Topics in

Ophthalmology
Pharm 534
11/11/2015
Dan Hu, Pharm.D
 Whats pharmacy like out there?
Pokemon*

Baby birds
When I was your age
You could still get a hospital
job without a PGY-3
When do people call you
Dr. _____ as a Pharm.D?
 Whats next?
P4 rotations
Residencies/fellowships
Its hard to find PGY-7s
Oh I just use the
electronic version
 Whats next?
Scandal! April 1, 2015

NABP representative Ashton Gotya announced yesterday, We have

evaluated the oversupply of students and are responding appropriately.
Beginning in 2016 all PharmD degree students will now begin a 10-
year course of study.

The new 10-year PharmD is expected to boost tuition revenues at

Pharmacy schools by 9.3 billion dollars annually, while at the same
time reducing the number of graduating students to address the flooded
market.
 Whats next?
Pharmacy Forecast 2015-2019: Strategic Planning
Advice for Pharmacy Departments in Hospitals
and Health Systems

Salaries of entry-level health-system pharmacists are expected to

decline by at least 10% over the next five years

48% of panelists believe it is very likely and 35% said it is

somewhat likely that at least 50% of health systems will require
accredited residency training for entry-level clinical positions in
pharmacy practice.
Blank C. Entry-level salaries for hospital pharmacists expected to decline. Drug Topics website. http://drugtopics.modernmedicine.com/drug-topics/news/entry-level-salaries-hospital-pharmacists-expected-decline-0?page=full. February
10, 2015. Accessed April 1, 2015.
 [Not being very good] at something is
the first step to becoming sorta good at
something. - Jake the Dog
 Objectives
Compare and contrast pharmacokinetic and pharmacodynamic
properties of ophthalmic medications with systemic medications
Recognize anatomical features of the eye
Compare drugs used to treat glaucoma and ocular infections
Mechanisms of action
Frequency of dosing
Side effects
Explain patient education techniques for administration
List medications that have the potential to cause ocular toxicity
Non-objectives
Non-topical routes of administration
Closed-angle glaucoma
Ophthalmic drugs used in cataract surgery
Immunosuppressive and antimitotic agents
Diagnostic use of opthalmic drugs
Strabismus, blepharospasm
OTCs
See patient education slides
Ocular anatomy
Ocular anatomy
From: Chapter 64. Ocular Pharmacology
Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e, 2011

Legend:
Anatomy of the globe in relationship to the orbit and eyelids. Various routes of administration of anesthesia are demonstrated by the blue needle pathways.

Date of download: 9/8/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 64. Ocular Pharmacology
Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e, 2011

Legend:
Anatomy of the lacrimal system.

Date of download: 9/8/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 64. Ocular Pharmacology
Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e, 2011

Legend:
A. Anatomy of the eye. B. Enlargement of the anterior segment, revealing the cornea, angle structures, lens, and ciliary body. (Adapted with permission from
Riordan-Eva P. Anatomy and embryology of the eye. In, Vaughan & Asbury's General Ophthalmology, 17th ed. (Riordan-Eva P, Whitcher JP, eds.) McGraw-Hill,
New York, 2008. Copyright 2008 by The McGraw-Hill Companies, Inc. All rights reserved.)

Date of download: 9/8/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
 PK-PD
The time the drug remains on the surface of the
eye depends on the formulation
Prolonging the time in the cul-de-sac facilitates
drug absorption
Usually ocular drugs are administered topically

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs. Philadelphia; Elsevier-Saunders; 2008.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001; 2:4:1541-1552.
PK-PD
 PK-PD: absorption
Typically zero-order kinetics
Affected by
Residence time
Binding to tear proteins
Metabolism by tear and tissue proteins
Diffusion across cornea and conjunctiva
Nasolacrimal drainage
Highly vascular mucosal epithelium
First pass effect
Systemic absorption

