Ocular Pharmacology > Drugs > Flashcards
Drugs Flashcards
Can oral therapeutic agents and topical glaucoma therapy be prescribed in Massachusetts
Yes, since 2021 MA can only prescribe class 4 and 5
Which state excludes oral therapies from being prescribed by optometrists
NY
Routes of ocular injections
Roll of excipients/vehicles in ocular medication
Stabilize pH
Tonicity
Viscosity
What is an emolient
Softens tissue
Prevent drying and cracking
Mineral oil, petrolatum
What is a Demulcent
Protect/lubricate mucous membranes, mimics mucins
Cellulose derivatives:
Hydrogels
Polymeric viscosity agents
Polyols:
PEG
Glycerin
Gelatin
Povidone
PG
PVA
What is an Emulsifyer
Keeps solids well dispersed in liquids
egGellan gum
What is an Astringent
Precipitates proteins, clears mucous
eg Zinc sulhate
What do Buffers do
Stabilize pH:pH 8.5 is most comfortable for dry eye px
eg Borate
Sodium citrate
What is a surfactant/mucolytic
a substance which tends to reduce the surface tension of a liquid in which it is dissolved
Breaks down mucous
eg Tyloxapol
What are viscosity modifiers
Affect viscosity of a drop thereby retention time on ocular surface
eg Polyacrylic acid (Durasite)
What do osmoprotectants do
Reduce high osmolarity, absorbed by dehydrated cells
eg Erythritol
L-carnitine
What do stabilizers do
Prevent drug from being broken down
Gellan gum
What do tonicity stabilizers do
Deliver a physiologic for of salt level such as physiologic saline
eg KCl
CaCl
MgCl
What are humectants
Promote hydration
eg hyaluronic acid
Which class of drug do cap colours indicate
Yellow- Beta blockers
Dark blue- Beta blocker combo
Red- mydriatics & cycloplegics
Dark green- Miotics
Orange- Carbonic anhydrase inhibitors
Gray- NSAIDs
Pink- Steroidal anti-inflammatories
Tan- anti-infectives
Teal- Prostaglandin analogues
Purple- Adrenergic agonists
Ocular derug delivery devices
Improvised topical delivery
- Morgan lens ocular irrigation system
Used to irrigate the ocular surface when the patient gets a ocular surface burn or other injury that
has a saline bag and contact lens like end to cover the ocular surface and keep it moist
Ophthalmic drops: the problem
- In the eye care arena, topical application of therapeutic agents in 50-70ul drops supersedes all other routes of drug delivery
- Readily accepted by patients but this method has long been subject to rapid pre-corneal drug loss (90%) and increasing risks of ocular surface toxicity and systemic toxicity with continued dosing
- To improve ocular drug bioavailability, reduce toxicity and enhance therapeutic outcomes, development of new drug delivery systems for ophthalmic administration continues to be a topic of immense attention in big pharma
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- Combined efforts to reduce dosing requirements and enhance drug absorption with deliverysystems that release micro-doses show great promise
Lotemax SM Gel 0.38%
Submicron particle size for faster drug dissolution in tears
2X greater penetration to aqueous humor vs Lotemax gel 0.5%
Gels have lowest BAK 0.003% concentration in Lotemax family
difficulty with absorption of drugs:
- The body is surrounded by boundary tissues that prevent foreign matter from penetrating
- The mucus that coats these tissues – the eyes, lungs, cervical/vaginal tract and GI tract – serve as a protective barrier to trap and eliminate particulate matter such as viruses, bacteria and allergens, before these agents can enter the underlying tissues and cause infection or elicit reactions. However, in playing this pivotal role of protection, mucus may also hinder medical treatments by limiting the penetration to mucus-protected tissues, thereby reducing their therapeutic effect
- Mucus can interfere with the ability of drugs to reach ophthalmic tissue
- The tear film protecting the eye’s surface can trap and eliminate traditional suspension eyedrops as the eyelid blinks. This process can limit the penetration of drugs to target ocular tissue when treating conditions in the front of the eyes, such as dry eye disease and post-operative inflammation and pain
- Traditional suspension eye drops adhere to mucins and can be rapidly cleared through blinking
- Novel technologies to circumvent this barrier are an important advance in delivering therapeutic agents to the target tissue. The company Kala looked to nature for inspiration and found a dense, net neutral and hydrophilic coating of viruses which minimizes interaction within the mucosal barrier and increases transport to underlying tissue
EYENOVIA® microdose technologies
- Piezostatic microdose therapeutics is based upon piezo ejection technology used by many popular inkjet printers
- Using piezo-print technology, ejected drops are micro-ionized and charged for smooth application and high ocular adhesion
-
- The OptejetTM dispenser offers unprecedented precision, providing smooth, gentle application to the ocular surface of drops as small as 7ul
-
- “Smart” technology permits dose tracking history
- Could be an up and coming therapy to provide small dosing of therapeutics, tracking doses to smart phone.
