Anti-Inflammatory Drugs 2020-21 PDF

Ophthalmic Drugs 1 Anti-Inflammatory Drugs Part 1 Professor John Lawrenson Ocular Therapeutic Drugs 1. Anti-inflammatory Drugs 2. Anti-infective Drugs 3. Dry eye preparations 4. Anti-glaucoma drugs Lecture Outline Pharmacology, indications and side effects of: Part 1...

Ophthalmic Drugs 1 Anti-Inflammatory Drugs Part 1 Professor John Lawrenson Ocular Therapeutic Drugs 1. Anti-inflammatory Drugs 2. Anti-infective Drugs 3. Dry eye preparations 4. Anti-glaucoma drugs Lecture Outline Pharmacology, indications and side effects of: Part 1 Corticosteroids Non-steroidal anti-inflammatory drugs (NSAIDs) Ciclosporin Part 2 Anti-allergy drugs (anti-histamines, mast cell stabilizers) Total Ophthalmic – United Kingdom figures 33% Anti-Infectives 1% Glaucoma 10% 3% Steroids Combinations 0% 0% Tears 17% Allergy 36% Nsaid (Data in EQUN Thousands MAT JUNE 06) Anti-inflammatory drugs Corticosteroids Non-steroidal anti-inflammatory drugs (NSAIDs) Ciclosporin Corticosteroids Corticosteroids are hormones produced by the adrenal cortex Include glucocorticoids and mineralocorticoids Levels are regulated by hormones e.g. adrenocorticotrophic hormone (ACTH) from the pituitary Glucocorticoids e.g.cortisol, maintain normal levels of blood glucose and promote recovery from injury Mineralocorticoids (e.g. aldosterone) affect Na + balance causing Na+ reuptake and water retention and so influence blood pressure Corticosteroids Glucocorticoids used therapeutically in the treatment of inflammation Glucocorticoids have two main pharmacological actions. anti-inflammatory and immunosuppressive effects through reduction in activity of inflammatory mediators e.g. eicosanoids, platelet-activating factor, and interleukins metabolic effects on carbohydrates, proteins and fat Corticosteroids:action Corticosteroids:action Corticosteroids:action Eicosanoid Synthesis Phospholipids Inhibited by Inhibited by NSAIDs Phospholipase A2 Corticosteroids Arachidonic Acid Cyclo-oxygenase Lipoxygenase Endoperoxides Leukotrienes and (PGG2, PGH2) related compounds PGE2 Thromboxane A2 PGF2 PGD2 Prostacyclin (PGI2) Corticosteroids Therapeutic uses (systemic) Anti-inflammatory effects (systemic or topical) e.g. asthma, eczema, inflammatory bowel disease, rheumatic disease Replacement therapy for diseases of the adrenal gland Chemotherapy e.g. acute leukaemia/ Hodgkin lymphoma Immunosupression eg post transplantation Corticosteroids Adverse effects Adverse effects of corticosteroids are common and can be severe Adverse effects are dependent on dose and duration of treatment Adverse effects include: Impaired glucose tolerance or sometimes diabetes mellitus Osteoporosis Cushings syndrome Immune suppression Ophthalmic Corticosteroids Indications Used for the treatment of acute and chronic inflammation e.g. anterior uveitis, vernal conjunctivitis Used to reduce post-operative inflammation Intravitreal steroids used to treat macular oedema and some cases of posterior uveitis Ophthalmic Corticosteroids Indications There is no official potency hierarchy for topical ocular glucocorticoids The efficacy of a particular glucocorticoid preparation depends not only upon its strength but also upon: the salt used, prednisolone acetate reduces inflammation more effectively than prednisolone sodium phosphate the integrity of the cornea, the drug will penetrate the eye better if the cornea is abraded Ophthalmic Corticosteroids Indications It is generally accepted that prednisolone acetate and dexamethasone are used when inflammation is severe and low strength prednisolone sodium phosphate (0.05% or 0.1%) or hydrocortisone are used in mild inflammation or when glucocorticoid side effects need to be minimal, e.g. in the presence of viral infection Ophthalmic Corticosteroids Available preparations Betamethsone Betnesol Dexamethasone Maxidex Fluorometholone FML Loteprednol Etabonate Lotemax Prednisolone Predsol, Pred Forte Combined preparations with antibiotics e.g. Betnesol N, Maxitrol, Tobradex Intravitreal corticosteroids (Ozurdex intravitreal implant of dexamethasone for macula oedema following retinal venous occlusions and non-infectious posterior uveitis) Ophthalmic Corticosteroids Adverse reactions Prolonged use of steroids associated with an increased risk of posterior sub-capsular cataract Dose dependant Account for approx 4% cataracts Usually only occur in patients taking high dose steroids for >1yr Ophthalmic Corticosteroids Adverse reactions Principal acute adverse reaction to short-term use is raised IOP in steroid responsive individuals Raised IOP can occur with topical inhaled or systemic steroids Non-steroidal Anti-inflammatory Drugs (NSAIDs) Topical NSAIDs provide mild to moderate anti- inflammatory potency without the side effects of corticosteroids NSAIDs prevent the formation of a family of compounds called eicosanoids Biological Actions of Eicosanoids Eicosanoids are important mediators