Drugs and the eye Flashcards
(89 cards)
1
Q
What are the types of TOPICAL drugs used by optometrists and examples of them:
A
- Diagnostic drugs e.g. mydriatics e.g tropicamide, cycloplegics e.g cyclopentolate, topical anaesthetics
- Lubricants e.g. Hypromellose, Sodium Hyaluronate
- Anti-infectives e.g. Fusidic acid, Chloramphenicol
- Anti-allergy (anti-histamines and mast cell stabilizers)
2
Q
Types of specialist Therapeutic Prescribers for TOPICAL drugs :
A
- Corticosteroids
- Anti-glaucoma
3
Q
What are the types of SYSTEMIC drugs used by optometrists and examples of them:
A
- Antihistamines e.g. Cetirizine, Loratidine
- NSAIDs e.g. Ibuprofen, Aspirin
- Eye-nutrients e.g. Anti-oxidant vitamins/ Essential Fatty Acids – AMD and dry eye
4
Q
Types of specialist Therapeutic Prescribers for SYSTEMIC drugs :
A
- Oral antibiotics e.g. Tetracyclines
- Carbonic Anhydrase Inhibitors e.g. Acetazolamide
5
Q
What are antihistamines used for:
A
Allergic symptoms of eye e.g. hayfever to relieve the symptoms
6
Q
What are NSAIDs:
A
Non steroidal anti inflammatory drugs – pain associated with eye disease
7
Q
What is the % of each therapeutic agents used by optometrist in the minor eye condition’s scheme:
A
- Lubricants - 79.9%
- Antibiotic eye drops - 32.5%
- Anti -allergy eye drops - 16.3%
- Oral analgesics - 1.3%
8
Q
What are the different routes of administration for drugs:
A
- Topical
○ Solutions – soluble
○ Suspensions – insoluble
○ Ointments - Intra-ocular
○ Injection
○ Insert - Systemic
○ Oral
Injection
9
Q
Give an example of an eye disease where injections are used for treatment:
A
- Wet AMD
- Anti vascular endothelial growth factor drugs ( anti VEGF drugs ) used for wet AMD = need to be injected directly into eye
10
Q
Give an example in eye where antibiotics or steroids are used for treatment:
A
- Ocular infections or inflammations
- Antibiotics/steroids need to be put into eye cause topical application will result in insufficient amount being delivered so need higher therapeutic concentration to work
11
Q
What are the Pharmacological /Therapeutic classes:
A
- Anti-infectives
- Corticosteroids/anti-inflammatory
- Anti-glaucoma
- Dry eye
- Mydriatics/cycloplegics
- Local anaesthetics
- Peri-operative
12
Q
What is drug bioavailability determined by:
A
The unique pharmacokinetic properties of the eye
13
Q
What is the primary barrier that needs to be crossed for topical agents:
A
The ocular surface
14
Q
What factors influence drug delivery to the eye:
A
- Topical Drugs
- Pre-corneal factors – in front of cornea
- Corneal penetration
- Inside the eye
15
Q
What pre - corneal factors influence drug delivery to the eye and absorption:
A
Tear turnover rate has a major influence on pre-corneal retention time and is the main factor to determine absorption of drug
16
Q
How does tear turnover rate influence amount of drug absorbed:
A
The higher the tear turnover rate = greater amount of tear drainage = more drug is dissipated
17
Q
Does drop size and amount of drops put into the eye affect absorption of drug and explain why:
A
- NO multiple drops or greater drop size doesn’t lead to more absorption of drug
- Theres little difference between 10ul and 50 ul drop
- Because the more you add in single drop, the more overspill you get of the drug and wouldn’t be absorbed
18
Q
What can larger drop size result in:
A
- Higher rates of drainage occur
- Which can lead to an increased risk of systemic toxicity
19
Q
Explain how nasolacrimal drainage of drug affects drug absorption and risks of it:
A
- A single drop from a conventional dropper bottle exceeds the capacity of the conjunctival sac
- Nasolacrimal drainage i.e once drug gets into tears the amount of drug leaving eye via nasolacrimal drainage system , exceeds corneal penetration of drug
- Want to minimize amount of drug passing through nasolacrimal route cause that would increase risk of systemic absorption
- Once the drug gets into nasal pharynx – crosses mucosa into circulation
20
Q
Give an example of a situation where systemic absorption of ophthalmic drug is dangerous:
A
- Timolol - this is a topical beta blocker to treat glaucoma
- Blocking beta receptors in eye would reduce aqueous secretion
- But also blocking beta blockers in lungs would lead to bronchoconstriction = fatal
- So glaucoma px’s are asked if they have asthma or chronic obstructive airway disease before prescribing topical beta blockers
21
Q
What is the main route of entry for topical medication:
A
The cornea
22
Q
What sort of drugs penetrate the epithelium rapidly but stay in corneal stroma and why:
A
- Lipid soluble drugs i.e strongly lipophilic
- The hydrophilic stroma limits the passage of lipophilic formulations
23
Q
Which sort of drugs have optimal penetration through cornea:
A
- Drugs which possess a combination of hydrophilic and hydrophobic properties
- This tends to be the case for weak acids and weak bases used to formulate ophthalmic drugs
- THESE DRUGS STRUGGLE TO PASS THROUGH MEMBRANES OF EPITHELIUM AND ENDOTHELIUM
