ophthalmic medication review and update - 20/20 memphis
TRANSCRIPT
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Ophthalmic Medication Review and Update
Scott Ensor, OD, MS
Associate Professor
Southern College of Optometry
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Financial Disclosures…
• None!
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About Me…
• Native Memphian
• 2001 SCO Graduate
• Primary Care Residency 2004
• Joined SCO faculty in 2008
• Started teaching Systemic Pharmacology I and II in 2011
• Master’s Degree in Pharmacology and Toxicology in 2013• Michigan State University
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Basic Pharmacology Review
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Routes of Administration
• Determined by• Properties of the drug
• Solubility, ionization, etc
• Therapeutic objectives• Rapid onset
• Chronic adminstration
• Restriction to a local site
• Setting in which it will be used
• 2 major routes• Enteral (by mouth)
• Parenteral (any other route)
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Ocular Medications
• 3 primary methods of administration• Topical
• Injection• Sub-conjunctival
• Intravitreal
• Retrobulbar
• Etc…
• Systemic (oral)
• Tissues of the anterior segment respond well to topical administration but posterior segment tissues usually require a different route
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Topical Administration
• Delivery of medication directly to ocular tissues• Eye drops
• Solution
• Suspension
• Ointment
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Topical Administration
• Advantages• Ease of administration
• Don’t forget to educate your patients
• Low cost (?)
• Good patient compliance (?)
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Topical Administration
• Disadvantages• Waste
• Requires frequent dosing• Less than 5% of administered drug enters the eye
• Some medications are formulated for longer contact with ocular tissue and/or increased drug concentrations
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Topical Administration
• Where does all of the medication go?• Nasolacrimal drainage
• Tear dilution
• Natural barriers• Cornea
• Conjunctiva
• Systemic absorption• All topically delivered medications can/will enter systemic absorption
• Conjunctival tissue is highly vascularized
• Bypasses first pass metabolism
• Watch for side effects
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Enteral Administration
• Administration by Mouth• Pill, Capsule, Liquid
• Under tongue (sub-lingual)• Directly absorbed into the blood stream
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Enteral Administration
• Advantages• Easily self-administered
• Low risk of systemic infections
• Easily overcome toxicities and overdose
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Enteral Administration
• Disadvantages• Complicated pathway to absorption
• Harsh environment of stomach• Acidic environment breaks down many compounds
• Metabolism by liver• First-pass metabolism
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Antibiotics
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• ALL topical antibiotics that have widely used oral counterparts will eventually develop resistance• However, ophthalmic preparations of antibiotics achieve a very high MIC
(minimal inhibitory concentration) and almost always overpower resistant bacteria• Frequency of dose appears to be more important than choice of antibiotic
• Use of broad-spectrum drugs is important
A Word About Resistance
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• Indication:• Evidence of a bacterial infection or a condition in which there is judged to be
a significant risk of opportunistic infection• IF no discharge – NO infection
• IF sector injection to conj – NO infection
• Usual dosage (depending on the choice of antibiotic)• Use frequently (every two hours) for first few days then switch to q.i.d. for 4
to 6 more days• Never use for less than 5 days
• Never taper antibiotics
Topical Antibiotics
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• Mechanism of Action• Inhibit bacterial DNA Gyrase and topoisomerase IV
• Broad spectrum, potent• Gram positive
• Gram negative (including Pseudomonas)
• MRSA
• Widely prescribed systemically• Resistance is developing
• Higher concentrations are more potent
Fluoroquinolones
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Ciprofloxacin
• Ciloxan (Ciprofloxacin .3%)
• Good against Pseudomonas
• Occasionally precipitates into the cornea• Not visually significant
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Moxifloxacin
• Moxeza (Moxifloxacin .5%) formally Vigamox
• Preservative free
• Xanthan gum base allowing easier dosing schedule
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Gatifloxacin
• Zymaxid (Gatifloxacin .5%) formally Zymar
• Effective choice
• Higher concentration allows for easier dosing schedule
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Besifloxacin
• Besivance (Besifloxacin .6%)
• Suspension• Shake before using
• Unique chemistry among the fluoroquinolines
• NO systemic equivalent
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• A 2013 article in Ophthalmology reported that repeated exposure to azithromycin and fluoroquinolones caused an increase in the number of Staph. epidermidis on the conjunctival surface.
• You may want to limit your use of these medications to severe corneal infections…
Think about it…
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• Mechanism of Action• Inhibits protein synthesis
• Effective against gram positive and gram negative• NO systemic equivalent!
