Jenny’s PHARM TABLES .pdf

Jenny’s Tables For Pharm Fuck Her :) Ocular Manifestations Systemic Drugs (Pharm II) Ocular Manifestations of Systemic Drugs Conjunctiva Drug Chloroquine Cornea Optic Nerve -Mottling -Bull’s eye damage to Photoreceptor -Flying saucer sign -Photoreceptor IS/OS affected monitored every 3 years > ~ -Ca...

Jenny’s Tables For Pharm Fuck Her :) Ocular Manifestations Systemic Drugs (Pharm II) Ocular Manifestations of Systemic Drugs Conjunctiva Drug Chloroquine Cornea Optic Nerve -Mottling -Bull’s eye damage to Photoreceptor -Flying saucer sign -Photoreceptor IS/OS affected monitored every 3 years > ~ -Can cont when drug dc -Cases of reversible mac changes Lens Retina -Reversible -Epithelial punctuate deposits > whorl -No relation cornea & retinopathy Hydroxychloroquine (Plaquenil) > - -Intracellular deposits [RA, SLE, Collagen Disease, malaria] Phenothiazine Derivatives: - Slate blue conj a more retinal 2. Local toxicity Pigment loc Pallor Disc. 3 RPE Pigment w/ [Psychiatric disorders] * loca RPE [RA] E -Reversible ChrysiasisGold deposit (yellow/brown) Stroma Respiratory absolution mucosa - 99 % and ↑ Systemic toxicity 30 % remains a Topical Consideration also = hazy vision mg/day x 6 montha -Bind to melanin -Ret pigment change-Often permanent -Retinopathy may progress d/c Disc pallor (late stage) i n nose Of Swallowed Symptoms Mx Can get permanent VF defects (para/ pericentral) -CV affected, D15 Cornea: Halos Glare Photophobia -Frequency exam: Baseline, 5 yrs, then annual;↳ Win 1styear Consider risk factors Mydriasis Cycloplegia Diplopia ↓ tears Glare Retina: -Dec VA -VF disturbance -Metamorphopsia Retina: ↓ VA ∆ CV Nyctalopia Miscellaneous Objective Tests: -SD OCT -VF: 10-2 non-Asian 24-2 or 30-2 Asians Hydroxychloroqui ne less ability to cross blood retinal barrier (less toxicity) +6vs chloroquine Lens: monitor yearly Retina: initial, then q6mos Nystagmus -Irreversible -Enter fiber > rx amino gr >prot aggregation -PSC Cataracts ^risk with Tamoxifen f -Bind melanin Central serous ↑ a capillary Pseudotumor fragility hyper permeability of Choroidal retinal Vasculature - Sub Fluid leak # Est Stress releases ↑ IOP Reversible Chrysiasis: skin pigmentation Lens: glare, ↓VA, lite sensitivity BKC acts !! Lens: monitor 6-12 mos Min>none symptoms UV filters Monitor ONeuropathy: d/c Intranasal less/no affect vs inhaled = -o Other HOP -Ret function (often reverse) -Reversible Chrysiasis AntCapsule, subcapsular, suture Cat & , un ↑ IOP · halos , clumping 2, 000 Steroids Oral Inhaled Nasal glare , ↳ Antipsychotic meds -Reversible ChrysiasisBrownish deposit (5009) i * Pepper fundus salt dose related -Irreversible -Fine dots ant subcapsular lens>stellate>pearl -May occur s/p dc = granular and ↑ -Reversible Mild Endo, D’s: pigment 1. Gold Salts (NOT Available cells - C AT Chlorpromazine Thioridazine IOP glucocorticoids pass [Various] Amiodarone [Cardiac abnormalities] Erythmias -Reversible stay Epithelium Horizontal line>whorl Golden brown deposits Verticillate keratopathy = Accumulation of phospholipids in lysosomes of corneal epithelial cells -Ant subcapsular opacities (cateract) 2 (Can see in 6 dys) 4 Stages total Optic (l 24 ) Neuropathy D/C>resolve -. Intracytoplamic inclusions >block axoplasmic flow Photo- * sensitizing Cornea: Glare Halos Light sensitivity & Baseline, Q6Mos Cornea Differential: Fabry’s, chloroquine toxicity, netarsudil ON: Variable VA (mild reversible to severe permanent blindness) ↳ a months Note: table is not all inclusive, but salient findings Diane T. Adamczyk, OD Copyright 2024 © 1 Ocular Manifestations Systemic Drugs (Pharm II) Conjunctiva Drug Tamoxifen - SERM = Selective estrogen receptor Modulator [Breast cancer] Lens Retina Optic Nerve -Reverse Corneal opacity Whorl Subepith deposits Linear Cataract Refractile crystals sensory retina Foveal cystoid spaces Crystals and spaces -may Persist Optic neuritis > 2 Estrogen Antagonist ! IOP Cornea - * * To ~ - - Aromatase Inhibitors (Breast cancer – postmenopausal) Sildenafil (Viagra) Cataract wh Oral Symptoms Mx Miscellaneous Asymptomatic Baseline, yearly Structure similar chloroquine, chlorpromazine, thorazine, amiodarone More frequent as needed macular hole To Aceta Zolamide Y AntivEGF Other Macular edema-reverse triamcinolone Retinal heme Dry Eye dre to PDE5 Serous retinal detachment Retinal vascular occlusion [Erectile dysfunction] ischemic optic Neuropathy NAION Ca Non arteritic Ischemic ↓ Blue color tinge Anterior = impaed color vision A OphC Neuropathy Light sensitivity -Inhibit - Vasodilation phospodiesterase5 (some PD6) --PD6=retinal phototransduction inhibited α1a-adrenergic blocker - Tamsulosin (Flomax) [Benign prostatic hyperplasia] = and Urinary a , antagonist * retention Topiramate (Topamax) * Sulfa Choroidal effusion allergies ↑ IOP M Intraopera tive Floppy Iris Syndrome Myopia. 2^ ACG & - > - Precaution if cataract surgery L complications stops bk Froward mydrasis + al more of D/C topiramate Aq suppressant Cyclo/atropine lens Closure [Migraine, Seizures] Isotretinoin (Accutane) glaucoma Pseudotumor [Acne] Tetracycline Ciliary NO: PI NO: miotic NO: systemic CAI& = Pilocarpine spasms Sulfa based -Dec ↓ TBUT -Abnorm meibom secrete -Night Blindness Pseudotumor [Various] Digitalis derivatives: Visual Reversible disturbances: Reversible *CV dyschromatopsia *Impaired vision Flicker Snowy vision Dimness Digitoxin Digoxin > - [Congestive Heart, Cardiac arrhythmias] color vision Sodium Potassium ATPase inhibitor disturbance - Note: table is not all inclusive, but salient findings Diane T. Adamczyk, OD = Copyright 2024 © 2 Ocular Manifestations Systemic Drugs (Pharm II) - * Diane T. Adamczyk, OD Copyright 2024 © 3 Ocular Manifestations Systemic Drugs (Pharm II) Ophthalmology 2016;123:1386-1394 Diane T. Adamczyk, OD Copyright 2024 © 4 Ocular Manifestations Systemic Drugs (Pharm II) - Diane T. Adamczyk, OD Copyright 2024 © Asian Non = = 211-2 or 30-2 10-2 5 Glaucoma Medications and Pharmacology Ocular Pharmacology Beta Blockers Beta Blockers Mechanism: Decrease aqueous production Contraindications/Caution: *COPD *Asthma, emphysema *Bradycardia Dosage: QD or BID Decrease ADR: IOP: *Lethargy 22-25% *Bronchospasm *Bradycardia *Decreased libido Features: *Effective waking hours only *Drift *Escape *Consensual effect Drug Brand/ Generic Preserve Dosage IOP Δ Features Timolol Maleate 0.25% or 0.50% Timoptic (0.25, 0.5%) BAK BID/QD 27-35% (30%) ≤24 *Washout: 2 weeks *AM instillation Timoptic XE=D/C (0.25, 0.5%) (gel forming) Benzododecinium bromide QD Ocudose (0.25, 0.5%) None BID/QD Generic (0.25, 0.5%) (solution or gel forming) BAK – solution Benzododecinium bromide – GFS BID/QD QD (gel) *Less effect heart rate Receptor B1 or B2 Duration (hr) * Timolol Hemihydrate Betimol (0.25%, 0.5%) B1 or B2 BAK BID/QD 22% ≤24 Levobunolol 0.50% Betagan 0.5%=D/C Generic 0.5% B1 or B2 BAK QD*/BID 27% ≤24 Betaxolol 0.25%or 0.50% Betoptic S 0.25% (suspension) Generic 0.5% solution B1 BAK BID 18-26% (VF preserve? *Selective * - , * Brimonidine 0.1%, 0.15% & Brimonodine IOP Δ Contraindications: Monoamine oxidase inhibitors Tricyclic antidepressants ADR Features veins for Apracionodine ! Q6-8h Similar , 20 - * > - 50 % taste abnormal *Dry mouth *Fatigue *Hyperemia *Allergic reaction (blepharoconjunctivitis) 15 - 20 %1 *Penetrates > Epi *Prodrug *Former Category B *Onset 1 hr/Peak 3-5hrs *Surgical use drugd *Tachyphylaxis *Former Category B Prevent > - > - TIOP Response to *Miosis *30x>selective α2 than apraclonidine *No significant dec nocturnal IOP *Former Category B Same as generic (but < allergic *Same as generic rx?) - - - *Use: relieve redness *No tachyphylaxis [t] P [t] = blc[t] = hyperemia a2 in veins ! 