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Jane Goodwin BSc, MScNurse Practitioner
Drugs and the Eye
A&P
A & P
Pharmacology
• A solution is a liquid vehicle for drug delivery to the eye.
• Solutions have a shorter contact time.
• Drops drain into lacrimal apparatus, into the nose and are absorbed systemically.
• Drops needs to be sterile therefore free from bacteria, viruses, and fungi.
• Preservatives are added to inhibit the multiplication of organisms.
• Some solutions oxidise when exposed to air which can alter their chemistry.
• The shelf life of drops are 1 month
• Most eye solutions are expressed as ‘per cent’. This translate to grams / 100ml.
EG – 0.5% Chloramphenicol = 500mg of Chloramphenicol in 100ml of solution.
•Preservative free drops are supplied in single dose units ‘Minims’ and used once
• Advantages of administering the drug locally is that is delivers the agent directly to the site of action.
• Its effects are more immediate.
• Smaller doses are used.
• Systemic side effects are minimised.
Administration
• Locally – direct into lower eye lid.
Subconjunctival injection – space between conj and sclera
Retrobulbar Injection - into muscle cone behind the eye
• Peripubulbar – into space around the eye
• Intraocular – into the eye eg Anterior Chamber
Intraocular Lens
•Contact lens – impregnated and placed on cornea
Edge of lens
Absorption
• Drugs applied topically enter the eye through the cornea
• There are 5 layers to the
Cornea
Descemet’s Membrane
Internal LayerEndothelium
• The outer most layer have a high lipid content (lipophilic)
• The innermost layer have a high water content (Hydrophilic)
• Drugs therefore have to require both lipophilic and Hydrophilic properties
• PH of eye drops range between 3.5 – 10.5 which is to aid absorption
• Factors that can influence absorption include trauma to the cornea – increasing the amount absorbed
• Drugs can also bind to contact lenses therefore reducing their effectiveness and cause damage to the contact lens
Other factors affecting absorption
• Drops can be lost from the eye before they cross the cornea.
Occlude Inner Canthus
Types• Antibiotics• Antihistamines• Anti-virals• Mydriatics – dilation of pupil 2 types – parasympatholytic
& Sympathomimetic• Miotics – constrict the pupil• Glaucoma drugs -Carbonic anhydrase inhibitors, Beta-
blockers, Alpha 2 agonists• Steroids• Local anaesthetics• Diagnostic• Tear Replacement
Mydriatics- are used to dilate the pupil for the following reasons
• To examine the retina• To maintain dilatation of the pupil in
uveitis, with corneal ulcers, severe corneal abrasions and after surgery
• To break down posterior synaechiae in uveitis
• To allow a cataract to be extracted and retinal surgery
• Refraction in children
2 types• Parasympatholytics – which cause
mydriasis and cycloplegia (relaxing circular iris muscle causing paralysis of the ciliary muscles)
E.g. atropine, tropicamide and cyclopentolate
• Sympathomimetics - mydriasis (stimulating the radial muscle of the iris to contract causing the pupil to dilate)
E.g. adrenaline and phenylephine
Side Effects and Cautions
• Causes blurred vision therefore driving not advised• Systemic absorption can occur causing anticholinergic
effects such as tachycardia, dizziness, dry mouth, constipation and hypertension
• Due to risk of systemic absorption should be used with caution in people with hypertension, heart disease and thyrotoxicosis
• Can cause a rise in intra ocular pressure (IOP)• Contraindicated in glaucoma especially narrow angle
glaucoma• Contra-indicated with MAOI’s (monoamine oxidase
inhibitors) – risk of hypertensive crisis
Miotics• Miotic drugs constrict the pupil and ciliary
muscle which opens up the drainage channel for aqueous flow. It main use is in the treatment of Acute Glaucoma
• Pilocarpine 1% 2% and 4% (most common)
Acute Glaucoma
IS SIGHT THREATENING!
Is a sudden rise in intra ocular pressure. This is caused by an acute blockage in the drainage system – stopping the aqueous humour drain from the eye. Symptoms include a red painful eye, reduced vision, nausea, headache and can be in one or both eyes.
Normal Flow
Acute blockage
Miotics - Cautions• Causes - Headache/browache in long term use..
Usual burning itchy and sensitivity with drops.
• Blurred vision and restricted vision -
• Patient on long term treatment need monitoring for field s and IOP’s.
• Avoid in conditions where a miosed pupil would be undesirable ie Iritis and Uvietis
Chronic Open Glaucoma
• The angle is open – but other parts of the drainage system can be affected.