• Known to cause ototoxicity
• Occasional allergic reaction• Not serious• Patient often knows ahead of time
• Available in solution and ointment• Gentamicin • Tobramycin (Tobrex)• Neomycin
• No pseudomonas coverage – usually combined with Polymyxin B
Aminoglycosides
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• Mechanism of Action• Prevents synthesis of Folic Acid
• Broad spectrum• Better against strep than staph
• Allergy is common• Patient will report sulfa (or sulfur) allergy
• Burns upon instillation
• Available in solution and ointment
Sodium Sulfacetamide
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• Mechanism of Action• Inhibits Protein Synthesis
• Broad Spectrum
• Non-toxic to cornea/conj
• Very safe in pregnancy
• Only available as ointment
• Limited therapeutic role due to high resistance• Used mainly in prophylactic role
Erythromycin
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• Mechanism of Action• Destroys bacterial cell wall
• Great gram-positive coverage
• Toxicity and allergic reactions are rare
• Safe in pregnancy
• Only available in ointment
• Used mainly for infectious blepharitis and for overnight coverage in treatment of bacterial corneal ulcers
Bacitracin
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• Bacitracin + Polymyxin B• Polymyxin B
• Mechanism of Action – destroys cell membranes
• Highly effective against gram negative
• Toxicity and allergic reactions are rare
• Good to use due to increased gram negative coverage over Bacitracin alone
• Available only in ointment
Polysporin
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• Polymyxin B + Trimethoprim• Trimethoprim
• Bacteriostatic
• Mechanism of Action – inhibits bacterial dihydrofolate reductase (similar MOA to sulfonamide)
• Not effective against pseudomonas
• VERY effective against Haemophilus and Strep. Pneumoniae
• Available in solution only• Solution of choice for peds!!
Polytrim
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• Be comfortable prescribing!
• Can be VERY effective in treating ocular conditions• Esp internal soft-tissue infections where eye drops are unlikely to penetrate
• Indications• Meibomian gland disease
• Rosacea blepharitis
• Internal hordeola
Systemic Antibiotics
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• Amoxicillin + Clavulanic Acid
• Useful in treating soft tissue infections• Great for pre-ceptal cellulitis or severe hordeolum
• CAN NOT use if patient is allergic to PCN
• Usual dosage is 500 mg or 875 mg bid x 1 week
• Can be taken with meals
• Digestive problems are a common side-effect• Make sure patient is aware
Augmentin
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• 1st Generation Cephalosporin• Same MOA as PCN
• 5-10% cross-sensitivity with PCN• Avoid in pts allergic to PCN
• Useful in soft tissue staph infections• Hordeola or pre-ceptal cellulitis
• Usual dosage is 500mg bid x 1 week
Cephalexin (Keflex)
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• Member of tetracycline family• Disrupts bacterial protein synthesis
• Contraindicated in pregnancy, nursing mothers, under age 8
• Photosensitivity warning
• Indicated in • Meibomianitis
• Adult Inclusion Conjunctivitis (Chlamydia)• Dose is 100 mg bid
• Recurrent Corneal Erosion
Doxycycline
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• Doxycycline is primarily an antibiotic• Has a secondary property
• Modify and enhance the lipid metabolism in oil producing glands• Restores more physiological lipid production
• This is why doxy is so useful in treating tear film dysfunctions• Dose is 50 mg bid x 2 weeks then qd x 3-6 months
Unique Property
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• Maintains effective concentration in soft tissue long after usual dose
• Usually given as Zpak (250 mg) or TriPak (500mg)• 2 tabs on day one followed by one tab for 4 days
• 1 tab a day for 3 days
• Drug of choice for chlamydial infections• 1000mg once for one day
• Very effective for hordeolum
• Potential cardiovascular problems…• May cause arrhythmias in some patients
Azithromycin (Zithromax)
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Sulfamethoxazole + Trimethoprim
• Bactrim or Septra• Use “DS”
• Two tablets BID for one week
• Caution if allergic to sulfa medications
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Corticosteroids
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• General Principles• Correct diagnosis is essential before prescribing
• Dose is given on an individual basis
• Avoid prolonged use if possible• Aggressive short-term use is better than under treatment
• Incidence of side-effects increases with time
• Should be tapered• Maybe not if one week use or less…
Corticosteroids
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• The hypothalamus produces corticotropic releasing factor (CRF)
• CRF travels to the pituitary and triggers the release of adrenocortotropic hormone (ACTH)
• ACTH causes the adrenal cortex to up-regulate the production of hydrocortisone and corticosterone
• When the level of steroid in plasma increases, production of ACTH declines
Biochemistry Review
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• 2 reasons• 1. Taking synthetic steroids slows production of physiologic steroids and the
taper allows the body time to re-start production• More pronounced with systemic steroids but studies have shown that .1%
dexamethasone four times a day for 6 weeks resulted in a decreased level of natural hormones
• 2. Rebound inflammation• Steroids suppress inflammation but do not resolve – abruptly discontinuing topical
steroids may allow the suppressed inflammation to come back
Why Taper?