24
Q
What factor can influence the rate of drug penetration:
A
Ocular morbidity
25
Where and lipids present in eye and what is hydrophilic:
- Lipids on surface on corneal epithelium
- Lipids on posterior surface on corneal endothelium cell membranes
- Hydrophilic stroma in between
26
How can a drug penetrate sufficiently through cornea:
Drug needs to have balance between its hydrophilic and hydrophobic properties
27
When is a drug hydrophilic:
When in ionized form
28
When is a drug lipophilic:
When in non ionized form
29
Explain route of drug through cornea and its changes in ionisation:
* Weak base
* Eqbm between two forms
* Ph of tears, drug is non ionized form = arrow at top shows loses proton ( loses H+) = becomes non ionized and so can readily penetrate through corneal epithelium in this form
* Once penetrate epithelium and stroma it flips into ionized form ( R3NH+)
* It then passes through corneal stroma cause stroma is largely water so ionized form can penetrate through
* And then it reverses back to its non ionized or lipophilic form to get through the epithelium
This is ph driven as it passes through cornea
30
What sort of drugs don’t penetrate readily:
Drugs that are hydrophilic
31
What sort of drugs penetrate readily:
Drugs that are lipophilic
32
What happens once the drug is in the eye - how is some of it lost:
* After corneal penetration drugs are distributed into aqueous humour and mixed with it
* Some of drug is lost in the process of aqueous production and drainage before it reaches its target
* And some proportion of drug isabsorbed into tissues of anterior chamber
- So not all of drug that penetrates through cornea will meet its target
33
How are drugs eliminated from the anterior chamber:
By a combination of aqueous turnover and absorption across the tissues of the anterior uvea
34
What other factor can influence bioavailability:
- Melanin binding
- As both cyclopentolate and tropicamide strongly bind to melanin
35
What are the targets for tropicamide and cyclopentolate:
- They have intraocular targets
- Tropicamide – target is muscarinic receptors in sphincter pupillae of iris
- Cyclopentolate – target is muscarinic receptors in ciliary body
36
Where is drug target for eye drugs and give an example:
- Target is on the ocular surface
- E.G. topical anaesthetic
- So doesn’t need to penetrate far to achieve desired effect
37
Melanin effect in drugs:
- High concentrations of melanin would need to be used in those with darker pigmented iris
- But solution is not to put more of the drug in
- Because that interaction between melanin and drug is not being neutralized
- Instead that drug binds to melanin
- And then overtime the drug is released and will interact with its target
- So solution is to allow more time for the drug to work, may use high conc e.g 1%rather than 0.5%
38
Examples of drug enzymes used in eye:
Carbonic anhydrase inhibitors for management of glaucoma e.g. dorzolomide
39
Examples of receptor enzymes used in eye:
- Beta blockers e.g. timolol
- Muscarinic e.g. cyclopentolate
40
What sort of drug is phenylephrine and where are its receptors found:
- Acts on sympathetic ns
- Adronergic receptor agonist
- These receptors are found in dilator pupillae
41
What drugs are used to treat acute open angle glaucoma:
- Acetazolamide = brings pressure down = this is a tablet
- So instead invented topical carbonic anhydrase inhibitor e.g. dorzolomide for treating open angle glaucoma
42
Examples of enzymes involved in ocular drug metabolism:
- Esterases
- Monoamine oxidase
- N-acetyltransferase
- Oxidoreductase
- Catechol-O-methyltransferase
43
What happens to some drugs on transit through cornea:
* Some drugs are broken down by ocular tissues during penetration which limits their effectiveness
* I.e broken down on transit through cornea
* But sometimes these drug metabolising enzymes in cornea are exploited
- This happens in the case of pro drug
44
What is a pro drug and why is it good:
- A drug that in its parent form is inactive but becomes activated under action of enzyme
- This is to make drug more efficient than parent compounds
- Where the breakdown product is more effective than the parent compound which is in the inactive form
45
Give an example of pro drug and explain its process:
- The anti-glaucoma drug latanoprost
- It is metabolised by esterases on its transit through the cornea
- Which turns it into its active compound making it more efficient
46
Where are some drug metabolizing enzymes found:
- In cornea
- In liver
47
Which drug metabolizing enzymes is it good for to be located in liver:
For those topical drugs that are to be systemically absorbed and need to be excreted through normal mechanisms through which the body eliminates drugs
48
How are drugs eliminated after corneal penetration:
- Following corneal penetration drugs are distributed into, and then eliminated from the aqueous humour
- This is done by a combination of aqueous turnover and absorption into the tissues of the anterior uvea
