Pharmacologic principles

Question 1

Are lipophilic or hydrophilic compounds more likely to penetrate the blood ocular/retinal barriers

Answer 1

lipophilic

Question 2

Define bioavailability

Answer 2

rate at which an active drug reaches the site of action and the extent to which it is available to the target tissue

Question 3

Define biologic agent

Answer 3

product made from living organisms or containing components of living organisms and used in the prevention, diagnosis, or treatment of disease

Question 4

Define emulsion

Answer 4

mixture of 2 immiscible components

Question 5

Define pharmacodynamics

Answer 5

study of the biochemical and physiological effects of drugs/
agents on a biological system, including the mechanisms of their actions

Question 6

Define Pharmacokinetics

Answer 6

study of the absorption, distribution, metabolism, and excretion of drugs/agents in a biological system

Question 7

Define pharmacology

Answer 7

study of drug action, the interactions of living organisms with therapeutic substances through biochemical processes

Question 8

Define pharmacotherapeutics

Answer 8

study of how to achieve the desired effects, or prevent/ minimize the adverse effects or toxicity, of a drug or agent

Question 9

Define suspension

Answer 9

mixture of a substance with poor solubility and a dispersion medium in which the substance is evenly distributed

Question 10

Do topically applied medication increase or decrease systemic bioavailability

Answer 10

avoids the first-pass metabolism of the liver and increases systemic bioavailability

Question 11

Examples of preservatives used in topical treatment

Answer 11

benzalkonium chloride and benzododecinium bromide; mercurial agents such as thimerosal, chlorobutanol, and parahydroxybenzoates; and aromatic alcohols

Question 12

How are topical drops absorbed into the eye

Answer 12

The drug gradient, from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, forces a passive route of absorption

Question 13

How much of a topically administered medication is retained

Answer 13

20% at most due to rapid turnover of fluid in tear lake. For slowly absorbed drugs at most only 50% absorbed

Question 14

What is the residence time of a medication

Answer 14

The amount of time that a drug remains in the tear reservoir and tear film. This time is affected not only by drug formulation but also by the timing of subsequent medication, tear production, and drainage

Question 15

Examples of suspension medication

Answer 15

Prednisolone acetate and brinzolamide

Question 16

Examples of emulsion medications

Answer 16

emulsions have the advantages of increased contact time (because of the adsorption of nanodroplets on the corneal surface) and greater bioavailability. Difluprednate and cyclosporine are examples of a topical emulsion.

Question 17

What is the effect of high viscosity medication

Answer 17

addition of high-viscosity substances such as methylcellulose and polyvinyl alcohol (PVA) to a drug increases drug retention in the inferior cul-de-sac, aiding drug penetration. An example is timolol maleate

Question 18

What is the optimal viscosity for drug delivery

Answer 18

the optimal viscosity is 12–15 cP

Question 19

What is important in corneal permeability

Answer 19

Lipid solubility is more important than water solubility

Question 20

How to increase partition coefficients and drug penetration

Answer 20

by raising the pH of the water phase, thereby increasing the proportion of drug molecules in the more lipid-soluble, uncharged form

Question 21

Effect of surfactants on ocular medication delivery

Answer 21

preservatives used in topical drops to prevent bacterial contamination are surfactants (also called surface-active agents) that alter cell membranes in the cornea as well as in bacteria, reducing the barrier effect of the corneal epithelium and increasing drug penetration

Question 22

When does reflex tearing occur

Answer 22

Ocular irritation and secondary tearing wash out the drug reservoir in the tear lake and reduce the contact time of the drug with the cornea. Reflex tearing occurs when topical medications are not isotonic and when they have a nonphysiologic pH or contain irritants

Question 23

How can binding of medications lead to toxicity

Answer 23

Tear and ocular surface proteins, as well as ocular melanin, may bind topical or systemic medication, making the drug unavailable or creating a slow-release reservoir. An example of this effect is the retinal toxicity that progresses even after discontinuation of the aminoquinoline antimalarial drugs chloroquine and hydroxychloroquine.

Question 24

Condition which can occur if preservative containing antibiotics are used intraocularly

Answer 24

Toxic anterior segment syndrome (TASS)

Question 25

Does chloramphenicol or penicillin have greater lipid solubility

Answer 25

rugs with higher lipid solubility more readily penetrate the blood–ocular barrier. Thus, chloramphenicol, which is highly lipid-soluble, penetrates 20 times better than does penicillin, which has poor lipid solubility

Question 26

What is the relationship between plasma protein bound medications and blood-ocular barrier permeability

Answer 26

Only the unbound form can cross the blood–ocular barrier. Sulfonamides are lipid-soluble but penetrate poorly because, at therapeutic levels, more than 90% of the medication is bound to plasma proteins. Similarly, compared with methicillin, oxacillin has reduced penetration because of its increased binding of plasma proteins

Question 27

Why is the intraocular penetration of an intravenous medication better in the inflamed eye

Answer 27

because of the disruption of the blood–aqueous and blood–retina barriers that occurs with inflammation

Question 28

What are ophthalmic prodrugs

Answer 28

They are therapeutically inactive derivatives of drug molecules that are designed to be activated by enzymatic systems within the eye in order to improve ocular penetration. Prostaglandin analogues are successful examples of this drug delivery strategy. Latanoprost, travoprost, and tafluprost are prostaglandin analogues that interact with the prostaglandin FP receptor. They require hydrolyzation prior to becoming active compounds in the eye.

Question 29

How do soluble drug inserts work

Answer 29

Soluble inserts release the drug via interaction between the polymeric matrix of the device and the tear film. Removal of these inserts is unnecessary

Question 30

How do insoluble drug inserts work

Answer 30

Insoluble inserts may achieve a more constant rate of drug release than soluble inserts, but removal of the device is required

Question 31

Examples of intravitreal implants

Answer 31

The first-available sustained-release implant was the ganciclovir intravitreal implant for treatment of cytomegalovirus (CMV) retinitis. After surgical implantation, the device delivered a steady source of ganciclovir for 5–8 months. Current intraocular sustained-release products include 2 fluocinolone acetonide intravitreal implants (0.59 mg and 0.19 mg) and a dexamethasone intravitreal implant.

Question 32

Use of 0.59mg 2 fluocinolone implant

Answer 32

a nonbiodegradable intraocular polymer implant requiring surgical placement in the pars plana region for the treatment of chronic noninfectious posterior uveitis over approximately 30 months

Question 33

Use of 0.19mg fluocinolone implant

Answer 33

treatment of diabetic macular edema in patients who are not steroid responders over 36 months

Question 34

Use of 0.7-mg dexamethasone implant

Answer 34

The poly- mer degrades to lactic acid and glycolic acid, and dexamethasone is slowly released within the vitreous cavity. The implant is indicated for the treatment of macular edema secondary to retinal vein occlusion, noninfectious posterior uveitis, and diabetic macular edema

Question 35

What is an agonist

Answer 35

If the drug–receptor interaction stimulates the receptor’s natural function, the drug is termed an agonist

Question 36

What is an antagonist

Answer 36

Stimulation of an opposing effect characterizes an antagonist. Corresponding effectors of enzymes are termed activators and inhibitors