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs. Philadelphia; Elsevier-Saunders; 2008.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001; 2:4:1541-1552.
 PK-PD: absorption
Approximately 1-10% of the Cul-de-sac can hold 25-40 L,
drug will penetrate blinking reduces to 10 L
Maximum bioavailability with Average blink rate 15-20
20 L drop size times/min
How big is a normal drop?
Lid manipulation increases basal
Most solutions leave cul-de- tear flow (15%) by 2-3 times
sac within 15-30 seconds Tear turnover is 30%/minute
Average cul-de-sac volume 7 after instillation, drop washout
L, precorneal tear film ~5 min.
volume 1 L
Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs. Philadelphia; Elsevier-Saunders; 2008.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001; 2:4:1541-1552.
Tasman W, Jaeger EA. Duane's Foundations of Clinical Ophthalmology. Lippincott, Williams, and Wilkins; 2007.
 PK-PD: absorption
Primary routes for local effects: transcorneal and
transconjunctival/scleral
Cornea
Trilaminar fat-water-fat (five per Tangri: epithelium, Bowmans
layer, stroma, Cescemets membrane, and endothelium)
Favors small lipophilic drugs
Epithelium is the rate-limiting barrier to hydrophilic
drugs/macromolecules
Conjunctiva
17 times the surface area of the cornea
Relatively permeable to hydrophilic drugs
Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs. Philadelphia; Elsevier-Saunders; 2008.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001; 2:4:1541-1552.
Tasman W, Jaeger EA. Duane's Foundations of Clinical Ophthalmology. Lippincott, Williams, and Wilkins; 2007.
 PK-PD: absorption
Sclera
Hydrophilic drugs can pass through 80 times faster than cornea
Lacrimal system can remove drug 100 times faster than cornea and
conjunctivas absorption rate

Small lipophilic molecules primarily absorbed by cornea

Large hydrophilic molecules primarily absorbed by
conjunctiva/sclera

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs. Philadelphia; Elsevier-Saunders; 2008.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001; 2:4:1541-1552.
Tasman W, Jaeger EA. Duane's Foundations of Clinical Ophthalmology. Lippincott, Williams, and Wilkins; 2007.
 PK-PD: distribution
Systemic distribution
Intraocular distribution
Aqueous humor, trabecular meshwork pathway
Melanin
Retinal pigment epithelium

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Ophthalmic formulations
Gels release drugs through the erosion of soluble
polymers
Ointments usually contain mineral oil/petrolatum base
Solid inserts zero-order rate of delivery via steady state
diffusion
Soft contact lenses
Collagen shields
Prolonging time in the cul-de-sac facilitates drug
absorption

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
Glaucoma
Open-angle aqueous humor accesses
trabecular meshwork
Closed-angle obstruction
Visual field changes, progressive optic
neuropathy, structural changes
 Glaucoma
Epidemiology
Primary open angle glaucoma (POAG) is the most
common type
Leading cause of blindness in African Americans
Second leading cause of blindness worldwide
Angle closure glaucoma (ACG) highest in Inuit
population, also in East Asians

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Levin LA, Albert DM. Ocular Disease: Mechanisms and Management, 1st Edition. Saunders; 2010.
 Glaucoma -risk factors
IOP previously considered to be the sole cause of damage
IOP >30 usually causes damage to optic nerve
IOP >21 was previously considered abnormal
Some patients can tolerate high 20s (ocular hypertensives)
Normal- and low-tension glaucoma
Many factors (ischemia, autoimmune, abnormal
physiologic processes) lead to retinal ganglion cell death
loss of vision
Reduction of IOP by 30% reduction in progression
from 35% to 10% (even for normal-tension)
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Levin LA, Albert DM. Ocular Disease: Mechanisms and Management, 1st Edition. Saunders; 2010.
 Glaucoma
Open-angle
Aqueous humor accesses trabecular meshwork
Visual field loss usually the first symptom
IOP elevated or normal
Visual field changes, progressive optic
neuropathy, structural changes

