Lecture 1 PrincDrugAdmin152.pdf

Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservatives: Chemical ◦ Mercurials ◦ Thimerosal ◦ Contact sensitivity/allergic reactions 82 Diane T. Adamczyk, OD_Copyright © 2024 77 -rarely see or prescribe it due to contact sensitivity and allergic reactions are ve...

Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservatives: Chemical ◦ Mercurials ◦ Thimerosal ◦ Contact sensitivity/allergic reactions 82 Diane T. Adamczyk, OD_Copyright © 2024 77 -rarely see or prescribe it due to contact sensitivity and allergic reactions are very common -still in the market 77 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservatives: Detergent (NOT surfactant) ◦ Chemical: Alcohols ◦ Chlorobutanol ◦ < effective antimicrobial than BAC ◦ Fewer allergic reactions ◦ More effective when combined with EDTA (Ethylenediaminetetraacetic acid) 83 Diane T. Adamczyk, OD_Copyright © 2024 78 -not as effective as an antimicrobial -EDTA is not a preservative but when combined with preservative the drug works better 78 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservatives: Oxidative ◦ Neutralized by cells, no accumulation ◦ Effective microorganism, low toxicity ◦ Stabilized Oxychloro Complex (Purite) ◦ Refresh Tears ◦ Dissipates into water and sodium chloride (light exposure) ◦ Sodium Perborate ◦ GenTeal ◦ Converted to hydrogen peroxide and then oxygen and water when in contact with the eye (in eye) 84 Diane T. Adamczyk, OD_Copyright © 2024 79 -seen in ocular lubricants à refresh tears—put drop in the eye and dissipates into water and sodium chloride which is basically tears when exposed to light 79 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservative: Stabilized oxychloro complex (SOC) (Purite®): ◦ Broad antimicrobial effect (bacterial, fungal, viral) ◦ Composed of chlorite (99.5%), chlorate (0.5%), trace chlorine dioxide ◦ SOC + Light dissociates >>> water, oxygen, sodium and chlorine free radicals ◦ Mechanism by oxidizing antimicrobial activity ◦ Chlorine free radical believed to inhibit microorganism protein synthesis within cells via glutathione oxidation resulting in microbe cell death 85 Diane T. Adamczyk, OD_Copyright © 2024 80 -summary slide 80 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Preservative: Sodium perborate (GenAqua®, Dequest®) ◦ Oxidative preservative ◦ Effective against bacteria and fungus (Aspergillus niger) ◦ Alters protein synthesis within bacterial cells by oxidizing cell membranes and altering membrane-bound enzymes causing enzymatic inhibition ◦ When combined with water, sodium perborate is converted to hydrogen peroxide ◦ When applied to the eye, catalyzed by enzymes on oc surface ( e.g. catalase) to decompose to water, and oxygen ◦ Hydrogen peroxide kills microbes ◦ Low concentration of hydrogen peroxide can cause sting, but definitive clinical data lacking with sodium perborate 86 Diane T. Adamczyk, OD_Copyright © 2024 81 -summary slide 81 Pharm II Principles of Oc Drug Administration Drug Formulation Properties PRESERVATIVES: MISCELLANEOUS ◦ Methylparaben, propylparaben ◦ Artificial tears ◦ Ethylenediaminetetraacetic acid (EDTA): ◦ Chelating agent ◦ Chelates calcium for cell junction formation ◦ Not sufficient antimicrobial alone unless combined with preservative ◦ Assist action of thimerosal, BAC ◦ Contact dermatitis ◦ May be cytotoxic prolonged use PRESERVATIVES: MISCELLANEOUS ◦ Sorbate (sorbic acid) ◦ Limited antimicrobial activity ◦ Passes through plasma membrane, dissociate in cytoplasm, release protons, inhibit growth via acidification ◦ Results in inefficient intracellular activities ◦ SofZia à preservative that is gentle ◦ Composed of boric acid, propylene glycol, sorbitol, zinc chloride ◦ In Travatan Z 87 Diane T. Adamczyk, OD_Copyright © 2024 82 82 Principles of Oc Drug Administration Pharm II Preservatives (Class Overview) Detergent preservatives ◦ Cause bacterial cell death by interrupting lipid component of cell membrane ◦ E.g. Benzalkonium chloride, chlorobutanol, polyquad ◦ Chlorobutanol (unlike BAK) does not act like a surfactant. Action is cell lysis via disruption of microbial cell membrane lipid configuration Oxidative preservatives à breakdown into oxygen and water when in contact with the tears ◦ Penetrate membrane