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• The human body possesses abundant esterases but no ketones• Most topical steroids are ketone-based
• Ketone-bases steroids can not be broken down by the human body and thus linger in tissues• Good for therapeutic effect but bad for side effects
• Ester-based steroids generally have fewer side effects because they are broken down in the body
Another Biochemistry Review
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• Topical ketone-based steroids• Prednisolone
• Fluorometholone
• Dexamethasone
• Medrysone
• Rimexolone
• Topical ester-bases steroids• Loteprednol
Ester vs. Ketone
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• Ester-based• Greater safety profile
• Generally less chance of steroid-response increase in IOP
• Lotemax• Loteprednol 0.5% gel
• Becomes a liquid when out of bottle and even more when on the eye• Do NOT need to shake
• Loteprednol 0.5% ointment
• Alrex• Loteprednol 0.2%• Approved for treating allergic conjunctivitis
Loteprednol
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• Greatest anti-inflammatory efficacy of all topical ophthalmic steroids
• Prednisolone acetate 1% suspension• Pred Forte
• Omnipred
• Econopred
• Generic equivalent
• Pred Forte is proven to be the most effective of the topical ohpthalmicsteroids for the treatment of uveitic and corneal inflammations
Prednisolone
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• Prednisolone acetate .12%• Pred Mild
• Generic Equivalent
• Clinical Pearl:• Do not substitute generic for Pred Forte in the treatment of anterior uveitis
• Generic pred settles out of suspension too quickly (in my opinion…)
Prednisolone
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• Ketone-based
• Less clinically effective than pred
• Greatest ocular hypertensive effect
• Rarely used alone
• Available as .1% susp• Maxidex
• Generic
• Common steroid used in combo drops
Dexamethasone
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• Good to excellent anti-inflammatory properties
• Diminished effect on IOP
• Available as .1% susp and ointment• FML 0.1%
• Flarex
• FML Forte (0.25%)
• FML 0.1% ointment
Fluorometholones
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• Durezol - Difluprednate 0.05% oph emulsion• Difluorinated derivative of prednisolone
• Emulsion• Do not need to shake
• Enhanced ocular surface contact time• Reduced dosage
• Studies are showing as effective as Pred Forte with half the dose
Difluprednate
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• Methylprednisolone• Medrol dose pack
• Easily prescribed – dose is pre-divided
• Prednisolone
• Prednisone
• Triamcinolone• Also effective topically (cream)
Commonly Prescribed Systemic Steroids
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Figure 26.6 (part 1)
Chapter 26 MENU >
Adverse Effects
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Figure 26.6 (part 2)
Chapter 26 MENU >
Adverse Effects
Don’t forget cataracts!!
