prof. hanan hagar pharmacology unit physiology department college of medicine king saud university...
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Prof. Hanan HagarPharmacology Unit
Physiology DepartmentCollege of MedicineKing Saud University
Pharmacology of drugs acting on the eye
• Drugs can be delivered to ocular tissue as:– Locally (Topically): more common
1) Eye drop2) Ointment3) Injection :
–Periocular injection e.g. subconjunctival, peribulbar, or retrobulbar– Intraocular injectione.g. Intracameral or intravitreal
– Systemically:• Orally• IV
Routes of drug administration into the eye
Eye drops
• Eye drops- most common• one drop = 50 µl• volume of conjunctival
cul-de-sac 7-10 µl
Ointment
Increase the contact time of ocular medication to ocular surface thus better effect
Disadvantages The drug has to be high lipid soluble with some water solubility to have the maximum effect as ointment
Intraocular injections• Intracameral or intravitreal• E.g.
– Intracameral acetylcholine (miochol) during cataract surgery
– Intravitreal antibiotics in cases of endophthalmitis
– Intravitreal steroid in macular edema
Peri-ocular injections• subconjunctival, peribulbar, or
retrobulbar • reach behind iris-lens
diaphragm better than topical application
• bypass the conjunctival and corneal epithelium which is good for drugs with low lipid solubility (e.g. penicillins)
• steroid and local anesthetics can be applied this way
Systemic drugs• Oral or IV• Factor influencing systemic drug penetration
into ocular tissue:– lipid solubility of the drug: more penetration with
high lipid solubility– Protein binding: more effect with low protein
binding– Eye inflammation: more penetration with ocular
inflammation
• Drugs used for the treatment of eye• Drugs that can produce harmful effects on the
eye
Pharmacology of drugs acting on the eye
Ophthalamic Uses of Drugs Autonomic drugs:
Affect the size of the pupil: Miotics MydriaticsAffect accommodation (Cycloplegics).
Anti-inflammatory drugs: Glucocorticoids NSAIDs
Chemotherapeutics (antibacterial, antifungal and antiviral agents).
Local Anesthetic drugs
Autonomic Nerve supply of the Eye
Parasympathetic N.S. Constriction of the pupillary sphincter muscle (miosis) Contraction of the ciliary muscle (accommodation for
near vision). Decrease in intraocular pressure ↓ IOP. increases aqueous outflow through the trabecular meshwork into
canal of Schlemm by ciliary muscle contraction Increased lacrimation Conjunctival Vasodilatation
The aqueous humor is secreted by the ciliary body. Produced by a combination of active transport of ions and ultrafiltration of interstitial fluid. The fluid flows over the surface of the lens, out through the pupil into the anterior chamber. Flows through the trabecular meshwork into Schlemm’s canal and is collected in the scleral veins.
Sympathetic N.S. Contraction of dilator Pupillae ( Mydriasis) α1 Relaxation of ciliary muscles (accommodation for far
vision) β receptors Increase in intraocular pressure Lacrimation α1 Vasoconstriction of conjunctival blood vessels α1 β receptors in the blood vessels of the ciliary processes
→production of aqueous humour. β antagonists reduces the production of aqueous humor α agonists increase outflow of aqueous humor and ↓ IOP
Eye Parasympathetic N.S. Sympathetic N.S.
Iris radial musclecircular muscle
No effectContraction (miosis)
M3
Contraction (Mydriasis) α1 No effect
Ciliary muscle Contraction M3 Relaxation β2
Accommodation for near vision accommodation for far vision
Conjunctival blood vessels
Conjunctival Vasodilatation
Conjunctival Vasoconstriction
Intraocular pressure(IOP)
Decrease Narrow filtration angle
Drugs acting on parasympathetic systemCholinergic agonists
• Direct agonists– Methacholine, carbachol, pilocarpine
• Indirect acting agonists (anticholinesterases)– Reversible :Physostigmine– Irreversible: Ecothiophate
USES:-Glaucoma (open angle glaucoma)-Counteract action of mydriatics- To break adhesions- in accommodative esotropia (ecothiophate)
Adverse Effects of cholinergic agonists: Miosis Salivation Sweating bronchial constriction vomiting and diarrhea CNS effects: high doses (physostigmine & pilocarpine)
Ocular side effects: diminished vision (myopia), headache,
Contraindications of cholinergic agonists:Bronchial asthma.Peptic ulcer.Angina pectorisIncontinenceIntestinal obstruction
Cholinergic drugsDrugs Ocular usesAcetycholineCarbacholMethacholine
Induction of miosis in surgeryGlaucoma
Pilocarpine In open angle glaucoma
Physostigmine Glaucoma, accommodative esotropia
Ecothiophate Glaucoma, accommodative esotropia
Passive mydriasis due to relaxation of circular muscles
Cycloplegia (loss of near accommodation) due to relaxation of ciliary muscles
Loss of light reflex. increased I.O.P # glaucoma. Lacrimal secretion sandy eye
Drugs Duration of effect
Natural alkaloids Atropine Scopolamine (hyoscine)
7-10 days3-7 days
Synthetic atropine substitutes Homatropine Cyclopentolate Tropicamide
1-3 days24 hour6 hour
Cholinergic antagonists (Muscarininc antagonists)
USES:- To prevent adhesion in uveitis & iritis - Funduscopic examination of the eye- Measurement of refractive error
Side effects: blurred vision, tachycardia, constipation, urinary retention, dryness of mouth , dry sandy eyes, feverCNS effects: sedation, hallucination, excitation (toxic dose).