4 Diane T. Adamczyk, OD/ Copyright © 2024 Glaucoma Medications and Pharmacology Ocular Pharmacology Carbonic Anhydrase Inhibitors Carbonic Anhydrase Inhibitors Mechanism Decrease aqueous formation Pharmacology Sulfonamide derivatives Drug Brand and/or Generic Preserve Dosage IOP Δ ADR Contraindication/ Caution Features ORAL Acetazolamide 125,250,500 mg, 500 mg sustained 500 mg IV Diamox (D/C) --- OAG: 125-250mg bidqid Or 500mg ER BID 2030% *Intolerable adr *Numbness/tingling extremities, perioral *Metallic taste *Fatigue *Metabolic acidosis *Transient myopia *Severe COPD *Renal disease (kidney stones) *Liver disease *Sickle cell and hyphema *Hypersensitivity to sulfonamides *Also used to treat pseudotumor; altitudinal sickness, epilepsy *Also used for macular edema *95% bind plasma protein *> tolerance acetazolamide but similar ADR *similar acetazolamide *55% bind plasma proteins *Corneal decompensation *Hx sulfonamide adr Diamox Sequels 500 ER Generic (125,250, 500ER, IV) ACG: Start 500mg, 125-250mg Q4H Pseudotumor: 1-2g/day divided bid-qid Or 500-1000mg ER BID Methazolamide 25,50 mg Neptazane (D/C) (25, 50mg) Generic (25, 50mg) --- 50-100mg BID/TID TOPICAL Dorzolamide 2% Trusopt 2% Generic 2% BAK TID/BID 2226% (2226%) *Sting *Bitter taste Azopt 1% BAK TID/BID 1920% * Ptosis Pharmacologic Testing Cocaine 10% Upside-down ptosis Category Mechanism Localize Normal Pupil Abnormal 1st/Central 2nd Pre Pupil Neuron Neuron 3rd/Post Neuron Adrenergic Prevents reuptake No No Dilation No Dilation/ No Dilation No Dilation Agonist norepi @ dilator Dilation Impaired Miosis, Anhidrosis Dilation Lag (No Norepi Released >>>>>>>>>>>>>>>>>) Apraclonidine 1% Alpha2 Unmasks Alpha 1 Adrenergic Upregulation No No Dilation May get miosis Dilate Dilate Dilate Dilate Yes Dilation Fail Safe Dilation Dilation No Dilation Agonist Hydroxyamphetamine Adrenergic Dilates only in Agonist presence of norepi (indirect acting (Release norepi fr (Postgang (Postgang (Postgang (Postgang (Postgang sympathomimetic) intact postgang) intact) not intact) intact) not intact> intact) no norepi) Phenylephrine 1% OTHER Direct acting Denervation sympathomimetic Supersensitivity Yes Dilation Sweat No Dilation No Dilation Entire half Dilation WholeFace/ Brow only body affect neck affect 3rd N Palsy > < Eye down/out Pilocarpine 1% Fixed Dilated Adie's Cholinergic Constrict Constrict Agonist >(initial) < (initial) TonicAccomodation Pilocarpine 0.125% Cholinergic Cholinergic NoConstrict Constrict Vary Vary Tonic light reaction Pilocarpine 0.1% Agonist hypersensitivity NoConstrict~ Constrict TendonReflex(possible) Slight Vermiform mov't iris Females Pharm > < Dilated Fixed, dilated Pilocarpine 1% Cholinergic Constrict NoConstrict Agonist Pupil Copyright (c) 2024 Diane T. Adamczyk, OD 1 Autonomic Pharmacology (Tbl 2) Ocular Pharmacology Autonomic Drugs and Pupils: Summary Drug Cocaine 10% Normal Pupil Use or Tests for Action Adrenergic agonist Dilate Horner’s Classification Apraclonidine 1% α2 adrenergic agonist Hydroxyamphetamine 1% Miosis possible Effect on Abnormal Pupil Miscellaneous Fail to dilate Horner’s Pupil Non-localizing Non-Localizing Predominant α2 , some α1. α1 denervation, hypersensitivity results in dilation Horner’s Dilates Horner’s Pupil Adrenergic agonist Dilate Horner’s Fails to dilate 3rd neuron lesion Brimonidine α2 adrenergic agonist Decrease Horner's Dilates Horner’s Anisocoria Pilocarpine 0.125% Cholinergic agonist No affect Adie’s tonic pupil Constricts Adie’s Pilocarpine 1% Cholinergic agonist Miosis Pharmacologically No effect dilated pupil Miosis possible Localizing Predominant α2 , some α1. α1 denervation, hypersensitivity results in dilation Hypersensitivity reaction 3rd N pupil dilation Constrict Diane T. Adamczyk, OD Copyright (c) 2024 2 Retinal and Ocular Neovascular Treatment (Ocular Pharmacology/Dr. Adamczyk/Copyright © 2024) Drug Generic ANTI-VEGF Macugen Pegaptanib Discontinued US Lucentis Ranibizumab Pharmacology Administer Frequency Action Use Misc Aptamer Intravitreal Injection Q6wk x 48 wks AntiVEGF165 Wet AMD All types of macular neo Monoclonal Antibody Intravitreal injection Q4wk AntiVEGF – all isoforms ADR: endophthalmitis Slows vision loss; no significant improvement in VA Modified bevacizumab Implant Intravitreal injection Refills q24wks Q4wk Neovascular ARMD Macular Edema in retinal VO Diabetic Macular edema Improves vision Diabetic Retinopathy Myopic choroidal neo ____________________________ NARMD ADR: conj heme,hyperemia,iritis Neovascular ARMD Biosimilar ranibizumab Macular Edema in retinal VO Myopic choroidal neo IgG antigenbinding fragment (Fab) Susvimo Byooviz Avastin RanibizumabNUNA Biosimilar of ranibizumab Bevacizumab Monoclonal Antibody Intravitreal Q4wk Injection (off label) AntiVEGF – all isoforms AntiVEGF – all isoforms Full-length IgG antibody IV (cancer) Fc Domain EYLEA 2 mg Aflibercept VEGF Trap Intravitreal Injection EYLEA 8 mg Aflibercept HD Recombinant fusion protein consisting of portions of VEGF receptors Beovu Brolucizumab Single chain Intravitreal variable fragment Injection Vabysmo Faricimab-SVOA Bispecific monoclonal antibody Intravitreal Injection ARMD: VEGF Trap Q4wks x 3 then Binds VEGF-A and Q8wk (HD:q8-16wks) PIGF (placental MacEdema (RVO) growth factor) Q4wk DME: q4wk x 5 then q8wk(HD:q8-16wks) DR:q4wk x5 then q8wk(HD:q8-16wks) Off Label: Macular Edema in retinal VO Diabetic Macular edema Diabetic Retinopathy Myopic choroidal neo Neovascular glaucoma Corneal neovascularization ARMD neo Macular edema, RVO associated Diabetic macular edema Diabetic retinopathy Q4wks x 3 Then q8-12 wks AntiVEGF-110, 125, Neovascular ARMD 165 isoforms Q4wkx4 (ARMD +DME) (or DME also Q4wkx6) Followed by OCT +VA to determine addn inject Targets: Angiopoiten-2 and VEGF-A Neovascular ARMD Diabetic macular edema Anatomic/visual improvement Parent drug of ranibizumab Approved colorectal cancer Personalized treatment interval 1 Retinal and Ocular Neovascular Treatment (Ocular Pharmacology/Dr. Adamczyk/Copyright © 2024) Drug PDT Visudyne Generic Pharmacology Administer Frequency Action Use Misc Verteporfen Photosensitizing IV infusion Dye Q3mos Occlude CNV Predominant classic CNV (subfoveal) Off