Decisions for the provider/prescriber:
- choice of drug
- route of drug administration
- when to refer patient, if at all
T/F, the Review of Systems (ROS) is essential to the Medical History?
patients who have cardiovascular disease may have problems with what drugs?
- phenylephrine (raises blood pressure) and
- beta blockers (slows heart rate)
Patients with respiratory dz may have complications with what drugs?
1) ASA and NSAIDs (can decrease inflammation and block production of prostaglandins)
2) beta blockers (using a non-selective beta blocker can exacerbate asthma or COPD)
3) opiate narcotic analgestics (can depress the respiratory rate, causing cardiac arrest)
Patients with hyperthyroidism may have complications with which drugs?
phenylephrine--can causes vasoconstriction and cause arrythmia and raise bp!
Patients with diabetes may have complications with which drugs?
1) hyperosmotic agents
(i.e. mannitol can increase blood glucose level)
2) systemic corticosteroids
--can increase blood glucose levels
3) mydriatic agents
--can increase BGL
4) beta blockers
--blocks beta cells which release insulin to absorb glucose
Patient with a CNS disorder may have complications with which drugs?
--can cause anxiety, confusion, disorientation, nervousness, insomnia, memory changes
Patients with affective mental disorders may have complications with which drugs?
phenylephrine--may cause dizziness, drowsiness, HA, nervousness, excitability and irritability
True or false: systemic drugs are discouraged during pregnancy unless absolutely necessary
Which portions of the eye exam are best performed prior to drug use?
VA, pupils, refraction, binocular tests, tonometry, SLE/biomicroscopy, amplitudes, assessment of cardiovascular status
What are different types of ocular side effects from topical ophthalmic drugs?
Other (IOP or conjunctival change etc)
What are the common causes of an infection from a topical ophthalmic medication?
Contamination of the dropper tip. Educate proper disposal
What are common side effects of drug toxicity from topical ophthalmic drugs?
punctate keratitis, itching, burning, stinging caused by preservatives
What OSE can ophthalmic topical steroids cause?
increased IOP, cataracts
What OSE can topical anti-glaucoma meds cause?
What OSE does prolonged use of anesthetic drops cause?
corneal abrasions, infiltrate keratitis
What OSE can ointment cause?
Describe the route that drugs go through when they get absorbed through the conjunctival sac.
drug-->conjunctival sac-->conjunctival capillaries-->systemic circulation
Describe the route that drugs go through when they gets absorbed through the lacrimal drainage
1) drug-->lacrimal drainage-->nasal mucosa/capillaries-->systemic circulation
2) drug-->lacrimal drainage-->pharynx-->GI tract-->systemic circulation
What are the side effects of beta blockers when used for glaucoma.
decrease in heart rate
emotional and psychiatric changes
What are the side effects of using echothiophate when used for open angle glaucoma?
can cause apnea if given with succinylcholine
What are the side effects of pilocarpine for glaucoma?
bradycardia and tremors
What are the side effects of cyclopentolate?
a cycloplegic agent--excessive use can cause hallucinations
What are the side effects of brimonidine?
used for open angle glaucoma
can lead to dry mouth, fatigue, and lethargy
What are ways to reduce systemic drug absorption?
- Store out of reach of children
- Wipe excess solution or ointment
- Use lowest concentration/minimal dose
- confirm doses before prescribing infrequently prescribed drugs
- weigh benefits to adverse effects
- consider use of manual occlusion (nasolacrimal) if necessary
- recognize ADE when they occur, lacrimal occlusion, consult with PCP
What are the two groups who require special consideration by optometrists - when prescribing topical or oral meds?
- women who are pregnant or breastfeeding
T/F: Nearly all the therapeutic drugs administered to or taken by a pregnant woman can cross the placenta
T/F: Topically applied drugs can affect the fetus
What are the factors that contribute to the concentration of the drug in the fetus?
- concentration of drug in mom
- age of fetus
- degree of placental development
- drug size
- lipid solubility
- protein binding characteristics
- drug ionization (pH)
- dose-related effects
- drug's pharmacokinetic properties
- potential maternal or fetal disease states
- specific stage of pregnancy
- timing of exposure
- degree of exposure over time
What are teratogenic effects (effects on fetus) resulting in fetal malformations, related to?
Dose and time
When is the period of greatest risk for malformation to occur in the fetus?
First 3 months of gestation--but can also occur throughout the entire gestational period
The Pregnancy risk factor should only be considered as a....
starting point in prescribing!
T/F, Studies conducted in humans cannot fully address all possible areas or types of human risk, including genetic differences in populations.
Does the FDA pregnancy risk factor address the safety of using the drug while breastfeeding?
When prescribing drugs to breast feeding moms, what does the prescriber need to consider?
1) gestational stage
2) more detailed information about risk
3) individual factors such as other medical conditions that the mother may have
What is the best use of the FDA pregnancy risk factor?
The optometrist should contact the physician and discuss the rating and the advisability of proceeding with the proposed therapy, given the patients stage of pregnancy and health
Pregnancy Risk Factor Category A
No evidence of risk in any trimester, possibility of fetal harm appears remote
Pregnancy Risk Factor Category B
No studies in animal studies or human women have shown and/or confirmed adverse effect
Pregnancy Risk Factor Category C
Should only be given if the benefit justifies the potential risk to the fetus
Pregnancy Risk Factor Category D
Positive evidence of human fetal risk, but benefits to pregnant women may be acceptable despite the risk (life-threatening situation)
Pregnancy Risk Factor Category X
Contraindicated in women who are or may become pregnant. Risk outweighs benefit.
Why is it difficult to draw conclusions about the safety of drugs absorption in breast milk, even though tests have been done in animals?