• Slow onset, irreversible sight loss, hereditary, more common in elderly and Afro-Caribbean's
• Caused by a persistent low grade rise in intraocular pressures (normal readings are between10 - 21mmHg). Therefore readings above 22 - 35 mmHg may require monitoring and treatment.
• It causes damage to the retinal nerve fibres known as cupping of the disc making the disc pale and a change in shape.
Circulation of Aqueous
= problem with aqueous drainage
Other Glaucoma Drugs
• Carbonic anhydrase inhibitors
• Beta blockers
• Alpha 2 agonists
• Prostaglandin analogues
• Sympathomimetics
• Combinations of the above i.e. Carbonic anhydrase inhibitors and Beta blockers
Carbonic anhydrase inhibitors
• Carbonic anhydrase is an enzyme necessary for the production of aqueous. These drugs therefore reduce the production of aqueous.
• Uses - Acute, Chronic and secondary Glaucoma• Ocular SE – Local eye irritation and taste disturbance• Systemic SE –drowsiness, GI, nausea, upset potassium
levels and is a weak diuretic• Types – Oral and IV -Acetazolamide (Diamox) not used
long term mostly in acute cases• Examples - Topical – Dorzolamide (Trusopt) and
Brinzolamide (Azopt)
Beta Blockers
• Are relatively safe, efficacious and usually first line treatment.
• Work by affecting the production of aqueous in the ciliary body and increase the outflow of aqueous in trabeculae meshwork
• Uses – primary open angle glaucoma• Ocular SE – dry eyes, blurred vision, eye irritation• Systemic SE – bronchospasm in asthmatics,
bradycardia and can mask manifestations of hypoglycaemia
• Examples – Timolol (Timoptil), Betaxolol (Betoptic), Carteolol (Teoptic) and Levobunolol (Betagan).
Alpha 2 Agonists
• Is used as add on therapy when beta blockers are not enough to reduce IOP or when B’blockers are contra-indicated.
• Works by enhancing drainage from the eye and decreasing production of aqueous.
• Uses – primary open angle glaucoma and pre op• Ocular SE – dry eyes, blurred vision, eye irritation and
stinging• Systemic SE – Headache, changes in heart rate, rhythm
an BP as well as anxiety and tremor• Examples – Apraclonidine (Iopidine) and Brimonidine
(Alphagan)
Prostaglandin Analogues
• Work by increasing uveoscleral outflow
• Uses – open angle glaucoma and *ocular hypertension
• Ocular SE – brown colour changes in the iris and lengthening of the eyelashes
• Examples – Bimatoprost (Lumigan) and Latanoprost (Xalatan)
• *NB – ocular hypertension is when the IOP is normal but there is signs of the disease from the visual field tests and optic disc defects.
Sympathomimetics
• Dipivefrine is a pro drug of adrenaline. It is claimed to pass more rapidly than adrenaline through the cornea and is then converted to the active form.
• Works by increasing the outflow of aqueous through the trabecular meshwork.
• It is contra indicated in angle closure glaucoma because it is a mydriatic (dilating drug)
• Ocular SE – severe smarting and stinging• Systemic SE – caution with pt’s with
hypertension and heart disease.
Tunnel Vision
Coffee Time !
Microbiology of the eye
Micro-organisms can gain access as a result of:-
• Direct Contact e.g. Herpes simplex• Air-Bourne infections• Insect-Bourne infections e.g. Trachoma• Migration of bacteria from nasopharynx• Trauma• Infected contact lenses• Infected eye drops and lotions• Infected instruments
Conjunctivitis – most common cause of Red Eye
Types of conjunctivitis• Bacterial
• Viral
• Allergic
• Secondary
• Chronic
Bacterial Conjunctivitis
• Acute onset• Bilateral• Red, gritty, sore, puffy
lids and purulent discharge
• Resolves within 5-10 days
• Rx G.Chlor or Fusidic acid
Viral• Acute onset
• Related to other URTI
• Likely to be Unilateral
• Red, gritty sore, Watery discharge
• Corneal staining with Fluorescien
• Diagnosis difficult in Primary Care therefore refer a unilateral red eye if no improvement within 48hrs of Rx
• Last for 3 -4 weeks
Allergic
• Acute onset• Bilateral• Hx of exposure to allergens• Hx Atopy or Fhx• Sx – very itchy,watery,
chemosis (jelly like) of conj, puffy lids, follicles on Tarsal Plate (under eye lid)
• Responds to antihistamines, remove from cause
• Should respond immediately to Rx
• Prophylactic treatment recommended.