Label: ARMD Pathologic Myopia Presumed Oc Histoplasmosis Central Serous Choroidopathy Polypoidal Choroidopathy PDT (light activated) Nonthermal light Intravitreal Q3-6mos Anti-inflammatory Injection ___________ _______________ Suprachoroidal Single dose Various Can use with PDT __________________________ Macular edema associated with uveitis ____________________________ Intravitreal Implant Duration: 1-3 months Anti-inflammatory Macular edema (BRVO, CRVO) Non-infectious posterior uveitis Diabetic macular edema Biodegradable implant= NOVADUR polymer drug delivery system Intravitreal Implant Duration: 36 months Anti-inflammatory Diabetic macular edema = Off Label: AMD RVO Non-erodible intravitreal implant Prevents downstream Geographic atrophy effectors of complement activation Prevents downstream Geographic atrophy effectors of complement activation 2 regioisomers *Avoid direct sunlight or bright indoor light for 48hrs *Protect eyes and skin from natural sunlight and bright indoor light for at least 5 days Steroids Kenalog Triamcinolone Acetonide Corticosteroid ___________ Xipere injection Ozurdex Dexamethasone Intravitreal Corticosteroid Iluvien Fluocinolone acetonide Intravitreal Corticosteroid Syfovre Pegcetacoplan Complement inhibitor (C3+C3b) Intravitreal injection Q25-60 days Izervay Avacinacaptad pegol Complement inhibitor (C5) Intravitreal injection qMos Proteolytic Enzyme Intravitreal injection Once - - - ↳ lasts 36 months ! Geographic Atrophy Treatment Other Jetrea Ocriplasmin Discontinued US Proteolytic activity; dissolves protein matrix responsible for vitreomac adhesion Treatment of symptomatic vitreomacular adhesion 2 Allergy Treatment: Antihistamines, Decongestants, Mast Cell Stabilizers/Oc Pharmacology/Dr. Diane Adamczyk - Copyright © 2024 - Decongestants Pharmacology Dosage Phenylephrine 0.12% (availability?) ↳ Decongestant Alpha 1 adrenergic agonist Dilates Pupil QID Dilates Pupil W BI c can I Blood Pressure Naphazoline (Various [0.012-0.1%]) (Advanced Eye Relief Redness) Imidazole Mixed alpha 1&2 adrenergic agonist (2:1=alpha2:alpha1) az Oxymetazoline 0.025% (available?) > Contra/ Considerations Cardiovascular NAG MAOI use * Q3-4h >>QID Cardiovascular NAG MAOI use Q6h Cardiovascular NAG MAOI use al Imidazole Mixed alpha 1&2 adrenergic agonist (~5:1=alpha2:alpha1) ADR Other Rebound congestion Tachyphylaxis Pigment AntChamber Pupil dilate possible UpLid retraction Rebound Tachyphylaxis Pupil dilate c 0.1% ^IOP possible UpLid retraction Rebound Tachyphylaxis UpLid retraction al QID Q6-8hrs Antihistamine/Decongestant Alpha-2 adrenergic receptor agonist (1000:1 alpha2:alpha1) Pharmacology Naphazoline/pheniramine (Naphcon-A) Imidazole/ Alkylamine QID (Visine Red Eye Comfort) Brimonidine tartrate 0.025% (Lumify) ↑ doce ↓ = dose= hyperemia blanch No effect IOP Unlikely effect pupil Hyperemia Punctate keratitis Upneeq: use acquired blepharoptosis Cardiovascular NAG MAOI use Hypersensitivity to drug Rebound Tachyphylaxis UpLid retraction Decreased potential for tachyphylaxis May decrease IOP No effect pupil Contra/ Considerations Cardiovascular NAG MAOI ADR Other QD Imidazole Alpha 1 Tetrahydrozoline 0.05% Can be in combination with antihistamine ______________________ a l > al Oxymetazoline 1% (Upneeq) Min to no dec IOP More likely rebound vs. imidazole derivatives Dosage Please check website for most up to date availability of brand and generic drugs OTC Act on venules# See above under naphazoline 1 Allergy Treatment: Antihistamines, Decongestants, Mast Cell Stabilizers/Oc Pharmacology/Dr. Diane Adamczyk - Copyright © 2024 AntiHistamine (oral) ↳ Dilates BV = itch (H1) Hyperemia (H2) Pharmacology Dosage 1st generation 4mg QID-Q4H , Chlorpheniramine maleate Diphenhydramine hydrochloride (Benadryl) 1st generation Cetirizine (Zyrtec) 2nd Generation Long-acting tricyclic antihistamine with selective peripheral H1 receptor antagonist 2nd Generation Fexofenadine (Allegra) Loratadine (Claritin) 25mg,50mg Q2-4h or Q4-6h (max 300mg/dy) 10mg QD Contra/ Considerations NAG Breastfeed: may use shortterm NAG Breastfeed: may use shortterm Breastfeed: may use shortterm 5-10mg QD Breastfeed: may use shortterm 2nd Generation 60 mg BID 180 mg QD Breastfeed: may use shortterm Desloratadine (Clarinex) Metabolite loratadine 5 mg QD Breastfeed: may use shortterm Levocetirizine Enantiomer of cetirizine 2.5-5mg QD Breastfeed: may use shortterm (XYZAL=d/c XYZAL Allergy 24hr=available) Antihistamine (topical) Emadastine difumarate (Emadine) (not available) Levocabastine HCl (Livostin) (not available) Cetirizine Ophthalmic 0.24% (Zerviate) Pharmacology Cyclohexylpiperidine ADR Other Somnolence Headache Dry Mucous Membranes Blurred vision Mod Anticholinergic Somnolence Headache Dry Mucous Membranes Blurred vision Strong anticholinergic and antiemetic Headache Somnolence Dry mucous membranes Pharyngitis Absorb delayed with food Amiodarone (torsades de pointes may occur) Headache Somnolence Dry mucous membranes Pharyngitis Headache Somnolence Potential for drowsiness greatest 2nd generation Absorb delayed with food Headache Pharyngitis Somnolence Dry mouth Somnolence Pharyngitis Dosage Onset ADR That wqgtfq awawwgweyeeeewy QID 10 min Headache Bad taste Cyclohexylpiperidine QID 15min AAa Sting HA Antihistamine BID 15 min Sting Please check website for most up to date availability of brand and generic drugs Absorption&concentration dec with juices Concentration increases with erythromycin or ketoconazole More active than loratadine > half-life than loratadine > effective loratadine 2-fold affinity H1 receptor vs cetirizine (unknown clinical relevance) >half-life than cetirizine Other Suspension Not Available 2 Allergy Treatment: Antihistamines, Decongestants, Mast Cell Stabilizers/Oc Pharmacology/Dr. Diane Adamczyk - Copyright © 2024 Mast Cell Stabilizer Cromolyn sodium (Crolom=d/c, generic) Pharmacology Dosage Onset -Blocks calcium influx across mast cell membranes -Inhibits mast cell degranulation Q4-6h 7 days ADR Other /Approval Days Burn/sting HA Allergic conjunctivitis VKC GPC Inhibit eosin chemotaxis VKC 2500xpotent cromolyn Lodoxamide tromethamine (Alomide) Nedocromil sodium (Alocril) -Blocks calcium influx across mast cell membrane -Inhibits mast cell degranulation QID -Inhibits mast cell degranulation -Decreases chemotaxis BID Minutes HA Burn/sting Unpleasant taste HA Sting/burn Pemirolast potassium (Alamast) (not available) Inhibits mast cell degranulation QID Allergic Conjunctivitis Allergic Conjunctivitis AntiHistamine/Mast Cell Stabilizer Pharmacology Dosage Onset ADR Other Azelastine 0.05% (Optivar, generic) H1antagonist, inhibit release histamine from mast cells BID 3 minutes Inhibit eosin chemotaxis Epinastine HCL 0.05% (generic) H1antagonist, inhibit release histamine from mast cells BID Olopatadine HCl 0.1% (Pataday Twice Daily Relief) Olopatadine HCl 0.2% (Pataday Once Daily Relief) Olopatadine HCl 0.7% (Pataday Once Daily Relief