Week 2 Flashcards
List the Pros and Cons of Topical administration?
Pros
- Easy - Convenient - Self-administered - Targeted therapy to the eye - Less systemic side effects
Cons
- Eyes designed to keep things out
- High local concentrations required
Drug drains into the systemic circulation (occlude the puncta to counter this)
What are the types of topical ocular medications (formulations)?
Eye Drops
- Solutions
- Suspensions
Gels and Ointments
- cream
- gel
- lotion
- ointment
- paste
Ocular Inserts
What is the effective dose?
dose at which response is 50% of maximum effect
What the is drug bioavailabilty?
Amount of drug available at desired receptor site
What are active ingredients in ophthalmic drug formulations?
- It is the therapeutic or diagnostic drug
- Can affect uptake/absorption through changes in tissue permeability, blood flow and fluid secretion (examples below)
- Affecting corneal epithelium, e.g. pilocarpine and cocaine
- Decrease aqueous humour formation, which slows removal of the drug, e.g. dorzolamide
Can come in drug salts, nanoparticles, mixed with other molecules
What Drug schedule are local anaesthetics?
Schedule 4
What are the 3 schedules that optometrist can use drugs from?
Schedule 2, 3 and 4
What are preservatives in ophthalmic drug formulations?
Surfacts, chemical toxins and antiodative and others
List the 4 types of Preservatives?
○ Surfactants
○ Chemical toxins
○ Oxidative preservatives
Miscellaneous
Give an example of 3 common preservatives?
- Benzalkonium chloride (BAK)
- Chlorhexidine
- Mercurials
- Chlorobutanol
- Ethylenediaminetetraacetic acid (ETDA)
- Stabilized oxychloro-complex (purite), sodium perborate
SofZia
What are surfactants in ophthalmic drug formulations?
- Surfactants (most common)
- Ionically charged molecules that disrupt plasma membrane; usually bactericidal
Common facts about Benzalkonium Chloride (BAK)
○ Found in household cleaning products
○ Single drop of 0.01% BAK can break the tear film lipid layer, e.g. like putting detergent on oil
○ Toxic to the corneal epithelium; increased drug penetration
§ Toxicity increases with acidity of the solution
§ Particularly high risk of toxicity with increased used, e.g. anti-inflammatory drops
§ Very low concentrations (e.g. 0.00001% BAK) arrests cell growth and death in the corneal conjunctiva
Stable, excellent antimicrobial properties, long shelf life
Common facts about Chlorhexidine
○ Works similarly to BAK; often used at lower concentration than BAK so does not alter corneal permeability
○ Due to structure, does not disturb the lipid layer the same way as BAK, also toxicity neutralised by tear film
Also an active ingredient used for treating Acanthamoeba keratitis
Common facts about Polyquaternium - 1 (polyquad)
○ Detergent-like quaternary ammonium
Larger molecule than BAK so is not internalized by the corneal epithelium (in mammalian cells) – less toxicity
Common facts about Thimerosal (Chemical toxins)
§ Mercury-based chemical, highly effective against fungi
§ Most effective in weakly acidic nitrate
§ Patients can develop sensitivity, e.g. allergic reaction in the conjunctiva
Needs to present in high continuous concentrations to have a biologic effect; diluted by tear film to prevent corneal epithelial toxicity
Common facts aboout Chlorobutanol (chemical toxin)
○ Alcohol based chemical, less effective compared to BAK, loss from bottles in prolonged storage
○ Can affect many microbes but not highly effective when used alone
○ Often used with ethylenediaminetetraacetic acid (ETDA)
§ ETDA is a chelating agent: reacts with metal ions to form a stable water-soluble complex
By itself, ETDA is not highly toxic but can cause contact dermatitis
What are some common - oxidatives?
Stabilized Oxychloro Complex (Purite, OcuPure)
Sodium Perborate
Oxidative preservatives can be neutralized by mammalian cells; no accumulation, and less toxic than chemical toxins
Common facts about Oxycholoro Complex
○ Stabilized Oxychloro Complex (Purite, OcuPure)
§ Oxidases microbial cellular components but does not significantly affect human ocular tissues
§ Breaks down into water and sodium chloride when exposed to light
Purite is found in alphagan
Common facts aobut Sodium Perborate
○ Sodium perborate
§ Alters protein synthesis within bacterial cell
Converted into hydrogen peroxide and then broken down into oxygen and water in the eye by catalase
Common facts about other preservatives
○ Sofzia (boric acid, propylene glycol, sorbitol, zinc chloride)
§ Ionic buffer, works similar to a detergent or surfactant (causes oxidative damage and death of cells that do not have cytochrome oxidase or catalase enzymes), converted to non-toxic components on contact with cations on the ocular surface
§ Found in travoprost
§ Causes less superficial epithelial punctate staining of the cornea compared to BAK
Protects against a wide range of microbes e.g. pseudomonas aeruginosa, candida albicans, aspergillus
What are the benefits of viscosity agents?
Help with osmolarity, pH, thickness of the drug, increase time the drug stays on the eye
○ Delay washout from the tear film, increase bioavailability Can affect vision, cause blur
Some viscosity polymers contain both hydrophilic and lipophilic sites, enables better combination with different drugs
○ Nonlinear relationship between molecular weight and concentration; viscosity needs to be measured at the appropriate concentration of the drug Can interact with drug salts to change viscosity; maybe incompatible
What are the types of viscosity agents and how do they differ?
○ Polyionic molecules
§ Bind to corneal surface, increase drug retention, stabilize the tear film (eye drops and gels
○ Petrolatum or oil-based
Provide longer retention of drugs on the eye, acts a temporary lipid depot (ointments); generally thicker than polyionic molecules
○ Gel-forming systems (e.g. Gelrite) § Large molecules that change with temperature, pH and electrolyte composition § Forms a clear gel by binding to cations found in the tears to prolong corneal penetration and drug action Increased viscosity = blurred vision
What are some common viscosity agents?
- Polyvinylpyrrolidone
- Polyvinyl alcohol
- Hydroxypropyl methylcellulose
- Carboxymethylcellulose
Sodium hyaluronate
What do wetting agents do?
- Wetting agents
○ Increase spreading and penetrating properties of a drug by lowering surface tension; increases contact time- Buffer (changes pH of a solution)
○ Drug stability is very important; storage in different conditions and varying amounts of time
§ If a drug less than 18 months shelf life, would be impractical as unable to distribute to other locations
○ Drugs (particularly weak bases) that are formulated in an acidic solution are more stable than at a neutral or alkaline pH
○ Low concentration buffer allows tears to re-establish normal pH after drug instillation
Some drugs break down quickly as soon as it dissolves, can use a physical barrier
- Buffer (changes pH of a solution)
What does osmolarity do?
- Osmolarity
○ Usually, combination of active drug, preservative and vehicle results in a hypotonic solution
○ Simple or complex salts, buffering agents or certain sugars can be added to adjust osmolarity to 290 mOsm/L (isotonic solution = 0.9% saline)
§ Creates drug osmotic gradient to allow drug into the eye
Increasing tonicity above tears causes dilution of the tears, and there
Common facts about eye drops - ocular solutions
○ Most common ○ Drug salt dissolved ○ High concentrations ○ Risk of stinging ○ Low cost ○ High patient acceptance Low absorption
Common facts about eye drops - ocular suspensions
○ Salt suspended in liquid
○ Sterilizations required
○ Requires shaking (20 times - 1 minute)
○ Low bioavailability due to manufacturing
○ High concentrations
Higher cost to make