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Levin LA, Albert DM. Ocular Disease: Mechanisms and Management, 1st Edition. Saunders; 2010.
 Glaucoma
Closed-angle
Obstructive
Asymptomatic, or prodromal or acute symptoms
Markedly elevated IOP
Acute attack usually treated with pilocarpine,
hyperosmotic agents, and a secretory inhibitor
Treatment is usually surgical

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Levin LA, Albert DM. Ocular Disease: Mechanisms and Management, 1st Edition. Saunders; 2010.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/24/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/24/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
 Glaucoma

Distelhorst JS, Hughes GM. Open Angle Glaucoma. American Family Physician. 2003; 1;67(9): 1937-1944.
 Glaucoma

Distelhorst JS, Hughes GM. Open Angle Glaucoma. American Family Physician. 2003; 1;67(9): 1937-1944.
 Glaucoma

Distelhorst JS, Hughes GM. Open Angle Glaucoma. American Family Physician. 2003; 1;67(9): 1937-1944.
 Glaucoma drug induced
Topical anticholinergics (mydriasis) can increase
IOP
Glucocorticoids cause accumulation of
extracellular material in the trabecular
meshwork reduce aqueous outflow

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/26/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/26/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/26/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
From: Chapter 75. Glaucoma
Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014

Date of download: 9/26/2014 Copyright 2014 McGraw-Hill Education. All rights reserved.
 Glaucoma - treatment
Start with one eye first to assess efficacy and
tolerance
Pharmacologic options
Beta-blocking agents
Alpha-2 adrenergic agonists
Nonspecific adrenergic agonists
Carbonic anhydrase inhibitors
Prostaglandin analogs
Direct cholinergic agents
Cholinesterase inhibitors
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Beta-blockers
Commonly first agents of choice
Lower IOP by 20-30%
Mechanism
Reduce aqueous production of ciliary body, exact MOA
uncertain
Decrease cAMP by preventing catecholamine
stimulation at receptor
Decrease ocular blood flow ultrafiltration aqueous
production
All generally reduce IOP to a similar degree
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Beta-blockers - ADR
Systemic events decreased rate/BP,
bronchospasm, etc (same as systemic
beta-blockers)
One drop of timolol 0.5% in each eye
is similar to taking 10 mg orally. PL
Use with caution in patients with
pulmonary disease, heart block, CHF,
diabetes, and concomitant PO beta-
blockers

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Ophthalmology. Pharmacists Letter. Pharmacist's Letter 2013; 29(7): Detail-Document #290705. http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?
cs=&s=PL&pt=6&fpt=31&dd=290705&pb=PL&searchid=48823811#dd
 Beta-blockers
Betaxolol - relatively beta-1 selective, Betoptic-S is a suspension
formulation
Better tolerated but not as effective
Carteolol non-selective
Levobunolol (Betagan)
Metipranolol (OptiPranolol)
Timolol (Timoptic, Betimol, Istalol) Timoptic-XE is a gelling
solution
All are BID except timolol (1 drop 1-2 times daily for solution, 1 drop
daily for gelling solution)
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Break

Tetrahydrozoline
 Break

Spiller HA, Rogers J, Sawyer TS. Drug facilitated sexual assault using an over the counter ocular solution containing tetrahydrozoline (Visine). Legal Medicine. 2007; 9: 192-195.
 Alpha agonists
Structurally similar to clonidine
Mechanism
Decrease rate of aqueous humor production (with some increase in
uveoscleral outflow)*

*Goodman and Gilman apply uveoscleral outflow to both,

DiPiro only to brimonidine

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Alpha agonists - ADR
High rate of adverse reactions
Keratitis, loss of eyelashes, stenosis of nasolacrimal
duct
Allergic-type reaction (lid edema, eye discomfort,
itching, etc)
Apraclonidine 30%, brimonidine 8%
Use >1 year may result in pigmentation of
conjunctiva/cornea
Transient increase in IOP on initiation

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Alpha agonists - ADR
Systemic reactions
Headache, faintness,
increase BP, tachycardia,
perspiration
Use cautiously in patients
with cardiovascular
disease