Human breast milk has a different composition than animals, so we cannot make an absolute conclusion of its safeness.
Drug concentration in breast milk can be affected by which drug characteristics?
1) lipid solubility
2) protein binding and
3) degree of ionization
What are the two things that an OD must be advise to do when prescribing drugs to breastfeeding moms?
1) analyze the risk to benefit assessment
2) seek advice from PCP who is caring for patient
Why is it important in doing a culture and sensitivity test on breast feeding patients?
Can confirm the prescribing therapy, and may help look for other anti-infective meds that could have better risk factors
What can the optometrist recommend to minimize systemic absorption when administering topical ophthalmic medications to pregnant women?
Nasolacrimal Occlusion (punctual plugs)
Nasolacrimal compression for 3-5 min after instillation of drops
Diagnostic drugs (pregnancy category)
C (fluorescein, indocyanine green, phenylephrine)
Analgesic drugs (pregnancy category)
C (proparacaine and tetracaine)
Tetracaine and Lidocaine compatible with breastfeeding
Cycloplegic (pregnancy category)
C (atropine, homatropine, cyclopentolate, tropicamide)
Atropine and Homatropine compatible with breastfeeding
Ocular decongestants (pregnancy category)
C (Naphazoline, Oxymethazoline, phenylephrine, Tetrahydrozoline)
Ocular Anti-histamines and Mast cell stabilizers (pregnancy category)
B (Cromolyn, Lodoxamide, emedastine, nedocromil)
C (Azelastine, Pemirolast, olopatadine, ketotifen, epinastine)
Corticosteroids (pregnancy category)
C (Dexamethazone, difluprednate, flurometholone, loteprednol, rimexolone)
Bromenfac (pregnancy category)
Flurbiprofen (pregnancy category)
Diclofenac (pregnancy category)
Nepafenac (pregnancy category)
Ketorolac (pregnancy category)
compatible with breastfeeding
Cyclosporine (pregnancy category)
Dipivefrin (pregnancy category)
Brimonidine (pregnancy category)
Diprivefrin (pregnancy category)
Echothiophate (pregnancy category)
Pilocarpine (pregnancy category)
Beta blockers (pregnancy category)
Timolol compatible with breastfeeding
Calcium channel inhibitors (pregnancy category)
C (acetazolamide, brinzolamide, dorzolamide, methazolamide)
Acetazolamide compatible with breastfeeding
Prostaglandins (pregnancy category)
C (latanoprost, bimatoprost, travoprost)
Anti-infectives (pregnancy category)
B (acyclovir, valacyclovir, famciclovir)
Aspirin (pregnancy category)
Ibuprofen (pregnancy category)
compatible with breastfeeding
Acetaminophen (pregnancy category)
compatible with breastfeeding
Naproxen (pregnancy category)
compatible with breastfeeding
Codeine (pregnancy category)
compatible with breastfeeding
Hydrocodone (pregnancy category)
C or D
-cyclovir drugs (pregnancy category)
acyclovir and valacylovir compatible for breastfeeding
Trifluridine (pregnancy category)
Natamycin (pregnancy category)
Penicillins (pregnancy category)
compatible with breastfeeding
Clindamycin (pregnancy category)
compatible with breastfeeding
Bacitracin (pregnancy category)
Sulfonamides (pregnancy category)
Cephalosporins (pregnancy category)
B (cefadroxil, cefprozil, cefuroxime, cephalexin)
compatible with breastfeeding
Fluroquinolones (pregnancy category)
Ciprofloxacin and Ofloxacin compatible with breastfeeding
Azithromycin (pregnancy category)
Clarithromycin (pregnancy category)
Erythromycin (pregnancy category)
B (Excluding erythromycin estolate)
compatible with breastfeeding
Aminoglycosides (pregnancy category)
C (gentamicin, tobramycin, neomycin)
Gentamicin compatible with breastfeeding
Tetracyclines (pregnancy category)
(classified as compatible with breastfeeding??)
What form of Erythromycin should NOT be prescribed to pregnant patients?
(also not compatible with breastfeeding)
True or false: Young Clark's rule can be used for pediatric dose calculations
FALSE, because the calculations are based on age and assumptions about weight vs. adult doses
What is the most accurate method to access the dosage for children?
- the body surface area --->height and weight
- Pharmokogenetics--based on serum concentration in the child
- Area under the curve
- (body surface area nomogram)
What are the options when determining dosage to children?
1) look at manufacturer dose recommendations on package insert
2) call physician
3) call pharmacists
4) call drug center
5) use ointments vs. drops
Why are geriatric patient more at risk for more ADE?
1) they have more systemic diseases
2) are on a lot of drugs - multiple drug therapy (more important)
On average, what is the number of drugs an 85 y.o. is taking?
What are the things you should be concerned about when prescribing to the elderly?
1) have diminished lid turgor (dry eyes risk)
2) lid laxity/ectropion (increase retention time of drugs, can have preservative build up in conj sac, exacerbate drug effect and cause toxicity)
3) cognitive difficulties
4) hearing impairment
5) socioeconomic factors
6) arthritis and tremors (diminished dexterity)
7) age related dose adjustment
8) Polypharmacy - patient taking numerous drugs
What are the types of teaching devices to help with compliance in the elderly population?
1) dosage charts and calendars
2) teaching care givers
3) color coding and markers
4) medication regimen cards
What should be the minimum font size for patients with no visual impairment?
What kind of font do you use with visually impaired patients?
San Serif (22 or 24) font
What are the things you need to do with patients who are visually impaired?
1) large font
2) demonstrate techniques, guided practice
3) make sure they understand your recommendations
4) use aids (magnifier, small light source)
What are the things you need to do with patients who are hearing impaired?