- Absorption of drug across tissue of anterior uvea i.e iris and anterior ciliary body, so once they enter these vascular tissues they can be removed by intraocular circulation
49
What can influence bioavailability and predispose to toxicity
Drug binding to the pigmented tissues of the iris and ciliary body i.e melanin
50
Why is the process of production and drainage of aqueous humour important:
- Because the drug is then mixed in with the aqueous humour
- This limits the access of the drug to its target and reduces availability
- But is important because it’s the primary mechanism through which drugs are eliminated from body
51
What factors influence drug delivery to the eye:
* Systemic Drugs – need to have intraocular targets
* Blood-ocular barriers = vasculature of ocular tissue e.g blood aqueous barrier, blood retinal barrier
* Plasma protein binding
- Active transport
52
What does the blood-aqueous barrier do:
- Limits the free access of systemic drugs to the anterior chamber
- DRUGS NEED TO TRANSIT ACROSS BAB TO BE EFFECTIVE
53
What are the main components of the BAB:
The “tight” ciliary epithelium and low permeability of iris blood vessels
54
What happens when the eye is inflamed:
The BAB can break down and increase drug bioavailability
55
Where is the blood-aqueous barrier found:
Inside the systemic circulation moving to ocular circulation
56
What form the blood aqueous barrier:
Tight junctions between cells of ciliary epithelium and blood vessels of iris between endothelial cells
57
What bad thing can happen to blood aqueous barrier:
- If eye is inflamed in conditions such as anterior uveitis
- BAB can break down which allows material to pass from plasma into eye
58
What is the blood-retinal barrier formed by:
Tight junctions between capillary endothelial cells and retinal pigment epithelial cells
59
Role of blood-retinal barrier:
- Limits the passage of all but the smallest lipid-soluble molecules
- So to get drugs into the retina, this barrier needs to be crossed
60
What can and cant get across BRB:
* Several drug transporters have been identified at the BRB
* But anti VEGF agents for vaso proliferative retinal disorders e.g. wet AMD and diabetic macula oedema cant get across BRB so need to be delivered in intraocular injection, if gave that drug systemically, wouldn’t get high dose of drug
61
What is needed for drug to be stable:
* No drug is indefinitely stable
* Ideally a drug should have a long shelf-life
* Certain formulations of drugs require specific storage conditions e.g. low temperature, absence of light, cool place, refrigerated
* High temp can lead to drug instability
* Soluble drugs may need a specific pH to retain solubility – at ph that maintains solubility of drug
* Insoluble drugs can be prepared as suspensions
* Once a multi-dose bottle is opened the drug is subject to oxidative damage and bacterial contamination so need to add agents into solution to minimize this damage
62
Single use drugs vs multi dose bottle:
- Single use drugs – minims - preservative free – single use – throw it away after use
- Multi use dose bottle – cheaper
63
What is problem with corticosteroids - how are they designed:
- Corticosteroids are lipophilic so they don’t dissolve in water i.e are insoluble
- But they can still be formulated as topical ophthalmic drugs to formulate the drug as a suspension
- So the drug is suspended in solution rather than being dissolved in solution BUT….
- Problem with this is that overtime the drug will sediment out of solution and sit at bottom of bottle – have to shake to reestablish suspension
64
What is important in ophthalmic preparations and why:
- Sterility of ophthalmic preparations is critical
- Because you don’t want to be instilling a drug that is contaminated with microorgansisms
65
What are the different sterilisation methods available:
* Heat – not impacting stability
* Sterile filtration – force drug through filter which holds back microorganisms – sterile solution passes through leaving any potential contaminants on the filter membrane
- Once drug sterilized, UV or gamma radiation can kill microbial contaminants
66
What are added to multi-dose formulations and why:
- Preservatives are added to multi-dose formulations
- To maintain sterility and make sure little to no microbial growth during life time of drug
- Intra-ocular products are preservative free
67
Excipients (inactive ingredients) used in ophthalmic formulations to ensure sterility and stability:
* Preservatives
* Buffers
* Antioxidants
* Viscous agents
* Tonicity-adjusting agents – more hypotonic or hypertonic
- pH adjusting agents to keep it acidic or alkaline
68
What do buffers do in ophthalmic formulations to ensure sterility and stability:
Maintain constant ph
69
What do viscous agents do in ophthalmic formulations to ensure sterility and stability:
- Increase viscosity of ophthalmic formulation
- Maintains contact time on ocular surface and enhance absorption stays around longer.