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Alpha agonists
Brimonidine
Similar efficacy to beta-blockers
Contraindicated in infants due to apneic spells and hypotension
Combination with timolol Combigan
Apraclonidine
Tachyphylaxis
Better tolerated than clonidine (no longer used)
Less systemic effects
*Goodman and Gilman occasionally label this as a beta-2 agonist

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Prostaglandin analogs
Mechanism
Increase uveoscleral outflow of aqueous humor
Some increase in trabecular outflow
Once daily doses are attractive to patients
Often greater reduction in IOP than seen with timolol
Given at nighttime why is this important?
Well tolerated, 10-15% local intolerance

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Prostaglandin analogs
Latanoprost (Xalatan)
Bimatoprost (Lumigan) ALSO FDA approved for?
Tafluprost (Zioptan) preservative free
Travoprost (Travatan Z)
Unoprostone (Rescula)

All are one drop nightly except unoprostone which is BID

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Prostaglandin analogs - ADR
Altered iris pigmentation in
15-30% of patients
browner eyes
Irreversible
Hypertrichosis,
hyperpigmentation around
lashes and lids
Reversible
ADR?
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Tosti A, Pazzaglia M, Voudouris S, Tosti G. Hypertrichosis of the eyelashes caused by bimatoprost. Journal of the American Academy of Dermatology. 2004; 51 (6): S149-S150.
 Break

Jones D. Enhanced eyelashes: prescription and over the counter options. Aesth Plast Surg. 2011; 35: 116-211.
Jones D. Enhanced eyelashes: prescription and over the counter options. Aesth Plast Surg. 2011; 35: 116-211.
Jones D. Enhanced eyelashes: prescription and over the counter options. Aesth Plast Surg. 2011; 35: 116-211.
 Carbonic anhydrase inhibitors
Mechanism
Reduce IOP by decreasing ciliary body production of
aqueous humor
Block sodium and bicarbonate ion excretion
Topical and systemic agents

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Carbonic anhydrase inhibitors
Topicals - 1 drop q8-12h
Brinzolamide
Less stinging, more blurry vision than
dorzolamide
Simbrinza (suspension) combination
product with brimonidine
Dorzolamide
Cosopt combination product with
timolol

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Carbonic anhydrase inhibitors
Systemic carbonic anhydrase inhibitors
If patient fails maximum topical therapy
Topical + systemic CAI for maximum benefit?
Reduce IOP by 25-40%

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Carbonic anhydrase inhibitors - ADR
Often produce intolerable adverse reactions
only 30-60% can tolerate long-term
Symptom complex due to acidosis including malaise,
fatigue, anorexia, nausea, altered taste, renal calculi,
blood dyscrasias, diuresis
Third-line, short term administration
Use with caution in patients with sulfa
allergies
Hypokalemia with other diuretics
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Kelley TE, Hackett PH. Acetazolamide and Sulfonamide Allergy: A Not So Simple Story. High Altitude Medicine and Biology. 2010; 11 (4): 319-323.
 Parasympathomimetics
Mechanism
Increase aqueous humor
trabecular outflow, may increase
uveoscleral outflow do not
affect aqueous production
Ciliary muscle contraction
pulls trabecular meshwork open
Frequent dosing
requirements/adverse
reactions
DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Parasympathomimetics - ADR
Can worsen ocular inflammatory conditions
Systemic effects diaphoresis, nausea, vomiting,
diarrhea, cramping, urinary frequency, bronchospasm
opposite of the anticholinergic song
Miosis (decrease night vision, vision in patients with
central cataracts)
Young patients often unable to tolerate miotic therapy
due to induced myopia
Frontal headache, periorbital pain, eyelid twitching,
conjunctival irritation lessens after 3-5 weeks

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Parasympathomimetics
Pilocarpine
Parasympathomimetic agent of choice in
POAG
Multiple formulations (solution, ocular
insert, hydrophilic polymer gel)
Similar IOP reduction as beta-blocking
agents
Darkly pigmented eyes require higher
concentrations of pilocarpine

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Whats next? Coming 2016?