- Provide printed information
- Demonstrate techniques and give guided practice
- Have sign language charts with medical information and terminology in the office
What are the things you need to do with patients who are cognitively impaired?
- Provide instructions to caregiver and make sure that they understand.
- Demonstrate techniques, guided practice
- Extra time may be needed on these patients during exams.
Distinct factors and processes whereby drugs are absorbed and distributed in the body, biotransformed, metabolized, and excreted from the body
What does drug absorption depend on?
1) molecular property of the drug
(small, hypo/lypophillic drugs)
2) viscosity of drug vehicle
(drugs that are suspended in gel sits in gel longer and lasts longer)
3) functional status of the tissue that forms a barrier to penetration
(aqueous and lens)
- aphakic patients will absorb drugs faster because they have no lens (barrier)
What can help predict the drug distribution over time and bioavailability of the drug at the desired target?
Interrelationships of the compartments and barriers of the eye
Lipid molecules that are composed of ____molecular weight and ionized/nonionized pass through plasma membranes better.
smaller, not ionized
How does the body prevent accumulation of drugs to the point of toxicity?
Drugs are inactivated, metabolized, and excreted.
T/F some drugs can be excreted in unchanged form.
T/F some drug metabolites may be MORE or LESS active than the parent drug.
Tissue types of the eye?
- Smooth musculature
- Striated musculature
- Different simple and mucoid epithelia
- Connective tissues
- Sympathetic nerves
- Parasympathetic nerves
How is it that the eye allows drug to be passed through without high absorption into the systemic system?
The front surface of the eye is avascular --which enables direct route for drug penetration without a high degree of drug absorption into the systemic circulation
Describe the outermost tear layer and its function.
- Oily lipid monolayer, produced by meibomian glands
- Stabilizes the surface of the aqueous layer and retards evaporation.
- Saline can flush away the lipid layer and increase evaporation
Describe the center tear layer
Aqueous phase, 95% of total volume, approx. 7 microliters thick. thins at each blink.
What is the average healthy TBUT?
Describe the inner (basal) layer.
Composed of glycoprotein and mucin (secreted by goblet cells), a thin hydrophilic coating that covers the cornea and conj
What kinds of proteins do tears contain?
lysozymes, lactoferrins, gamma gobulins and other immune factors
What supplies the oxygen requirements of the corneal epithelium?
what is the tear pH?
What is the normal tear volume?
what is the normal tear flow?
.5-22mcl per minute
What is the major site of absorption for ophthalmic topical meds?
The corneal epithelium is ____ cell-layers thick and has ___ layers.
5-10 cell layers thick
How do lipid soluble drugs get through the epithelium?
through the tight junctions (zona occludens). Zona occludens also repels hydrophilic drugs such as sodium fluorescein.
Ionization (increases/decreases) lipid solubility and (increases/decreases) water solubility.
What does the rate of release of drug from the epithelium depend on?
- the drug's tendency to re-enter the aqueous phase.
- A drug that is highly lipophilic has a longer half life and stays in the epithelium longer.
- drugs need to be hydrophilic and lipophilic to effectively penetrate the cornea
What is the major functional barrier to ocular penetration?
What is the most significant storage depot for drugs that partition into lipid media?
How are drugs stored in the corneal stroma? (stroma = 90% of corneal thickness)
- Collagen slows diffusion and stores hydrophilic drugs.
- Keratocytes store lipophilic drugs.
Why isn't the corneal ENDOTHELIUM a major reservoir for storing drugs?
- The endothelium is thin and has small overall volume
- No tight junctions
- Has fluid pump
When fluorescein that is given PO or IV, where does it accumulate in the eye?
It accumulates in the stroma from the aqueous
What is the function of the iris?
adjust the amount of light and DOF
What kind of innervation does the sphincter have?
What kind of innervation does the dilator have?
What in the iris can act as a reservoir for drugs?
- Pigment granules can store lipophilic drugs--- but is reversible so can also release drugs over time.
- Concentrations may need to be different for darker pigmented irises than for blue irises
Where do drugs enter and exit from the aqueous humor?
Enter from the bloodstream or cornea
Exit via the blood or schlemm's canal
Which part of the ciliary body can store drugs?
the pigmented ciliary epithelium
How do systemic drugs enter the anterior and posterior chambers?
By passing through ciliary body vasculature and diffusing into the iris
T/F, the ciliary body contains the major ocular source of drug metabolizing enzymes that start drug breakdown and removal from the eye
How are conjugated drugs and metabolites removed from the ciliary body?
Through the uveal circulation blood flow
How are drugs absorbed in the lens
1) liphophillic drugs are absorbed slowly through the lens
2) hydrophilic drugs absorb minimally through the lens (especially those with high MW)
What drug types can increase cataract formation?
Miotics, steroids, phenothiazines
What happens if the lens is removed?
The kinetic relationship between the aqueous and the vitreous changes, because a physiologic barrier is removed and rapid drug exchange can take place.
What is the blood-retinal barrier?
Tight junctions in the RPE that prevent hydrophilic drugs from being absorbed
How does glucose get transported into the retina?
It is actively transported from the blood to the retina ==>too much glucose can damage cells
(lipophilic drugs can easily cross the blood-retinal barrier in either direction)
What are the drugs that can cause retinal toxicity?
Phenothiaziine, Digoxin, Quinine, Fluroquinolones, Sildenafil
Which drugs can cross through the retina and achieve concentrations in the vitreous/posterior segment?
Fluoroquinolones, Linezolid, Fluconazole, Voriconazole
What are the drugs that have toxic effects on the optic nerve tissue, resulting in optic neuritis?
Ethambutol, Isoniazid and Streptomycin, Digoxin and Sulfonamides
Parenteral doses are only effective with what type of drug?
