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Pharmacology A to Z I. II. Review of Goals and Objectives of Lecture a. Be comfortable with the medications discussed. b. Be able to recognize the uses for each of the medications discussed. c. Know the indications and contraindications of each of the medications discussed. d. Be able to recognize the potential ocular effects of these medications. e. Be able to interact with the presenters and other attendees. Review of Medications A to Z a. Azasite i. Indications, contraindications, dosages b. Botox i. Indications, contraindications, dosages c. Combigan i. Indications, contraindications, dosages d. Doxycycline i. Indications, contraindications, dosages e. Elestat i. Indications, contraindications, dosages f. FreshKote i. Indications, contraindications, dosages g. Gabapentin i. Indications, contraindications, dosages h. Hytrin i. Indications, contraindications, dosages i. Istalol i. Indications, contraindications, dosages j. Januvia i. Indications, contraindications, dosages k. Keflex i. Indications, contraindications, dosages l. Lotemax i. Indications, contraindications, dosages m. Macugen i. Indications, contraindications, dosages n. Nevanac i. Indications, contraindications, dosages o. Optivar i. Indications, contraindications, dosages p. Plaquenil i. Indications, contraindications, dosages q. Quixin i. Indications, contraindications, dosages r. Retisert i. Indications, contraindications, dosages III. s. Salagen i. Indications, contraindications, dosages t. Tamoxifen i. Indications, contraindications, dosages u. Ultram i. Indications, contraindications, dosages v. Vigamox i. Indications, contraindications, dosages w. Warfarin i. Indications, contraindications, dosages x. Xibrom i. Indications, contraindications, dosages y. Yodoxin i. Indications, contraindications, dosages z. Zylet i. Indications, contraindications, dosages Potential Ocular Sequelae of A to Z Medications Pharmacology A to Z Jeffrey R. Varanelli, OD, FAAO Nicholas Colatrella, OD, FAAO A Azasite (azithromycin ophthalmic solution 1%) Inspire Pharmaceuticals Broad-spectrum coverage against the most common gram-positive and gram-negative bacteria as well as atypical bacteria Gel-forming drop persists on the ocular surface much longer than conventional aqueous drops with minimal blurring Indications treatment of bacterial conjunctivitis caused by the following organisms: CDC coryneform group G, Staphylococcus aureus, Streptococcus mitis group, Streptococcus pneumoniae, and Haemophilus influenzae Adverse events most common was eye irritation (1-2%) Other adverse events (<1%) burning, stinging, and irritation upon instillation contact dermatitis corneal erosion dry eye nasal congestion ocular discharge punctate keratitis sinusitis Dosage 1 drop BID for 2 days, followed by 1 drop QD for the next 5 days 9 drops total use in patients with lid margin disease B Botox® Botulinum Toxin Type A produced from fermentation of Hall strain Clostridium botulinum type A Indications treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above. efficacy in deviations over 50 prism diopters, in restrictive strabismus, in Duane's syndrome with lateral rectus weakness, and in secondary strabismus caused by prior surgical overrecession of the antagonist has not been established Blepharospasm EMG guidance Injected into medial and lateral pre-tarsal orbicularis oculi Avoid levator to avoid ptosis Initial effect seen within 3 days May see swelling/ecchymosis Strabismus EMG guidance or surgical exposure recommended Creates paralysis of injected muscle Lasts 2-6 weeks Recommendations Vertical muscles and horiz 1.25-2.5 units in any one muscle Horizontal strabismus (202.5-5.0 units in any one muscle Persistent CN VI palsy (> 1 month) 1.25-2.5 units in medial rectus C Combigan™0.2/0.5% Allergan 2 mg/mL of brimonidine tartrate and 5 mg/mL of timolol Dosage 1 drop in affected eye(s), twice daily, approximately 12 hours apart Indications indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP Contraindications Bronchial asthma, a history of bronchial asthma, severe COPD Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock Hypersensitivity to any component of this product D Doxycycline Tetracycline family Bacteriostatic Inhibit protein synthesis Careful of resistance Good gram positive and gram negative coverage Indications Blepharitis Meibomian Gland Disease Recurrent Corneal Erosion Rosacea Contraindications Pregnancy Category D Children under 8 Precautions Photosensitivity Dosage 100 mg BID x _____ days Taper as needed Monitor closely E Elestat (epinastine HCl 0.05%) Inspire Pharmaceuticals Anti-histamine with mast cell-stabilizing activity Indications For the prevention of ocular itching associated with allergic conjunctivitis Contraindications In patients who have shown hypersensitivity to epinastine or to any of the other ingredients Administration BID dosing Adverse effects burning sensation, hyperemia, pruritus Non-ocular adverse events were infection (cold symptoms and upper respiratory infections), headache, rhinitis, sinusitis, increased cough, and pharyngitis Recent studies about the ocular surface after ELESTAT® treatment