Jane Goodwin BSc, MSc Nurse 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

Preservative free drops are supplied in single dose units ‘Minims’ and used once Most eye solutions are expressed as ‘per cent’. This translate to grams / 100ml. EG – 0.5% Chloramphenicol = 500mg of Chloramphenicol in 100ml of solution.

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 Layer Endothelium

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

Secondary Herpes – Dendritic Ulcer Corneal Abrasion Corneal Ulcer, with pus in AC Corneal Foreign Body

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 * Known Activity Fusidic Acid Chloramphenicol Staph’ Aureus * Staph’ epidermis Strep’ pyogenes Sensitive Strep pneumoniae Gonorrhoea Escherichia coli Resistant Haemophilus influenzae Pseudomonas

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 Blurred Vision Optic Neuritis Corneal Deposits

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 Drugs Ethambutol 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

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

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