Vermes K. New glaucoma treatment on track for approval. Pharmacy Times website. http://www.pharmacytimes.com/product-news/new-glaucoma-treatment-on-track-for-fda-
approval. September 28, 2015. Accessed October 29, 2015.
 Bacterial infection
Dacryoadenitis lacrimal gland
Dacryocystitis lacrimal sac
Hordeolum stye
Blepharitis eyelids
Conjunctivitis conjunctiva
Keratitis cornea
Endophthalmitis intraocular tissues

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Bacterial infection
GENERIC NAME (TRADE NAME) FORMULATIONa TOXICITY
Azithromycin(azasite) 1% solution H
Bacitracin 500 units/g ointment H
Besifloxacin (besivance) 0.6% suspension
Chloramphenicol 1% ointment H, BD
Ciprofloxacin hydrochloride(ciloxan, others) 0.3% solution; 0.3% ointment H, D-RCD
Erythromycin(ilotycin, others) 0.5% ointment H
Gatifloxacin(zymar) 0.3% solution H
Gentamicin sulfate(garamycin, genoptic,gent-ak, 0.3% solution; 0.3% ointment H
gentacidin, others)
Levofloxacin(quixin, iquix) 0.5% solution H
Levofloxacin(iquix) 1.5% solution H
Moxifloxacin(vigamox) 0.5% solution H
Ofloxacin(ocuflox, others) 0.3% solution H
Sulfacetamide sodium(bleph-10,cetamide,30% 1%, 10%, 15%, and 10% ointment H, BD
solution;isopto cetamide, others)
Polymyxin Bcombinationsb Various solutions and ointments
Goodman LS, Brunton LL, Gilman A, cChabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Bacterial infection

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs, 1st Edition. Philadelphia; Elsevier-Saunders; 2008.
 Bacterial infection
Neonatal conjunctivitis
Infection of the birth canal can infect the infant
Chlamydia is the most common cause
Erythromycin within 1 hour of birth
Fun fact what else is erythromycin used for?

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Viral infection
Primary indications for antivirals
Keratitis corneal inflammation
Herpes zoster ophthalmicus
Reinitis
Treatment usually requires systemic therapy

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Fungal infection
Only one topical available natamycin (Natacyn), others
must be compounded
2005-2006 epidemic of Fusarium fungal keratitis
The findings from this investigation indicate that this
outbreak ofFusariumkeratitis was associated with use
of ReNu with MoistureLoc contact lens solution. Contact
lens users should not use ReNu with MoistureLoc.
Chang et al, 2006

Chang DC, Grant GB, ODonnell K, et al. Multistate Outbreak ofFusarium Keratitis Associated With Use of a Contact Lens Solution. JAMA.2006;296(8):953-963.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York; McGraw-Hill Medical; 2011.
 Fungal infection

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs, 1st Edition. Philadelphia; Elsevier-Saunders; 2008.
 Steroids
Dexamethasone (Dexasol)
Prednisolone (Pred Forte)
Fluorometholone (FML)
Ioteprednol (Alrex)
Rimexolone (Vexol)
Difluprednate (Durezol)
Other steroids can be used for treatment via systemic or
intravitreal injection

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Steroids
Mechanism
Anti-inflammatory effects useful for may ocular
conditions
Allergy, anterior uveitis, external eye inflammatory
diseases associated with some infections and ocular
cicatricial pemphigoid, and postoperative inflammation
following refractive, corneal, and intraocular surgery
Can reduce post-surgical scarring

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Steroids
Adverse reactions
Development of cataract, secondary infection, secondary
open-angle glaucoma (pathophysiology not well
understood)
Can reversibly elevate IOP, especially with family
history

