Ocular Pharm MT1

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FDA pregnancy risk factor

starting point; doesn't address the safety while breast-feeding

Fluorescein

C, excreted in breast milk, avoid in 1st trimester (small dose and 1 time, okay for us to use)

Lissamine Green

no FDA rating

Rose Bengal

no FDA rating

proparacaine

C, safe use not estab

lidocaine

B, AAP says its compatible w/ breastfeeding. local anesthetics generally cross into breast milk, 40% (don't worry unless patch or IV)

tetracaine

C, WHO- compatible with breastfeeding

phenyephrine

C, use punctal plugs

Atropine, homatropine

C, AAP says compatible with breastfeeding

cyclopentolate

C

tropicamide

c

naphazoline

C, ocular decongestant

oxymetazoline

no FDA rating, ocular decongestant

tetrahydrozoline

no FDA rating, ocular decongestant

Azelastine

C, ocular antihistamine, not reccomm when breastfeeding. antihistamines generally appear in breast milk

Cromolyn

B, ocular antihistamine

emedastine

B, ocular antihistamine

epinastine

C, ocular antihistamine

ketotifen

C, ocular antihistamine

lodoxamide

B, for allergic conjunctivitis

nedocromil

B, for allergic conjunctivitis

olopatadine

C, for allergic conjunctivitis

pemirolast

C, for allergic conjunctivitis

Corticosteroids, cycloplegics, sulfas, fluoroquinolones

all preg C category

Dexamethasone

C, corticosteroid

difluprednate

C, corticosteroid

Fluorometholone

C for class related, no indiv FDA rating

loteprednol

C, corticosteroid

rimexolone

C, corticosteroid

bromfenac

C, NSAIDs (thin blood causes placenta to detach)

flurbiprofen

B, NSAIDs (thin blood causes placenta to detach)

diclofenac

D, NSAIDs (thin blood causes placenta to detach)

nepafenac

C, NSAIDs (thin blood causes placenta to detach)

ketorolac

D, NSAIDs (thin blood causes placenta to detach), AAP says compatible w/ breast feeding

cyclosporine (restasis)

C, for dry eyes, excreted into breast milk. safer to use Artificial tears( A or B)

Dipivefrin

B, for glaucoma

Apraclonidine

C, for glauc

Brimonidine

B, for glaucoma

Echothiophate

C, for glaucoma

pilocarpine

C, for glaucoma

betaxolol

C, for glaucoma

carteolol

C, for glaucoma

levobunolol

C, for glaucoma

metipranolol

C, for glaucoma

timolol

C, for glaucoma, AAP says compatible for breastfeeding

acetazolamide

C, for glaucoma, AAP says compatible for breastfeeding

brinzolamide

C, for glaucoma

dorzolamide

C, for glaucoma

methazolamide

C, for glaucoma

latanoprost

C, for glaucoma

bimatoprost

C, for glaucoma

travoprost

C, for glaucoma

Aspirin

D. AAP caution with bf. just avoid it during preg and lactation

Acetaminophen

B, AAP says compatible with bf eventhough known to cross into breast milk

ibuprofen

D, compatible w/ breastfeeding

naproxen

C, analgesic, compatible w/ breastfeeding

codeine

C, analgesic, compatible w/ breastfeeding

hydrocodone

C or D depending on how much is taken. Avoid while breastfeeding

acyclovir

B, anti-infectives, compatible w/ breastfeeding, drug easily crosses placenta

valacyclovir

B, anti-infective,appears to be compatible with breastfeeding

famciclovir

B, anti-infective, avoid while breastfeeding

Trifluridine

C, anti-infective

Natamycin

C, antifungal. Manufacturer rec. that drug only rx preggies in life or death

all pencillins (amoxicillin, amox/clavulanate, ampicillin, penicillin VK, dicloxacillin) are

