NBEO Ocular Pharm

Pilocarpine

MOA: opens up trabecular mesh work to increase outflow and decrease IOP
0.125% Dx Adies Tonic pupil vs Pharmacological
1% Dx sphincter tear from 3rd N palsy
Used before PI surgery, after AC GLC
S/E: brow ache, HA, myopic shift, cataracts, RD, pupillary block

Edrophonium

Myasthenia Gravis Dx, if ptosis improves= + MG

Cholinergic Antagonists

Scopolamine, tropicamide, atropine, cyclopentolate, homatropine (STopACH)

Scopolamine

Patch for motion sickness
S/E: CNS toxicity, hallucination, amnesia, unconsciousness,

Tropicamide

(15-20 min onset, 40 min max effect) standard of care for dilation.
Rare S/E

Atropine

("Big guns") (60-180 min onset, 7-12 days duration)
Amblyopia tx (penalization)
S/E: young children, Down's syndrome, elderly

Cyclopentolate

(Fastest onset, shortest duration) routine cycloplegic refraction, Tx anterior uveitis

Homatropine

Weak cycloplegic, Tx standard of care for anterior uveitis, dilates, prevents Post syn, reduce pain, stabilizes BAB
* always keep patients on steroid longer than homatropine for Ant. Uveitis BC can have an irreversible PS.

Adrenergic Agonists

phenylephrine, naphazoline, tetrahydrozoline

Phenylephrine

Used in combo w tropicamide, palpebral widening, Horner's Dx, 10% to break Post Syn
MOA: alpha 1 agonist. Dilation w out cycloplegic
C/I: MOAIs, TCAs, atropine, Grave's disease

Adrenergic agonist (alpha2)

Brimonidine, apraclonodine

Brimonidine

Alpha 2 agonist
Neuroprotective properties, miosis (reducing glare, halos, night vision probs)
S/E: follicular conjunctivitis (alphagan-P is better)
C/I: MAOIs

Apraclonidine

Alpha 2 agonist
Used to control IOP spikes after surgery
Also in Acute angle closure (rapid and potent!) 30-40% IOP decrease, but tachyphylaxis (reduced potency w use)
Dx Horner's

Adrenergic Antagonist ( B-blocker)

Timolol, cartelolol, betaxolol, levobunolol, metipranolol

Timolol

B blocker (adrenergic antagonist)
Crossover effect (IOP a reduction in other eye)
C/I: diabetics, hyperthyroidism, myasthenia Gravis (symptoms of weakness worsen, DV can occur)

Cosopt

Timolol + dorzolamide

Combigan

Timolol + brimonadine (alphagan)

GLC drugs reducing production

ABC's: Alpha 2 agonists (brimonadine), beta blockers (timolol), CAI (acetazolamide, brimzolamide)

GLC drugs increasing outflow

PAP's: Pilocarpine (ONLY corneoscleral outflow) alpha 2 agonists, prostaglandins (uveoscleral outflow)

Carbonic Anhydrase inhibitors

Brimzolamide, acetazolamide

Brinzolamide

CAI
Decrease bicarbonate ions (which increase aqueous production)
C/I : sulfa allergies (SJS)

Acetazolamide

CAI
During angle closure attacks
S/E: metallic taste, tingling in hands, metabolic acidosis
Aplastic anemia, gray baby syndrome

Prostaglandin Analogs

First line tx in POAG (27-35% IOP decrease)
Latanprost, travoprost, bimatoprost
FP receptors, uveoscleral mesh work outflow
PM dosing
C/I: CME, active inflammation, HSK
S/E: it is heterochromia, increase pigmentation, conjunctival hyperemia

Proparacaine

Proparacaine w Benoxinate: ester, onset 10-20 seconds, duration 15 min

Emedastine

H1 antihistamine (only 1)

Cromolyn, lodoxamide, pemirolast, nedocromil

(Crolom, Alomide, alamast, alocril) Mast Cell Stabilizers prevent calcium influx and degranulation
Effects begin in days to weeks after admins

Bepotastine, epinastine, ketotifen, loop standing, azelastine, olopatadine

(Bepreve, elestat, zaditor, patanol, optivar, pataday) mast cell stabilizer and H1 antihistamine
Combo is very effective for ocular itching, allergic conjunctivitis, and acute relief
All BID except pataday

Corticosteroids

Inhibits phospholipids A2-- arachidonic pathway (decrease fibroblast and collagen formation which prevents healing)
S/E: increase risk of secondary infxn, PSC, GLC
Potent steroid: prednisolone acetate, rimexolone, difluprednate (durezol), dexamethaxone
Soft steroid: FML, lotemax

NSAIDs

(Voltaren, acular LS, Nevanac, bromday, ocufen)
Block cyclooxygenase 1&2 inhibit conversion of arachidonic acid to prostaglandins and thromboxanes
Decreases CME, post op inflammation, RCE, and allergic conjunctivitis
S/E: corneal melting in Voltaren, stinging w ketorolac (Acular)