and alter DNA, protein and lipid components of the bacterial cell ◦ E.g. sodium perborate, stabilized oxychloro complex Ionic-buffered preservatives ◦ Similar to oxidizing preservatives ◦ E.g. SofZia 88 Diane T. Adamczyk, OD_Copyright © 2024 83 83 Pharm II Principles of Oc Drug Administration 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) Oxidative *Dissociates into water, oxygen, sodium and chlorine free radicals Sodium perborate Oxidative *Catalyzed into hydrogen peroxide; water and oxygen *Less toxic than BAK SofZia Oxidative (ionic buffered) *Less toxic than BAK 89 Diane T. Adamczyk, OD_Copyright © 2024 84 -summary slide 84 Pharm II Principles of Oc Drug Administration Steven DW, et al. Br J Ophthalmol 2018;102:1497–1503. doi:10.1136/bjophthalmol-2017-311544 90 Diane T. Adamczyk, OD_Copyright © 2024 85 85 Principles of Oc Drug Administration Pharm II Let’s Go for a Drive… 91 Diane T. Adamczyk, OD_Copyright © 2024 86 86 Pharm II Principles of Oc Drug Administration Vehicle Body= Viscosity Wax shine = wetting agent Undercoat=Preservative Bumper=Buffer Convertible top up or down = tonicity Air System Filters = Antioxidant Driver=Drug 92 Diane T. Adamczyk, OD_Copyright © 2024 87 87 Pharm II Principles of Oc Drug Administration Vehicle (also known as excipient=which are various components but not the drug) Wetting agent Thickness = Viscosity Antioxidant Preservative Buffer Tonicity (can also be same as buffer) Drug 93 Diane T. Adamczyk, OD_Copyright © 2024 88 88 Principles of Oc Drug Administration Pharm II Excipients Defined Excipients are components of a finished drug product other than the active pharmaceutical ingredient (API) and are added during formulation for a specific purpose. Although listed as inactive ingredients by FDA, excipients generally have well-defined functions in a drug product. USP Guideline for Submitting Requests for Revision to USP-NF V3.1 April 2007 U S. PHARMACOPEIA 94 Diane T. Adamczyk, OD_Copyright © 2024 89 -excipient is another term for vehicle, its everything within the drug without the actual drug -these components have an effect on the ocular surface to penetrate thru the ocular tissue 89 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicles (Excipient) ◦ Provide proper tonicity, buffering, and viscosity to complement drug action ◦ Increased viscosity ◦ Delay washout, increase drug bioavailability ◦ Petrolatum or oil based ointments: longer retention, temporary lipid depot 95 Diane T. Adamczyk, OD_Copyright © 2024 90 -increase viscosity of the drug it has more staying power on the ocular surface it allows the drug to act but the bad thing is it causes blur factor 90 Principles of Oc Drug Administration Pharm II Ophthalmic Formulations Excipients Antioxidants ◦ Sodium sulfites ◦ Ethylenediaminetetraacetic acid (EDTA) Wetting agents ◦ Polysorbate ◦ Poloxamer ◦ Tyloxapol 96 Diane T. Adamczyk, OD_Copyright © 2024 91 91 Principles of Oc Drug Administration Pharm II Ophthalmic Formulations Excipients Buffers ◦ A chemical system that prevents the change in concentration of another chemical system; To give a solution the property of resisting a change in pH ◦ Examples: ◦ ◦ ◦ ◦ ◦ Acetic, boric, hydrochloric acids Potassium and sodium bicarbonate Potassium and sodium borate Potassium and sodium phosphate Potassium and sodium citrate 97 Diane T. Adamczyk, OD_Copyright © 2024 92 -buffers give the drug the resistance to change in pH 92 Principles of Oc Drug Administration Pharm II Ophthalmic Formulations Excipients Tonicity agents ◦ The osmotic pressure or tension of a solution, usually relative to that of blood ◦ Examples ◦ ◦ ◦ ◦ ◦ ◦ Buffers Dextrans (high molecular wt polymer of D-glucose) Dextrose (D-glucose monosaccharide) Glycerin Propylene glycol Potassium and sodium chloride 98 Diane T. Adamczyk, OD_Copyright © 2024 93 93 Principles of Oc Drug Administration Pharm II Ophthalmic Formulations Excipients Viscous agents ◦ Methylcellulose (MC) ◦ Polyvinyl alcohol (PVA) ◦ Polyvinylpyrrolidone (povidone) (PVP) ◦ Propylene glycol ◦ Polysorbate 80 ◦ Dextran ◦ Gelatin ◦ Carbomers (e.g. 934P, 940) 99 Diane T. Adamczyk, OD_Copyright © 2024 94 -allows more staying power but more blur factor 94 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicles and viscosity ◦ Include: ◦ ◦ ◦ ◦ Polyvinyl alcohol (PVA) Polyvinylpyrrolidone (povidone) (PVP) Hydroxypropyl methylcellulose (HPMC) Carboxymethlycellulose ◦ Shear thinning: shear exposure (blinking), viscosity decreases ◦ High viscosity in open eye ◦ Mucin, sodium hyaluronate (SH) 100 Diane T. Adamczyk, OD_Copyright © 2024 95 -everytime you blink it’s like a windshield wiper so when theres a thicker viscous, you need to blink more to clear up the drug 95 Pharm II Principles of Oc Drug Administration Drug Formulation Properties Vehicles and viscosity ◦ Gel-Forming Systems ◦ ◦ ◦ ◦ Large molecules exhibit reversible phase transitions Aqueous drop reversibly gel on contact precorneal tear film Longer contact time Viscous property changes induced by: ◦ Alterations in temperature, pH, electrolyte composition 101 Diane T. Adamczyk, OD_Copyright © 2024 96 -ex. Gluacoma drug timolol has a transformation from liquid to gel and translates clinically into taking the drug instead of twice a day you can take it once a day or decrease the concentration from 0.5% to 0.25% bc of viscosity it has a longer staying time 96 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicles and viscosity ◦ Gel-Forming Systems ◦ Gelrite ◦ Polysaccharide, low-acetyl gellan gum forms clear gel in presence of mono/divalent cations in tear ◦ Enhance corneal penetration, prolongs drug action ◦ Timoptic XE à brand name for timolol ◦ Xanthan gum vehicle ◦ Heteropolysaccharide ◦ Falcon gel-forming (timolol) 102 Diane T. Adamczyk, OD_Copyright © 2024 97 97 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicle: Cation Exchange Resin (Amberlite) ◦ Binding agent (polyacrylic acid polymer carbopol 934P) ◦ Enhance stability ◦ Ease of resuspendability 103 Diane T. Adamczyk, OD_Copyright © 2024 98 -enhances the stability of the drop -resuspension means that the drug is scattered through the liquid but if the bottle is sitting for a while the drug will settle at the bottom like sementation so you have to shake the bottle before putting the drops in bc if they don’t shake it pt is just putting liquid without the actual drug - 98 Pharm II Principles of Oc Drug Administration Amberlite-Cation Exchange Resin Drug + Resin Carbopol gel (ex. Carobopol 934P) =gelling agent, viscosity enhancer + Tears (Na)=> Free Drug + Na-Resin 104 Diane T. Adamczyk, OD_Copyright © 2024 99 -vehicle has carbopol gel -within the vehicle, there is a drug that will be attached to a resin -when the amberlite cation exchange system comes into contact with the tears, the sodium in the tears frees the drug from the resin so you’re just left with the drug -makes the drug more effective since it will guarantee the getting of the drug 99 Pharm II Principles of Oc Drug Administration Drug Formulation Properties Vehicle: Cation Exchange Resin (Amberlite) ◦ Betaxolol suspension (Betoptic S) ◦ Drug binds with cation exchange resin >> ◦ Reduced free drug in solution, enhanced comfort ◦ Plus vehicle (with carbopol 934P) ◦ Increase viscosity, contact time ◦ 4 weeks no resuspending ◦ Betaxolol 0.25% suspension = 0.5% solution 105 Diane T. Adamczyk, OD_Copyright © 2024 100 -S stands for suspension -drug is utilizing amberlite system so it doesn’t need to be shaken before putting in the drops -when you put this drug in contact with the tears, it’s liberated 100 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicles ◦ Polyacrylic Acids ◦ Carbopol gels (component of cation exchange resin) ◦ Decrease viscosity with increase shear rate, blink ◦ Drug examples: Betoptic S, Azopt 106 Diane T. Adamczyk, OD_Copyright © 2024 101 101 Principles of Oc Drug Administration Pharm II Drug Formulation Properties Vehicles (see Drug Delivery) ◦ Ointments ◦ Drug Release Systems ◦ Examples: ◦ SCL, collagen shields ◦ Punctal plugs ◦ Intravitreal implant 107 Diane T. Adamczyk, OD_Copyright © 2024 102 102 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery 108 Diane T. Adamczyk, OD_Copyright © 2024 103 103 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Topical Administration ◦ Most common ophthalmic drug route ◦ Convenient, noninvasive, simple, self-administered ◦ Drug loss: diffusion into circulating blood ◦ BV of conjunctiva, episclera, intraocular vessels, nasal mucosa, oral pharynx ◦ Little benefit posterior segment ◦ Second passage: liver biotransforms ◦ Vs oral meds: metabolized before “first pass” (<toxic than topical drugs) 109 Diane T. Adamczyk, OD_Copyright © 2024 104 104 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Topical Administration ◦ Solutions ◦ Advantage: easy installation, <affect vision ◦ Disadvantage: short contact time, imprecise, contamination, injury ◦ Suspensions ◦ ◦ ◦ ◦ Shake Prolonged contact time Steroids Generic: suspend poorly, clog dropper tip ◦ 1% prednisolone acetate suspension 110 Diane T. Adamczyk, OD_Copyright © 2024 105 -purpose of suspension is to prolonged contact time in the eye 105 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Topical Administration ◦ Emulsions ◦ No Shake ◦ Improved drug solubility and bioavailability ◦ Oil in water 111 Diane T. Adamczyk, OD_Copyright © 2024 106 106 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Standard bottle cap colors ◦ Yellow, blue: beta blocker ◦ Red: mydriatic, cycloplegic ◦ Green: miotic ◦ Orange: CAI ◦ Gray: NSAIDs ◦ Pink: steroid ◦ Brown or tan: anti-infective 112 Diane T. Adamczyk, OD_Copyright © 2024 107 107 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Eyedrop size varies: ◦ Traditional:50-70ul ◦ Range: 27-70 ul ◦ 5-15ul should be adequate ◦ Standard eyedropper dispenses: ◦ 0.05 m l/ 1 drop===20 drops/1 m l of m edication ◦ 5m l bottle=100 doses (QD OU=60 drops/m onth) ◦ 2.5m l bottle=50 drops Vs (these num bers can vary depending on source) 2.5m l bottle: Lum igan (96.7 drops); Xalatan (94 drops); Travatan Z (81.7 Drops) (IOVS M arch 2012, 53:5025) 113 Diane T. Adamczyk, OD_Copyright © 2024 108 -if the drop is more than what the ocular surface can hold, it will spill out -1 mL is about 20 drops -if pt is required to put 1 drop a day for a month in both eyes, that’s two drops or 60 drops for the month so pt would need a 5ml bottle to have enough drops -2.5 mL bottle is about 90 drops à for glaucoma drops -the key point to understand here is that there is a wide variety of drop range within the same bottle size 108 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery B&J 4th ed 115 Diane T. Adamczyk, OD_Copyright © 2024 109 -want to keep things in the ocular surface and don’t want it to drain out so you would punctual occlude and prevents it from going into systemic circulation -it is shown that pt who have glaucoma and punctual occlude can change either IOP from 1-2 mmHg which is a big diff 109 Principles of Oc Drug Administration Pharm II 116 Diane T. Adamczyk, OD_Copyright © 2024 110 -spray bottle dilation drop for child that is not cooperative 110 Pharm II Principles of Oc Drug Administration • Poor eye drop instillation technique negatively impacts the patient’s ability to achieve good IOP control. • Study: • Examined medication administration adherence by observing patient experience with 3 eye drop instillation aids • Take assigned device home and use for 6 weeks. • Over 60% found AutoDrop and AutoSqueeze drop instillation easier, and would use long-term. • Less positive response for SimplyTouch device. J Glaucoma Volume 30, Number 8, August 2021 117 Diane T. Adamczyk, OD_Copyright © 2024 111 -pts who have arthritis can use this to help squeeze the bottle to get adequate instillation 111 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Ointment ◦ Slower systemic absorption ◦ Blurred vision ◦ Petrolatum, mineral oil (allows vehicle to melt at body temperature), lanolin (absorb water) ◦ Increase contact time ◦ 2x blinking eye ◦ 4x patched 118 Diane T. Adamczyk, OD_Copyright © 2024 112 112 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Gels ◦ Pilocarpine: carbomer gel vehicle ◦ QD ◦ SPK, corneal haze ◦ Artificial tears ◦ GenTeal: carbopol 980 ◦ Transforms gel to liquid on contact with ocular tissue ◦ Minimize blurred vision 119 Diane T. Adamczyk, OD_Copyright © 2024 113 113 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Gels ◦ Converted by temperature changes and ionic movement into a gel like viscosity ◦ Prolonged contact ◦ Gellan gum (Gelrite) and heteropolysaccharide (xanthan gum): timolol ◦ 0.5% gel QD = BID solution ◦ Well tolerated, no blurred vision, no discomfort 120 Diane T. Adamczyk, OD_Copyright © 2024 114 114 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Solid Delivery Devices ◦ SCL (soft