Extra Strength) Olopatadine 0.1% or 0.2% (Generic) Ketotifen fumarate 0.025% H1 antagonists, inhibits Type I rx BID (0.1%) Burn/sting HA Bitter taste Flu syndrome Burn Itch Cold Symptoms URI HA Cold syndrome Taste perversion HA Flu syndrome Inhibit eosin chemotaxis (Zaditor,Alaway, generic) QD (0.2%, 0.7%) Generic 0.1% q6-8h H1 antagonist, mast cell stabilizer Ketotifen 19mcg (Acuvue Theravision) Bepotastine besilate 1.5% (Bepreve) Alcaftadine 0.25% (Lastacaft Once Daily Relief) Inhibit eosin chemotaxis H1antagonist, inhibit release histamine from mast cells H1antagonist, inhibit release histamine from mast cells BID Minutes _____________ Daily disposable CL BID QD Please check website for most up to date availability of brand and generic drugs CL: relieves itch up to 12 hours (will be d/ced) HA Taste 3 min Inhibit eosin chemotaxis 3 Allergy Treatment: Antihistamines, Decongestants, Mast Cell Stabilizers/Oc Pharmacology/Dr. Diane Adamczyk - Copyright © 2024 Chemical and Functional Classification of Sample H1 Antihistamines Chemical Class Functional Class st nd 1 Generation 2 Generation Alkylamines Chlorpheniramine Pheniramine (Topical) Acrivastine Piperazine Hydroxyzine Meclizine Cetirizine Levocetirizine Piperidines Azatadine Cyproheptadine Diphenylpyraline Ketotifen (topical) Loratadine (OTC) Desloratadine Fexofenadine Levocabastine (topical) Olopatadine (topical) Ethanolamine Clemastine Diphenhydramine Ethylenediamines Antazoline Pyrilamine Phenothiazines Methdilazine Promethazine Other Doxepin (H1 and H2 activities and also tricyclic antidepressant) Please check website for most up to date availability of brand and generic drugs Azelastine (topical) Emadastine (topical) Epinastine (topical) 4 Allergy Treatment: Antihistamines, Decongestants, Mast Cell Stabilizers/Oc Pharmacology/Dr. Diane Adamczyk - Copyright © 2024 Figure 13- 3: Potential Adverse Effects of H1-Antihistamines through central nervous system and effect on various receptors and through ion channels. N Engl J Med 351:2204, 2004. Please check website for most up to date availability of brand and generic drugs 5 Local Anesthetics Ocular Pharmacology Topical Linkage Linkage Onset Duration ADR Other Cocaine (not commercially available in ophthalmic solution) Tetracaine (ophthalmic solution) Benzoic Acid Ester 5-10min (2%) 20min (2%) Epithelial toxic Dilated pupil Nausea Anesthetic Adrenergic Agonist ParaAminobenzoic Acid Ester 10-20sec 10-20min Corneal epithelial disruption* Sting:tetra >benox>proparacaine CornEpith:tetra>propar>benoxinate CornPenetrate:tetra>proparacaine Allergic reaction No cross sensitivity with proparacaine Benoxinate (ophthalmic solution with fluorescein) Proparacaine (ophthalmic solution) ParaAminobenzoic Acid Ester 10-20sec 10-20min Sting:benox>proparacaine great potency and duration *Not with sulfonamide *pKa(35% uncharged) >faster onset Amide 0.8 (21) 27.5 (346) 2 7.6 (Intermediate) 8 8.1 (High) 3-5min (fast) 5-10 (11) min 78% (75%) 96% (95%) 40-60min (1-2hr c epi) (intermediate) 2-3 hour (intermediate) 4-12 hour *High protein (long) >long duration *Add butyl group to amine of mepivacaine. Resulting in (compared with mepivacaine): >^lipid solubility, protein bind >^potency, duration 5-10 hour *Lipid solubility high (long) >high potency Lidocaine (Xylocaine) Metaaminobenzoic Acid Mepivacaine Amide of Benzoic Acid Bupivacaine Amide of Benzoic Acid Linkage Partition Coefficient (Lipid Solubility) Amide (Immediate) Etidocaine (Duranest) (? available) Amide of Benzoic Acid Amide 141 (800) 6 (High) 7.7 3-5min (fast) 94% (Red Parentheses indicate different source findings); *=Partition Coeff c buffer Onset: pKa: Higher pKa = higher % charged =slow onset >>>>> lower pKa=lower charged = faster onset Higher pKa = lower % uncharged =slow onset >>> lower pKa=higher % uncharged= faster onset Duration: Protein Bind: Less protein bind =shorter duration; More protein bind=longer duration Lipid Solubility: Greater lipid solubility=longer duration; Lower lipid solubility=shorter duration Potency: Lipid solubility: Greater lipid solubility=greater potency; Lower lipid solubility=lower potency Diane Adamczyk OD – Copyright © 2024 Local Anesthetics Ocular Pharmacology Injectable Anesthetics Injectable Anesthetics Onset (slower to faster based on initial potential onset time): – bupivacaine (4-12hr)(long) > etidocaine (94%) (5-10hr)(long) > mepivacaine (78%) (2-3hr)(intermediate) > tetracaine (76%) (3-5hr,2-2.3hr)(intermediate) > lidocaine (64%) (0.666-1hr) > procaine (6%) (0.5-0.75hr) (short) – procaine (7-8 min) (slow) > tetracaine-bupivacaine (5-9~10 min) (intermediate) > lidocaine (4-6 min)(fast) >etidocaine –mepivacaine (3-5 min) (fastest) pKa (high pKa=slower; low pKa=faster): – – – – – – procaine (8.9) >tetracaine (8.5)(95%charged) > bupivacaine (8.1) > lidocaine (7.9)(65% charged) > etidocaine (7.7) >mepivacaine (7.6) Diane Adamczyk OD – Copyright © 2024 Duration (longest to shortest): Protein bind (most to least): – bupivacaine (96%) > etidocaine (94%) > mepivacaine (78%) > tetracaine (76%) > lidocaine (64%) > procaine (6%) 1 DYES 2024 Fluorescein Rose Bengal Pharmacology Sodium Salt Derivative Fluorescein Chemical grouping Preparation Xanthene dye Xanthene dye Strips Solution (combo anesthetic) Solution (IV use 10% or 25%) Powder (oral)(?available?) Vital Cobalt Blue Cornea Conjunctiva Retina Stain epithelial defects TBUT Herpes Seidel sign CL fit Lacrimal drainage Strip Solution Type Illumination Use Clinical use Stains Retinal vasculature Iris vasculature Healthy cells Dead cells Damaged cells Other Topical: vasovagal response IV: nausea, vomit, discolor skin and urine Vulnerable bacterial contamination (inactivates BAK) Diane T. Adamczyk, OD copyright © 2024 Triarylmethane dye Ocular surface assessment Herpes Ocular surface assessment Sting Toxic to cells Tryptan Blue Thiazine dye Azo Dye Solution Vital White light Conjunctiva (cornea) Healthy cells Dead cells Damaged cells Mucous strands Methylene Blue Indocyanine Green Contains sodium iodide Vital-no White light Conjunctiva Cornea Intracellular spaces ADR Lissamine Green Vital Cyanine dye Solution (IV) Vital Evaluate corneal endothelial cell viability Lac sac prior Stains dacryocystorhinostomy damaged/dead endothelial cells in donor corneas Vital Choroid/retina Choroidal abnormalities Dead cells Damaged cells Mucous strands Irritating Sensitivity to shellfish or iodine 2 Dyes 2024 Diane T. Adamczyk, OD copyright © 2024 Analgesics: Controlled Substances/Pharm II 2024 (Diane T. Adamczyk, OD) 1 Analgesics: Controlled Substances/Pharm II 2024 (Diane T. Adamczyk, OD) 2 Analgesics: Controlled Substances/Pharm II 2024 (Diane T. Adamczyk, OD) 3 Analgesics: Controlled Substances/Pharm II 2024 (Diane T. Adamczyk, OD) 4 n COX COX1 NSAIDS/Ocular Pharmacology = Platelet COxZ Mechanism Inhibit cyclooxygenase enzyme needed in biosynthesis of prostaglandins = Pain + Fever NSAIDs Topical Trade Pharmacology Flurbiprofen