Ketoralac (Acular LS)

NSAID
Only one approved for seasonal allergic conjunctivitis

Diclofenac sodium (Voltaren)

NSAID
Withdrawn from market due to corneal melting

Bromfenac (Xibrom)

NSAID
Contains BAK

Flurbiprofen (Ocufen)

NSAID
Contains
Thimerosal

Fluorescein

Water soluble that is quickly dissolved in aqueous part of tears
Allows viewing of epithelial defects and tear film quality

Rose Bengal & Lissamine Green

Stains dead and devitalized cells (stains edges of dendrites in HSVK)
Mild antiviral properties

Methylene Blue

Similar staining as rose Bengal but also stains corneal nerves

Exudative ARMD agents

Pegaptanib (Macugen)- antineoplastic agent that decreases angiogenesis and inhibiting VEGF), Ranibizumab (Lucentis)- monoclonal antibody (Fab portion) anti VEGF

Glycerine (Osmoglyn)

High molecular weight, water soluble, unable to cross BAB, lowers IOP
Acute angle closure
Served w crushed ice and sipped to avoid vomiting
C/I: diabetics

Sodium Chloride (Muro 128)

Hypertonic solution to reduce corneal edema

Methylcellulose

Increases viscosity of solutions, allowing more contact time to cornea. Often used in tear substitutes.

Polyvinyl alcohol

Commonly incorporated into tear substitutes but less viscous than Methylcellulose.

Restasis

Cyclosporine 0.05% inhibits T cell activation by stopping production of interleukin-2

Benzalkonium chloride

BAK very common preservative known to cause corneal toxicity

Thimerosal

Preservative that is rarely used anymore due to corneal toxicity. Had Mercury components.

Ethylenediaminetetraacetic acid

EDTA preservative, chelating agent that commonly sequesters Calcium.

Purite/ sodium perborate

Oxidative preservatives found in Refresh tears and Genteal. Favored over traditional chemical preservatives bc they are effective and w less toxicity.

Drugs causing whorl keratopathy

Chloroquine, hydrochloroquine, amiodarone, indomethacin, tamoxifen (CHAI-T) and Fabry's Disease

Drugs causing SPK

Isotretinoin (accutane) topical aminoglycosides (gentamicin)

Drugs causing endothelial/Descemet's pigmentation

Chlorpromazine, thioridazine

Drugs causing stromal gold deposit

Gold salts

Drugs causing delayed healing

Steroids

Drugs causing anterior subcapsular effects

Chlorpromazine, thioridazine, amiodarone, and miotics (vacuoles)

Drugs causing PSC

Steroids

Drugs causing Dry Eye Syndrome

Anticholinergics, antidepressants (TCAs), antihistamines, accutane, ADHD meds (methylphenidate), oral contraceptives, B-blockers, Diuretics

Drugs affecting EOMS

Nystagmus: Phenytoin, phenobarbital, salicylates (NSAID)
DV: antidepressants, anti anxiety meds, phenytoin
Smooth pursuits: alcohol
Oculogyric crisis: phenothiazines, cetirizine** (abnormally positioned eye, usually elevated)

Drugs causing blue sclera

Minocyline, steroids

Drugs causing floppy iris

Tamsulosin (Flomax)

Drugs causing optic neuritis

Digoxin (retro bulbar), ethambutol (retro and bilateral), chloramphenicol, streptomycin, sulfonamides, isoniazid/methotrexate, oral contraceptives

Drugs causing B/Y color defect

Digoxin

Drugs causing NAION

Sildenafil, sumatriptan, amiodarone

Drugs causing papilledema

Oral contraceptives

Drugs causing pseudo tumor cerebri

Oral contraceptives, tetracyclines (doxycycline & minocycline), isotretinoin

Drugs causing Bulls eye maculopathy

Chloroquine, and less often in hydrochloroquine, thioridazine/chlorpromazine

Drugs causing CME

Epinephrine

Drugs causing white or yellow crystalline deposits

Tamoxifen (can also have macular edema)

Drugs causing retinal hemes

Indomethacin, NSAIDs, oral contraceptives

Drugs causing retinal pigmentary changes

Indomethacin

Drugs causing color vision loss & nyctalopia

Isotretinoin (Accutane)

How much topical ophthalmic drop is lost due to evaporation upon instillation?

25%

Where does drainage of an ophthalmic drug occur?

Nasolacrimal duct

Where does absorption into systemic circulation occur for an ophthalmic drug?

Conjunctival and lid vasculature

Bioavailability

Unchanged drug delivered

Lipid soluble in eye

Lipid layer, epithelium and endothelium

Water soluble in eye

Aqueous layer, stroma

How to maximize bioavailability in opthalmic drops?

Small, uncharged, lipid soluble molecules penetrate best (weak base)

Half life of a drug=?

0.693(Vd)/clearance
Larger Vd means longer half life