- Microstat is a dispenser that distributes 2.5% phenylephrine and 1% Tropicamide to the ocular surface for dilation
MediprintTM Medicated contact lens
Mediprint claims they will initially develop, clinically test and commercialize drug-eluting, comfort-
enhancing contact lenses to treat millions of patients worldwide suffering from glaucoma, dry eye and
ocular allergies
Acuvue Theravision
March 24, 2021 J&J announced approval from the Japanese Ministry of Health, Labour and Welfare for
the first and only contact lens indicated for allergic conjunctivitis containing Ketotifen
- The lens combines etafilcon A material with a 0.019mg dose of Ketotifen
- Patient reported relief within 15 min and long lasting relief up to 12 hr
FDA Requirements of Viable drugs
Since 1979 FDA requires expiration date listed to indicate the date that the FULL potency of the sealed
rx or OTC drug can be guaranteed.
Drugs commonly have a 12-24 month expiration date
Not much incentive for manufacturers to create drugs that last longer (patients wouldn’t have to
replace and rebuy as frequently)
-
- Controversy over the use of outdated drugs exists.
Antimicrobial preservation is essential for all drugs excluding preservative-free unit dosing vials
According to the manufacturer, the stability of a drug cannot be guaranteed once the original
bottle is opened
-
Sealed containers become prone to bacterial contamination once opened; this represents an
extraneous concern that can affect the drug integrity at any time, before or after the expiration
date, depending on handling
-
Liquids are more prone to breakdown and contamination than solids
○ Bacteria thrive in a moist environment
-
Most pharmacies arbitrarily limit the use of dispensed products to 1 year regardless of if the
expiration date extends beyond that time, with labels indicating: “do not use after…” or “discard
after…”
-
*NOTE: topical preparations do not need to show equivalent bioavailability, just the same active
ingredient; vehicles may vary
Drug Formulations
Gel: enhanced time on the ocular surface compared to gtts
Ointment: enhances drug retention up to 6hr
Solids: contact lenses, collagen shields, filter strips, cotton pledgets, Lacrisert® (lubricant), Vitrasert®
(introduced to vitreous), Lucentis® (introduced into the posterior chamber)
Solution: most common ophthalmic drug formulation
Suspension: must be shaken; solids settle
- Good option for drugs that cannot be made into solutions
Colloid: may be lipid bilayers or polymeric nanoparticles
Emulsion: Uniform mix of oils in water (eg milk)
Sprays: great for dilating kids; eyes closed
Micronized: reduced solid particle diameter (um or nm)
Ophthalmic excipients/vehicles
Stabilize pH, tonicity, viscosity
Broad variety of excipients:
- Emolient (softens tissue; prevents drying and cracking)
- Mineral oil, petrolatum
- Demulcent (protect/lubricate mucous membranes; mimic mucins)
- Cellulose derivatives
- Hydrogels: HPMC, HPC, HMC, HEC
- Polymeric viscosity agents: CMC
- Polyols: PEG, PG, PVA, Glycerin, Gelatin, Povidone
- Cellulose derivatives
- Astringent (precipitates protein; clears mucous)
- ZnSO4
- Buffers (stabilize pH: pH 8.5 is most comfortable for dry eye patients
- Borate, Na-Citrate, tromethamine (an organic amine proton acceptor)
- Surfactant/mucolytic
- Tyloxapol (soothe long lasting, blink-n-clean)
- Viscosity modifiers
- Enhancers: HP Guar, sodium hyaluronate, Xanthan Gum, Gellan gum (eg Gelrite®), polyacrylic acid (eg Durasite®), PEG, hydrogels, PG
- Reducers: PVA
- Osmoprotectants (reduce high osmolarity; absorbed by dehydrated cells)
- Erythritol, L-carnitine
- Stabilizers (keep the drug from being broken down)
- Hydroxyalkyl- phosphonate, Gellan Gum
- Tonicity stabilizers
- KCl, CaCl, MgCl, ZnCl, sorbitol
- NaCl (physiologic saline levels are 0.9% (308 mOsM)
- Humectants (promote hydration)
- PG, hyaluronic acid, glycerin
Commercial antimicrobials
- Antiseptics are disinfectants that are relatively safe for cleaning wounds, membranes and skin
- Disinfectants are bacteriostatic or bactericidal
- Neither disinfectants nor antiseptics are designed for use in medications though examples of disinfectants that routinely contact the eyes are those used to disinfect contact lenses
- All preparations that contain water are at risk of microbial spoilage
- Preservatives are tasteless, odorless chemicals which serve to preserve organic material from decay or spoilage and protect from microbial contamination
- Preservatives stabilize products, protect from oxidation and increase shelf life
- Preservatives are not used directly on humans but rather they are found in most every product that is designed for application, injection, inhalation or consumption
- Single dose, sterile prepared agents may be unpreserved
Chelators/anticoagulants
Chelators/anticoagulants
Complex with reactive metals that aid in bacterial growth and facilitate oxidative reactions; inhibit
bacteria, mold, yeast growth, EDTA and citrate complex with blood calcium (EDTA irreversibly
complexes)
- EDTA is recognized for its risk of contact dermatitis
- Anticoagulant effect
Organic acids
Organic Acids
Act by disrupting microbial metabolic pathways intracellularly therefore most active at low,
undissociated pH; alteration of pH affects enzyme function ect.