No change in corneal staining No change in tear volume No change in tear-film break-up time F FreshKote Focus Laboratories 2.0% Polyvinyl pyrrodilone 0.9% Polyvinyl alcohol (87% hydrolyzed) 1.8% Polyvinyl alcohol (99% hydrolyzed) Treats all 3 tear film layers Lipid layer Aqueous layer Mucin layer Has a high oncotic pressure Re-establishes integrity of epithelium Reduces microcystic edema Prevents recurrent damage Indications: a lubricant indicated for the treatment of moderate to severe dry eye Contraindications: in patients with known severe hypersensitivity to any of the ingredients in the formulation Prescription only Supplied in 3.5 ml or 15 ml bottles Dosage 1 or 2 drops in affected eye(s) as needed G Gabapentin (Neurontin, Gabarone) GABA analog initially synthesized to mimic the structure of gamma-aminobutyric acid (GABA) Mechanism of Action: unknown Indications Epiliepsy Post-herpetic neuralgia Contraindications/Cautions Impaired renal function Elderly patients Hypersensitivity to drug/class/compound Off label uses Migraines Neuropathic pain Neuropathic pain Post-PRK use 100-300 mg tid x days Benefit to prescribing before surgery? Maximum daily dose 3600 mg H Hytrin (terazosin) alpha-adrenergic blocker causes the blood vessels to dilate also relaxes muscles in the prostate and bladder neck used to treat hypertension and benign prostatic hyperplasia (BPH) Sympathetic stimulation of ANS causes pupillary _____ Alpha 1 blocker Leads to miosis Challenges in cataract surgery IFIS Intraoperative Floppy Iris Syndrome poor pre-operative pupil dilation iris billowing and prolapse progressive intra-operative miosis Optometrist’s role Be cautious of patient medications Review case with co-managing surgeon Ophthalmologist’s role Iris hooks, iris retractors, OVD (Healon 5) I Istalol 0.5% (timolol maleate 0.5%) Ista Pharmaceuticals non-selective beta-blocker has the action of reducing elevated as well as normal IOP Indications treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma Contraindications bronchial asthma history of bronchial asthma severe COPD sinus bradycardia second or third degree atrio-ventricular block overt cardiac failure cardiogenic shock hypersensitivity to any component of this product Cautions Same as other beta blockers Dosage/Administration 1 drop in affected eye(s) qAM Concomitant treatment with other beta blocker not recommended Onset of Action usually detected within 30 minutes after a single dose maximum effect usually occurs in 1-2 hours significant lowering of IOP can be maintained for periods as long as 24 hours with a single dose repeated observations over a period of one year indicate that the IOP lowering effect of ISTALOL is well maintained J Januvia (sitagliptin) Merck Increases insulin made in pancreas Decreases sugar made in liver Combine with proper diet and exercise Indications as an adjunct to diet and exercise to improve glycemic control in adults with Type 2 DM JANUVIA should not be used in patients with type 1 diabetes JANUVIA should not be used for the treatment of diabetic ketoacidosis JANUVIA has not been studied in combination with insulin Contraindications History of a serious hypersensitivity reaction to sitagliptin Dosage/Administration 100 mg tablet once a day With or without food No ocular side effects noted Newer studies K Keflex (cephalexin) Cephalosporin Gram positive and Gram negative Indications treatment of the following infections when caused by susceptible strains of the designated microorganisms: Respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes Otitis media due to Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Moraxella catarrhalis Skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes Bone infections caused by Staphylococcus aureus and/or Proteus mirabilis Genitourinary tract infections, including acute prostatitis, caused by Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae Contraindications Those with known allergy to cephalosporin group of antibiotics Supplied as: 250 mg capsules 333 mg capsules 500 mg capsules 750 mg capsules Relevance to Optometry Pre-septal cellulitis 250-500 mg qid Hordeolum 250 mg tid Any external lid disease Red, swollen eyes/lids L Lotemax (loteprednol etabonate 0.5%) Bausch and Lomb 0.5% ophthalmic suspension Unique site active mechanism of action Less effect on IOP Highly lipid soluble Indications treatment of steroid responsive inflammatory conditions associated with the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe Contraindications most viral diseases of the cornea and conjunctiva and in mycobacterial and fungal diseases of the eye Precautions Prolonged use may result in secondary glaucoma, cataract formation, and secondary ocular infections Dry eye treatment QID x 2(or 4) weeks, then BID x 2 (or 4) weeks Works well in conjunction with Restasis Better than with artificial tears M Macugen (pegaptanib sodium injection) Eyetech/Pfizer (VEGF) Inhibitor inhibits VEGF, which is responsible for inducing angiogenesis, increasing vascular permeability and inflammation. VEGF has also been implicated in blood retinal barrier breakdown and pathological ocular neovascularization First anti-VEGF approved by FDA (2004) Indications For the treatment of neovascular age-related macular degeneration Contraindications Ocular or peri-ocular infections Administration 0.3mg by intra-vitreous injection once every 6 weeks Adverse reactions Anterior chamber inflammation blurred vision Cataract conjunctival hemorrhage corneal edema eye discharge, eye irritation, eye pain increased IOP ocular discomfort punctate keratitis reduced visual acuity visual disturbance vitreous floaters and vitreous opacities N Nevanac (nepafenac 0.1% suspension) Alcon Topical NSAID Indications Treatment of pain and inflammation associated with cataract surgery Contraindications Hypersensitivity to any ingredients in the formula or to other NSAIDs Warnings/Precautions Increased bleeding due to increased thrombocyte aggregation Delayed healing Corneal effects (including keratitis) Adverse Reactions Capsular opacity Decreased VA Increased IOP Sticky sensation Dosage/Administration 1 drop applied to the affected eye(s) beginning three-times-daily 1 day prior to cataract surgery, continued on the day of surgery, and through the first two weeks of the postoperative period Off-label uses Allergies Foreign Bodies Corneal Abrasions RGP Adaptation Topical NSAIDs Study by Weaver et al: Compared topical NSAID to placebo in corneal abrasion patients Patients had similar corneal healing time Quicker pain relief with topical NSAID O Optivar (azelastine hydrochloride ophthalmic solution 0.05%) Meda Pharmaceuticals Relatively selective histamine H1 antagonist and an inhibitor of the release of histamine and other mediators involved in the allergic response Indications treatment of itching of the eye associated with allergic conjunctivitis Contraindications in persons with known or suspected hypersensitivity to any of its components Warnings for ocular use only and not for injection or oral use Dosage/Administration one drop instilled into each affected eye twice a day Adverse reactions most frequently reported adverse reactions were transient eye burning/stinging (30%), headaches (15%) and bitter taste (10%). The occurrence of these events was generally mild. The following events were reported in 1-10% of patients: Asthma Conjunctivitis Dyspnea eye pain fatigue influenza-like symptoms pharyngitis, pruritus, rhinitis temporary blurring P Plaquenil (hydroxychloroquine sulfate) Sanofi-Aventis Quinine derivative Indications Suppression and treatment of acute attacks of malaria in adults and children. Treatment of discoid and systemic lupus erythematosus and rheumatoid arthritis (RA) in adults Contraindications Long term therapy in children or if retinal/visual field changes due to 4-aminoquinoline compounds Optometrist’s role Visual acuity Color vision HVF 10-2 (Macular field) Dilated fundus exam Baseline fundus photos Letter to patient’s doctor(s) Plaquenil toxicity Drug accumulates in RPE Gives Bull’s eye appearance to retina Frequency <5% when dose is under 400 mg/day Plaquenil Toxicity Risk factors daily dose greater than 6.5 mg/kg >400 mg/day greater than 10 years of use liver problems kidney problems age over 60 Q Quixin (levofloxacin ophthalmic 0.5%) Vistakon/Santen Good Gram positive and Gram negative coverage Inhibits both topoisomerase IV and DNA gyrase enzymes Interferes with DNA replication, transcription, repair, and recombination Appropriate for children >1 year Indications treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms Corynebacterium species Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus (Groups C/F) Streptococcus (Group G) Viridans group streptococci Acinetobacter Iwoffii* Haemophilus influenzae Serratia marcescens Contraindications contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication Dosage Days 1 and 2: Instill one to two drops in the affected eye(s) every 2 hours while awake, up to 8 times per day. Days 3 through 7: Instill one to two drops in the affected eye(s) every 4 hours while awake, up to 4 times per day. R Retisert (fluocinolone acetonide intravitreal implant 0.59 mg) Bausch and Lomb Indications indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye Contraindications most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infections of the eye and fungal diseases of ocular structures in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids Contains specially formulated ocular steroids Slowly releases the steroid medication in precise, measured amounts into the eye, on a daily basis for about 2.5 years Most frequently reported ocular adverse events in the overall study population were: cataract increased IOP procedural complications eye pain occurred in approximately 50% to 90% of patients Surgical procedure Generally implanted under local anesthesia Implanted using a limbal conjunctival peritomy and creating a 3.5-mm pars plana sclerectomy Secured in vitreous cavity with 8-0 Prolene™ anchoring suture Sclerectomy closed in with 8-0 or 9-0 Prolene suture S Salagen (pilocarpine hydrochloride) cholinergic parasympathomimetic agent can increase secretion by the exocrine glands sweat, salivary, lacrimal, gastric, pancreatic, and intestinal glands and the mucous cells of the respiratory tract Indications treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck treatment of symptoms of dry mouth in patients with Sjögren's syndrome Contraindications patients with uncontrolled asthma known hypersensitivity to pilocarpine when miosis is undesirable acute iritis and narrow-angle/angle closure glaucoma Potential ocular side effects Visual disturbances, especially at night, that could impair their ability to drive safely Cataract Conjunctivitis Dry eyes Eye disorder Eye hemorrhage Glaucoma Lacrimation disorder Retinal disorder Abnormal vision T Tamoxifen (Novaldex, Soltamox) Anti-estrogen Indications Treatment of metastatic breast cancer in women and men Treatment of node-positive and axillary node-negative breast cancer in women following mastectomy, axillary dissection and breast irradiation To reduce risk of invasive breast cancer in women with DCIS Reduction of breast cancer incidence in high risk women Use for up to 5 yrs Contraindications Reduction in breast cancer incidence in high risk women and women with DCIS who require Coumadin-type anticoagulant therapy or have a history of DVT, PE. Potential Ocular Side Effects crystalline retinal deposits macular edema corneal changes extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms Papilledema optic neuritis color vision defects decreased vision visual field abnormalities vortex keratopathy toxic crystalline maculopathy cataract Tamoxifen Retinopathy -Superficial yellowish-white crystalline deposits -Reversible upon discontinuation of drug -Any macular deposition may be permanent Tamoxifen Keratopathy -Bilateral white, whorl-like, central, subepithelial opacities in the cornea U Ultram (tramadol HCl) Central acting analgesic Synthetic analog of codeine Binds to opioid receptors Not a controlled substance Low abuse potential Opioid-type dependence has been reported Ultram tablets 50 mg Tramadol HCl 1-2 tablets every 4-6 hours Do not exceed 400 mg/day Safe for geriatric patients Indications Management of moderate to moderately severe pain Contraindications Acute intoxication with any of the following: alcohol, hypnotics, narcotics, centrally-acting analgesics, opioids or psychotropic drugs V Vigamox (moxifloxacin HCl 0.5%) Alcon 4th generation fluoroquinolone Indications Treatment of bacterial conjunctivitis caused by susceptible organisms Contraindications Patients with a history of hypersenstivity to moxifloxacin, to other quinolones, or to any of the components of this medication Non-approved uses Corneal ulcers, corneal abrasions Approved for children >1 year Recommended dosage: 1 drop TID x 7 days W Warfarin (Coumadin) an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors Indications prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. prophylaxis and/or treatment of the thrombo-embolic complications associated with atrial fibrillation and/or cardiac valve replacement reduce the risk of death, recurrent myocardial infarction, and thrombo-embolic events such as stroke or systemic embolization after myocardial infarction Potential ocular side effects Subconjunctival hemorrhage Retinal/macular hemorrhage Consult with patient’s physician and ophthalmologist when referring for any ocular surgery X Xibrom (bromfenac sodium 0.09%) ISTA Pharmaceuticals Topical NSAID No safety information on patients <18 years old Indications treatment of post-operative inflammation and reduction of ocular pain in patients who have undergone cataract extraction Contraindications in patients with known hypersensitivity to any ingredient in the formulation Dosage/Adminstration one drop should be applied to the affected eye(s) two times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period Adverse Reactions (2-7%) abnormal sensation in eye conjunctival hyperemia eye irritation (including burning/stinging) eye pain, eye pruritus, eye redness headache iritis Y Yodoxin (iodoquinol) Glenwood amebicidal against Entamoeba histolytica and is considered effective against the trophozoite and cyst forms Anti-protozoal Indications treatment of intestinal amebiasis Contraindications known hypersensitivity to iodine and 8-hydroxyquinolines patients with hepatic damage Potential ocular side effects optic neuritis optic atrophy decreased vision eye pain Z Zylet (loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension) Bausch and Lomb Anti-inflammatory and anti-infective First and only ophthalmic corticosteroid/antibiotic combination to contain an "ester" corticosteroid First FDA approved anti-inflammatory/anti-infective ophthalmic combination since the 1980’s Indications steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists and where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation Contraindications in most viral diseases of the cornea and conjunctiva and also in mycobacterial infection of the eye and fungal diseases of ocular structures Dosage/Administration Apply one or two drops of Zylet into the conjunctival sac of the affected eye(s) every four to six hours During the initial 24 to 48 hours, the dosing may be increased to every one to two hours Frequency should be decreased gradually as warranted by improvement in clinical signs Care should be taken not to discontinue therapy prematurely