CL) ◦ Drug soaked CL-higher efficiency in drug delivery compared to conventional eye drops ◦ Short term drug release ◦ 1st order kinetics à going from higher to lower concentrations ◦ However…alterations to SCL designed to deliver drugs may result in zero order kinetics ◦ Development of particle laden CL, with drug entrapped in vesicles (e.g. liposome, nanoparticles) and then vesicles dispersed in CL 127 Diane T. Adamczyk, OD_Copyright © 2024 115 -zero order kinetics: developing a CL in which drug is continuously being released -in some drugs you want to advise the pt to put the drug before or after CL removal to decrease toxicity to the ocular surface -in other drugs, if they don’t have the preservative, then it’s less bothersome 115 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Nanotechnology: systems with appropriate particle size designed to ensure low irritation, adequate bioavailability and ocular tissue compatibility Include: World J Pharmacol. 2013 ; 2(2): 47–64 127 Diane T. Adamczyk, OD_Copyright © 2024 116 -small particles that help deliver the drug 116 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Solid Delivery Devises ◦ Filter paper strips (fl, rose bengal) ◦ Artificial tear inserts (Lacrisert) 127 Diane T. Adamczyk, OD_Copyright © 2024 117 117 Pharm II Principles of Oc Drug Administration Ocular Drug Delivery Punctal Plug DEXTENZA (dexamethasone ophthalmic insert) indicated for: *Treatment of ocular inflammation and pain following ophthalmic surgery. *Treatment of ocular itching associated with allergic conjunctivitis. 127 Diane T. Adamczyk, OD_Copyright © 2024 118 -punctual plug contains dexamethasone a which is a steroid due for inflammation and plain or for allergic conjunctivitis -zero order kinetics and is constantly releasing drug to the ocular surface and dissolves overtime 118 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Periocular Administration ◦ Higher drug concentration delivered ◦ Subconjunctival Injection ◦ Between anterior conjunctiva and Tenon’s capsule ◦ Severe corneal disease (bacterial ulcer), endophthalmitis, anesthesia 127 Diane T. Adamczyk, OD_Copyright © 2024 119 -where the injection is put varies depending on what you are treating -anti-inflammatory à subjconj or tenon’s capsule -anesthetics the entire globe à retrobulbar conj 119 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Periocular Administration ◦ Anterior Sub-Tenon’s Injection ◦ Vs subconjunctival: ◦ < drug, > risk ◦ Severe uveitis ◦ Posterior Sub-Tenon’s Injection ◦ Equatorial, midzone posterior uveitis, CME 127 Diane T. Adamczyk, OD_Copyright © 2024 120 -uveitis à intravitreal injection 120 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Periocular Administration ◦ Peribulbar Injection ◦ Not into muscle cone B&J 4th ed Periocular Administration ◦ Retrobulbar Injection ◦ Anesthetize globe ◦ Muscle cone http://iv.nucleusinc.com 127 Diane T. Adamczyk, OD_Copyright © 2024 121 121 Principles of Oc Drug Administration Pharm II Complications of Retrobulbar or Peribulbar Injections Anterior Segment ◦ Conjunctival and eyelid ecchymosis (black eye) ◦ Lid swelling ◦ Ptosis (lid droops due to build up of fluid in the lid) ◦ Chemosis ◦ Exposure keratopathy ◦ Elevated IOP ◦ EOM palsy ◦ Pupillary abnormalities 129 Diane T. Adamczyk, OD_Copyright © 2024 122 -potential side effects with doing these infections 122 Principles of Oc Drug Administration Pharm II Complications of Retrobulbar or Peribulbar Injections Posterior Segment ◦ Central retinal artery/vein occlusion ◦ Optic atrophy Orbital ◦ Retrobulbar hemorrhage ◦ Proptosis 130 Diane T. Adamczyk, OD_Copyright © 2024 123 123 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery Intracameral ◦ Anterior chamber injection ◦ Viscoelastic substances: cataract and glaucoma filtering surgeries ◦ Protect endothelium and flat anterior chamber ◦ Implant Intravitreal à try to suppress an infection ◦ Endophthalmitis, CMV retinitis, macular edema ◦ Antifungal, bacterial, viral ◦ Implant 131 Diane T. Adamczyk, OD_Copyright © 2024 124 124 Principles of Oc Drug Administration Pharm II Sustained Release Biodegradable Implant Bimatoprost (Durysta) Biodegradable implant of sustained release bimatoprost Intracameral-settles inferior angle, eventually reabsorbed