ocular pharmacology
TRANSCRIPT
DR. KEERTHI SAGAR J
OCULAR PHARMACOLOGY
ANATOMY
Factors which influence penetration of the drugs into ocular structures
Nature of the drug
Chemical structure
Molecular weight
Physicochemical properties
Lipid water solubility ratio or partition co-efficient
Polarity
Ionization
Factors which influence penetration of the drugs into ocular structures contd..
Topical Ophthalmic Solution Ophthalmic
Suspension Gel forming solution Ophthalmic ointment Ophthalmic emulsion Ophthalmic gels Ocular inserts
Subconjunctival injections
Subtenon injections Retrobulbar injections Intraocular injections Intravitreal injections
or implants
Method of administration
Nature of the ocular structure Integrity of the corneal epithelium(particularly polar
compounds)- abrasion, ulceration Inflammation(dilated vasculature- increases the
permeability of the ciliary and iris vessels and increases drug concentration in the eye)
Status of the lacrimal outflow passages and conjunctival vasculature(which carry the drug away from the eye)
Presence of the lens(influences drug penetration into the vitreous body)
Factors which influence penetration of the drugs into ocular structures contd..
Ocular pharmacokinetics
Absorption
Distribution
Melanin binding
Metabolism
Local enzymatic biotransformation
Glaucoma
Major cause of irreversible visual disability
Accounts for 10-20% of diagnosed causes of blindness
Characterized by progressive damage to the optic nerve resulting in increased cupping of optic disc and subsequent loss of retinal nerve fibers
Formation of aqueous humor
Mechanisms
Ultra filtration
Secretion (by active transport)
Diffusion
Drainage of aqueous humor
Ciliary processes
Aqueous in the posterior chamber
Anterior chamber
Trabecular meshwork
Ciliary body
Suprachoroidal space
Venous circulation of ciliary body, choroid and sclera
Schlemm’s canal
Episcleral veins
Classification of anti-glaucoma agents
Topical drugs Beta blockers
Timolol Carteolol Levobunolol Metipranolol Betaxolol
Prostaglandin analogues Latanoprost Bimatoprost Travoprost Unoprostone
Adrenergic agonists Epinephrine Dipevifrene Brimonidine Apraclonidine
Carbonic anhydrase inhibitors Dorzolamide Brinzolamide
Cholinergic agents Pilocarpine Carbachol Demecarium bromide Echothiophate
Classification of anti-glaucoma agents contd..
Systemic Carbonic anhydrase
inhibitors Acetazolamide Methazolamide
Osmotic agents Glycerine Mannitol Urea
Miscellaneous drugs Ethacrynic acid ACE inhibitors Forskolin
Neuroprotective agents Brimonidine Latanoprost Memantine- NMDA
antagonist Iomarizine-CCB Riluzole-glutamate
antagonist
Pilocarpine
Alkaloid of pilocarpus jaborandiPK
OOA: rapid Peak effect: 30-60min Duration:4-8hrs MOA: ciliary body contraction- increased aqueous
outflowSide effects
Superficial punctate keratitis Ciliary muscle spasm Retinal detachments
Formulations of pilocarpine
Topical ophthalmic solution form Pilocapine hydrochloride Pilocarpine nitrate
Gel 1%,2%,4%Device
Membrane controlled delivery system Ocusert P 20, Ocusert P 40
Beta blockers
Timolol maleate MOA: Acts directly on ciliary epithelium to block
active transport or ultra filtration Side effects
ocular irritation, Conjunctivitis, blepharitis, decreased corneal sensitivity
dosage: Ophthalmic solution 0.25%, 0.5% Gel form in solution 0.5%
Carteolol Preferred in hypercholesterolemic patients Metabolite has 2-3 times longer half-life Dosage
1% ophthalmic solution
Levobenolol Longer half-life than timolol Side effects: transient ocular burning,
blepharoconjunctivitis, decreased corneal sensitivity Dosage: 0.25%, 0.5% topical drops
Beta blockers contd..
Metipranolol Associated with more eye burning and stinging Risk of respiratory and cardiac toxicity Dosage: 0.3%, 0.6% (BD)
Betaxolol Cardioselective Less efficaceous More burning and stinging than non selective beta
blockers Neuroprotective action Dosage: 0.25%, 0.5% ophthalmic solution BD
Beta blockers contd..
