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824 > Ophthalmic > Flashcards

Ophthalmic Flashcards

1
Q

Historical Info

A
  • Dates back to Egyptians, Greeks, and Romans
  • 1950s - mostly compounded by pharmacists
  • Rarely compounded now, manufacturers exist that specialize in ophthalmics
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2
Q

Drug Delivery

A

-For topical treatment of surface/intraocular conditions
-Usually NOT systemic
EX: lubrication, infections, inflammations, glaucoma

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3
Q

Lens

A

Changes shape for focusing

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4
Q

Iris

A

Regulates light entry into back of eye through the pupil

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5
Q

Sclera

A

“White” of eye. Fibrous, protective outer layer of eye, contains microcirculation

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6
Q

Conjunctiva

A

Covers the sclera. Highly vascularized. Helps lubricate the eye

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7
Q

Cornea

A
  • Transparent layer, devoid of blood vessels
  • 0.5-1 mm thick
  • Physical/chemical barrier which makes resistant to infections when intact
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8
Q

Retina

A
  • Innermost area of the eye

- Transforms light into electrical signals to be sent to the brain via optic nerve

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9
Q

Aqueous Humor

A

Watery fluid behind iris responsible for maintaining appropriate IOP

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10
Q

Vitreous Humor

A

Gel-like fluid, just behind lens to retina

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11
Q

Blood-Retina Barrier

A
  • Similar to BBB
  • Protects back of eye
  • Prevents systemic entry of drugs into eye, particularly the retina
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12
Q

Cornea Layers

A
  1. Epithelium - lipophilic
  2. Stroma - hydrophilic
  3. Endothelium - lipophilic
  • THEN you reach the target, aqueous humor
  • Drug has to readily switch between ionized and unionized to transverse the layers
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13
Q

Ophthalmic Challenge

A

Usually <1% drug actually reaches the target out of what is applied to the surface

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14
Q

Reasons for Ophthalmic Challenge

A
  • Poor permeation into the eye
  • Limited capacity of the eye to retain liquid (usually only a small amount can be administered)
  • Dilution due to lacrimal fluids
  • Washed out due to blinking
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15
Q

Amount of fluid eye can hold

A

7 uL

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16
Q

Average eye drop volume

A

50 uL

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17
Q

Lacrimal Fluid Function

A
  • Moisten cornea
  • Clear foreign objects away
  • Protect eye
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18
Q

Lacrimal Fluid pH

A

~7.4

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19
Q

Cornea Absorption Factors - Physiological

A
  • Lacrimal dilution
  • Lacrimal drainage
  • Blinking
  • Spilling onto cheek
  • Corneal barrier condition
  • Physiologic pH
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20
Q

Cornea Absorption Factors - Chemical

A
  • Size/structure of drug
  • Lipophilicity of drug
  • Degree of ionization
  • Viscosity of product
  • Drug solubility/[drug]
  • Particle size if its a suspension
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21
Q

Ophthalmic Similarities to Parenteral

A
  • Must be sterile
  • Requires preservatives (unless unit dosed)
  • Should be isotonic to minimize irritation/damage
  • May include buffer agents
  • Viscosity is important
  • Package for ease of use
  • Consider patient comfort/lack of irritation
22
Q

Preservatives

A
  • ONLY unit-dose are preservative free

- Used for surgery, traumatized eye, packaging

23
Q

Detergents - MOA

A

-Cause of bacterial cell death by interrupting lipid component of cell membranes

24
Q

Oxidizing - MOA

A
  • Penetrate lipid membrane and alter DNA, protein, and lipid components of bacterial cells
  • Spontaneously reduced once administered (reacts with cations in tears, become inactive, decrease toxicity to humans on ocular surface)
25
Q

Detergent

A
  1. Benzalkonium Chloride
  2. Chlorobutanol
  3. Polyquaternium-1 (Polyquad)
26
Q

Benzalkonium Chloride

A
  • Most common - in ~70% of ophthalmics
  • Stable over wide pH range
  • Incompatible with anionic drugs
27
Q

Chlorobutanol

A
  • Preservative agent in artificial tears

- Can be unstable over long periods of time (decreased stability with increased pH)

28
Q

Polyquad

A
  • Developed in 80s for contact lens solution

- Didn’t enter contact lens itself, making the lens a reservoir to release preservative

29
Q

Purite

A
  • Example of oxidizing preservative
  • Stabilized oxychloro complex
  • 1990s
  • Broad antimicrobial, antibacterial, antifungal, and antiviral
  • Lacks cytotoxicity in vivo
30
Q

Other Preservatives

A
  1. Thimerosol - many people sensitive to this
  2. Methyl and propyl parabens - not common in ophthalmics, need [high] for antibacterial effect, low aq. solubility. Binds to polymers and nonionic surfactants, can sting/burn eye
31
Q

