PHARMACOLOGY OF THE EYE

Physiological Anatomy of the Eye

Sympathetic Nervous System mydriasis- contract pupillary dilator muscle (1 receptor) Relax ciliary muscle for distant vision (ß2 receptors) Enhance aqueous humor formation (ß2 receptors) Inhibit aqueous humor formation (2 receptors)

Parasympathetic Nervous System Actions focus eye for near vision (ciliary muscle contraction) constrict pupil (miosis)-(pupillary sphincter contraction) Enhance drainage of aqueous humor All of these effects mediated by muscarinic receptors

Drugs promoting mydriasis (pupil dilation) Sympathomimetics (stimulate or mimic stimulation of sympathetic nerves) Inhibitors of parasympathetic nervous system (Atropine)

Pupillary Muscles

Mydriasis

Miosis

Mydriatics Agents releasing norepinephrine NICOTINE activates nicotinic receptor (also activates parasympathetics to produce miosis, which is the more common reaction) . Cocaine increase norepinephrine concentrations of adrenergic receptors Amphetamine hydroxyamphetamine (0.1% solution) used to diagnose post-ganglionic nerve damage vs. a defect prior to the postganglionic nerve (no reaction means postganglionic nerve defect). response to amphetamine indicates normal post-ganglionic nerve

Alpha1 adrenergic stimulants PHENYLEPHRINE (mydrifrin) is a drug used in eye drops to dilate pupil 2.5% to 10% solution used to produce mydriasis Epinephrine (Epitrate) 0.5 to 2% solution to treat glaucoma increases aqueous humor outflow

Muscarinic receptor antagonists ATROPINE (Atriposol)- (0.5 to 3% solution) to produce cycloplegia (is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.)

Drugs producing miosis Nicotine activates parasympathetic nerves Muscarinic agonists such as Pilocarpine (Pilocar) used as 2% solution acetylcholine (Miochol)

Agents preventing acetylcholine degradation Physostigmine , Ecothiophate (phospholine iodide), Alpha1 receptor antagonists Norepinephrine depleting agents- Reserpine (Serpasil)- have the potential of causing ocular side effects (miosis; ptosis)

Drugs for Treatment of Glaucoma ß Blockers Timolol (Timoptic); Metipranolol (Optipranolol)- they decrease aqueous humor formation Muscarinic Receptor Agonists- Pilocarpine (Pilocar)- enhances aqueous humor drainage through canal of Schlemm Anticholinesterases- Physostigmine (Isopto eserine), Ecothiophate (Phospholine iodide)- enhances aqueous humor drainage through canal of Schlemm

Drugs used to treat ptosis disruption of sympathetic innervation of superior tarsalis muscle of the eyelid (Horner’s Syndrome)- can reverse with Phenylephrine

Routes of Administration eye drops, ointments, injections

Eye drops Factors affecting absorption: 1- drug concentration and solubility (aqueous solution v’s suspension) 2- viscosity (increased residence time) 3- lipid solubility: lipid rich epithelial cell membrane v’s water rich site 4- pH and ionic charge - most eye drops are weak bases existing in both charged and uncharged forms enhancing absorption

Eye ointments increases contact time of drug with ocular surface mixture of petrolatum and mineral oil water-soluble drugs are insolvent in the ointment and are present as microcrystals. The surface microcrystals dissolve in the tears, the rest are trapped until the ointment melts

Eye ointments Only drugs with high lipid solubility and some water solubility will get into both tears and corneal epithelium Ex . chloramphenicol and tetracycline both achieve higher aqueous levels as ointment rather than drops

Peri-ocular injections subconjunctival, allow drugs to bypass the conjunctival/corneal epithelial barrier and reach therapeutic levels in the posterior segment eg anaesthetic agents, steroids,

Intraocular injections allow instant drug delivery at therapeutic concentrations to target site Intracameral( within a chamber, such as the anterior or posterior chamber of the eye.EX :an anaesthetic agent into the anterior chamber of the eye, usually during surgery

Intravitreal injection  is an injection into the vitreous, which is the jelly-like substance inside the eye. It is performed to place medicines inside the eye, near the retina. The medicines may help stop growth of new blood vessels. eg, avastin

Systemic drug getting into eye from systemic circulation limited drugs with higher lipid solubility pass through blood-ocular barrier more readily

Systemic extent of drug bound to plasma proteins also effects access of drug into eye - only unbound form can pass blood-ocular barrier