Prostaglandin analogues
Latanoprost PK
Highly lipophillic prodrug Undergoes enzymatic hydrolysis Selective action on FP receptor OOA: 3-4hrs
MOA: increase uveo-scleral outflow Dosage: 0.005% Side effects: increased iris pigmentation, lengthening
and thickening of eye lashes, punctate corneal erosions, blurred vision, burning and stinging sensation
Bimatoprost Appear to mimic prostamides Highly efficacious and long acting drug Active parent drug Stable in solution MOA: reduction in tonographic resistance to outflow-
enhances the pressure sensitive outflow pathway Decreases episcleral venous pressure Dosage: 0.03% topical ophthalmic solution
Prostaglandin analogues contd..
Unoprostone isopropylate
Docosanoid derivative
Dosage: 0.15% topical ophthalmic solution
Travoprost
Highly selective affinity for FB receptor
Prostaglandin analogues contd..
Adrenergic drugs
Epinephrine MOA:
decreased aqueous humor formation- α-adrenergic effect Increased trabecular outflow – β2 adrenergic effect
PK: OOA: 1hr DOA: 72hrs
Dosage: available as salts of hydrochloride, bitartarate, borate 0.25-2%(BD)
Side effects: conjunctival decongestion, transient mydriasis, ocular allergy, adenochrome deposits
Adrenergic drugs contd..
Dipevefrine Prodrug- de-esterification of epinephrine Lipophillicity(penetration) more than 17 times PK
OOA: 30min Peak effect: 1hr
Advantage over epinephrine Lower CV side effects Lower incidence of adenochrome deposits Dosage: 0.1% salts of hydrochloride and bitartarate Side effects: follicular conjunctivitis and ocular allergy
Adrenergic drugs contd..
Apraclonidine Increased polarity of apraclonidine decreases cns
effects MOA:
increased trabecular meshwork outflow by decreasing episcleral venous pressure
Increase in prostaglandin synthesis Incresed uveo-scleral outflow
Side effects: local allergic reaction
Adrenergic drugs contd..
Brimonidine High α2 selectivity Lower incidence of ocular side effects High systemic safety profile PK
Metabolized in liver Excreted in urine Due to its high selectivity no adverse effects such as
mydriasis, lid retraction, intra ocular vasoconstriction Dosage: 0.2% ophthalmic solution, brimonidine purite
0.15% Side effects: less than 3%
Carbonic anhydrase inhibitors
Topical Dorzolamide
Hydrophillic in nature Less CV side effects compared to other topical blockers Less ocular side effects than pilocarpine MOA: inhibits carbonic anhydrase 2-decreases local
bicarbonates Dosage: 2% dorzolamide HCl TID Adverse effects:
irreversible corneal oedema ocular burning and stinging, conjunctival hyperemia,
blurred vision; low incidence of conjunctivitis, keratoconjunctivitis, diplopia
Carbonic anhydrase inhibitors contd..
Topical contd.. Brinzolamide
Patient compliance better with brinzolamide than topical dorzolamide
Low incidence of burning and stinging But increased incidence of blurred vision TID
Systemic Acetazolamide
PK Oral absorption is good Peak plasma concentration: 2hrs and persists for 4-6hrs Sustained effect is seen with coated granules form
Dosage: orally 250mg 6th hourly IV – powder 500mg(sodium) per vial
Side effects: 40-50% of patients are unable to tolerate Malaise, metallic taste, fatigue, depression, anorexia,
weight loss, loss of libido
Carbonic anhydrase inhibitors contd..
Systemic contd..Methazolamide
More potent than acetazolamide Better penetration(50 times)
Good lipid solubility Low protein binding
Dosage: 50-100mg TID
Carbonic anhydrase inhibitors contd..
Hyperosmotic agents MOA: enhances the osmotic pressure of plasma with
respect to intraocular pressure Indications:
Acute angle closure glaucoma Pre operative control of raised IOP
Side effects: Systemic HTN, nausea, vomiting, diuresis, electrolyte
imbalance, pulmonary edema, hyperglycemia, diarrhea, headache
Systemic drugs
Systemic drugs contd..
Hyperosmotic agents contd.. Glycerol
50% and 75% lime flavored oral solutions Topical glycerine – to clear corneal oedema
Isosorbide 45% mint flavoured solution
Mannitol 25-100ml slow IV push
Miscellaneous drugs Forskolin
Methanolic extract of roots of Coleus forskohlii Doesnot have cell membrane receptors Potent stimulator of adenylate cyclase Available as 1% solution
Ethacrynic acid Substantially lowers IOP on topical administration
ACE inhibitors Controls aqueous humor production, retinal blood flow
Systemic drugs contd..
Neuroprotective agents
Brimonidine tartarate α2 agonist Preserves retinal ganglion cell survival and photo
receptor functionalityMemantine – NMDA receptor antagonist
Blockade of toxic effects of glutamate
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