Drugs for allergic conjunctivitis
• Topical antihistamine drops (H1 antagonists) – antazoline, azelastine and levocabastine provide rapid relief and can be used for up to 4/52.
• If prolonged relief is required a mast cell stabiliser eg lodoxamide, nedocromil and sodium cromoglycate
• Start their use ideally 1/12 before allergy season• Diclofenac is also licensed and steroids can be used only
after examination on a slit lamp and seen by an ophthalmologist
• Eye sx alone are best treated topically, however if a pt has other sx oral antihistamines are recommended
Corneal Abrasion Herpes – Dendritic Ulcer
Corneal Foreign Body Corneal Ulcer, with pus in AC
Secondary
Chlamydia
• Serotypes D-K are genital• Serotypes A-C causes
Trachoma – worlds leading cause of blindness
• It attacks mucous membranes & inhibits host cell protein synthesis
• Topical Rx tetracycline ointment QDS 6/52
• Systemic - Doxycycline, Tetracycline or Erythromycin
Under surface of eye lid (sub tarsal plate)
Chloramphenicol
• Broad Spectrum Abx with least overall resistance
• It is a bacteriostatic and inhibits bacterial syntheses by reversibly binding to ribosome's which disrupts peptide bond formation and protein synthesis
• Acts on Gram +ve and –ve organisms• MUST be stored in the fridge• Bathe away discharge before use• Regime – 2 hourly in severe cases for 24 hours
then QDS for 5 – 7 days.
Side Effects/Cautions
• Stinging, local discomfort• Greater chance of allergy than Fusidic acid• Aplastic anaemia (bone marrow suppression)
check FHx and GH• Gray Baby syndrome• Avoid in pregnancy, breast feeding and with
caution in under ones• Check bloods regularly if using long term• Not sensitive to Pseudomonas
Fusidic Acid
• Is a bacteriostatic and bactericidal agent with a steroid-like structure of no glucocorticoid activity.
• Inhibits bacterial protein synthesis and prevents elongation of the peptide chain.
• It is chemically unrelated to any other antibacterial in clinical use
• There is no cross-resistance nor cross sensitivity between Fusidic acid and other antibacterials
• It is microcrystalline giving it sustained release properties therefore concentration is maintained for 12 hours in lacrimal fluid and aqueous humour (BD dose regime)
Side Effects/Cautions
• Stinging, local discomfort, burning redness and watering on initial instillation
• Allergic reactions are less than Chloramphenicol
• Not known to be harmful in pregnancy
• Is excreted in breast milk – not known to be harmful – weigh up risks/benefits.
• Can be local variations of resistance
Antibiotic efficacy against common ocular pathogens
Pathogen
* Known Activity
Fusidic Acid Chloramphenicol
Staph’ Aureus * *
Staph’ epidermis * *
Strep’ pyogenes Sensitive *
Strep pneumoniae Sensitive *
Gonorrhoea * *
Escherichia coli Resistant *
Haemophilus influenzae Sensitive *
Pseudomonas Resistant Resistant
OTC products for conjunctivitis
• Brolene and Golden Eye are antiseptic not antibiotic
• They are of little use
• They commonly cause an allergic reaction which compounds the patients symptoms
• They are used in acanthamoeba keratitis (organism grown on contact lenses)
• Chloramphenicol is now OTC
Advice to patients
• Conjunctivitis is self limiting and will resolve without Rx in mild cases
• Clean eyes with cooled boiled water• Avoid touching and rubbing eyes• Wash hands after touching eyes• Avoid sharing towels/face cloths• Throw away make up that may be contaminated• Contact Lenses SHOULD NOT be worn due
episode and leave for 48hours after finishing Rx
Contact Lenses
• Types include soft, hard (gas permeable) disposable and extended wear.
• Should not be worn during infections
• Strict hygiene, cleaning and maintenance should be encouraged at all times
• Soft CL are not compatible with drops that contain preservatives
• Soft CL absorb Fluorescein and permanently stain
Instilling eye medication• Drops contain preservatives
to prevent micro-bacterial growth
• 1/12 shelf life-throw out after• Clean discharge away first• Wash hands• Pull on lower eyelid to make a
‘well’ – drop solution or squeeze ointment into eye.
• Avoid touching the tip of the bottle with the eye
Anti-virals
• Herpes Simplex and Zoster
• Acyclovir (Zovirax) comes in tablet and oral form and used for both types of herpes. Ointment is used 5 x a day and compliance is essential to ensure disruption of the DNA synthesis.