A drug with low toxicity that can enter the eye at therapeutic concentrations
Ex: endophthalmitis - an internal ocular infection that must
If a drug has high toxicity as a systemic medication, what are the other options?
it can be used as a topical drug on the eye or injected into the eye--> where it will be diluted by the blood stream to non-toxic levels
The blood stream is responsible for removing drugs and drug metabolites from the eye, what are the two circulatory pathways?
1) retinal blood vessels--remove from the vitreous and retina by active transport
a. cephalosporins and penicillins have short T1/2s in the vitreous because of this
2) uveal blood vessels--remove by bulk transport via iris and ciliary body
What parts of the eye are considered barriers and what are considered compartments?
Barriers: epithelium, lens
Compartments: aqueous and vitreous, tear layer and cornea
What is a compartment?
A region of tissue or fluid through which a drug can diffuse and equilibriate with relative ease.
Which tissues are compartments or barriers is influenced by the molecular properties of the drugs
What is a barrier?
A region of lower permeability or restricted diffusion that exists between compartments
What is Fick's law?
The rate of diffusion across a barrier is proportional to the concentration gradient btween the two compartments. When concentrations are equal, no additional drug penetrates
T/F, Drug absorption from the tears to cornea is similar to from the cornea to the aqueous humor, except that the aqueous humor gets the majority (a major proportion) of the drug from the corneal depot.
TRUE, occurs in a parallel fashion
T/F, Lipophilic drugs that are also water soluble will penetrate corneal epithelium easier than more hydrophilic drugs.
What affects corneal absorption?
- Tear film concentration in the first 10-20 min of instillation
- Other drugs
- Neuronal control
Describe zero order kinetics.
When release of drug is constant over time and is independent of concentration present
Describe first order kinetics.
- The rate of the drug molecule movement is directly proportional to the concentration difference across the barrier
- Most common situation in ocular drug movement
- Rate of movement changes with time as the concentration differential changes
What is an example of a first order kinetic?
Passive diffusion over a non-saturated barrier
Precursors of the active drug
Metabolites can be active drug compounds derived from a prodrug.
Latanoprost and travoprost are examples of what? and what is the mechanism?
- They are examples of prodrugs
- Their ester linked molecule gets cleaved off when it penetrates the cornea and then becomes active in the aqueous
How are active metabolites formed?
It is formed through the hepatic metabolic process as well as ocular enzymatic process
What is an example of an active metabolite?
Loteprednol (corticosteroid) this is an active metabolite of prednisone that is transformed by the eye into an inactive form that will have fewer side effects in the eye
What is bioavailability?
The amount of drug that is available at the receptor site
What is ED50?
The dose level that is needed to produce 50% of the maximum therapeutic effect
Describe the process of drug effectively binding to receptors.
- The amount of drug going to the receptor site depends on the passage through several compartments
- There needs to be sufficient drugs bound the receptors
- There must be a sufficient time that the drug and receptors be in contact
What are active ingredients?
Ingredients that give therapeutic or diagnostic effects
T/F, Products other than the active ingredients can affect drug absorption.
TRUE, and active ingredients can also affect uptake of other drugs
What factors can affect drug stability?
- Acidic drugs are more stable
- contamination (can affect formulation)
- heat (accelerate breakdown of drug-->keep in fridge)
What is the osmolarity of blood?
290mOsm (equivalent to 0.9% saline)
Due to drugs and preservative, the blood osmolarity is usually HYPOTONIC. What can be used to bring Osm back to physiological level?
Salts, buffers and sugars can be added to adjust for osmolarity
What are the reasons we put preservatives in drugs?
They help to prevent the growth of microorganisms
What are types of preservatives put into drugs?
- Benzalkonium chloride/benzethonium chloride
- mercurial component
- stabilize oxychoro-complex and sodium perborate (oxidation)
Benzalkonium chloride/benzethonium chloride (preservative)
- aka BAK or BAC.
- Surfactant: charged molecules that block bacterial plasma membranes
- can have toxic effect on tear film and epithelium
- Block microbes metabolism, alters corneal permeability less than BAK/BAC
Mercurial compounds ie. Thimerosal (preservative)
- blocks microbe metabolism
- most effective in weak acidic solutions
- patients can develop sensitivity and allergies
- in artificial tears, less effective, no allergic reactions
- Often combined with EDTA
- blocks microbe metabolism
- found in artificial tears
- can cause allergies
- unstable at high pH
Stabilized oxychoro-complex (Purite) and sodium perborate (oxidation)
Preservative in artificial tears
Purite dissipates to water and NaCl with light exposure
Sodium perborate converts to H2O2, then into water and O2 in eye
- antioxidant properties that delay deterioration of products by oxygen in the air
- can cause contact dermatitis
- assists thimerosal and BAC
What are drug vehicles?
Agents other than active drugs or preservatives added to formulations to provide proper:
tonicity, buffering, and viscosity
- complements drug action
nonionic polymer with binding and detoxification properties
- low systemic properties, no immune rejection characteristics
- can support viscosity
Polyvinyl alcohol (PVA)
water soluble viscosity enhancer
- commonly used at 1.4% concentration in ophthalmic preparations—Boards
- non-irritating and can enhance healing of abraded corneal epithelium
- useful in dry eye syndrome and corneal epithelial erosion
Hydroxypropyl methylcellulose (on last year's exam)
- viscosicty enhancer
- can prolong tear film wetting time (long acting AT)
- can enhance ability of fluorescein and dexamethasone to penetrate cornea
similar properties to hydroxypropyl methylcellulose
- greater adhesion to mucins than other viscosity vehicles
- often in artificial tears
- high viscosity in eye, and changes with motion of blinking
- stabilizes tear film
using larger molecules that demonstrate reversible phase changes
- aqueous drop in eye reversibly gels on contact with precorneal tear film
- enhance corneal penetration and prolong action of topical applications
vary in their lipophilic nature and in binding (not on exam)
- enhance bioavailability of lipophilic durgs (ie: corticosteroids)
pseudoplastic properties where viscosity decreases with increasing shear rate (blinking) and ocular movement
- good microadhesive and wetting properties
mixtures of white petrolatum and liquid mineral oil with or without a water-miscible agent (ie: lanolin)
- purpose: increase ocular contact time of applied drugs
prolong drug effect at site of action with less toxicity
- common system is using liposomes (bioerodible/biocompaticle microscopic vesicles composed of lipid bilayers surrounding aq compartments)
cyclic oligosacchardies that are water soluble and which can incorporate lipid-soluble drugs in their centers
- used to improve solubility, stability of various compounds
What are 3 drug delivery systems into the eye?