Contraindications of antimuscarinic drugsGlaucoma (angle closure glaucoma)Tachycardia, Prostate hypertrophy in old patients.Constipation, paralytic ileus.
Drugs acting on sympathetic systemAdrenergic agonistsNon-selective agonists (α1, α2, β1, β2), eye drops• e.g. epinephrine, depevefrin (pro-drug of epinephrine)• Uses: open angle glaucoma• Mechanism: uveoscleral outflow of aqueous humor• Side Effects: cardiovascular arrhythmia, tachycardia • C/I in closed angle glaucoma in patients with narrow anglesα1 agonists e.g. phenylepherine• mydriasis (without cycloplegia), decongestantUses: - Funduscopic examination of the eye- To prevent adhesion in uveitis & iritis - Decongestant in minor allergic hyperemia of eye
• C/I in closed angle glaucoma in patients with narrow angles• Can cause significant increase in blood pressure
α2 agonists e.g. apraclonidine (eye drops)
Uses: glaucoma treatment, prophylaxis against IOP spiking afterglaucoma laser procedures
Mechanism: production of aqueous humor
Side Effects: Lethargy, fatigue, dry mouth
[apraclonidine is a derivative of clonidine (antihypertensive) which cannot cross BBB to cause systemic hypotension.
β blockers– non-selective: timolol, carteolol– selective: betaxolol (beta 1 “cardioselective”)– Given topically as eye drops
Uses: open angle glaucoma
Mechanism: Act on ciliary body to production of aqueous humor
Advantages can be used in patients with hypertension/ischemic heart disease
Contraindications• Bronchospasm (less with betaxolol)• Cardiovascular (bradycardia, hypotension, asystole, syncope)• Depression• C/I in asthmatic patients or patients with pacemaker.
Treatment of open angle glaucoma (chronic)
The main goal is to decrease IOP and this can be obtained by:
Decreasing production of aqueous humor Beta blockers Alpha-2 agonists Carbonic anhydrase inhibitors
Increasing outflow of aqueous humor Prostaglandins Adrenergic agonists, nonspecific Parasympathomimetics
Prostaglandins and Beta blockers are the most popular drugs.
Carbonic anhydrase inhibitors
e.g. acetazolamide (oral), dorzolamide (topical)
Mechanism: production of aqueous humor by blocks carbonic anhydrase enzyme required for production of bicarbonate ions (transported to posterior chamber, carrying osmotic water flow).
Side Effects: myopia, malaise, anorexia, GI upset, headachemetabolic acidosis, renal stonebone marrow suppression “aplastic anemia”Contraindication: sulpha allergy
Prostaglandins
Latanoprost, travoprost
Are prostaglandins F2α analogs
Mechanism:
uveoscleral outflow by relaxing ciliary body muscle
Uses: open angle glaucoma
Administration: Topical drops
Side Effects: Iris color change
Drug Therapy of acute angle closed glaucoma(narrow angle)
• Is associated with occlusion of the outflow drainage pathway• Acute, painful increases of pressure • emergency situation that require treatment before surgery
(Iridectomy)
The use of drugs is limited to : • Oral Acetazolamide• Topical cholinomimetics e.g.: pilocarpine• Dehydrating agents: IV infusion Of hypertonic solution
( Mannitol, Glycerol)• Analgesics: pethidine or morphine (for pain)
Osmotic agents
• Dehydrate vitreous body which reduce IOP significantly
• E.G. – glycerol 50% syrup (cause nausea, hyperglycemia)– Mannitol 20% IV (cause fluid overload and not
used in heart failure)
Corticosteroids
• Mechanism: inhibition of arachidonic acid release from
phospholipids by inhibiting phosphlipase A2
• Topical– E.g. prednisolone, dexamethasone, hydrocortisone– Uses: postoperatively, anterior uveitis, severe allergic
conjunctivitis, scleritis, prevention and suppression of corneal graft rejection
• Systemic:– E.g. prednisolone, cortisone– Uses: posterior uveitis, optic neuritis
CorticosteroidsSide effects: – Glaucoma, cataract, mydriasis– Suppression of pituitary-adrenal axis– Hyperglycemia, Osteoporosis– Peptic ulcer, Psychosis, susceptibility to infections
NSAID• E.g. ketorolac, diclofenac• Mechanism: inhibition of cyclo-oxygenase • Uses: postoperatively, mild allergic conjunctivitis,
episcleritis, mild uveitis, cystoid macular edema, preoperatively to prevent miosis during surgery
• Side effects: stinging
Harmful drugs for the Eye
Drugs that ↑ IOP: Mydriatic cycloplegics, tricyclic antidepressants Chronic steroid use
Cataractogenic drugs: steroids, phenothiazines, heavy metals…
Drugs causing corneal deposits: chloroquine, amiodarone,•Amiodarone , a cardiac arrhythmia drug•causes optic neuropathy (mild decreased vision, visual field defects)•causes corneal keratopathy which is pigmented deposits in the corneal epithelium.
•Digitalis , cardiac failure drug•Causes chromatopsia (objects appear yellow) with overdose
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