Veterinary Pharmacology and Therapeutics PDF

PHARMACOLOGY AND THERAPEUTICS II PHARMACOLOGY IN OPHTALMOLOGY Catarina Jota Baptista Assistant Professor DVM, MSc, PhD in Veterinary Sciences [email protected] BIBLIOGRAPHY TABLE OF CONTENTS Anatomy of the eye and my...

PHARMACOLOGY AND THERAPEUTICS II PHARMACOLOGY IN OPHTALMOLOGY Catarina Jota Baptista Assistant Professor DVM, MSc, PhD in Veterinary Sciences [email protected] BIBLIOGRAPHY TABLE OF CONTENTS Anatomy of the eye and mydriasis/miosis physiology Options of treatment Pharmacokinetics of the eye treatments Eye lubricants and moisturizers Eye exam drugs: ocular topical anaesthetics and mydriatic drugs Glaucoma and glaucoma treatment drugs Ocular ABs Ocular AIs Ocular antiviral and antifungal drugs Immunomodulators ANATOMY OF THE EYE ANATOMY OF THE EYE OPTIONS TO TREAT THE EYE Solutions, suspensions, lipid or oil emulsions for frequent application to the surface of the cornea. Conjunctival implants or therapeutic contact lenses for prolonged release - not well tolerated by most animals! Subconjunctival “depot” injections for slow and continuous absorption. Systemic (not very effective due to the ocular blood barrier, as well as poor irrigation of some structures in the eye, especially in the anterior chamber). Intracameral injection (either anterior or posterior) - directly into the aqueous or vitreous humor. Retrobulbar injection - into the retrobulbar space. Intravitreal or suprachoroidal implants. TOPIC OCULAR TREATMENT - SPECIFICATIONS Always requires physical restraint during application. Requires frequent administration (more for eye drops than ointments). It has the advantage that the drug reaches high concentrations locally and quickly, without systemic toxicity, but attention must be paid to ocular toxicity. In most cases, it works well on the conjunctiva, sclera, cornea and anterior chamber. PHARMACOKINETICS The blood–ocular barriers to drug penetration are complex, protective mechanisms that complicate drug delivery to the interior of the uninflamed eye. In corneal and conjunctival diseases where the epithelium is compromised or removed, resistance to drug absorption/corneal penetration is reduced or eliminated. The eye is a complex organ with an intricate vascular supply to nourish highly specialized neuroreceptors and unique tissues that must remain transparent to focus light on the photo receptors deep within the organ, and a system for secretion, circulation, and absorption of a fluid to nourish and maintain intraocular pressure compatible with the primary function of vision. EYE DROPS VS EYE OINTMENT EYE LUBRICANTS AND MOISTURIZERS Eye wash can be done with neutral saline solution (NaCl 0.9%) to remove small particles and eye discharge. To avoid dry eyes and “keratoconjunctivitis sicca” veterinary formulas should be used instead of human products. For surgery, to avoid dry eyes, gel formulas are better options Pylocarpine also provides direct stimulation to the lacrimal gland. FOR SURGERY… EYE EXAM - OCULAR TOPICAL ANAESTHETICS They produce anaesthesia only in the cornea, 5 to 10 minutes after application. Useful to remove foreign bodies or perform an intraocular ultrasound. Poorly tolerated by animals in single use, without sedation. Tetracaine hydrochloride Oxybuprocaine hydrochloride EYE EXAM – PARASYMPATHOLYTIC MYDRIATICS They compete with acetylcholine (they are acetylcholine antagonists), by blocking the receptors and preventing the iris sphincter and ciliary muscles from contracting, leading to pupil dilation (mydriasis). They inhibit natural accommodation - useful in examining the posterior chamber of the eye. Cycloplegic action (ciliary muscle paralysis) - important in relieving pain (due to ciliary muscle spasm) in cases of anterior uveitis. Blocks pupillary spasm (miosis) associated with anterior uveitis; Tropicamide Atropine Cyclopentolate PRODUCTION OF AQUEOUS HUMOUR Source: MoranCORE PRODUCTION OF AQUEOUS HUMOUR - GLAUCOMA PRODUCTION AND DRAINAGE OF AQUEOUS HUMOUR Miosis Normal Mydriasis SO IF WE WANT TO REDUCE THE EYE PRESSURE, WE HAVE 2 THERAPEUTIC OPTIONS (SINGLE OR COMBINED): Reduce the production of aqueous humour Increase the drainage of the aqueous humour -> increase the iridocorneal angle INCREASING THE DRAINAGE OF THE AQUEOUS HUMOUR (INCREASE THE IRIDOCORNEAL ANGLE) PARASYMPATHOMIMETIC MIOTIC DIRECT DRUGS These are cholinergic drugs that cause miosis (pupil constriction) by activating muscarinic receptors and contracting the iris sphincter and ciliary