Pharmacologic principles Flashcards
Are lipophilic or hydrophilic compounds more likely to penetrate the blood ocular/retinal barriers
lipophilic
Define bioavailability
rate at which an active drug reaches the site of action and the extent to which it is available to the target tissue
Define biologic agent
product made from living organisms or containing components of living organisms and used in the prevention, diagnosis, or treatment of disease
Define emulsion
mixture of 2 immiscible components
Define pharmacodynamics
study of the biochemical and physiological effects of drugs/
agents on a biological system, including the mechanisms of their actions
Define Pharmacokinetics
study of the absorption, distribution, metabolism, and excretion of drugs/agents in a biological system
Define pharmacology
study of drug action, the interactions of living organisms with therapeutic substances through biochemical processes
Define pharmacotherapeutics
study of how to achieve the desired effects, or prevent/ minimize the adverse effects or toxicity, of a drug or agent
Define suspension
mixture of a substance with poor solubility and a dispersion medium in which the substance is evenly distributed
Do topically applied medication increase or decrease systemic bioavailability
avoids the first-pass metabolism of the liver and increases systemic bioavailability
Examples of preservatives used in topical treatment
benzalkonium chloride and benzododecinium bromide; mercurial agents such as thimerosal, chlorobutanol, and parahydroxybenzoates; and aromatic alcohols
How are topical drops absorbed into the eye
The drug gradient, from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, forces a passive route of absorption
How much of a topically administered medication is retained
20% at most due to rapid turnover of fluid in tear lake. For slowly absorbed drugs at most only 50% absorbed
What is the residence time of a medication
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
Examples of suspension medication
Prednisolone acetate and brinzolamide
Examples of emulsion medications
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.
What is the effect of high viscosity medication
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
What is the optimal viscosity for drug delivery
the optimal viscosity is 12–15 cP
What is important in corneal permeability
Lipid solubility is more important than water solubility
How to increase partition coefficients and drug penetration
by raising the pH of the water phase, thereby increasing the proportion of drug molecules in the more lipid-soluble, uncharged form
Effect of surfactants on ocular medication delivery
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
When does reflex tearing occur
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
How can binding of medications lead to toxicity
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.
Condition which can occur if preservative containing antibiotics are used intraocularly
Toxic anterior segment syndrome (TASS)
Does chloramphenicol or penicillin have greater lipid solubility
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
What is the relationship between plasma protein bound medications and blood-ocular barrier permeability
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
Why is the intraocular penetration of an intravenous medication better in the inflamed eye
because of the disruption of the blood–aqueous and blood–retina barriers that occurs with inflammation
What are ophthalmic prodrugs
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.
How do soluble drug inserts work
Soluble inserts release the drug via interaction between the polymeric matrix of the device and the tear film. Removal of these inserts is unnecessary
How do insoluble drug inserts work
Insoluble inserts may achieve a more constant rate of drug release than soluble inserts, but removal of the device is required
Examples of intravitreal implants
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.
Use of 0.59mg 2 fluocinolone implant
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
Use of 0.19mg fluocinolone implant
treatment of diabetic macular edema in patients who are not steroid responders over 36 months
Use of 0.7-mg dexamethasone implant
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
What is an agonist
If the drug–receptor interaction stimulates the receptor’s natural function, the drug is termed an agonist
What is an antagonist
Stimulation of an opposing effect characterizes an antagonist. Corresponding effectors of enzymes are termed activators and inhibitors