Osmotic Pressure

A
  • Want ophthalmic to be equal to tears OP
  • Use excipients to adjust isotonicity
  • Boric acid and NaCl are common in ophthalmics
  • 1.9% boric acid = 0.9% NaCl OP
  • Isotonic phosphate behicle has a mixture of mono and dibasic sodium phosphate in water to get the pH between 5.9-8.0
32
Q

Lacrimal Fluid

A
  • Limited buffer capacity
  • Therefore buffers are used to change pH
  • Reason: decrease discomfort, ensure stability, can adjust drug solubility/therapeutic activity
33
Q

pH

A
  • 7.4 not always possible due to solubility, stability, or ionization issues
  • THEREFORE this is always a compromise between stability and therapeutic activity
34
Q

Packaging

A
  • Small: 5-30 mL
  • Single dose
  • Easy to use container usually with build in dropper
  • Maintain sterility of product
35
Q

Eye Drop Use

A
  1. Wash hands thoroughly
  2. Examine container
  3. Lie down or tilt head completely back
    * *3.5 - Shake if suspension**
  4. Pull down lower lid to form pocket
  5. Squeeze bottle to drop dose in eye, DON’T TOUCH TO EYE
  6. Close eye and wipe away excess liquid
  7. Recap container
  8. Wait several minutes between multiple drops
36
Q

Emulsions

A

-Deliver poorly water soluble drugs
-Drugs dissolved in oil then emulsified with water using surfactants
-Less irritating and better tolerated
-May be opaque to slightly translucent
EX: Restasis (cyclosporine) - dry eye treatment, single use, preservative free OR multi-dose

37
Q

Improving Ocular Delivery

A
  • Increase contact time

- Increase corneal penetration

38
Q

Ways to Improve Contact Time

A
  • Suspensions
  • Viscosity
  • Gel
  • Ointments
  • Mucoadhesion
  • Ocular inserts
39
Q

Ways to Increase Corneal Penetration

A
  • Prodrugs

- Liposomes

40
Q

Suspensions

A
  • Increase corneal contact time
  • Drug tends to sit in conjunctiva and dissolve slowly over time
  • Prefer <10um size, need <50 um to decrease irritation
  • SHAKE BEFORE USE
41
Q

Gels

A
  • Increase corneal contact time
  • More viscous than a solution
  • May cause blurred vision
42
Q

Gel-Forming

A

-Become gel AFTER administration
-Triggered by change in temperature, pH, or electrolyte composition
-Increase viscosity and therefore contact time
EX: Timoptic-XE - for glaucoma, gels from cation exposure

43
Q

Ointments

A
  • Increase corneal contact time
  • Usually mineral oil or petrolatum base
  • MUST be sterile
  • 2-4x increases exposure than solution/suspension
44
Q

Ointment Disadvantages

A
  • Blurred vision for extended time
  • Not pharmaceutically elegant
  • Dose not controlled
  • Slower onset of action
45
Q

Ointment Packaging

A
  • Small, narrow tubes
  • Plastic or tin
  • ~3.5 g on average
  • Narrow gauge tip to get “thin ribbon” of ointment
46
Q

Proper Use of Ointments

A
  1. Same clean-up precautions
  2. Use mirror for ease
  3. Hold tube between thumb and forefinger and place tube close to eye
  4. Slightly tilt head back and pull down lower lid
  5. Squeeze ribbon of ointment on inside, lower lid
  6. Roll eyes around with eyes closed to distribute medication
  7. Wipe excess
  8. Release tube, don’t touch tip to body!!!
47
Q

Ointment Counseling

A
  1. Blurred vision - don’t drive, lasts ~20-30 miutes, place warm towel on eye to lessen
  2. Warm ointment in HAND before use
  3. Drop first then wait 5 minutes before ointment
  4. 10-30 minutes between multiple ointment use
48
Q

Mucoadhesive Polymer

A

-Increases patient compliance by decreasing dosing frequency

EX: Azasite - BID x 2 days then QD x 5 days, store in fridge, trash after 14 days at room temperature

49
Q

Ophthalmic Inserts

A
  • Releases drug slowly over time
  • Placed into lower lid
  • Less frequent dosing and eliminates peaks/troughs
  • Packaged individually to increase sterility
  • No preservatives, place into eye once out of packaging or trash
  • Wash hands prior to handling
50
Q

Insert Requirements

A
  • Patient comfort
  • Doesn’t interfere with vision or oxygen permeability
  • Ease of handling
  • Sterile
  • Lack of expulsion
  • Stable
51
Q

Ocusert System

A
  • Drug sandwiched between two rate-controlling polymer layers
  • Released by diffusion through the polymers
52
Q

Lacrisert

A

-Treating severe dry eye
-HPMC - thickens tears to lubricate eyes
-Erodible
PROBLEMS: blurred vision, matting of eye lids, irritation, poor patient acceptance

824 (15 decks)

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