muscles. Consequently, they increase the irido-corneal angle and aqueous humour drainage, reducing intraocular pressure and treating glaucoma. Less used nowadays Pilocarpine Carbacol PARASYMPATHOMIMETIC MIOTIC INDIRECT DRUGS They are cholinergic drugs that cause miosis (pupil constriction) by inhibiting acetylcholinesterase, leaving more acetylcholine available to bind to muscarinic receptors and cause contraction of the iris sphincter and ciliary muscles. Consequently, they increase the iridocorneal angle and aqueous humour drainage, reducing intraocular pressure and treating glaucoma. Demecarium Bromide Ecothiophate Physostigmine PROSTAGLANDIN ANALOGUES These drugs decrease the intraocular pressure by increasing uveoscleral aqueous humour outflow. A marked rapid reduction of intraocular pressure is noted, but the exact mechanism is unknown. The long-term intraocular pressure reduction is achieved due to structural alterations in the iridocorneal angle, opening it. Latanoprost Bimatoprost REDUCING THE PRODUCTION OF AQUEOUS HUMOUR SYMPATHOLYTIC DRUGS SELECTIVE α ANTAGONISTS. Not very used because they cause bradycardia and vomiting. Useful in regulating post-operative intraocular pressure. Apraclonidine Brimonidine SYMPATHOLYTIC DRUGS SELECTIVE ß ANTAGONISTS. They are useful in combination with other ocular hypotensive drugs, such as mycotic parasympathomimetics, to treat or prevent glaucoma, thus achieving a 50-60% reduction in intraocular pressure. May cause bradycardia rarely. Timolol Levobunolol Carteolol Metipranolol Betaxolol CARBONIC ANHYDRASE INHIBITORS Reduce the production of aqueous humour by inhibiting carbonic anhydrase. In humans, used to treat open-angle or secondary glaucoma. Used as adjuvants to beta-adrenergic drugs or as monotherapy. Brinzolamide Dorzolamide OCULAR ANTIBIOTICS Intraocular inflammation that often accompanies infections damages the blood-ocular barrier, impairing drug penetration. Ineffective systemic route for treating corneal and conjunctival infections. Used for the posterior chamber and vitreous. In a corneal ulcer cases, it is not relevant whether AB is able to penetrate the cornea, as the action is local. Frequent administration. OCULAR ANTIBIOTICS Prophylactic use is always indicated for superficial, uncomplicated corneal ulcers and after eye surgery. Therapeutic use is indicated for infected, complicated corneal diseases, such as ulcers and abscesses and bacterial endophthalmitis. When possible, cytology and culture/sensitivity results should guide antibiotic selection, specially after ineffective treatments. OCULAR ANTIBIOTICS Neomycin - ulcers and superficial corneal infections. Often in combination with AI. More for Gram-negative. Fusidic acid. Chloramphenicol - widely used. Gram-positive and gram-negative bacteria, and intracellular organisms. Oxytetracycline/chlortetracycline. Good activity against intracellular organisms Ofloxacin - most commonly used for serious, relapsing infections and with antibiogram. Gram-negative bacteria, but newer agents (moxifloxacin, gatifloxacin) also have increased gram-positive efficacy OCULAR ANTIINFLAMATORY DRUGS NSAIDs Reduces inflammation, relieves pain and discomfort. Allergic conjunctivitis. Bromfenac Nepafenac Diclofenac sodium Flurbiprofen Suprofen Ketorolac OCULAR ANTIINFLAMATORY DRUGS Glucocorticoids Reduction of inflammation. Allergic conjunctivitis. Not used for corneal ulcers or abrasions, or for herpesvirus keratitis (cats). Side effects, more frequent in humans: cataracts, increased IOP, infection, decreased wound healing, mydriasis and keratopathy with calcium deposition. Prednisolone Dexamethasone Betamethasone Hydrocortisone OCULAR AB + AI Gentamicin + Dexametasone ANTIVIRAL DRUGS Herpesvirus keratoconjunctivitis, especially in cats Acyclovir Valacyclovir Famciclovir Trifluridine Idoxuridine Other compounds that help with viral infections, because they strengthen immunity, hinder viral replication and help recovery from corneal damage. Vitamin A Lysine ANTIFUNGAL DRUGS Treatment of fungal keratitis and keratoconjunctivitis, e.g. by Aspergillus spp. in horses Natamycin Povidone-iodine Amphotericin B Itraconazole Miconazole IMUNOMODELATORS Cyclosporine Tacrolimus Useful in immune-mediated eye diseases (e.g. keratoconjunctivitis sicca) Cyclosporine intraocular implants have been developed in 2006. These implants are administered to horses to treat anterior uveitis. This method of treatment slowly releases the medication and can produce a long-term sustained therapeutic effect.