OCULAR PHARMACOLOGY I

Pharmacologic Principles• Pharmacokinetics deals with the cycle of a drug

through the body, including the absorption, distribution, metabolism, and excretion of that drug.

• To achieve a therapeutic effect, a drug must reach its site of action in sufficient concentration.

• Pharmacokinetics and dose together determine• bioavailability or concentration of the active drug at

the therapeutic site

• Pharmacodynamics refers to the biological activity and clinical effect of drugs

• Included within the area of pharmacodynamics are the tissue receptor for the drug and the intracellular changes initiated by the binding of the active drug with the receptor.

• Pharmacotherapeutics is the application of a drug in order to reach a given clinical endpoint,

• such as the prevention or treatment of disease

• The therapeutic dose may vary for any• patient, based on the patient's age, gender,

race, other currently prescribed medications,• and preexisting medical conditions

• Toxicity refers to the adverse effects of either medication or environmental chemicals

• influenced by pharmacokinetics and/or pharmacodynamics

Pharmacokinetics

• Amount administered• Drug concentration and solubility• Viscosity• Lipid solubility• pH and ionic charge• Surfactants• Reflex tearing• Tissue binding of medication

• Topical Administration – Eyedrops• maximizes the anterior segment concentrations while

minimizing systemic toxicity.• Very little of an administered drop is retained by the eye• The amount of time that a drug remains in the tear

reservoir and tear film is• called the "residence time" of a medication. It is affected

not only by drug formulation but• also by the timing of subsequent medication, tear

production, and drainage

• simple measures to improve ocular absorption of materials

• Patients using more than one topical ocular medication should be instructed to allow 5 minutes between drops

• Blinking also diminishes a drug's effect by activating the nasal lacrimal pump mechanism

• compressing the nasolacrimal duct with digital pressure at the medial canthus or closing the eyelids for 5 minutes after instillation of each drop.

• a drug with poor solubility may need to be provided in a suspension.• A suspension requires agitation so that the active medication is

redistributed prior• to administrat ion. Suspensions may be more irritating to the

ocular surface than solutions

• Ointments• Another strategy for increasing the contact time of ocular

medications is the use of ointments.• Commercial oil-based ointments usually consist" of petrolatum and

mineral oil.• The mineral oil allows the ointment to melt at body temperature

Local AdministrationPeriocular injections• Injection of medication beneath the conjunctiva or

the Tenon capsule• allows drugs to bypass the conjunctival and corneal

epithelial barriers and absorb passively down a concentrat ion gradient into the sclera and intraocular tissues

• allow medications to reach therapeutic levels behind the lens-iris diaphragm-especially useful for drugs with low lipid solubility

• helpful in delivering medication closer to the local site of action

Periocular injections

In anterior segment inflammation or infection

Intraocular medications• instantly delivers effective concentrations at the

target site. 2 types of intraocular injections:• intracameral injections into the anterior chamber • intravitreal injections into the vitreous cavity• Intraocular implants allow the slow release of

medication over months to years

Systemic Administration• Drugs with higher lipid solubilities more readily

penetrate the blood- ocular barrierThe ability of systemically administered drugs to gain access to the eye is also influenced • by the degree to which they are bound to plasma

proteins. Only the unbound form can cross the blood-ocular barrier.

• bolus administration of a drug exceeds the binding capacity of plasma proteins and leads to higher intraocular drug levels than can be achieved by a slow intravenous drip

Sustained-release oral preparations

• offer a more steady blood level of the drug,

• avoid marked peaks and valleys, and

• reduce the frequency of administration.

Intravenous injections

• diagnostic or therapeutic• sodium fluorescein and indocyanine green, are

used for retinal angiography to diagnose retinal and choroidal disease.

• Edrophonium chloride is used intravenously in the diagnosis of myasthenia gravis.

• intravenous administration of an antibiotic is an effective way of maintaining intraocular levels in endogenous infections

Methods of Ocular Drug Design and Delivery

Prodrugs• inert compounds that are activated by one of the

enzymatic systems within the eyeSustained-release devices and gels:• Delivery devices Devices have been developed that deliver

an adequate supply of medication at a steady-state level, thus achieving beneficial effects with fewer adverse effects.

• The gel form - thickens on contact with the tear film, maintaining therapeutic levels while decreasing the dosing to once daily.

Collagen cornea shields – • Porcine scleral tissue is extracted and molded into

contact lens-like shields that are useful as a delivery system to prolong the contact between a drug and the cornea.

• Drugs can be incorporated into the collagen matrix during the manufacturing process, or absorbed into the shield during rehydration, or applied topically while the shield is in the eye.

• the drug is released gradually into the tear film, and high concentrations are maintained on the corneal surface and in the conjunctival cul-de-sac.

• Liposomes are synthetic lipid microspheres that serve as multipurpose vehicles for the topical delivery of drugs, genetic material, and cosmetics

Antibiotics

Penicillins – bactericidal, gram positive cocci, poor ocular penetration on systemic administration, freshly prepared topical penicillin in ophthalmia neonatorum

Cephalosporins – intravitreal cephazolin & ceftriaxone

Aminoglycosides – intravitreal amicacin, topical tobrmycin, gentamycin

Tetracyclines – broad spectrum, doxycycline good occular penetration

Macrolides – trachoma, toxoplasmosis, lyme disease

Vancomycin – bactericidal, gram positive, intravitreal

Fluroquinolones – topical drops

Chloramphenicol – lid infections

Antibiotics• Principal Antibiotic Agents

Combination Ocular Anti-Inflammatory and Antibiotic Agents

AntifungalPolyene antibiotics – Amphotericin B: Fungal corneal ulcer Fungal endophthalmitis (intravitreal)Nystatin – Candida albicansNatamycin (5%)– filamentous fungi, Candida albicans

Imidazoles – also acanthamoeba, miconazole, ketoconazole

Triazoles – fluconazole, itraconazole

Antifungal Agents

Antiviral

Treat herpes infections

Pyrimidine derivatives – IDU topical

Purine derivatives – Acyclovir: 3% oint, Oral (400mg), EB virus, CMV.Gancyclovir: intravitreal implants

Foscarnet – herpes, CMV

Zidovudine - CMV

Antiviral Agents

• What are the different modes of ophthalmic drug delivery?

• What are the advantages of eye drops/ eye ointments?

• What are the indications and advantages of periocular injections?

• Enumerate the commonly used anti-biotics/anti fungals/anti virals in ophthalmology?

• How will you avoid systemic absorption of topically applied medications?

• What advice would you give to a patient regarding administration of any eye drops?