Ophthalmic Medication Review and Update. Scott Ensor, OD, MS Associate Professor Southern College of Optometry
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1 Ophthalmic Medication Review and Update Scott Ensor, OD, MS Associate Professor Southern College of Optometry
2 Financial Disclosures None!
3 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
4 Basic Pharmacology Review
5 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)
6 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
7 Topical Administration Delivery of medication directly to ocular tissues Eye drops Solution Suspension Ointment
8 Topical Administration Advantages Ease of administration Don t forget to educate your patients Low cost (?) Good patient compliance (?)
9 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
10 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
11 Enteral Administration Administration by Mouth Pill, Capsule, Liquid Under tongue (sub-lingual) Directly absorbed into the blood stream
12 Enteral Administration Advantages Easily self-administered Low risk of systemic infections Easily overcome toxicities and overdose
13 Enteral Administration Disadvantages Complicated pathway to absorption Harsh environment of stomach Acidic environment breaks down many compounds Metabolism by liver First-pass metabolism
14 Antibiotics
15 A Word About Resistance 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
16 Topical Antibiotics 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
17 Fluoroquinolones 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
18 Ciprofloxacin Ciloxan (Ciprofloxacin.3%) Good against Pseudomonas Occasionally precipitates into the cornea Not visually significant
19 Moxifloxacin Moxeza (Moxifloxacin.5%) formally Vigamox Preservative free Xanthan gum base allowing easier dosing schedule
20 Gatifloxacin Zymaxid (Gatifloxacin.5%) formally Zymar Effective choice Higher concentration allows for easier dosing schedule
21 Besifloxacin Besivance (Besifloxacin.6%) Suspension Shake before using Unique chemistry among the fluoroquinolines NO systemic equivalent
22 Think about it 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
23 Aminoglycosides 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
24 Sodium Sulfacetamide 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
25 Erythromycin 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
26 Bacitracin 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
27 Polysporin 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
28 Polytrim 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!!
29 Systemic Antibiotics 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
30 Augmentin 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
31 Cephalexin (Keflex) 1 st 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
32 Doxycycline 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
33 Unique Property 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
34 Azithromycin (Zithromax) 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
35 Sulfamethoxazole + Trimethoprim Bactrim or Septra Use DS Two tablets BID for one week Caution if allergic to sulfa medications
36 Corticosteroids
37 Corticosteroids 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
38 Biochemistry Review 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
39 Why Taper? 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
40 Another Biochemistry Review 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
41 Ester vs. Ketone Topical ketone-based steroids Prednisolone Fluorometholone Dexamethasone Medrysone Rimexolone Topical ester-bases steroids Loteprednol
42 Loteprednol 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
43 Prednisolone 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 ohpthalmic steroids for the treatment of uveitic and corneal inflammations
44 Prednisolone 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 )
45 Dexamethasone 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
46 Fluorometholones 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
47 Difluprednate 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
48 Commonly Prescribed Systemic Steroids Methylprednisolone Medrol dose pack Easily prescribed dose is pre-divided Prednisolone Prednisone Triamcinolone Also effective topically (cream)
49 Adverse Effects Figure 26.6 (part 1) Chapter 26 MENU >
50 Adverse Effects Don t forget cataracts!! Figure 26.6 (part 2) Chapter 26 MENU >
51 NSAIDS
52 Non-Steroidal Anti-Inflammatory 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
53 Prolensa Bromfenac.07% Lower preservative concentration Does not burn Now approved for once a day dosing Formally bromday
54 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
55 Ilevro Nepafenac.3% NSAID pro-drug Effective in controlling pain and post-operative inflammation associated with cataract surgery Dosage is qd Formally Nevanac
56 Ketorolac 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
57 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
58 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
59 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
60 Treatment of Glaucoma
61 Topical Glaucoma Medications 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
62 Beta Blockers Timolol first introduced in 1978 Decreases aqueous production Shown to decrease IOP an average of 25% Exist in.25% and.5% concentrations
63 Beta Blockers 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!
64 Beta Blocker Reminders 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?
65 Beta Blockers 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
66 Prostaglandins 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
67 Prostaglandins 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
68 Prostaglandins 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
69 Carbonic Anhydrase Inhibitors Usually a second line medication Decreases aqueous production (as well as CSF) Averages a 15% reduction in IOP
70 CAIs 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
71 Alpha-adrenergic Agonists 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
72 Glaucoma Combinations Cosopt Timolol.5% + dorzolamide 2% Bid Also available PF Combigan Timolol.5% + brimonidine.2% q12h Simbrinza Brinzolamide 1% + brimonidine.2% tid
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