Ocufen – d/c Generic 0.03% Aryl Propionic Acid Suprofen 1%-d/c Profenal -d/c Aryl Propionic Acid Intraop miosis Not available Diclofenac Voltaren – d/c Aryl Acetic Acid Ocular Inflammation Post Cataract surgery Corneal refractive surgery Decrease corneal sensation Allergic Conjunctivitis Inflammation Post-Cataract extraction Corneal refractive surgery Acular LS 0.4% ( Amfenac Ilevro 0.3% Suspension Diane T. Adamczyk, OD Copyright © 2024 Postop Cataract pain and inflammation CME Shake 0.1%=TID 0.3%=QD & StromalHSV Acetate > alcohol > Phosphate Adrenal Suppression Steroids/Ocular Pharmacology/Dr. Adamczyk Copyright © 2024 STEROIDS Trade Concentration Formulation Prednisolone Acetate Pred Mild Pred Forte Generic Generic 0.12% 1% 1% 1% Suspension Prednisolone Sodium Phosphate Dexamethasone Dexamethasone Alcohol Dexamethasone Sodium Phosphate Dexamethasone > - Maxidex 0.1% Suspension Generic 0.1% Solution 0.4mg Intracanalicular Insert Plug Intravitreal implant Dextenza Plug FML FML Forte Generic Flarex 0.1% 0.25% 0.1% 0.1% Medrysone (alcohol) Rimexolone Not Available US 1% Suspension Vexol No Available US 1% Suspension Difluprednate Durezol Generic 0.05% Emulsion - - External/ Intraocular Inflammation Shake suspensions Adrenal 15mg/day = Suppression irevesible Ketone Inflammation Propensity to ^IOP for all administrations Shake suspension Lasts up to 30 days Ketone Also: ocular itch associated with allergic conjunctivitis Also: macular edema (Diabetic or VO) Inflammation - - Progesterone - Suspension PSC 0.2% 0.5% Generic 0.5% Eysuvis 0.25% Gel Suspension Suspension 0.05% Injectable suspension Suspension XIPERE Same Lower potential ^IOP Shake suspensions - Bellers to id Suspension Alrex Lotemax Gel Lotemax ung Lotemax susp Lotemax SM Inveltys 0.38% 1% Duration of effect 1-3 months - Loteprednol Etabonate Triamcinolone acetonide Clobetasol propionate Other Solutions ? 0.7mg Fluorometholone acetate Indications Solution Ozurdex Fluorometholone Fluorometholone alcohol Ketone vs Ester Based Ketone Children > Cortisol ↳ Dexamethasone Structurally related to Cortisol in - - Progesterone Ketone Minor lid/conj rx Ketone Post Cat Ant Uveitis Prednisolone Ketone Inflammation/Pain with oc surgery Prednisolone Ester (ketone group absent at position 20) Suspension Gel Ointment Suspension Gel Suspension TM has steroid Allergic conjunctivitis Inflammation, postop, pain Limited corneal penetration Lower potential ^IOP Lower potential ^IOP Minimum shake (carbomer934P) Sorbic Acid (preservative) No shake =effective PredForte with half dosing frequency Soft/Site drug -Lower potential ^IOP Shake suspensions Submicron technology AMPPLIFY delivery Esther receptors which Resistance in Dry Eyes AMPPLIFY delivery DED Macular edema associated with uveitis Inflammation/pain post op Injected into suprachoroidal space APNT™ nano formula Approved March 2024 outflow and &IOP Anti-Infective (Anti-Viral)Drugs/Pharm II a Salvage AntiViral Drug Pharmacology Viral Vidarabine (Vira-A) Discontinued Idoxuridine (IDU,Stoxil) Discontinued Trifluridine (Viroptic) Generic Ganciclovir (Zirgan 0.15%) Acyclovir ophthalmic (Not availableUS) Povidone-Iodine 5% ophthalmic solution Diane T. Adamczyk, OD/Copyright © 2024 Pathway thimadine Kinase Use and viral DNA Dosage ADR Miscellaneous Sting Corneal changes Not available Toxic (corneal) Not available Ophthalmic Antiviral (Topical) Polymerase Adenosine analog > Inhibit viral DNA polymerase HSV cornea Ung Thymidine analog > Creates fraudulent DNA HSV cornea Thymidine analog 1-Inhibit thymidine synthetase>Inhibit DNA synthesis in virus infected & normal host cells 2-Incorporate DNA>faulty DNA > no virus replication Guanosine derivative Inhibit DNA replication; competitive inhibition of viral DNA polymerase; incorporate into viral DNA Guanosine analog > 1-Affects viral enzymes (DNA polymerase) 2-Incorporates into and terminates growing viral DNA chain Antimicrobial-broad spectrum HSV cornea Solution 9X (Q2H)(while awake)>reepithelization, Q4Hx7dy Toxic to cornea Corneal defects Hyperemia, chemosis May use during pregnancy HSV cornea Gel 5x/day (Q3H), then TIDx7days Blurred vision Eye irritation May use during pregnancy HS keratitis Ointment 5x/day until healed; then TID x 7 days Low toxicity Not available US EKC Periocular surg prep Solution 4-5 drops/lavage/anesthetic Corneal stippling Sting Use with anesthetic Use within 4 days of symptom onset Single in office use Guanosine analog 1-Competitively inhibits and inactivates viral DNA polymerase 2-Incorporates into and terminates growing viral DNA chain HS/HZ/Varicella Off-label: HZ: 800mg 5x/dy x 7dys (72hrs onset max efficacy 48hr; >72hrs if Epithelial Keratific still new lesions) HS keratitis: 400mg 5x/day HS keratitis prophylactic: 400mg BID Bell Palsy (new onset): 400mg 5x/dy x 10dys (with steroid)(within 72h) HZ: 1000mg TID X 7dys (72hrs onset) HS keratitis: 500mg TID HS keratitis prophylactic: 500mg QD Bell Palsy (new onset): 1g TID x 7dys (with steroid)(within 72h) Safe/Low toxicity Nausea, vomit, diarrhea, HA May be use during pregnancy ~ HZ: 500 mg TIDX 7dys (72hrs onset, max efficacy w/in 48h) HA Nausea, diarrhea, vomit Caution in renal impairment (Betadine) Systemic Antiviral Acyclovir (Zovirax) 2 mechanisms - 20 %. Valacyclovir (Valtrex) Need ↑ Dose and Frequency HS/HZ Off label use: 501. HSV prophylaxis Acute retinal necrosis HZO Bell palsy (new onset) Bio Selective inhibit viral DNA polymerase Rapid absorb GI> convert to penciclovir (Prodrug penciclovir) 77% bioavailability Ganciclovir (Cytovene) Foscarnet (Foscavir) = 20% bioavailability L-valyl ester acyclovir (prodrug of acyclovir) 50% bioavailability Famciclovir Bio · 77 % HS/HZ Off label use: Bio Deoxyguanosine analog (differ ACV by add hydroxymethyl group) Pyrophosphate analog Inhibits viral DNA polymerase and reverse transcriptase (RNA polymerase) Thymidine analog Zidovudine (Retrovir) Please confirm online for latest updates HSV prophylaxis HSV keratitis Acute retinal necrosis HZO Bell palsy (new onset) * HSV prophylaxis Acute retinal necrosis HZO Bell palsy (new onset) CMV retinitis in immunocompromised CMV retinitis-AIDS Associated HIV SystemicAntiviral Caution : HS keratitis: 250mg TID x 7-10dys Bell’s Palsy: 500mg TID x 7dys (with steroid) (within 72h) IV infusion IV infusion PO (post exposure-prophylaxis) Renal impaire a Caution in renal impairment and dehydration Nausea, vomiting HA May use during pregnancy ~ Caution in renal impairment and dehydration Weigh risk/benefit during pregnancy; inadequate human data; no known risk of fetal harm Not SAFE Bone marrow depression Fever GI disturb Renal Impairment Bone marrow hypoplasia 1 Anti-Infective (Anti-Viral)Drugs/Pharm II Diane T. Adamczyk, OD/Copyright © 2024 Antifungal Drug Mechanism Pharmacology Use Effect Dosage ADR Miscellaneous Natamycin 5% suspension (Natacyn) Bind irreversibly to ergosterol in cell membrane, ^membrane permeability Polyene Corneal