1) soft CTL - absorb drugs from solutions and release slowly into the eye
3) intraocular drug delivery system and intravitreal implants --treat viral infections
What is the most common route of ophthalmic drug administration?
What are the advantages of topically applied ophthalmic drugs?
Convenient, simple and non-invasive
Where do topically applied ophthalmic drugs clear through?
- diffuse through the circulatory system and via nasolacrimal duct
- diffusion into blood occurs via bv of conjunctiva, episclera, intraocular structures and nasal mucosa vessels
Do topical drugs penetrate in useful concentrations to the posterior ocular structures?
NO, must use an oral drug for that. Minimal systemic absorption--except NSAIDs
How big is a drop size?
25-50 mcl/drop average, sometimes up to 70mcl
What are advantages of topically applied ophthalmic solutions and suspensions?
- Ease of instillation
- Little interference with vision
- Few potential complications
What are the disadvantages for topically applied ophthalmic solutions and suspensions?
1) brief contact time
2) contamination potential
3) ocular injury by dropper tip
4) imprecise amounts
What are sprays?
An alternative mode of ophthalmic administration
Mydriatic or cycloplegic sprays can be applied to closed eyelids
What are the advantages of ointments?
- long contact time
- easy to instill
What are the disadvantages of ointments?
- blurry vision
- contact dermatitis
- can be trapped under corneal ulcer flaps
Application of solutions or other products directly to the lid margin
Advantages of gels?
- once daily administration
- good patient compliance
- little miosis during waking hours if applied at night
What are the disadvantages of gels?
- superficial corneal haze
- weak ocular hypotensive effects
- potential for SPK
Drug release from a CTL follows what kinetics?
First order--drug penetration through a thin lens delivers a greater proportion than through a thick lens
What are the factors that affect how drugs penetrate through a contact lens?
1) pore size
2) concentration of drug
3) soak time
4) lens water content
5) size of drug molecule
How is a filter strip advantageous?
Long shelf life
Artificial tear insert
- Consists of a pellet of hydroxylpropyl cellulose placed in inferior conjunctival fornix
- absorbs water and releases gel over eye surface
- used for treating dry eye
What is a disadvantage of artificial tear insert?
Can cause blurring and foreign body sensation
When do we use continuous flow devices?
Large volume irrigation of the eye to dislodge foreign bodies, or irrigating chemical splashes and burns
What are the 2 medical conditions for which we use lid scrubs?
Seborrheic or infection blepharitis
Areas of administration by injection
T/F, Ophthalmic suspensions mix with tears less quickly than solutions and remain in the cul-de-sac longer
What are the forms of a medical Rx?
Verbal, written, and electronic
When writing zeros in a prescription, what must be followed?
Use leading zeros (0.1) but NOT trailing zeros (1.0)
What abbreviations must be avoided in a prescription?
cc, qd, d
What information must be on a prescription?
- Patient name and address
- Medication Rxed
- Directions to pharmacist (strength, quantity)
- Directions to patient (Sig)
- Refill info
- Prescriber information (signature, prescriber address, license, license #s)
What is a schedule I drug?
Not commercially available, no approved indications
What is a schedule II drug?
strict limitations due to high abuse and dependency. CANNOT be refilled
What is a schedule III drug?
Significant abuse and dependence. Can be refilled up to 5X in 6months, though some states do not allow refills
What is a schedule IV drug?
lower abuse and dependency, some ODs can allow refills
What is a schedule V drug?
Low abuse and dependence. Most used to treat cough or diarrhea. none for ophthalmic use
For approval by the FDA, generic drugs must meet which criteria?
1) same active ingredients
2) same bioequivalency and bioavailability
3) same pharmacologic and therapeutic activity
4) manufactured to FDA requirements
5) meet FDA requirements for stability, purity, strength and potency
6) labeled with the same claims, warnings and other info
What are the consequences of non-compliance with drugs?
1) too much meds
2) too little meds
3) wrong reason
4) ADEs, increased risk of interactions
5) treatment failure
What are the factors that contribute to non-compliance?
1) complex regimen
2) can't understand regimen
3) don't know how to use it/indications
4) don't know the importance of medication
What is IMDA?
A method to support good patient compliance using layman's terms
4) ask questions, ADE, anything else, make sure patient understands
What is the trade name for fluorescein sodium?
What is the mechanism of sodium fluorescein?
Reveals defects in the corneal epithelium but does not stain tissues.
Indications for use of sodium fluorescein
CL fitting, GAT, diagnosis of corneal lesions, herpetic lesions.
Also available for use intravenously in angiography
What are the ADEs of topical fluorescein solutions?
Risk for bacterial contaminations, nausea, HA, allergies, GI, distress, yellow skin, strong taste, discoloration of urine and skin, local irritation, stains CTL
Use caution of fluorescein among which patient groups?
allergies, hypersensitivity and asthma
What is the pregnancy category for sodium fluorescein?
