Ocular Tissue Structure & Pharmacokinetics

pharmacodynamics

studies of what the drug does to the body

pharmacokinetics

studies of what the body does to the drug (absorption, modification, detoxification, excretion)

therapeutics

application of drugs to produce the desired effect

bioavailability

the degree & rate at which a substance is absorbed into a living system or is made available at the site of physiological activity

prodrug

pharmacologically inactive medication or compound that, after intake, is metabolized into a pharmacologically active drug; used to increase drug penetration through barriers

chemical name

description of the chemical structure of the compound

generic name

approved or official name

proprietary/trade name

usually trademarks & given to products to distinguish them from their competitors

evaporation, drainage into nasolacrimal system, systemic circulation absorption, penetration of the cornea

what 4 routes does a topical ophthalmic drug take once instilled?

25%

______ of a topical drug is lost from evaporation after instillation

no

does a larger drop size = a larger drug penetration in the cornea?

increased

an increased drop size = an ________ systemic load

inversely

drug absorption is _______ (inversely/directly) proportional to the tear flow rate & volume

nasolacrimal occlusion, tilting head back to decrease drainage

what are 2 ways to increase corneal drug absorption?

superficial

tight junctions of the cornea are localized to _____ (superficial/deep) layers

corneal epithelium

what corneal structure acts as the major functional barrier to ocular hydrophilic drug penetration?

long

lipophilic agents have a ______ (long/short) half-life in the corneal epithelium

lipophilic

________ (lipophilic/hydrophilic) drugs easily enter the corneal epithelium

corneal stroma

what structure is the major depot for topical hydrophilic drugs?

keratocytes

what structure is considered a depot for topical lipophilic drugs?

stroma

Bowman’s layer has similar drug penetration to what other structure?

stroma

Descemet’s membrane has similar drug penetration to what other structure?

no

is the corneal endothelium a good storage site for drugs?

epithelium, endothelium

which corneal structures are hydrophobic/lipophilic?

stroma

which corneal structures are hydrophilic/lipophobic?

increases

permeability increases with __________ (increases/decreases) in lipid solubility

iris

ocular structure with pigment granules that can absorb lipophilic drugs, reversible non-specific binding, acts as a reservoir for some drugs

ciliary body

ocular structure that is the major ocular source of drug-metabolizing enzymes for drug detoxification & elimination from the eye

lens

ocular structure that is the barrier to rapid penetration of drugs from the aqueous to vitreous

anterior lens epithelium

which portion of the lens is the most metabolically active & most prone to damage from drugs & toxins?

no

can high molecular weight, hydrophilic drugs be absorbed by the lens?

cataract extraction & IOL implant

what procedure allows for more rapid exchange between the aqueous & vitreous?

vitreous

ocular structure that acts as a major reservoir for ocular drugs, temporary storage for metabolites, & occupies 80% of the ocular mass

vitreous

where can drugs be administered to bypass the blood-retinal barrier?

lipophilic

________ (lipophilic/hydrophilic) drugs cross the blood-retinal barrier in both directions

retinal vessels

remove drugs & metabolites from the vitreous & retina by active transport

uveal vessels

remove drugs by bulk transport from iris & ciliary body

compartment

region of tissue or fluid through which a drug can diffuse & equilibrate easily

compartment theory

barrier between compartments results in flow b/t adjacent compartments requiring more time than diffusion within each compartment

integral tear film concentration during first 10-20 min after instillation

corneal absorption depends on what?

first-order kinetics

most common in ocular drug movement; rate of drug movement directly proportional to concentration across the barrier

zero-order kinetics

release of drug constant over time; concentration of drug released over time is independent of concentration

hypotonic (<290mOsm)

ophthalmic medications are typically ______ (hypotonic/hypertonic/isotonic)

290mOsm, 0.9% saline

desired osmolarity for ophthalmic meds

surfactants

increase solubility of hydrophilic drugs by altering permeability of the epithelium

high

______ (high/low) viscosity solutions increase drug contact time on the cornea

weak bases

many ocular drugs have what pH?