B, AAP says compatible w/ breastfeeding

Clindamycin

B, for bacterial infections, AAP says compatible w/ breastfeeding

bacitracin

C, for bacterial infections

sulfonamides

C (SMX/TMP included), compatible w/ breastfeeding in healthy infant, risky in THIRD trimester (jaundice, kernicterus, hemolytic anemia)

cephalosporins

B, compatible with breastfeeding

cefadroxil

B, compatible with breastfeeding

cefuroxime

B, compatible with breastfeeding

cefphalexine

B, compatible with breastfeeding

all fluoroquinolones are

C

besifloxacin

C

ciprofloxacin

C, AAP says compatible w/ breastfeeding

gatifloxacin

C,

levoflozacin

C

moxifloxacin

C

ofloxacin

C, AAP says compatible w/ bf

azithromycin

B, oral form in breast milk, no topical data

clarithromycin

C,

erythromycin (excludes estolate)

B, don't rx estolate to preggies

gentamycin

C, AAP says compatible w/ bf

tobramycin

C

neomycin

C

tetracycline

D, avoid during pregnancy. But AAP says compatible w/ breastfeeding

doxycycline

D, avoid during pregnancy. But AAP says compatible w/ breastfeeding

Preg Cat B

lidocaine, cromolyn & emedastine (antihistamine), lodoxamide & nedocromil (allergic conjunctivitis), flurbiprofen (NSAID), dipivefrin & brimonidine (glauc), acetaminophen, cyclovirs, penicillins, cephalosporins, clindamycin, azithromycin, erythromycin

Preg Cat D

ketorolac, diclofenac, aspirin, ibuprofen, tetracycline, doxycycline, some sulfonamides (diclofenac and aspirin not compatible w/ breastfeeding but the rest are)

preg Cat D but compatible w/ breastfeeding

ketorolac, ibuprofen, tetracycline, doxycycline, sulfonamides (in healthy infant)

Anti-infectives for pregs or lactators

1. effective (not excessive doses)
2. punctal plugs
3. culture and sensitivity tests

Reason for culture and sensitivity tests (for pregs and lactators)

-confirm drugs are effective
-assist in better preg risk factor ratings

Geriatric patients- eyelid laxity/ectropion can ? retention time in conj sac, exacerbating local drug effects/cause toxicity.

increase

Minimum font size for visually impaired

12 point

Which font is better for visually impaired

san serif (no serif)

pharmacokinetics

distinct drug processes, factors, and processes whereby drugs are absorbed and distributed in the body, biotransformed, metabolized, and excreted from the body

Drug distrib over time and bioavail of drug at target can be predicted by

interrelationships of compartments and barriers of eye

What does avascularity in the eye enable?

direct route for ocular drugs w/o high absorption into systemic circulation

Tear Film

3 layers:
1. outer: oil from meibomian, retards evaporation, saline and meds can wash away lipids
2. central: aqueous, 95%, 7mm,thin centrally after blink. TBUT healthy 25 sec
3. basal (inner): glycoproteins from goblet cells of conj. Mucous, hydrophilic coating

What proteins do the tears contain (5)?

lysozymes, lactoferrins, gamma globulins, and other immune factors

What do tears supply to the corneal epithelium?

oxygen

Tear pH

7.4

Normal volume of tear layer

8-10mcl

normal tear flow is

0.5-22mcl/min

What kind of drugs can penetrate the tight junctions (zona occludens)?

lipid-soluble, non-ionized

what kind of drugs have longer T1/2 once in epithelium

lipophilic

How can a drug effectively penetrate the cornea?

balancee of hydrophilic and lipophilic properties

What part of the cornea stores the most drug (that partition lipid media)?

epithelium

The stroma has collagen bundles and keratocyts- which sotre hydrophilic drugs?

collagen- hydrophilic
keratocytes- lipophilic

What cornea structure is major ocular depot for hydrophilic drugs

stroma

Does the endothelium have tight junctions?

no

What can pigment granules (in iris) in the eye store?

lipophilic drugs

How do drugs enter and exit the aqueous humor?

enter- blood stream or cornea
exitt- blood or Schlemm's Canal

How do systemic drugs get into aqueous?