- If low viscosity it would flow off the ocular surface and leave eye quickly
70
Excerpt from the summary of product characteristics for Chloramphenicol: Optrex infected eyes eyedrops:
- List of excipients - Borax powder, Boric acid powder, Phenylmercuric nitrate, Water for injections. -sterile water
- Incompatibilities = Not applicable.
- Shelf life = 18 months unopened. Although the shelf life once opened is 28 days, patients should be advised to discard the medicine after a 5 day course of treatment.
- Special precautions for storage = store at 2° to 8°C. = refrigerator, Protect from light.
Nature and contents of container = White pigmented bottle of high density polyethylene/low density polyethylene mix with white pigmented low density polyethylene plug and red pigmented polyethylene tamper evident cap.Pack size: 10 ml
- Instructions for use and handling = None
71
Excerpt from SPC for Fusidic acid 1% Viscous Eye Drops
- List of excipients = Benzalkonium chloride, disodium edetate, mannitol, carbomer, sodium hydroxide, water for injections.
- Incompatibilities = None known.
- Shelf life = 3 years.
- Special precautions for storage = Store below 2C. Keep the tube tightly closed. The tube should be discarded one month after opening.
- Nature and contents of container = Available in 5g tubes.
- Instructions for use and handling = None.
72
Role of anti-oxidants in drugs:
- Prevent or delay deterioration of the drug by oxygen in the air
- Prolong stability of drug
73
Examples of anti-oxidants:
* EDTA
* Sodium bisulphite
- Sodium metabisulphite
74
Role of preservatives in drugs:
- Destroy or inhibit the growth of micro-organsims
- Because once expose bottle to air it is potentially contaminated so need to add preservatives to prevent microbial growth
75
Examples of preservatives:
* Benzalkonium chloride (BAK)
* Phenylmercuric nitrate – mercury based – used in chloramphenicol
* Polyquad
- Newer (less toxic) preservatives e.g. Purite (stabilized oxychloro complex) and Sofzia (composed of boric acid, propylene glycol, sorbitol and zinc chloride)
76
Features of Benzalkonium chloride (BAK) preservative:
* Quaternary ammonium compound
* Most widely used
* Effective against a wide range of GM +ve and GM -ve organsisms
* Concentration; 0.004-0.02%
* Excellent chemical stability
* Can affect corneal penetration and penetration of drug into eye
* Binds to hydrogel lenses
* Not to be worn with cl’s
77
Advantages and disadvantages of preservatives:
+ = maintain sterility and stability
- = toxic and ocular symptoms shown in graph and ocular inflammation
78
Give examples of new ophthalmic preservatives:
- Polyquaternium-1 (Polyquad)
- Purite
79
Features of Polyquaternium-1 (Polyquad):
* Is a polymeric quaternary ammonium antimicrobial preservative.
* It’s found in contact lens solutions and several artificial tear formulations.
* Polyquad has been proven to have less toxicity on corneal epithelial cells than BAK
80
Features of Purite:
- Is a microbicide with a broad spectrum of antimicrobial activity and very low toxicity to mammalian cells.
- Purite preserves the solution in the bottle but when exposed to light, dissociates into water, sodium and chloride ions, and oxygen
81
Role of buffers in drugs:
Maintain ophthalmic products in the pH range 6-8 which is the most comfortable for ophthalmic instillation
82
Examples of buffers in drugs:
- Boric acid
- Potassium bicarbonate
83
Which pH is best for ophthalmic instillation:
6 - 8
84
Role of viscous agents in drugs:
* Increase contact time of drug with ocular surface
* By increasing viscosity of the preparation making it thicker
* And so increase absorption across cornea making it say longer on ocular surface
85
Examples of viscous agents in drugs:
* Methyl cellulose
* Poly vinyl alcohol
* Carbomers
86
Role of osmolarity adjusting agents in drugs:
- Create an isotonic solution
- To improve comfort and maximize shelf life and stability, stimulating tonicity of tears, usually 0.6-1.8%
87
Examples of osmolarity adjusting agents in drugs:
- Mannitol
- NaCl
88
Role of osmolarity adjusting agents in drugs:
Create pH that ensures optimal stability and tolerability and comfort
89
Examples of osmolarity adjusting agents in drugs:
- Hydrochloric acid
- Sodium hydroxide
