Ocular pharmacology notes for PHARM 261/ OEBC drug prep materials. Featuring 150 pages of organized study notes presented in easy-to-review tables with corresponding images.

OPTOM 261
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Review
- Development of drugs
o Modifying an existing agent
o Synthesizing new molecular entities
o Solubility of the molecule, physiochemical properties, stability, sterility
- Pharmacokinetics (PK): the amount of drug that is finally delivered to the site of action
o Processes
 Bioavailability – completeness of absorption, degree of non-specific binding, degree of inactivation
 Solubility
 Absorption
o Barriers
o Variations in chemical formulation
o Other
 Distribution
o Blood flow
o Regional differences in pH
o Extend of “non-specific binding”
 Biotransformation (metabolism)
 Activation
 No change
 Inactivation
 Affected by
o Amount of enzyme available
o Competition for the enzyme
o Other factors

,  Excretion
o For appropriate dosing, therapeutic margin (free dose available at the site of action)
o Drug dosing regimen
 Frequency of administration
 Amount of drug to administer
 Concentration of drug
 Duration of administration
- Pharmacodynamics (PD): the effect of the drug has on the body
o Mode of action -> effect
 Drug receptor interaction
 Signal transduction
o Factors affecting PD
 Sensitivity of tissues
 Efficacy of the drug
o Agonists (eg. Melanin): can be full or partial
 Have both AFFINITY + EFFICACY
 Potency -> EC50 or ED50
o Antagonists
 AFFINITY but NO EFFICACY
o Dose-response curve (concentration-effect)
 ED50: dose level producing a RESPONSE that is 50% of maximum (potency)
 LD50: dose that produce a TOXIC or lethal effect in 50% of individuals
 Therapeutic index = LD50/ ED50 (safety profile)
 Steeper slope = smaller therapeutic margin
- Side effects
o Receptors widely distributed in the body
o Receptor involved in diverse function on many cell types
o Reduce by
 Designing receptor subtype selective drugs
 Administering drug locally

,Pharmacology specific to ocular therapies
- Blood-ocular barriers
o Blood-aqueous barrier (ciliary body)
o Blood-retinal barriers (limits drugs to POSTERIOR segment from circulation)
o * Can be reduced by trauma, infection, admin of certain drugs…
- Drug distribution
o Aqueous drug => primary movement of fluid => filtration angle =>
mostly to TM and leave via canal of Schlemm
o Or some through posterior fibres to TM (between CB and sclera)
o Most drugs penetrate scleral tissue BUT some drugs access to CB
o More tearing => increased systemic absorption, decreased ocular
adsorption
 BAD! We want less systemic absorption
o We want to minimize
 Conjunctival vessels
 Overflow via tear
 Lacrimal passage
 Swallowing
o Corneal epithelium + melanin => most common reservoirs for non-
specific binding
 More drug required to achieve the same effect
 Bound drug is released more slowly = prolong effect
- Metabolism
o Prodrugs
o Inactivation
o Not much of a concern topically
 Ciliary body -> major ocular source of drug metabolizing enzymes
 Corneal epithelium -> many esterases
 * Some drugs aren’t biotransformed in the eye, but are removed via ocular circulation and transported to the
liver
- Advances in ocular drug delivery

, o Precorneal tear film
 Lipid, mucus, glycocalyx
o Direct route of penetration due to clarity + avascularity, 20% only to
conjunctiva/sclera to iris/CB
 * Prostanoids, sulfonamides penetrate the sclera well
o Cornea
 Cornea: FAT WATER FAT
 Bowman and Descemet membranes => not significant barriers
 Structures
 Epithelium (FAT)
o MAIN barrier (90% to hydrophilic drugs, 10% to
hydrophobic drugs)
o Tight junctions – reduced barrier once disrupted
o Storage depot – mostly lipophilic drugs
o AChE + ChE => delivery of esterified prodrugs
 Stroma (WATER)
o Mainly hydrated collagen
o Not a significant barrier
 Exception: corneal edema
 Endothelium (FAT)
o Tight junction – but not as important as epithelium
o Allow lipophilic drugs to be absorbed, so drug needs to be BIPOLAR
 Dual solubility



 Dissociated and undissociated forms
 Different solubility of two forms allows the drug to penetrate the cornea – tendency for equilibrium
o Penetration of a weak base
o Pre-corneal solution drainage (contact time)
 Single most important factor