• Pt’s should be monitored by an ophthalmologist as corneal scarring will occur
• Side effects from topical Rx include irritation, stinging, itching, inflammation, pain and photophobia
Oral & Topical Steroids
Overdose or prolonged use can exaggerate some of the normal physiological actions of corticosteroids leading to mineralocorticoid and glucocorticoid side effects
• Adrenal suppression amongst many things can cause Conjunctivitis.
• Suppression of infection - therefore masks sx and exacerbates infections e.g. bacterial, viral and fungal
• Causes – next slide
Cataract
Systemic steroids have a high risk (75%) of inducing a cataract
Glaucoma
Papilloedema
Sclera Thinning
Amiodarone
• Used in Rx for arrhythmias
• Has a very long half life extending to several weeks.
• SE’s can cause reversible corneal deposits (causes night glare), Optic neuritis – causing blindness
• Treatment MUST be stopped and expert advice taken
Amiodarone
Corneal Deposits
Optic NeuritisBlurred Vision
Antimalarials
• Hydroxychloraquine and chloroquine are also used to treat Rheumatoid arthritis and SLE
CAUSES
Ocular Toxicity
Retinal damage & Keratopathy (Corneal
Deposits)
Royal College of Ophthalmologists
• Recommend regular ophthalmic examination• Arrangement should be made locally between prescriber
and ophthalmologist and agreed management plan for those on long term treatment of 5 yrs or more.
• Va - distance and near recorded before, during and after Rx
• Any visual impairment needs to be assessed and recorded before, during and after Rx
• Any deterioration in vision MUST be assessed by ophthalmologist
• Children receiving treatment for Juvenile Arthritis should be screened for Uveitis
TB DrugsEthambutol is included in a Rx regime when
there is resistance to other TB drugs
• SE’s – Loss of VA
• Colour Blindness
• Reduction and restriction in Visual Field
The dark patches show loss of vision
• Side effects are more common when given in excessive doses
• The drug should be stopped at the earliest presentation of ocular toxicity
• Always advise pt’s to stop Rx and seek medical and ophthalmic help
• Eye sight is nearly always restored if discontinuation of drug is early enough
• Pt’s who may not understand warnings about visual sx should be given an alternative TB drug if possible
• Children under 5 may not be able to report changes
Visual Acuity should be
tested before starting
treatment
Other Systemic Drugs• Tamoxifen – oestrogen
antagonist Causes visual
disturbances including corneal changes, cataracts and Retinopathy
• Digoxin Toxicity – causes visual disturbance
• MAOI’s (monoamine oxidase inhibitors) – causes blurred Va, Nystagmus and interacts with Sympathomimetics e.g. Phenylephrine (drug used to dilate pupil)
Retinopathy
Diagnostic Drops
• Fluorescein – Orange die
• Stains conjunctival and corneal epithelial damage e.g. corneal ulcers, erosions, and conjunctival or corneal abrasions
• Assessment of dry eye
• Tonometry
• Fluorescein is available as drops or as paper strips
• Fluorescein grows pseudomonas therefore is always used in single dose units
• It is also used IV so photographs can be taken of retinal blood vessels, optic disc and macula
Scar
Optic disc
Blood vessels
Rose Bengal
• Stains dead conjunctival and corneal epithelium in dry eye syndrome.
• It causes pain and stinging on instillation
Dead Corneal epithelium
Dry Eyes
3 Layers of Tear Film
Artificial Tears
• Are used for dry eyes and must be used as often as possible to keep the eyes feeling comfortable.
• Can be as often as every hour• Once diagnosed – drops will be necessary
for life• Dry, hot, windy conditions exacerbate sx
also reading, using PC (Starring for long periods)
Types
• Drops include – Hypromellose, Tears Naturelle, Liquifilm
• Gel tears – ‘Viscotears’ – bind with own natural tears and stay in eye for longer
• Ointments – used at night, stay in eye for longer, can cause blurring of vision.
List 3 things you’ve learnt
• 1
• 2
• 3
• Try and remember them!!!!
Resources
• http://www.goodhope.org.uk/departments/eyedept/dropsfor.htm
• http://www.bnf.org• Maclean H (2002) The Eye in Primary Care,
Butterworth Heinmann.• Galbraith et al (1999) Fundamentals of
Pharmacology, Addison Wesley Longman Ltd• Spalton et al (2006) Atlas of Clinical
Ophthalmology 3rd Ed, Elsevier Mosby
Any Questions