What is the concentration of FulGlO strips?
What is the generic name for Fluorexon?
Compare the color of Fluorexon to sodium fluorescein
has a less fluorescent intensity
What does Fluorexon (Fluoresoft) stain?
Degenerated cells and mucus threads
Indications of Fluoresoft?
Aid to hydrogel (and other) CL fitting, GAT, corneal integrity, can be used for TBUT
What do you need to avoid use of when instilling Fluorexon?
Avoid use of hydrogen peroxide with CTL after instillation---because this will cause color to remain on the lens
What is the concentration of Fluoresoft?
How do you administer Fluoresoft?
You can place 1 drop onto the concave of a CTL, or 1 or 2 drop placed in the lower cul de sac, and 1 drop+1 drop of anesthetic for tonometry
What is the generic name for Indocyanine Green?
What does indocyanine green contain?
Water soluble tricarbocyanine dye + sodium iodide
What are the uses of indocyanine green?
Dye for retinal and choroidal angiography, characterize neovascularization in ARMD
What is indocyanine contraindicated in
Iodine sensitivity - risk for anaphylaxis, allergic reactions
What are the formulations for powder and aqueous form of indocyanine?
- powder (25mg injection)
- aqueous (10mL)
Which dye is only given intravenously?
What is the dose for the IV form of indocyanine green?
40mg of dye in 2mL of solvent
What is the purpose of a lissamine green dye?
Stains dead or degenerated corneal and conj cells and precipitated mucous
Which dye is used as a diagnostic when the superficial corneal of conjunctival tissue may have been damaged?
Which dye is used to dx dry eye conditions, corneal erosions and herpetic ulcers?
What conditions will lissamine help dx?
dry eyes, corneal erosions, herpetic ulcers
What are the cautions of lissamine green?
NO ADE or irritations
What is the formulation of lissamine green?
How do you administer lissamine green?
1-2 drops of saline on strip
What will rose bengal stain?
Stains living cultured cells, dead cells and degenerated cells and mucous strands
What is rose bengal used for?
To evaluate dry eyes, herpetic keratitis, corneal abrasions and foreign bodies
What are the ADEs of rose bengal?
Irritation, discomfort, staining, flush eyes and wait 1hr before applying CTL
What is the formulation of rose Bengal?
1.3 mg strips
Local anesthetics prevent generation and conduction of nerve impulses by:
- reducing sodium permeability
- increasing threshold of nerve excitation
- slowing propagation of nerve impulses
- reducing the rate of AP rise
Describe the chemical structure of local anesthetics.
- Aromatic lipophilic portion (aromatic ring)
- Intermediate alkyl chain (links to aromatic group by ester or amide)
Most topically applied anesthetics = esters
Most injectable anesthetic agents = amides
- Hydrophilic amine group
Aniline derivatives metabolized in the liver and excreted primarily renally as metabolites with a small fraction of unchanged drug.
PABA derivatives which are metabolized by hydrolysis of the ester linkage.
- Benoxinate (+fluorescein = Fluress®)
What are the two different groups of local anesthetics?
Esters and Amides
T/F, allergic reactions to local anesthetics occur almost exclusively to those with an amide linkage
FALSE, They occur in anesthetics with ester linkages
Indications of topical anesthetics
- Removal of FB
- suture removal
- nasolacrimal irrigation
- prevent pain with probing or surgical procedures
Potential adverse effects of local anesthetics
- CNS stimulation (can be followed by CNS or respiratory depression)
- Cardiovascular stimulation (can be followed by cardiovascular collapse)
- Allergic reactions (local and systemic)
Using local anesthetics with a vasoconstrictor such as epinephrine can cause what?
- Local hemostatis
- Decreased systemic absorption of the anesthetic
- Prolonged anesthetic duration of action
What are indications of Injectable local anesthetics?
- Used to produce facial block
- Retrobulbar or peribulbar anesthesia
- Eyelid infiltration
Injectable local anesthetics
- Bupivacaine HCL 0.75%
- Lidocaine HCL 4%
- Mepivacaine HCl 1%
T/F, with tetracaine, transient stinging, burning and conjunctival redness can occur
TRUE. Rare local reactions include lacrimation, photophobia, and chemosis.
T/F, A rare severe immediate-type allergic corneal reaction with acute diffuse epithelial keratitis and sloughing off of large areas of necrotic epithelium, diffuse stromal edema, and iritus has been reported with proparacaine and tetracaine.
Topical local anesthetics
- Proparacaine HCL
- Tetracaine HCL
- Local Anesthetic Combinations
Proparacaine HCl 0.5% dosages
- Deep anesthesia: 1 gtt q5-10 min 5-7x
- Removal of sutures: 1-2 gtt, 2-3 min before removal
- Tonometry: 1-2 gtt immediately before
- Removal of foreign bodies: 1-2 gtt prior to procedure
Tetracaine HCl dosage
Local Anesthetic Combinations
- proparacaine HCl 0.5% + Fluorescein sodium 0.25% (Flucaine®)
- Benoxinate HCl 0.4% + fluorescein sodium 0.25% (Fluress®, Flurox®)
- Benoxinate HCl 0.4% + fluorexon disodium 0.35% (FluraSafe®)
Benoxinate/fluorescein deep ophthalmic anesthesia dosage
2gtt OU q90seconds 3x
Used for dilation (affects pupil size, accommodation, aqueous flow)
Stimulates adrenergic division of autonomic nervous system
Anticholinergic drugs used in the eye to inhibit accommodation
Used to treat uveitis/inflammatory conditions of uveal tract
Inhibits the iris sphincter and ciliary body
Produces pupillary dilation and cycloplegia
Ex: Tropicamide, cyclopentolate, atropine, homatropine
Clinical uses of mydriatics
Testing for Horner's syndrome
Ocular decongestant (constriction of ocular blood vessels)
A synthetic alpha-receptor sympathomimetic agonist structurally similar to epinephrine.