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NSAIDS
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• NSAIDS
• Inhibit the action of cyclo-oxygenase• Inhibits prostaglandin synthesis
• Prostaglandins are mediators of inflammation
• Uses• Prevention of intraoperative miosis
• Prevention/treatment of cystoid macular edema
• Topical analgesia and corneal photophobia
• NOT very effective for ocular inflammation
Non-Steroidal Anti-Inflammatory
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• Bromfenac .07%
• Lower preservative concentration• Does not burn
• Now approved for once a day dosing
• Formally bromday
Prolensa
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BromSite
• Bromfenac 0.075%
• First NSAID specifically approved for prevention of pain after cataract surgery
• Delivery vehicle developed to increase contact time with the ocular surface
• BID dosing
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• Nepafenac .3%
• NSAID pro-drug
• Effective in controlling pain and post-operative inflammation associated with cataract surgery
• Dosage is qd
• Formally Nevanac
Ilevro
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• 0.4% and 0.5% ophthalmic solution
• Available as a generic (formally Acular)
• Burns upon instillation
• QID dosing• Can be confusing to patients when substituted following cataract surgery
Ketorolac
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Treatment of Dry Eye Disease
• Identify the cause• Meibomian glands
• Aqueous deficiency
• Treat any eyelid/meibomain issue first• Include lipid-based AT
• 2000 mg Omega-3 supplement
• 50mg Doxy
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Treatment of Dry Eye Disease
• Consider early use of topical corticosteroid• Control inflammatory symptoms of dry eye
• Restasis• Cyclosporine 0.05 oph emulsion
• Now available in multi-dose bottle
• Can take 4-6 weeks for patient to notice improvement• Consider “jump-start” with corticosteroid
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Treatment of Dry Eye Disease
• Xiidra• Lifitegrast 5% oph solution
• Specifically blocks the interaction of two different inflammatory molecules• Decreases T-cell activation
• BID dosing
• Most patients report relief of symptoms earlier than with Restasis
• Side effects (seem to ease up after 3-4 weeks)• Irritation
• Metallic aftertaste
• Blurred vision
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Treatment of Glaucoma
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• Controlled clinical trials have demonstrated that reduction of IOP slows the occurrence and progression of glaucoma• Many pharmacological options exist for the control of IOP
• The “weak-link” in glaucoma therapy seems to be in public health• Patient education
• Art is in balancing efficacy, cost, and effect on patient lifestyle
Topical Glaucoma Medications
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• Timolol first introduced in 1978
• Decreases aqueous production
• Shown to decrease IOP an average of 25%
• Exist in .25% and .5% concentrations
Beta Blockers
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• Traditionally prescribed .5% bid• Timolol has a very long half-life
• .25% has been shown to be as effective as .5%
• Aqueous production is naturally reduced during sleep
• Best dose may be .25% qam!
Beta Blockers
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• Melanin pigment can bind drugs• Dose .5% qam for patients with darkly pigmented tissues
• Contraindications:• Asthma
• Decompensated CHF
• Symptomatic bradycardia or heart block
• History of syncope without diagnosis
• Heart rate <55 beats/min without known etiology
• Symptoms/complaints of dizziness without known etiology
• Diabetes?
Beta Blocker Reminders
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• Timolol• Maleate
• Istalol
• Timoptic
• Timoptic XE• Timoptic PF (Ocudose)
• Hemihydrate• Betimol
• Levobunolol• Betagan
• Betaxolol• Betoptic-S
*Only Timolol and Levobunolol have half-lives appropriate for once-a-day dosing
Beta Blockers
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• Have become “gold standard”
• Enhance aqueous outflow
• Achieve an average of 30% IOP reduction
• Use is once daily• Time of dose does NOT effect how the drug works
• Evening is preferred but NOT required
• Some evidence that every other day dosing may be effective
Prostaglandins
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• Latanoprost (Xalatan)• Now available as a generic
• Travaprost (Travatan Z)• Travatan no longer produced
• Brimatoprost (Lumigan)• All three medications perform similarly
• Travatan Z does not contain BAK• Lumigan has been shown to cause increased conjunctival hyperemia
• Unoprostone (Rescula)• “prostaglandin like” – dosed bid
• Tafluprost (Zioptan)• Preservative free
Prostaglandins
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• Side effects:• Conjunctival hyperemia
• Usually improves after a few months of use
• Increased pigmentation• Lashes, skin under eye, iris
• CME• Has been shown to increase risk after cataract surgery but most surgeons do not
discontinue use
Prostaglandins
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• Usually a second line medication
• Decreases aqueous production (as well as CSF)
• Averages a 15% reduction in IOP
Carbonic Anhydrase Inhibitors
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• Dorzolamide ophthalmic solution (Trusopt)• Currently difficult to get…
• Brinzolamide ophthalmic suspension (Azopt)• Dose for above is two to three times a day
• Acetazolamide• Systemic CAI• Usually used in angle closure situations• Available in 250mg tabs and 500mg ER tabs
• Avoid in patients with sulfa allergy?• Shares similar chemical structure• Questionable clinical evidence
CAIs
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• Decrease aqueous production
• Average a 20% to 25% IOP reduction
• Brimonidine (Alphagan) is important example• .2%
• .15%
• .1% (Alphagan-P)
• Approved for tid dosing but often used bid when used as a second drop• 8 hr effective zone followed by 4 hr low level
• Sometimes described as “neuroprotector” but no evidence exists for this added benefit
Alpha-adrenergic Agonists
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• Cosopt• Timolol .5% + dorzolamide 2%
• Bid
• Also available PF
• Combigan• Timolol .5% + brimonidine .2%
• q12h
• Simbrinza• Brinzolamide 1% + brimonidine .2%
• tid
Glaucoma Combinations