approaches as they design manufacturing procedures. Ideally, as preferred by some regulators especially from Europe, all ophthalmic products would be terminally sterilized in the final packaging because it offers the best chance of assuring patients of then-sterility. In effect, this would rule out any aseptic processing for the manufacture of ophthalmic products however, the use of sterile filtration and/or aseptic assembly of ophthalmic products has been shown not to constitute a risk to public health. 

Table 4 AAO-Recommended Color Coding of Caps and Labels for Topical Ophthalmic Medications...

Classical pharmacokinetic models of systemicaUy administered drugs (see Chapter 1) do not fuUy apply to many ophthalmic drugs. Most ophthalmic medications are formulated to be apphed topically or may be injected by subconjunctival, sub-Tenon s, and retrobulbar routes (Figure 63-1 and Table 63-1). Although similar principles of absorption, distribution, metabolism, and excretion determine drug disposition in the eye, these alternative routes of drug administration introduce other variables in compartmental analysis. 

All ophthalmic medications are potentially absorbed into the systemic circulation (Figure 63-3), so undesirable systemic side effects may occur, as well as potential local toxic effects due to hypersensitivity reactions or to direct toxic effects on the cornea, conjunctiva, periocular skin, and nasal mucosa. Eyedrops and contact lens solutions commonly contain preservatives such as ben-zalkonium chloride, chlorobutanol, and chelating agents for their antimicrobial effectiveness. In particular, benzalkonium chloride may cause a punctate keratopathy or toxic ulcerative keratopathy. 

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