- sorbic acid (pKa of 4.8)
- Benzoic acid (a common food preservative and antiseptic)
Oxidants and antioxidants
Oxidants
A source of highly reactive free radicals
○ Hydrogen peroxide (gold standard in cls disinfectants)
-
Antioxidant
Preserve integrity of the drug by reduce oxidation of the active ingredient by free radicals
○ Ascorbic acid (a reducing agent with a low redox potential)
○ Butylated hydroxytoluene (BHT)
○ Butylated hydroxyanisole (BHA)
○ EDTA is added to chelate metal ions that facilitate oxidation reactions
Disappearing oxidants
- Borate complexes (pH sensitive)
- Genteal® /GenAqua®
- Thera Tears®/ Dequest®
- Tears again® / Dissipate®
- Ionic-buffering perservatives
- Travatan-Z® / SofZia®
- Stabilized Oxychloro Complexes
- Allergan Refresh® Purite® (light activated; neutralize on ocular surface)
- Blink® OcuPure® (light activated; metabolized by mammalian enzymes)
- Brimonidine Purite®
Alcohols & Parabens
Alcohols - Act by dehydrating the environment. Can kill bacterial by drying out)
- Chlorobutanol: a chloride-based alcohol; often combined with EDTA
- Phenol
- Benzyl alcohol
Parabens- An effective antiseptic and preservative; susceptible to decomposition; risk of hypersensitivity
- Methyl paraben
- Ethyl paraben
- Propyl paraben
Heavy metals
Act by irreversibly binding to key enzymes ect.
- Toxic to our bodies
Organomercuric compounds
- Thimerosal - once used in a multipurpose cls care system
- Phenylmercuric nitrate
Polymers
Povidone AKA Polyvinylpyrrolidone (PVP)
○ Synthetic, water soluble non-ionic polymer; absorbs 40% its weight in water
○ Used in WWII as a plasma expander following a traumatic hemorrhage
○ Its use since then has been curtailed due to stimulation of histamine release
As a chemical toxin, it’s combined with toxic metals (iodine, mercury, cyanide) to be used as
a preservative
Surfactants-ionic detergents
Biguanides:
- 1st line therapeutic agents for type 2 diabetes mellitus
- Polyhexamethylene biguanide (PHMB): the most common preservative used in cls solution
- Polyaminopropyl biguanide (PAPB) Dymed®
- Chlorohexidine
- Alexidine: linked to cls solution fusarium outbreak in 2007
Quaternary Ammonium Compounds
Benzalkonium Chloride (BAK or BAC): the most common preservative (in 72% of topical
ophthalmic drops) used in topical ophthalmic drops; a cationic surfactant
-
Polyquaternium (Quats)
○ PQ-1 aka Polyquad; more selective for bacterial cells
○ PQ-42 aka Polixetonium FreshKote®
-
Aminoamines
○ Myristamidopropyldimethylamine (MADP) Aldox®
Non- vs Self-preserved products
- Preservative-free (PF) unit dose vials
- ATs
- Ophthalmic therapeutic agents
- Preservative-free multidose bottles
- ATs
- Ophthalmic therapeutic agents
- Self-preserved
- Ophthalmic antibiotics: moxifloxacin