Acts primarily on alpha-receptors
A potent vasoconstrictor (conj blanching) and mydriatic agent
Contracts dilator muscle and smooth muscle of conjunctival arterioles
Phenylephrine 0.12% indications
OTC concentration, ocular decongestant
Phenylephrine 0.12% response
Maximal response: 30-90 min
Phenylephrine 2.5% indications
- 2.5% = concentration recommended for infants and elderly
- Pupillary dilation in uveitis
- Open angle glaucoma
- Prior to surgery
- refraction without cycloplegia
- ocular decongestant and vasoconstrictor
Phenylephrine 2.5% response/recovery
Maximal response: 15-60 min
Recovery time: 3 hours
Phenylephrine 10% indications
- used to break posterior synechiae
- for peripheral corneal vessel vasoconstriction during LASIK
- use should be minimized bc of greater risk of ocular, cardiovascular, and systemic side effects
Phenylephrine 10% response/recovery
Maximal response: 10-60 min
Recovery time: 6 hrs
Phenylephrine contraindicated in:
Narrow angle glaucoma
Narrow angle without glaucoma
Low birth weight infants
Elderly pts with severe ASCVD
Pregnancy category C
10% phenylephrine contraindicated in
Longstanding Type 1 Diabetes
Pts with intraocular lens implant
Development of transient pigment floaters (elderly)
Cardiovascular effects (Palpitations, Cardiac arrhythmias, HT, Coronary occlusion, AMI)
Increased blood glucose
Phenylephrine Topical effects
Phenylephrine + atropine interactions
Increased pressor effects of PE
Increased potential for tachycardia
Phenylephrine + tricyclic antidepressants or MAOIs interactions
Contraindicated, increased cardiovascular effects
Phenylephrine dosage: Vasoconstriction/dilation
1gtt after anesthetic
Phenylephrine dosage: Uveitis
To free recently formed posterior synechiae
1gtt 2.5% to upper cornea,
hot compresses 5-10 min TID using 1gtt 1or2% atropine before/after hot compresses
Phenylephrine dosage: Glaucoma
2.5% and 10% used in conjunction with miotics (open angle glaucoma)
Phenylephrine dosage: Surgery
2.5% or 10% solution 30-60min before procedure: short-acting mydriasis for wide dilation
Phenylephrine dosage: Refraction
2.5% solution used with homatropine, atropine, cyclopentolate or tropicamide
Adults: 1gtt cycloplegic followed in 5 min by 1gtt 2.5% phenylephrine
Followed in another 10 min by another gtt cycloplegic
Refraction can begin in 50-60 min
An indirect-acting adrenergic agonist that is similar to norepinephrine (NE) in structure
Works by release of NE from adrenergic nerve terminals and direct stimulation of alpha receptors
Onset 15 min
Max effect 60 min
Duration 6 hours
Cyclopegic effect in combination with Tropicamide
Help distinguish between central or preganglionic sympathetic denervation in Horner's
Changes in IOP, BP
Can be safer than phenylephrine in Type 1 Diabetes
1% hydroxyamphetamine + 0.25% tropicamide (Paramyd®)
Instill 1 gtt into eye, repeat as necessary
Contraindications of Cycloplegic mydriatics
Narrow anterior chamber angles
Hypersensitivity to belladonna alkaloids/products
Adhesions (synechiae) between the iris and lens
Children with Hx of severe reaction to atropine or other anticholinergic
Mydriasis peak: 30-40 min
Mydriasis recovery: 7-10 days
Cycloplegia peak: 60-180 min
Cycloplegia recovery: 6-12 days
Mydriasis peak: 30-60 min
Mydriasis recovery: 1 day
Cycloplegia peak: 25-75 min
Cycloplegia recovery: 0.25-1 day
Mydriasis peak: 40-60 min
Mydriasis recovery: 1-3 days
Cycloplegia peak: 30-60 min
Cycloplegia recovery: 1-3 days
Mydriasis peak: 20-30 min
Mydriasis recovery: 3-7 days
Cycloplegia peak: 30-60 min
Cycloplegia recovery: 3-7 days
Mydriasis peak: 20-40 min
Mydriasis recovery: 0.25 days
Cycloplegia peak: 20-35 min
Cycloplegia recovery: 0.25 days
Cycloplegic Mydriatic ADEs
- Increased IOP
- transient stinging/burning
- irritation including lid reactions
- redness/hyperemia/vascular congestion
- follicular conjunctivitis
- dry mouth and skin
- blurred vision
- visual hallucinations
psychotic reactions and behavioral disturbances may be caused by what cycloplegic mydriatics?
Tropicamide and Cyclopentolate
Cycloplegics must be used with great caution in which patients because they may cause a hyperactive pupillary response (especially atropine)?
Down's Syndrome and children with brain damage
What are toxic manifestations of anticholinergic drugs?
vasodilation, urinary retention
slowed GI motility
decreased salivary and sweat gland production
decreased secretion in pharynx, bronchi and nasal passages
Severe: coma, medullary paralysis, death
- Anticholinergic (parasympatholytic) drugs that block the responses of the sphincter muscle and muscle of the ciliary body to cholinergic stimulation.
- Produces pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia)
- Cyclopentolate faster onset and shorter duration than atropine
- Scopolamine greater anti-muscarinic potency than atropine
- Tropicamide can reach higher concentration at muscarinic receptor sites, faster onset/shorter duration than other anticholinergics.
