Keywords

1 Pharmacokinetic Considerations

1.1 Drug Formulation

Since the amount of drug absorption is proportional to the amount of time the drug remains over the surface of the eye and below the eyelids, various formulations have been developed.

They include ointments (e.g., penicillin), gels (e.g., pilocarpine), ocular inserts (e.g., ganciclovir), and collagen shields.

1.2 Absorption into the Eye

  • The rate of drug absorption is determined by the time the drug is present and available for absorption in the palpebral space. The drug absorption is directly proportional to its concentration in the tear film as the tear film is in contact with the absorptive surfaces of the cornea.

  • Factors that help in increasing absorption into the eye include corneal and conjunctival suffusion, binding to tear proteins. Factors that decrease absorption into the eye include elimination by the drainage into nasolacrimal duct, drug metabolism by tear and tissue proteins.

  • Drug absorption can be increased by blocking the nasolacrimal ducts by silicon plugs.

  • Alternatively, closing the eyes for 10–15 min after drug administration reduces nasolacrimal drainage by reducing the suction pressure by the lacrimal apparatus.

  • Nasolacrimal drainage increases the systemic absorption of the drug and results in increased toxicity.

  • The drug absorption through the corneal surface has to pass through the layers of the cornea. The layers of the cornea vary in hydrophilicity. The outer epithelium and the inner endothelium are hydrophobic while the central stroma is hydrophilic. Hence drugs must have both lipophilicity and hydrophilicity to achieve optimal absorption rates into the eye.

  • Certain drugs may not be absorbed because of the ionic nature of the drug. This can be circumvented by administering the ester formulation of the drug with more lipophilicity.

1.3 Distribution

  • Systemic distribution of drugs administered for ophthalmic purposes increases the side effects and toxicity.

  • As the drugs reach the nasal mucosa through the drainage via the nasolacrimal duct, due to high vascularity and the increased surface area, systemic absorption is maximum. Further, drugs absorbed through the nasal mucosa do not undergo any first pass metabolism.

  • Drug binding to proteins within the eye can affect its actions. Drugs like the alpha agonists bind avidly to melanin and hence, its action is slower in patients with higher melanin content in their iris.

  • Accumulation of certain drugs in the retinal pigment epithelium is responsible for the long-term toxicity of some of the drugs like chloroquine. Chloroquine accumulation in the retinal pigments causes bull’s eye maculopathy.

1.4 Metabolism

  • Various enzymes are present in the ocular tissues which degrade drugs as they are absorbed into the eye.

  • The esterases break down the prodrugs thus activating the parent drug in the eye.

  • Use of a drug with local anaesthetic effect must be avoided as it predisposes the patient’s cornea for microabrasions leading to corneal ulceration.

2 Chemotherapeutic Drugs in the Eye

2.1 Bacterial Infections (Box 68.1)

Box 68.1 Antibiotics Used in Bacterial Infections and Various Infective Conditions of the Eye

Antibiotics

Conditions requiring antibiotic therapy

Macrolides

 Erythromycin

 Azithromycin

Aminoglycosides

 Gentamicin

 Tobramycin

Sulfonamides

 Sulfacetamide

Fluoroquinolones

 Ciprofloxacin

 Ofloxacin

 Levofloxacin

 Moxifloxacin

 Besifloxacin

 Gatifloxacin

Miscellaneous

 Bacitracin

 Chloramphenicol

 Polymyxin

Conjunctivitis

Dacryoadenitis

Dacryocystitis

Hordeolum

Blepharitis

Conjunctivitis

Keratitis

Endophthalmitis

Panophthalmitis

2.2 Viral Infections (Box 68.2)

Box 68.2 Antivirals Used in Viral Infective Conditions of the Eye

Antivirals

Conditions requiring antiviral therapy

Trifluridine

Ganciclovir

Valganciclovir

Acyclovir

Valacyclovir

Famciclovir

Foscarnet

Cidofovir

Viral keratitis

Herpes zoster ophthalmicus

Viral retinitis

2.3 Fungal Infections (Box 68.3)

Box 68.3 Antifungals Used in Fungal Infective Conditions of the Eye

Antifungals

Conditions requiring antifungal therapy

Amphotericin B

Natamycin

Fungal corneal ulcer

Fungal injections of other parts of the eyeball

Fungal keratitis

Fluconazole

Itraconazole

Ketoconazole

Miconazole

Voriconazole

2.4 Protozoal Infections

  • Treatment of Acanthamoeba Keratitis.

    Antiseptics: Propamidine isethionate, Polyhexamethylene biguanide, and Chlorhexidine.

    Administered as topic therapy.

    Oral imidazoles: Added on to the topical medications.

  • Treatment of Toxoplasmosis

    Treatment is indicated when the inflammatory reaction reaches the macula and might interfere with visual acuity. The drugs that are commonly used are combinations of a dihydrofolate reductase inhibitor with a sulphonamide (e.g., pyrimethamine + sulfadiazine).

3 Drugs Used in Glaucoma

The established strategy in treating patients with open angle glaucoma is to reduce the intraocular pressure. Recent research has shown that a proportion of patients experience optic nerve damage without ocular hypertension. Further, reducing the IOP does not completely treat the disease. This has led to the development and active search for drugs that will have potent neuroprotective action.

The drugs of choice for maintenance therapy of open angle glaucoma are the prostaglandin analogues as they have the following beneficial actions.

  • Potent IOP lowering.

  • Once a day dosing.

  • Reduced systemic side effects.

Fixed dose combinations of these eye drops improve compliance by reducing the number of eye drops the patient has to self-administer (Table 68.1).

Table 68.1 Drugs for glaucoma
Full size table

4 Anti-Inflammatory and Immunomodulatory Drugs (Table 68.2)

Table 68.2 Anti-inflammatory and immunomodulatory drugs
Full size table

5 Antihistamines and Mast Cell Stabilizers Used in Allergic Conditions

  • H 1 antagonists

    Pheniramine

  • Mast cell stabilizer

    Cromolyn sodium

  • H 1 antagonist with mast cell stabilization

    Olopatadine

    Ketotifen

  • H 1 and H 2 antagonist with mast cell stabilization

    Epinastine

6 Ocular Toxicity of Systemic Agents (Table 68.3)

Table 68.3 Ocular toxicity of systemic agents
Full size table