Currently approved for single administration 132 Diane T. Adamczyk, OD_Copyright © 2024 125 -implant sits in the anterior chamber and over the course of time it dissolves and continuously releases it and also reabsorbs it -good for pts who its hard to get drops into 125 Principles of Oc Drug Administration Pharm II Ophthalmic Drug Delivery 133 Diane T. Adamczyk, OD_Copyright © 2024 126 -steroids, anti-VEGF, etc, 126 Pharm II Principles of Oc Drug Administration Retisert World ' s first intravitreal drug implant for chronic non-infectious posterior segment uveitis (steroid: fluocinolone) Delivers sustained levels of drug directly to the back of the eye for 30 months 134 Diane T. Adamczyk, OD_Copyright © 2024 127 -releases the steroid fluocinolone and delivers the drug to the back of the eye for 30 months 127 Pharm II Principles of Oc Drug Administration Ophthalmic Drug Delivery Iluvien • Non-erodible, intravitreal implant ◦ Cylindrical polyimide tube ◦ Contains steroid: fluocinolone acetonide (FA) Low, steady, daily, sustained release of FA ◦ Over 24-36 month period Intravitreal injection Use: treatment of Diabetic Macular Edema (DME) 135 Diane T. Adamczyk, OD_Copyright © 2024 128 -intravitreal implant and releases a steroid and lasts 2-3 years 128 Pharm II Principles of Oc Drug Administration Advantages & Disadvantages Various Ocular Drug Delivery Systems Advantage Disadvantage-Limitations ØEasy application ØPoor ocular bioavailability ØLeast invasive ØSometimes short duration ØGood pt acceptance ØIneffective posterior seg Suspensions ØProlonged contact time ØShake (pt compliance) Emulsion ØNo shake Gelifying Systems ØEnhance drug retention relative to drops ØDuration of ØIncreased drug absorption weeks Drops ØPotential ocular/systemic toxicity from high concentration or frequent instillation ØHx of generic poorly suspend, dropper tip clog ØMay be thermodynamically unstable ØImproved drug solubility and bioavailability drug activity ^ by hours not days or ØReduced dosing frequency ØPossible better compliance Nanotechnology ØLow irritation ØPotential toxicity ØAdequate bioavailability ØOcular tissue compatibility Current & future ophthalmic drug delivery systems. Drug Discovery Today, del Amo EM, Urtti A. 12-2007 (in part reference) 136 Diane T. Adamczyk, OD_Copyright © 2024 129 129 Pharm II Principles of Oc Drug Administration Advantages & Disadvantages Various Ocular Drug Delivery Systems Injections (Intravitreal, periocular, subconjunctival) Implants NonBiodegradable Biodegradable Systemic Administration Advantage Disadvantage-Limitations ØImproved drug absorption vs systemic or ØFirst order kinetics topical ØDrug delivery to post seg, no systemic toxicity ØDrug delivery to target site ØShort half life (repeat ØAlternate to repeat injections ØNonbiodegradable-surgical remove ØBiodegradable-no removal ØInvasive procedure ØZero order kinetics ØSide Effects: RD, ØMore effective for post seg diseases vs drops inject) pain, discomfort, IOP^, intraocular bleed, potential infection, RD, endophthalmitis ØPatient acceptance ØSide Effects: intravitreal heme ØMost do not pass bl-oc barrier ØPotential systemic toxicity Current & future ophthalmic drug delivery systems. Drug Discovery Today, del Amo EM, Urtti A. 12-2007. (In part reference) 137 Diane T. Adamczyk, OD_Copyright © 2024 130 130 Principles of Oc Drug Administration Pharm II Research continues for new and improved Drug Delivery Systems 138 Diane T. Adamczyk, OD_Copyright © 2024 131 131 Principles of Oc Drug Administration Pharm II Pediatric Considerations 139 Diane T. Adamczyk, OD_Copyright © 2024 132 132 Pharm II Principles of Oc Drug Administration F e d e ra l F o o d , D ru g a n d C o s m e tic A c t d e fin e s p e d ia tric p e rs o n s : A ge 21 and younger P e d ia tric co h o rts P e d ia tric A g e N e o n a te s -- b irth to < 1 m o n t h N e o n a te s : n e w b o rn to 1 m o n t h In fa n ts -- a g e 1 m o n t h to < 2 y e a rs In fa n ts : 1 m o n t h – 2 y e a rs C h ild re n -- a g e s 2 to < 1 2 y e a rs C h ild re n : 2 y e a rs – 1 2 y e a rs N e o n a te s : b irth to 2 8 d a y s In fa n ts : 2 9 d a y s to < 2 y e a rs C h ild re n : 2 y e a rs to < 1 2 y e a rs A d o le s c e n ts : 1 2 -2 1 (u p to b u t n o t in c lu d in g 2 2 nd b irth