no tight junctions in caps, pass thru CB and diffuse into iris

What is the major ocular source of drug metab enzymes (2 rxns to start drug breakdown and removal from eye)?

ciliary body

How does CB enzymes break down and remove drugs?

phase 1 CYP 450 (oxidation and reduction); phase 2- conjugation; 3- metab/drugs removed thru uveal circulation blood flow.

role of lens with drugs

a barrier to prevent drugs from entering vitreous. anterior epithel can be damaged by drugs. lipophilic can slowly pass but not hydrophilic

What 3 classes of drugs can lead to cataract formation?

miotics, steroids, and phenothiazines. (MSP-- cataracts. More senile people get cataracts)

Blood-retinal barrier

tight junction in RPE, prevents hydrophilic drugs from passing

What is actively transported from the blood to the retina

glucose

What 2 pathways can the bloodstream remove drugs/metabs from eye?

1. retinal blood vessels (vitreous and retina) by active transport
2. uveal blood vessels (CB and iris) by bulk transport

Compartment

a region of tissue or fluid thru which a drug can diffuse and equilibrate w/ relative ease. (transparent- no direct blood supply)

Why does is take more time for a drug to diffuse between compartments than w/in a compartment?

each compartment is separated by a barrier

barrier

a region of lower permeability or restricted diffusion that exists between 2 compartments

What is the barrier between the tears and the cornea?

the epithelium

Fick's Law of diffusion

the rate of diffusion across a barrier is proportional to the concentration gradient between the compartments on either side of the barrier.once concentrations are equal, no drug penetrates

What does corneal absorption of drug depend on in first 10-20 min?

tear film concentration

zero-oder kinetics

release of drug is constant over time and is independent of the concentration present; occurs when there's a rate limiting barrier (carrier)

first-order kinetics

drug movement directly proportional to concentration difference across barrier. (passive); rate changes

A drug that's metabolized to inactive form inside eye?

loteprednol (corticosteroid)

bioavailability

amt of drug present at desired receptor site

ED50

(an effective dose) dose level producing a response that's 50% of maximum response

complex drug molecules will loose

stability in solution form at some point in time. Some drugs must be dissolved or prepared immediately before use

What 4 factors can affect the stability of drugs?

Oxidation and heat can break down drugs. Microbial contamination. Drugs in acidic medium can be more stable

When you combine active drug, preservative, and vehicle it results in what kind of solution? give number

hypotonic, less than 290 mOsm

290mOsm is equal to %

0.9% saline (NaCl)= normal physiologic osmolarity

What is added to adjust osmolarity?

salts, buffering agents, certain sugar

preservatives

to prevent growth of microorganisms

BAC- Benzalkonium chloride (surfactant) and Benzethonium chloride

antimicrobial(disrupt plasma membrane). toxic effects on tear film and corneal epithelium. allergies

chlorhexidine

block microbial metab. less effect on cornea

mercurial compounds like thimerosal

blocks microbial metab. most effective in weak acid solutions. no effect on tear film stability. pts. allergis

chlorobutanol

block microb metab.less effective than BAC but no known allergies. not effective alone. combine w/ EDTA

Parabens

block microb metab. used in AT and non-med ointments. allergies. unstable at high pH.

stabilzed oxychloro-complex & sodium perborate (oxidation)

in AT, turns into water and NaCl or water and oxygen--- non toxic!

EDTA

assists thimerosal, BAC, and others. can cause dermatitis. also has antioxidant props

antioxidants

delay deterioration of product by oxygen in air

Vehicles

aid in achieving appropriate tonicity, buffering, and viscosity.

PVP-polyvinylpyrrolidine

non-ionic polymer w/ binding and detox properties. no immune rejection. viscosity

PVA-polyvinyl alcohol

water soluble viscosity. 1.4%.non-irritating and helps heal corneal epi and dry eye

hydroxypropyl methylcellulose

viscosity enhancer. can increase tear film wetting time. help fluorescein and dexamethasone to get in cornea

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