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 NSAIDs
Flurbiprofen (Ocufen) counters miosis during cataract
surgery
Ketorolac (Acular) seasonal allergic conjunctivitis
Diclofenac (Voltaren) post-operative inflammation
Bromfenac (Xibrom), Nepafenac (Nevanac) post-
operative pain and inflammation after cataract surgery

Adverse reactions occasionally associated with sterile

corneal ulcer

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Toxicity
Topiramate
Can cause choroidal effusions anterior rotation of
ciliary body angle closure glaucoma
Hydroxychloroquine, chloroquine
Retinal toxicity via unknown mechanism
Can be up to 6 years before toxicity manifests
Irreversible damage
Tamoxifen
Crystalline maculopathy

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Toxicity
Sildenafil, vardenafil, tadalafil
Inhibit PDE-6 which impacts the retina
Causes light sensitivity or bluish haze
Weak causative link
Systemic/topical steroids
Elevate IOP
Cataract formation

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Toxicity
Isotretinoin
Drying effect on mucosal membranes
Amiodarone
Drug deposits in cornea cornea verticillata
Generally do not affect vision
Disappears on discontinuation

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
 Toxicity
Gold treatments
Deposition in the cornea and
conjunctiva - chrysiasis
Generally do not affect vision
Tetracyclines
Yellow discoloration of
conjunctiva that is exposed to Chrysiasis is derived from chrysos, a Greek
light word which originated from chrysanthos,
Minocycline can cause blue-gray meaning golden flower

scleral pigmentation
Ahmed SV, Sajjan R. Chrysiasis: a gold curse! BMJ Case Reports. 2009; 2009.
Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New York; McGraw-Hill Medical; 2011.
Santos-Bueso E, Ahmed-Wasfy M, Saenz-Frances F, et al. Corneal chrysiasis. Gold salt deposits in the cornea in a patient with rheumatoid arthritis. An analysis with confocal microscopy.
Archivos de la Sociedad Espanola de Oftalmologia. 2013; 88 (6): 237-239.
 Toxicity
Chemicals
Bleach
Ammonia
Methanol

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs, 1st Edition. Philadelphia; Elsevier-Saunders; 2008.
Administration
Opthalmic drops can be used in the ears
Opthalmic drops can be used orally
 Patient education
Side effects
Pharmacoionics* Local
To go
Noncompliance in glaucoma
Systemic
24-83% per Tasman Contact lens wearers
25-60% per DiPiro Darrells Story
Once-daily vs. BID

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Tasman W, Jaeger EA. Duane's Foundations of Clinical Ophthalmology. Lippincott, Williams, and Wilkins; 2007.
 Patient education
Administration
Wash and dry hands, shake bottle if it contains a suspension
Remove contact lenses
Head tilted upward, pull lower eyelid down
Grasp bottle and brace hand against cheek or nose
Place dropper over the eye, look at the tip of the bottle, place
single drop in the eye
Close lids for 1-3 minutes, do not squeeze or rub, use
nasolacrimal occulsion

Many patients cannot put in their own eye

drops

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th Edition. New York; McGraw-Hill Medical; 2014.
Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs, 1st Edition. Philadelphia; Elsevier-Saunders; 2008.
Last remarks
Pharmacokinetics are often different for ophthalmic
drugs

Systemic medications can be used to treat local ocular

disease

Local ocular medications can cause systemic side effects

Patient education is VITAL

Last remarks

Marshmallows and pharmacy

 Last remarks
Whats next? Pharmacy Forecast 2015-2019
25% said it is very likely and 41% said it is somewhat
likely that at least 50% of health-system pharmacy
students on experiential rotations will provide essential
patient-care services.