d a y ) h ttp s :/ / w w w .fd a .g o v / m e d ic a l-d e v ic e s / p ro d u c ts -a n d -m e d ic a lp ro ce d u re s/ p e d ia tric -m e d ica l-d e v ice s A d o le s c e n ts -- a g e s 1 2 to < 1 7 y e a rs A d o le s c e n ts : 1 2 y e a rs – 1 6 y e a rs https://www.accessdata.fda.gov/s cripts/cderworld/index.cfm?action https://www.fda.gov/drugs/data=newdrugs:main&unit=4&lesson= standards-manual-monographs/pediatric1&topic=5 exclusivity-study-age-group Pediatric Prescribing Considerations 140 Diane T. Adamczyk, OD_Copyright © 2024 133 133 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations Young’s Rule (based on age) ◦ Ped Dose = Adult dose X Age (years)/Age+12 Clark’s Rule (based on weight) ◦ Ped Dose = Adult dose X Wt (kg)/70 Or Adult dose X Wt (lb)/150 141 Diane T. Adamczyk, OD_Copyright © 2024 134 134 Pharm II Principles of Oc Drug Administration Youhave a 40lb, 8 year old female in need of an oral antibiotic. You decide to give Amoxicillin. The adult dosage of Amoxicillin is 500 mg Q8H. Based on Young’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) 1. 125mg Q8H 2. 125mg Q4H 3. 200mg Q8H 4. 200mg Q4H 5. 500mg Q8H 142 Diane T. Adamczyk, OD_Copyright © 2024 135 -you can take out answers 2 and 4 bc dose required is every 8 hours 135 Pharm II Principles of Oc Drug Administration You have a 40lb, 8 year old female in need of an oral antibiotic. You decideto giveAmoxicillin. Theadult dosageof Amoxicillinis 500 mg Q8H. Based on Young’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mgtablets) 1. 125mg Q8H 2. 125mg Q4H 3. 200mg Q8H 4. 200mg Q4H 5. 500mg Q8H 143 Diane T. Adamczyk, OD_Copyright © 2024 136 136 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations You have a 40lb, 8 year old female in need of an oral antibiotic. You decide to give amoxicillin. The adult dosage of amoxicillin is 500 mg Q8H. Based on Young’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) ◦Young: ◦ Adult dose x Age (years)/Age+12 ◦ 500mg x 8/(8+12)=500x0.4=200mg Q8H >>>200mg Q8H 144 Diane T. Adamczyk, OD_Copyright © 2024 137 137 Pharm II Principles of Oc Drug Administration You have a 40lb, 8 year old female in need of an oral antibiotic. YoudecidetogiveAmoxicillin. Theadult dosage of Amoxicillin is 500 mg Q8H. Based on Clark’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) 1. 125mg Q8H 2. 125mg Q4H 3. 200mg Q8H 4. 200mg Q4H 5. 500mg Q8H 145 Diane T. Adamczyk, OD_Copyright © 2024 138 138 Pharm II Principles of Oc Drug Administration You have a 40lb, 8 year old female in need of an oral antibiotic. YoudecidetogiveAmoxicillin. Theadult dosage of Amoxicillin is 500 mg Q8H. Based on Clark’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) 1. 125mg Q8H 2. 125mg Q4H 3. 200mg Q8H 4. 200mg Q4H 5. 500mg Q8H 146 Diane T. Adamczyk, OD_Copyright © 2024 139 139 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations You have a 40lb, 8 year old female in need of an oral antibiotic. You decide to give amoxicillin. The adult dosage of amoxicillin is 500 mg Q8H. Based on Clark’s Rule, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) ◦ Clark: ◦ ◦ ◦ ◦ ◦ Adult dose x lb/150 (or kg/70) 2.2lb=1kg 40lb=18.18kg 500mg x 40/150=133 mg >>>125mg Q8H 500mg x 18.18/70=129.87>>>125mg Q8H 147 Diane T. Adamczyk, OD_Copyright © 2024 140 140 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations Body Surface Area (BSA) ◦ Weight and height considerations ◦ Average BSA: ◦ Adult: 1.73 m² ◦ Child 2 years: 0.5 m² Child 10 years: 1.14 m² ◦ Child 12-13 years: 1.33 m² ◦ Various formulas to determine BSA ◦ Example: Dubois and Dubois BSA formula: ◦ BSA = ((Weight(kg) 0.425 x Height(cm) 0.725)) x 0.007184 ◦ Pediatric Dosing Formula: ◦ Dose = (Child’s BSA/1.7m2 ) X adult dose 148 Diane T. Adamczyk, OD_Copyright © 2024 141 -won’t ask about body surface area but could ask about pediatric dosing formula and give the BSA 141 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations You have a 40lb 8 year old female, 57 inches tall, (BSA = 0.9) in need of an oral antibiotic. You decide to give amoxicillin. The adult dosage of amoxicillin is 500 mg Q8H. Based on Body Surface Area, what would you prescribe? (The drug comes in 125, 200, 250, 300, 500mg tablets) ◦ BSA: ◦ (Child’s BSA/1.7m2 ) X adult dose ◦ (0.9/1.7) X 500 = 0.5294 