of the inflammatory response The principal eicosanoids are the prostaglandins and the leukotrienes Ocular effects of eicosanoids include: vasodilation, increased IOP, miosis, macular oedema The anti-inflammatory action of NSAIDs is primarily due to the inhibition of the enzyme cyclo-oxygenase (COX) Corticosteroids:action Eicosanoid Synthesis Phospholipids Inhibited by Inhibited by NSAIDs Phospholipase A2 Corticosteroids Arachidonic Acid Cyclo-oxygenase Lipoxygenase Endoperoxides Leukotrienes and (PGG2, PGH2) related compounds PGE2 Thromboxane A2 PGF2 PGD2 Prostacyclin (PGI2) Ophthalmic NSAIDs: Indications Reduction of intra-operative and post-operative ocular inflammation In some centers have been used in the reduction of post-operative pain Reduction of pain following corneal trauma (diclofenac sodium) Allergic conjunctivitis (diclofenac sodium) Episcleritis (off license) Available topical NSAIDs Diclofenac sodium (Voltarol)* Flurbiprofen (Ocufen) Ketorolac trometamol (Acular) Nepafenac (Nevanac) Bromfenac (Yellox) * Licensed for pain following corneal epithelial trauma and also for SAC Ciclosporin ▪ Ciclosporin inhibits the release of cytokines from T- lymphocytes and therefore supresses the cell-mediated immune response ▪ Licensed for the treatment of severe keratitis in dry eye disease (which has not improved with ocular lubricants) (Ikervis) ▪ Licensed for the treatment of severe vernal keratoconjunctivitis (VKC) (Verkazia) Summary In the UK, ophthalmic corticosteroids are generally reserved for the treatment of moderate to severe inflammation by ophthalmologists and can also be prescribed by independent prescribing optometrists Topical NSAIDs are predominantly licensed for reducing post-operative inflammation, however diclofenac is licensed for treating seasonal allergic conjunctivitis and for analgesia following corneal traumatic abrasions Ciclosporin is an immunosuppressive medication that is licensed for the treatment of severe dry eye and severe vernal keratoconjunctivitis City, University of London Northampton Square London EC1V 0HB United Kingdom T: +44 (0)20 7040 5060 E: [email protected] www.city.ac.uk/department  Ophthalmic Drugs 1 Anti-Inflammatory Drugs Part 2 Professor John Lawrenson The Ocular Allergic Response The eye is a common site of allergic inflammation The majority of ocular allergies affect the conjunctiva The mast cell plays a central role Degranulation of mast cells releases several mediators including histamine The released mediators cause the signs and symptoms of ocular allergy Allergic Eye Disease Acute allergic conjunctivitis Seasonal/ perennial allergic Conjunctivitis (SAC/PAC) Giant papillary conjunctivitis Atopic keratoconjunctivitis Vernal keratoconjunctivitis The role of mast cells in ocular allergy Anti-allergy drugs Anti-histamines Mast cell stabilisers Corticosteroids NSAIDs Vasoconstrictors Anti-histamines Available in topical and systemic forms (include many OTC preparations) Systemic antihistamines used predominantly to treat symptoms of hay fever e.g diphenhydramine, cetirizine Topical antihistamines predominantly used to treat SAC and PAC Newer antihistamines posses antihistamine and mast cell stabilizing properties Available anti-allergy preparations Topical Antihistamines Antazoline (P) Otrivine Atistin (also contains xylometazoline) Azelastine (POM)* Optilast Epinastine (POM)* Relestat Ketotifen (POM)* Zaditen Olopatadine (POM)* Opatanol * dual action Topical Mast cell stabilisers Block calcium influx into mast cell membrane preventing degranulation May take 7-14 days to produce symptomatic relief Effective in the management of moderate to severe allergic eye disease e.g SAC, GPC, VKC Ca2+ Mast cell degranulation Mast cell stabilization Ca2+  Available anti-allergy preparations Mast cell stabilizers Sodium cromoglicate (GSL/P/POM) Opticrom Lodoxamide (POM) Alomide Nedocromil sodium (POM) Rapitil (Discontinued 2018) NSAID Diclofenac sodium (POM) is licensed for SAC Well-tolerated and produces symptomatic relief within 30 minutes of instillation Vasoconstrictors Vasoconstrictors are sympathomimetic drugs Vasoconstrictors cause constriction of conjunctival blood vessels by direct stimulation of alpha adrenoceptors on the conjunctival vasculature with a decrease in conjunctival hyperaemia and oedema Vasoconstrictors Xylometazoline (e.g. Otrivine Antistin) Naphazoline (e.g. Murine, Optrex Clear Eyes) Phenylephrine (currently no available preparation in the UK) Summary A variety of topical drugs are available for treating allergic eye disease including anti-histamines and mast cell stabilizers Newer antihistamines also display mast cell stabilising properties (dual-acting) Some of these drugs are available over the counter (antazoline, sodium cromoglicate) and can therefore be used and supplied by all registered optometrists Topical NSAIDs and vasoconstrictors have a limited role in treating allergic eye disease