Pharmacists reigned supreme in Forbes list of

best health care jobs in 2015.
The growth rate for pharmacists is 14% by 2022

Blank C. Entry-level salaries for hospital pharmacists expected to decline. Drug Topics website. http://drugtopics.modernmedicine.com/drug-topics/news/entry-level-salaries-hospital-pharmacists-expected-decline-0?page=full. February
10, 2015. Accessed April 1, 2015.
Ross M. Pharmacist Tops Forbes List of Best Health Care Jobs in 2015. Pharmacy Times website. http://www.pharmacytimes.com/news/Pharmacist-Tops-em-Forbes-em-List-of-Best-Health-Care-Jobs-in-2015. December 9, 2014.
Q/A
 References
Ahmed SV, Sajjan R. Chrysiasis: a gold curse! BMJ Case Reports. 2009; 2009.

Blank C. Entry-level salaries for hospital pharmacists expected to decline. Drug Topics website.
http://drugtopics.modernmedicine.com/drug-topics/news/entry-level-salaries-hospital-pharmacists-expected-decline-0?page=full . February 10, 2015.
Accessed April 1, 2015.

Chang DC, Grant GB, ODonnell K, et al. Multistate Outbreak ofFusarium Keratitis Associated With Use of a Contact Lens Solution.
JAMA.2006;296(8):953-963.

DiPiro J, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9 th Edition. New York; McGraw-Hill Medical; 2014.

Distelhorst JS, Hughes GM. Open Angle Glaucoma. American Family Physician. 2003; 1;67(9): 1937-1944.

Fraunfelder FT, Fraunfelder FW, Chambers WA. Clinical Ocular Toxicology: Drugs, Chemicals, and Herbs, 1 st Edition. Philadelphia; Elsevier-Saunders;
2008.

Goodman LS, Brunton LL, Gilman A, Chabner B, Knollman BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition. New
York; McGraw-Hill Medical; 2011.

Jones D. Enhanced eyelashes: prescription and over the counter options. Aesth Plast Surg. 2011; 35: 116-211.

Kelley TE, Hackett PH. Acetazolamide and Sulfonamide Allergy: A Not So Simple Story. High Altitude Medicine and Biology. 2010; 11 (4): 319-323.
 References
Levin LA, Albert DM. Ocular Disease: Mechanisms and Management, 1 st Edition. Saunders; 2010.

Ophthalmology. Pharmacists Letter. Pharmacist's Letter 2013; 29(7): Detail-Document #290705.

http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?cs=&s=PL&pt=6&fpt=31&dd=290705&pb=PL&searchid=48823811#dd

Ross M. Pharmacist Tops Forbes List of Best Health Care Jobs in 2015. Pharmacy Times website.
http://www.pharmacytimes.com/news/Pharmacist-Tops-em-Forbes-em-List-of-Best-Health-Care-Jobs-in-2015. December 9, 2014. Accessed April 1, 2015.

Santos-Bueso E, Ahmed-Wasfy M, Saenz-Frances F, et al. Corneal chrysiasis. Gold salt deposits in the cornea in a patient with rheumatoid arthritis. An
analysis with confocal microscopy. Archivos de la Sociedad Espanola de Oftalmologia. 2013; 88 (6): 237-239.

Spiller HA, Rogers J, Sawyer TS. Drug facilitated sexual assault using an over the counter ocular solution containing tetrahydrozoline (Visine). Legal
Medicine. 2007; 9: 192-195.

Tangri P, Khurana S. Basics of ocular drug delivery systems. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2001;
2:4:1541-1552.

Tasman W, Jaeger EA. Duane's Foundations of Clinical Ophthalmology. Lippincott, Williams, and Wilkins; 2007.

Tosti A, Pazzaglia M, Voudouris S, Tosti G. Hypertrichosis of the eyelashes caused by bimatoprost. Journal of the American

Vermes K. New glaucoma treatment on track for approval. Pharmacy Times website. http://www.pharmacytimes.com/product-news/new-glaucoma-
treatment-on-track-for-fda-approval. September 28, 2015. Accessed October 29, 2015.Academy of Dermatology. 2004; 51 (6): S149-S150.

Yanoff M, Duker JS, eds. Yanoff & Duker Ophthalmology, 3rd Edition. St. Louis, Mo: Mosby Inc; 2008.