Indications for use of ______: mydriasis and cycloplegia in diagnostic procedures, and in acute inflammatory condition of the iris and uveal tract
Atropine, cyclopentolate, scopolamine, homatropine, tropicamide
Scopolamine and homatropine also for pre/post operative uses
- Atropine sulfate ophthalmic ointment and solution (both 1%)
- Adults uveitis: 1-2 gtt QID
- Children uveitis: 1-2 gtt 0.5% TID
- Refraction: 1-2 gtt 0.5% BID 1-3 days before exam
- Ointment: in conjunctival sac TID
- transient stinging/burning
- increased IOP
- More CNS effects than atropine
(drowsiness, ataxia, disorientation, restlessness, emotional changes, hallucinations, incoherent speech)
- avoid in open angle glaucoma or narrow angles
-avoid in children, esp those with spastic paralysis or brain damage
- Cyclopentolate HCl ophthalmic solution (0.5%, 1%, 2%) Cyclogyl®
- Adults: 1-2 gtt any % solution, repeat 5-10 min later if necessary
- Children: 1-2 gtt 0.5% solution, repeat 5-10 min later if necessary
- small infants: 1 gtt 0.5%, observe closely for at least 30 min
Scopolamine hydrobromide (Isopto Hyoscine®) 0.25%
Uveitis: 1-2 gtt QID
Refraction: 1-2 gtt 1hour before refraction
Higher incidence CNS toxicity compared to atropine
Not a drug of first choice for treatment of anterior uveal inflammation or cycloplegic refraction
Higher incidence of idiosyncratic rxns than other
Homatropine HBr opththalmic solution (2%, 5%) Isopto Homatropine®
Uveitis: 1-2 gtt q3-4hr
Refraction: 1-2 gtt, repeat in 5-10 min if needed
Children: only use 2% strength
Tropicamide ophthalmic solution (0.5%, 1%) Mydral®, Tropicacyl®
Refraction: 1-2 gtt, repeat in 5 min if needed
Fundus exam: 1-2 gtt 0.5%, 15-20 min prior
Mydriatic combination products
0.2% cyclopentolate HCl + 1% Phenylephrine HCl
0.3% Scopolamine HBr + 10% Phenylephrine HCl
0.25% tropicamide + 1% hydroxyamphetamine HBR
T/F, Allergic reactions in the eye most frequently affect the cornea and eyelids.
FALSE, they most frequently affect the conjunctiva.
There are 5 types of allergic reactions. Which two types are most often involved in ocular reactions?
I & IV
Describe Type I Hypersensitivity reactions.
- Occur when antigens are reintroduced in people with previous exposure.
- After 1st exposure, B lymphocytes are activated and IgE makes mast cells more sensitive
- When re-exposed, large quantities of inflamm mediators are released
(prostaglandins, histamine, leukotrienes, eosinophile chemotactic factor)
- Commonly occur in hay fever, allerg conjunctivitis, asthma, hymenoptera stings
What happens when histamine activates H1 receptors on blood vessels?
Vasodilation, leakage of fluid, tissue swelling
The immediate response of a Type I reaction starts ___ min after exposure and resolves after ___minutes. A late phase reaction my occur ___ hours later and last up to __ days.
5-30 min, 30-60 min, 4-6 hours, 2 days
Signs and Symptoms of Type I reactions
Describe Type IV Hypersensitivity reactions.
- Cell-mediated immune responses
- Delayed hypersensitivity rxn involving T lymphocytes
- after sensitization, delayed response takes 24 hrs, peaking at 48-72hrs
Where are H1 receptors located?
bronchial smooth muscle
Gastric parietal cells
BV of eye
Where are H2 receptors located?
Bronchial smooth muscle
BV of eye
Ocular signs/symptoms caused by histamine
Itching, tearing, conjunctival and lid edema, dilation of conj vessels
Seasonal Allergic Conjunctivitis
Can result from many exogenous antigens
Includes dust, pollen, smoke particles, environmental contaminants
Seasonal disorder, peaks during warm months, Adolescent males
Bilateral inflammation involving upper tarsal conj and sometimes limbal conj
Papillary hypertrophy - gelatinous thickening of superior limbus
Histamine level in tears high
Itching, thick ropy discharge
Photophobia if cornea involved
Ptosis if signif. papillary
Caused by hereditary factors, not acquired hypersensitivity
Usually a family hx or personal hx (hay fever or asthma common)
Patches of thickened itchy dry skin
Conjunctival chemosis and hyperemia
Corneal involvement not common
Giant Papillary conjunctivitis
Conjunctival inflamm reaction to materials such as proteins on CL
Papillary hypertrophy usually upper tarsal plate
Lens thickness and diameter can be involved
Lens instability, CL intolerance, itching, mucoid discharge can occur
T/F, Ocular decongestants should only be used for a short time because they can mask the symptoms of more serious conditions (bacterial etc)
- narrow angle glaucoma
- narrow angles
- discontinue prior to use of anesthetics which sensitize the myocardium to sympathomimetic activity
Phenylephrine 0.12% duration
Naphazoline 0.012%, 0.03%, 0.1% duration
0.1% prescription only
Oxymetazoline 0.025% duration
Tetrahydrozoline 0.05% duration
Ocular sympathomimetic decongestant + general anesthetic agent (spec. anesthetic gases)
Sensitization of the myocardium to sympathomimetics
Ocular sympathomimetic decongestant + local anesthetic
Increased absorption of decongestant
Ocular sympathomimetic decongestant + beta blockers
Increased risk of systemic sympathomimetic ADEs
Ocular sympathomimetic decongestant + MAOIs
Exaggerated adrenergic effects can occur
Allow 21-day interval after discontinuation of MAOI to minimize risk