X 500 = 264.7 mg ◦ 250mg Q8H 149 Diane T. Adamczyk, OD_Copyright © 2024 142 142 Pharm II Principles of Oc Drug Administration Pediatric Dosing Considerations: Example A 40lb 8 year old female, 57 inches tall, (BSA = 0.9) is given amoxicillin. The adult dosage of amoxicillin is 500 mg Q8H. (The drug comes in 125, 200, 250, 300, 500mg tablets). Following is the dosage based on various dosage formulas: ◦ Clark: ◦ Adult dose x lb/150 (or kg/70) ◦ 2.2lb=1kg or 40lb=18.18kg ◦ 500mg x 40/150=133 mg >>>125mg Q8H ◦ 500mg x 18.18/70=129.87>>>125mg Q8H ◦ Young: ◦ Adult dose x Age (years)/Age+12 ◦ 500mg x 8/(8+12)=500x0.4=200mg Q8H >>>200mg Q8H ◦ Based on BSA: ◦ (Child’s BSA/1.7m2 ) X adult dose ◦ (0.9/1.7) X 500 = 0.5294 X 500 = 264.7 mg >>>250mg Q8H 150 Diane T. Adamczyk, OD_Copyright © 2024 143 -diff formulas give diff dosage 143 Pharm II Principles of Oc Drug Administration Epocrates Drugs.com 151 Diane T. Adamczyk, OD_Copyright © 2024 144 -look up the drug à amoxicillin tells you adult and ped dosage is and if it’s a capsule, chewable or suspension -tells you based on age as well (below 3 months and above 3 months) 144 Pharm II Principles of Oc Drug Administration Epocrates.com 152 Diane T. Adamczyk, OD_Copyright © 2024 145 145 Pharm II Principles of Oc Drug Administration Amoxicillin Dosing: 8 yo, 40 lb (18.18kg) Dose: 20-40 mg/kg/day q8h 1-Chose 40 mg/kg/day 2 Weight 18.18 kg 3 Dose is 727.2 mg per day or 242.40 mg TID 4- Chose 250 mg chewable TID OR SUSP: 1 Comes 125mg/5mL 2Dose 29.09mL per Day or 9.7mL TID Note: 1tsp=5mL 727.2/3=242.4 TID 250 mg chewable TID OR 29.09/3= 9.7 mL TID liquid dose 250 mg chewable TID OR 9.7 mL TID liquid dose Dosage forms: CAP: 250 mg, 500 mg; TAB: 500 mg, 875 mg; ER TAB: 775 mg; CHEWABLE: 125 mg, 250 mg; SUSP: 125 mg per 5 mL, 200 mg per 5 mL, 250 mg per 5 mL, 400 mg per 5 mL [>3 mo] Dose: 25-45 mg/kg/day PO divided q12h; Max: 875 mg/dose; Alt: 20-40 mg/kg/day PO divided q8h; Info: dose, duration vary by infection type/severity 153 Diane T. Adamczyk, OD_Copyright © 2024 146 -how med is calculated in real life 146 Pharm II Principles of Oc Drug Administration 8 yo, 40 lb (18.18kg) 125 mg chewable TID ??? mg chewable TID 250 mg chewable TID Dosage forms: CAP: 250 mg, 500 mg; TAB: 500 mg, 875 mg; ER TAB: 775 mg; CHEWABLE: 125 mg, 250 mg; SUSP: 125 mg per 5 mL, 200 mg per 5 mL, 250 mg per 5 mL, 400 mg per 5 mL [>3 mo] Dose: 25-45 mg/kg/day PO divided q12h; Max: 875 mg/dose; Alt: 20-40 mg/kg/day PO divided q8h; Info: dose, duration vary by infection type/severity 154 Diane T. Adamczyk, OD_Copyright © 2024 147 147 Principles of Oc Drug Administration Pharm II Pediatric Dosing Considerations Topicals: ◦ Infrequently adjust dosage ◦ Approximate considerations: ◦ Birth to 2 yo: ½ adult dose ◦ 2-3yo: 2/3 adult dose 155 Diane T. Adamczyk, OD_Copyright © 2024 148 148 Principles of Oc Drug Administration Pharm II Review WHAT IS IMPORTANT TO KNOW ABOUT YOUR PATIENT AND WHY – BEFORE YOU USE ANY PHARMACEUTICAL AGENT? 156 Diane T. Adamczyk, OD_Copyright © 2024 149 149 Principles of Oc Drug Administration Pharm II What you need to know about your patients: ◦ Medical conditions ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Kidney/liver à metabolism and excretion difficulty Cardiac Respiratory Etc. Other medications >>Drug Interactions Allergies (e.g. sulfa) Family history (e.g. POAG) Ocular history (e.g. inflammation) 157 Diane T. Adamczyk, OD_Copyright © 2024 150 150 Principles of Oc Drug Administration Pharm II Review How does the drug get into the eye? Your considerations? ◦ Pharmacokinetics ◦ Absorption ◦ Topicals mainly absorbed….where? ◦ Considerations: ◦ Molecular properties of the drug (also prodrugs, metabolites) ◦ Viscosity of its vehicle ◦ Tissue barriers (compartments) ◦ Distribution (Fick, Zero, First Order) 158 Diane T. Adamczyk, OD_Copyright © 2024 151 -topical drugs are absorbed at the cornea and barrier is also the cornea -biphasic drug is better to get thru the cornea -ficks law dealing with topicals going from higher to lower concentration - 151 Principles of Oc Drug Administration Pharm II Over-View History Pregnancy/Pediatric Considerations The Drug Absorption ◦ Compartments ◦ Drug Kinetics Drug removal Formulation Delivery 159 Diane T. Adamczyk, OD_Copyright © 2024 152 152