fungal infections Q1-2H/dy x 3-4 days, then 6-8x/day Hyperemia Only topical drug for fungal infection US Suspension Polyene Systemic fungal infection Aspergillus Fusarium Blastomyces Histoplasma Candida Coccidioides INJ Toxic HA Chills, fever Vomit, GI cramps Hypokalemia Renal toxicity (Intravitreal Subconj) Candida Oral Aspergillus Candida Fusarium Candida Aspergillus Oral/IV/Susp Use Effect Dosage ADR Miscellaneous Topical antiseptic Bacteria Fungi Viruses Single use Ophthalmic Antifungal (Topical) Includes: Aspergillus Fusarium Candida Similar Amphotericin Systemic Antifungal Amphotericin B Bind irreversibly to ergosterol in cell membrane, ^membrane permeability Fluconazole Alters fungal cell membrane Triazole Voriconazole Derivative of fluconazole Triazole Nystatin Alters fungal cell membrane Polyene Other Mechanism Pharmacology Povidone-Iodine (7.5% and 10%) (Betadine) Broad-spectrum microbicide Tea Tree Oil (Cliradex) Antimicrobial mechanism poorly understood Possible compromise of cytoplasmic membrane Ectoparasiticide Lotilaner 0.25% ophthalmic solution (xdemvy) Please confirm online for latest updates Terpinen-4-ol Off label: Fungal corneal ulcers Fungal endophthalmitis Fungal infection Off label: Fungal corneal ulcers Fungal endophthalmitis Fungal Infection Off label: Fungal corneal ulcer Fungal infection Off label: Fungal ulcers Demodex related blepharitis Topical Fortified Use Oral Topical (non-ocular) Betadine solution (10%) Betadine Surgical Scrub (7.5%) Prep for surgery Surgical scrub QD or BID x 6-8 weeks La 2 life Cy Clea Gammaaminobutyric acid (GABA) gated chloride channel inhibitor Demodex blepharitis Selective for Demodex mites BID x 6 weeks 2 Anti-Infective Drugs Antibiotics Classification Drug Ocular Pharmacology Broad Mechanism Specific Mechanism Diane T. Adamczyk, OD/Copyright © 2024 Pharmacology Effect Resist Use Dosage Consideration ADR Miscellaneous Pregnancy/ Lactation -Type I, II, III, IV (allergic rx) -Nausea/Vomit -Diarrhea -Superinfection Caution: BCP Inhibits Cell Wall Synthesis Penicillins Inhibit Cell Wall Synthesis β-lactam antibiotic Bactericidal 1-Effective G+ Penicillin G Penicillin V 2-Penicillinase resistant Dicloxacillin 3-Extended spectrum Inhibit peptide cross-linking of polysaccharide chains of peptidoglycan Amoxicillin Amoxicillin/ Clavulanate (Augmentin) *Nucleus: -thiazolidine ring -b-lactam ring → →bio/antibacterial activity *Side chain→ spectrum, pharmacokinetics G: from fungus Penicillium notatum V:semisynthetic derivative of G Modify structure →staphylococcal penicillinase cannot hydrolyze Modified basic penicillin structure G+ G- Broader spectrum (vs original penicillin) Inactivated by penicillinase BUT when with Clavulanate=inhibits Blactamase -B lactam ring -Similar penicillin -Different side chains G+ G-Penicillinase producing s. aureus Resist: inactivate by B lactamases G+(vs2nd Gen) >Resist(vs2ndGen) G+(vs2nd Gen) >Resist(vs2ndGen) >G-(vs1stGen) G(vs1st/2ndGen) (also pseudomonas) disrupt osmotic integrity G+ Ocular infect ( + ) Inj (single drug) Sol (drug combo) Ophthalmic Combo (sol & ung) Ophthalmic Combo No Orals Affect Protein Synthesis Affect Protein Synthesis Aminoglycoside Bactericidal Bind to an aminoglycoside site on ribosomal 30S subunit to block protein synthesis Neomycin Gentamicin - G+ G- G- bacilli Cross resist Anterior segment infections G+ GNot P.aeruginosa Gyay : G+ ----Pseudomonas Not P aeruginosa Anterior segment infections , Tobramycin Amikacin Please confirm online for latest updates Semisynthetic aminoglycoside G+ YAY !! GPotent p. & aeruginosa Preferred Gwhere resistant P aeruginosa System: -Neurotoxic (auditory, vestibular) -Nephrotoxicity Generally not effective against Streptococcus N Anterior segment infections Various ophthalmic Also PO Solution Ung Cross resist with Gentamicin Anterior segment infections Inject Solution Ung T Endophthalmitis (inject) Bacterial keratitis Inject No ophthalmic Contact dermatitis Rare:corneal/con junctival toxicity -AllergicRx(50% neomycin) Tear, burn Lid edema Hyperemia SPK -Poor absorb GI (why systemic> parenteral) -Penicillins may inactivate Topical: may use preg/lactation Ophthalmic Combo Ophthalmic Fortified: corneal ulcer Combo Ophthalmic Combo Extemporaneous prep for oc use 2 Anti-Infective Drugs Antibiotics Classification Ocular Pharmacology Drug Diane T. Adamczyk, OD/Copyright © 2024 Broad Mechanism Specific Mechanism Pharmacology Affect Protein Synthesis -Enter bacteria by active transport -Bind to the 30S subunit of ribosomes to block attachment of transfer RNA to its receptor site Isolated from Streptomyces and lab produced Effect Resist or Not Effective Use Dosage ADR Miscellaneous Pregnancy/ Lactation Photosensitivity GI irritation Bone growth Tooth develop Pseudotumor Blood dyscrasias Others -Potentiate effect coumarin type anticoag Consideration Affect Protein Synthesis Tetracycline Bacteriostatic Short Acting G+ GChlamydia Other S. Aureus P aeruginosa Enter bact via energy dependent process Tetracycline Gonococcal infect Chlamydial infect Meibomianitis Acne rosacea Noninfected corneal ulcers Absorption affected by: food (not doxy), antacids, iron, dairy, vit-mineral Chlamydia Rosacea Meibomiantis Sebaceous bleph Noninfect corn ulcer PO Empty stomach -Ophthalmic: NOT avail US>used for gonococ neonatum Chlamydia Rosacea Meibomianitis Oc Surface inflam Recalcitrant Recurrent Corneal Erosion PO No regard meals (Food may prevent stomach irritation) Except Oracea: not with food -Not in: - Azithromycin (Zithromax) Azithromycin Ophthalmic (AzaSite) · Chloramphenicol NotAvailableUS G+; GChlamydia Neisseria Other -Base>GI inactivates > remedy protective coat Stearate>Chem modify>better absorb Erythromycin * a 1000mg Single Semisynthetic derivate of erythromycin Dose Forchlamydia o Doxycyclin For prefered Change bacterial ribosome that binds drug Lid infect Ophthal neonatorum Chlamydia H. influenzae Toxoplasmosis >G- (vs erythromyc in) Chlamydia Rosacea Ophthalmicconjuctivitis Chlamydia ex cept 36 my immediate lomg delayed NEVER Reaches release and therapeutic level Low toxicity 6-O-methyl derivative of erythromycin with long half-life Not for Preggy > - Antiinflam properties (suppress interleukin) when - Peggy Topical, oral,IV Ung GI irritation Allergic rx Hear loss (rare) Oracea specific for rosacea Contraindication: with astemizole or terfenadine Weigh risk/benefituse only if clearly needed =for oral use pregnancy Base/Stearate: NO food Enteric: food if upset stomach Succinate ok w food PO No regard meals Ophthalmic: May use pregnancy/ lactation Stable in GI Half-life 2x erythro Avoid pregnancy *1g (1dose)=chlamydia *Z Pak *No regard meals (except Zmax 2g on empty stomach) GI irritation Others Inj Ophthalmic and oral not available in US Aplastic anemia Bone marrow depress Other Chlamydia May use pregnancy/lactation Safe durasit Vehicle Chloramphenicol Affect Protein Synthesis Bacteriostatic (some cidal) Please confirm online for latest updates Binds to the 50S subunit of ribosomes to block peptidyl transferase G+ GOther Resist: P aeruginosa Anthrax Ophthalmic: anterior seg infections * 3 Anti-Infective Drugs Antibiotics Drug Classification Ocular Pharmacology Broad Mechanism Specific Mechanism Pharmacology Affect Intermediary Metabolism (Folic Acid) Inhibit conversion of PABA to dihydropteroic acid Inhibit early step in folic acid synthesis Diane T. Adamczyk, OD/Copyright © 2024 Effect Resist or Not Effective Use Dosage Consideration ADR Miscellaneous Pregnancy/ Lactation Affect Intermediary Metabolism (Folic Acid) Sulfonamides G+ GOther (toxoplasmosis, chlamydia) Bacteriostatic · neededfa -Overproduce bact PABA -Dec enz affinity -Dec drug permeability -Inactivation Blepharitis Conjunctivitis Toxoplasmosis Reversed: PABA (anesthetic esters of, procaine, tetracaine, benoxinate) Inhibited by pus, blood Cross resistance Like Contraindicate: purulent discharge Proteins Orals: Sulfamethoxazole Sulfadiazine Topical: Sulfacetamide (Bleph Need lencovorir ! - Trimethoprim Trimethoprim Sulfonamide /Trimethoprim Triple - Sulfamethoxazole /Trimethoprim (Bactrim) * drug therapy : Pyramethamine 2-corticosteroid 3-Jolinic , PO Blepharitis Conjunctivitis Topical Contraindicate: PABA drugs Pus 10) Pyrimethamine Pyrimethamine Widespread resistance Toxoplasmosis Sulfadiazine Affect Intermediary Metabolism (Folic Acid) Bacteriostatic Inhibit reduction of dihydrofolic acid to tetrafolic acid Inhibit sequential step folic acid synthesis Affect Intermediary Metabolism (Folic Acid) Bacteriostatic (in combo may be cidal) Affect Intermediary Metabolism (Folic Acid) Inhibit reduction of dihydrofolic acid to tetrafolic acid Inhibit sequential step folic acid synthesis MRSA a Combo - above -o Toxoplasmosis e Please confirm online for latest updates Toxoplasmosis Bone marrow suppression leucovorin Jolinic G+ GNot pseudomonas Not pseudomonas Ocular infection PO Various (include MRSA) Acid ! Topical > 2 months Combo: steroids PABA drugs Pus Use folinic acid to counter toxicity Contraindication: megaloblastic anemia Pregnancy: weigh risk/benefit *Ophthalmic *Combo *Contraindication: megaloblastic anemia *As part of combo drug may be synergy result in bactericidal effect Pregnancy: weigh risk/benefit Trimethoprim Pseudomonas acid Toxoplasmosis GI disturbances Allergic skin rx Blood dyscrasias Transient myopia Sting Contact dermatitis Photosensitization Caution: pt taking oral hypoglycemic drug or anticoagulant Pregnancy: weigh risk/benefit Not Trimethoprim Pyramethamine and leucovorin 4 Anti-Infective Drugs Antibiotics Classification Drug Ocular Pharmacology Broad Mechanism Specific Mechanism Diane T. Adamczyk, OD/Copyright © 2024 Pharmacology Effect Resist or Not Effective Use Dosage Consideration ADR Pregnancy/ Lactation Miscellaneous Pregnancy/ Lactation Topical: Minimum toxicity Topical: may use pregnancy Interfere DNA Synthesis Fluoroqui nolones Systemic Interfere DNA synthesis Bactericidal Inhibit DNA gyrase (topoisomerase II) and / or topoisomerase IV Synthetic analogue of nalidixic acid Discontinued Ophthalmic Ofloxacin (Ocuflox) Generic Inhibit DNA gyrase (topoisomerase II) Ciprofloxacin (Ciloxan) Generic Norfloxacin (Chibroxin) Discontinued Inhibit DNA gyrase (topoisomerase II) Inhibit DNA gyrase (topoisomerase II) Levofloxacin 0.5% (Quixin-brand d/c) Generic Levofloxacin 1.5% (Iquix=brand d/c) Please confirm online for latest updates Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV Resist: Staphylococcal Ulcer: Dy1:2gttQ15minX6hr>Q30min Dy2:Q1H Dy3-14:Q4H BactConjunctivitis: Q2Hx2dy > Q4Hx5dy ↓ ↓ ulcers G->G+ (vs oflox) Bact conjunctivitis G- (excellent) G+ (>2nd Gen) G+ (>vs oflox, ciproflox) Bacterial conjunctivitis ↳ G+ (>vs oflox, ciproflox) Burn Bitter taste White precipitate Hyperemia Same as Oflox Corneal Lisomer of racemate, ofloxacin Systemic: GI disturbance; Tendon rupture Nausea HA Dizziness Corneal ulcer Bacterial conjunctivitis >G+ (vs cipro, norflox) G->G+ (vs oflox) Conjunctivitis Keratitis Corneal ulcer Pre/post op UTI Respiratory Infect Other Conjunctivitis Keratitis Corneal Ulcer Pre/post op G-: (cipro=gati=levo =moxiflox but > oflox) G+ G-(excellent); G+(variable) G-=G+ 3rd Generation Discontinued -Single step mutants -Multi-step mutants -Inhibit DNA gyrase or topoisomerase IV -Affect permeability -Efflux pump -Gene Ciprofloxacin (Cipro) Topical 2nd Generation G+ G>activity vs other antibiotics Not ! Same as Oflox Solution, ung Day1-2:Q2H Day3-5:Q4H Keratitis Corneal ulcer Day1-3: Q30minX2hr> >>>Q4-6H sleep Day4: Q1-4H awake Weigh risk/benefitpregnancy Pregnancy: may use 1yo >est aq [ ] 2nd Gen Corneal precipitates * 1yo Generic: 2yo 1yo overall/G+> oflox,cipro 1 yo 10x>soluble oflox 400x>soluble ciproflox ^penetration aq 6 yo 5 Anti-Infective Drugs Antibiotics Classification Drug Ocular Pharmacology Broad Mechanism 4th Generation Specific Mechanism Pharmacology Inhibit DNA gyrase (topoisomerase II) and > topoisomerase IVBreaka ↓ Moxifloxacin 0.5% (Vigamox) Generic * 2 mulations needed Diane T. Adamczyk, OD/Copyright © 2024 Effect Resist or Not Effective >G+ vs other generations Resist: 2 mutations (2 step) G- potency = other FQ Active against FQ resist organisms Use Dosage Consideration ADR Pregnancy/ Lactation Miscellaneous Excellent penetration Tendon chromosome C-8 (methoxy side chain): ^potency G+>cipro/oflox/ gatifloxacin C-7 (bicyclic ring): ^ conj penetration G- =gatiflox Rupture Bacterial Conjunctivitis TIDx7dy 1 yo No preservative pH6.8= H202 + tears=H20 +O2 Other Liquid Drops: Polyquad or preservative free = (hydroxypropyl methylcellulose) Thera Tears Hypotonic solution Electrolyte balanced Preservative free or Sodium perborate> H202 + tears=H20 +O2 -Unit dose or Bottle -Restores conjunctival goblet cells and promotes healing Supplement Example HYDROEYE Ingredient How Supplied Other -Omega-3 (100mgEPA/70mgDHA) -Alpha linolenic acid (Flaxseed oil, from Omega 3) -Black current seed oil (Gamma linolenic acid from Omega 6) Soft gels -Anti-inflammatory -Use with anticoagulants may increase their effect and prolong prothrombin time -4 capsules daily (2 capsules BID with meals) Feature Diagnostic s/p Refract Surgery Other 4-7 days 2-6 mos Visible Intracannular Intracannular One Size Permanent Permanent Permanent Conform to puncta Permanent Tear Stimulants Dosage Pilocarpine 5 mg QID (Salagen) Cevimeline (Evoxac) 30mg TID Action Parasympathomimetic Other Sjogren Radiation Sjogren Xerostomia Varenicline (Tyrvaya) 0.03 mg nasal spray BID iTear 100 device BID for 30 sec each side Pharmacologic neurostimulation parasympathetics; binds nicotinic acetylcholine receptor on trigeminal n Neurostimulation external branch of anterior ethmoidal nerve Punctal Occlude Collagen Implants Extended Temporary Plugs Freeman Plugs Herrick Smart Plug Form Fit Collagen Absorbable copolymer Silicone Silicone Thermodynamic hydrophobic acrylic polymer Hydrogel material Plug loss Cholinergic agonist mostly in 3 months 1 Ocular Surface Treatment/PharmII_2024/Dr. Adamczyk Dry Eye Treatment Action Other Perfluorohexyloctane Ophthalmic Solution (Miebo) QID Lipid layer (Prevents tear evaporation) Meibomian glands -Semifluorinated alkane liquid -Amphiphilic -Nonaqueous -No preservative Anti-inflammatory Formulation/Dosage Emulsion Castor Oil BID Emulsion Castor Oil BID How Supplied Unit dose (Preservative Free) MultiDose Unit Dose (Preservative free) Other Immunosuppressant Calcineurin inhibitor Unit dose Immunosuppressant Calcineurin inhibitor Single dose vials Immunosuppressant Calcineurin inhibitor Cyclosporine 0.1% (Vevye) Nanomicelle formulation Solution BID Emulsion Nanodroplets QID = For VKC Solution BID Immunosuppressant Calcineurin inhibitor Lifitegrast 5% (Xiidra) Solution BID MultiDose Perfluorobutylpentane Preservative Free Unit dose Cyclosporine 0.05% (Restasis) Cyclosporine 0.05% (generic) Cyclosporine 0.09% (Cequa) Cyclosporine 0.1% (Verkazia) Formulation/Dosage ↳ improve * Cyclosporin forms early * as a in Immunosuppressant Calcineurin inhibitor Lymphocyte functionassociated antigen-1 (LFA-1) z week complex wl cyclophilin to - Calcineurin , improvement I month Verkazia tacrolimus for VIC 1000X more Potent than Cyclosporin 2 in as Punctal Plugs-OcLubricants/PharmII_2024/Dr. Adamczyk L o Thermal 3 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk Preservatives Class/Type Mechanism Action Toxic/Allergy Miscellaneous Benzalkonium chloride (BAK)(BAC) Detergent (Surfactant) Ionic charge>disrupt Antimicrobial Toxic inflammatory effect Corneal cell disruption Absorbed cell membrane>membrane unstable>release of cell contents/rupture ^corneal penetration Disrupt cell membrane Mainly antibacterial Less Toxic than BAK Long shelf life Molecular size ~27x larger than BAK Antibacterial and antiseptic to microbial cell membrane Bactericidal Proteins neutralize toxicity Does not alter corneal penetration Contact sensitivity Allery Fewer allergic reactions < Effective than BAC (Cationic) Polyquaternium (Polyquad) Quaternary ammonium Detergent (Surfactant) (Cationic) Chlorhexidine Thimerosal Chlorbutanol Quaternary ammonium Biguanide Chemical (Mercurial) Detergent (with NO surfactant activity) Excellent antimicrobial Damages bacterial cytoplasmic membrane>leakage of cell contents + coagulation of cytoplasm Interfere cell membrane function Affects internal cell respiration Disorganize cell membrane lipid layer>^permeability> cell lysis Antibacterial, Antifungal Less toxic than BAK Chemical (Alcohol based) Stabilized oxychloro complex (SOC) (Purite®) Oxidative > effective c EDTA Does not affect stability of tear lipid layer Light+ SOC >water +O2+ sodium + chlorine free radical Broad antimicrobial (bacteria, fungal, viral) Oxidative: interfere with cell function Inhibit microorganism protein synthesis via glutathione oxidation>microbe cell death Low toxicity 1 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Sodium perborate (GenAqua®) Oxidative Sodium perborate + tears(H2O) = H2O2>H2O+O2 Oxidative: interfere with cell function Methylparaben Propylparaben EthyleneDiaminetetraAcetic Acid (EDTA) SofZia Sorbate (sorbic acid) Ester parahydroxybenzoic acid Chelating agent Oxidative (ionic buffered) Misc Dr. Adamczyk Bacteria + Fungus Low toxicity Alters protein synthesis by oxidizing cell membranes + enzymatic inhibition H202=cidal Sting? Artificial tears Not sufficient antimicrobial alone Compound of boric acid, propylene glycol, sorbitol, zinc chloride Contact dermatitis Enhances activity of other preservatives (thimerosal, BAC) Less toxic than BAK In Travatan Z® Limited antimicrobial Dissociate cytoplasm, release protons, inhibit growth by acidification 2 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk Preservatives (destroy or inhibit microorganism multiplication) Benzalkonium chloride Mercurial preservatives Sodium benzoate Benzethonium chloride Phenylmercuric nitrate Sodium propionate Benzododecinium bromide Phenylmercuric acetate Thimerosal Sorbic acid Cetylpyridinium chloride Methyl/propylparabens Sofzia Chlorobutanol Phenylethyl alcohol Sodium perborate (GenAqua) EDTA (enhance preservative activity) Stabilized oxychloro complex (Purite) Polyquaternium Viscosity-increasing agents (slow drainage from eye, increase retention time; increase bioavailability) Carbopol gels/Carbomers (e.g., 934P,940) Methylcellulose Propylene glycol Dextran PEG (Polyethylene Glycol) Polyvinyl alcohol Gelatin Poloxamer 407 Polyvinylpyrrolidone (povidone) Glycerin Polysorbate 80 Sodium hyaluronate: Healon Hydroxypropyl Guar Chondroitin sulfate Antioxidant (prevent or delay product deterioration by oxygen in air) EDTA Sodium bisulfite Thiourea Sodium metabisulfiute Sodium thiosulfate Wetting Agent (reduce surface tension > allow drug solution to spread across ocular surface) Polysorbate 20 and 80 Poloxamer 282 Tyloxapol Buffers (Maintain pH 6-8/comfortable range for ophthalmic product) Acetic acid Potassium bicarbonate Sodium acetate Boric acid Potassium borate Sodium bicarbonate Hydrochloric acid Potassium carbonate Sodium biphosphate Phosphoric acid Potassium citrate Sodium borate Phosphate Potassium phosphate Sodium carbonate Potassium tetraborate Sodium citrate Sodium hydroxide Sodium phosphate Tonicity Agents (help ophthalmic solutions to be isotonic with tears; 0.6-1.8% usually comfortable) Buffers Glycerin Potassium chloride Dextran Ions Sodium chloride Dextrose Propylene glycol 3 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk Polymers (Polysaccharides) (Enhance viscosity, lubrication, tear stability, wettability, vehicle) Mucilages – An artificial sticky paste used as a vehicle or excipient – Methylcellulose (MC), – Hydroxyethylcellulose, – Hydroxypropylcellulose, – Hydroxypropyl methylcellulose (HPMC), – Carboxymethylcellulose (CMC) Dextrans Viscoelastic substances (viscous and elastic) – Sodium hyaluronate: Healon – Chondroitin sulfate Vinyl derivatives – Polyvinyl Alcohol (PVA) – Polyvinylpyrrolidone (PVP) 4 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations tissue esterases Breakdown Dr. Adamczyk Site Specific druga 5 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk Preservative Class (Type) Points Benzalkonium chloride Detergent (Surfactant) *Corneal cell disruption *Excellent antimicrobial Chlorobutanol Detergent (Alcohol) Less toxic than BAK Polyquaternium-1 (Polyquad) Detergent Less toxic than BAK Stabilized oxychloro complex (Purite) Sodium perborate SofZia E Oxidative *Dissociates into water, oxygen, sodium, and chlorine free radicals Oxidative *Catalyzed into hydrogen peroxide; water and oxygen *Less toxic than BAK Oxidative (ionic buffered) *Less toxic than BAK 6 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk 8 Ocular Pharmacology 2024 Principles Drug-Lubricant Formulations Dr. Adamczyk 9 Cytotoxic = Methotrexate immune modulator = Humira Tacrolimuy