INTRAOCULAR PENETRATION OF DRUGS
Intraocular penetration of topically instilled drugs
It is mainly determined by the corneal epithelium which is lipophilic and is crossed readily by non-polar drugs. Stroma being hydrophilic allows rapid passage of the drug through endothelium into the anterior chamber. Following features will allow better penetration of the drug through the cornea:
• Solubility both in water and fat
• Pro-drug forms are lipophilic and after absorpiton through epithelium are converted into proper drugs which can easily pass through the stroma.
• Wetting agents increase the drug absorption.
The intraocular penetration of systemically administered drugs
It mainly depends upon the blood aqueous barrier. The two characteristics of the drugs which affect their passage through the blood aqueous barrier are:
• Low molecular weight
• Lipid solubility (e.g., sulphonamides being lipid soluble are 16 times more permeable than sucrose having almost same molecular weight).
Idoxuridine (IDU, 5 lodo-2 deoxyuridine)
• Inhibitis the synthesis Of DNA by substituting for thymidine and thus prevents replication of virus
• Used as 0.1% eiye drops one hourly during day and 0.5% eye ointment at night for 10-21 days
• Side effects: follicular conjunctivitis, punctal stenosis.
• Blocks synthesis of nucleic acids
• 3% ointment is applied 5 times a day for 14-21 days
• Not available commercially
• DNA inhibitor like IDU
• Advantages over IDU are: higher solubility, greater potency, lack of toxicity and allergic reactions
• Dose: 1% drops 4 hourly for 14 days
• Effective in most forms of herpes simplex and herpes zoster
• Penetrates deep and so is very effective in stromal keratitis
• Dose: (i) Topically 3% ointment is used 5 times a day in patients with herpes zoster ophthalmicus and recalcitrant cases of herpes simplex.
• Used for CMV retinitis
• Dose: 5 mg/kg body weight every 12 hour for 2- 3 weeks followed by maintenance dose of 5 mg/ kg once daily.
• As effective as ganciclovir in treating CMV retinitis with AIDS.
Zidovudine (Azidothymidine, AZT)
• Combined with immunoglobulins in treating HIV infection (AIDS).
I. Polyene antifungals
• Are isolated from streptomyces
• Act by binding to the sterol group in fungal cell membranes, rendering them permeable
• Effective against Candida and aspergillus
• Poor intraocular penetraiton
• 3.5% eye ointment is used 5 times a day.
2. Amphotericin B (Fungizone)
• Effective against Candida, histoplasma and cryptococcus
• Topically, effective as 0.75% to 0.3% drops in superficial comeal ulcers
• Intravitreal injection for fungal endophthalmitis
• Intravenously, it is used as 0.1 mg/ml in 5 percent dextrose for systemic infections.
3. Natamycin (Pimaricin)
• Broad spectrum antifungal (effective against Candida, aspergillus, fusarium and cephalos- porium).
• Drugs of choice for fusarium keratitis
• Used as 5% suspension.
II. Imidazole antifungal drugs
1. Miconazole: Broad spectrum fungicidal topically used as 1% solution.
2. Clotrimazole: Fungistatic, 1% suspension is effective aganst Candida and aspergillus keratitis.
3. Econazole: Used as 1 % econazole nitrate ointment.
4. Ketoconazole: used in single oral dose of 200- 400 mg daily in fungal keratitis and endophthalmitis.
III. Pyrimidine group
• Flucytosine used as 1.5% aqueous eye drops one hourly is very effective against Candida and yeast infections.
IV. Silver compounds
• Silver sulfadiazine eye drops are effective against aspergillus and fusarium keratitis.
Mechanisms of action
• In primary open-angle glaucoma, miotics lower the IOP by enhancing aqueous outflow facility by widening intertrabecular pores due to a pull exerted on the scleral spur by contraction of the longitudinal fibres of ciliary muscle
• In primary angle-closure glaucoma the miotics open the angle by pulling the iris away from the trabecular meshwork.
Miotics are not useful in:
• Epidemic dropsy glaucoma
• Glaucoma inversus
• Glaucomatocyclitic crisis
• Aphakic glaucoma
• Inflammatory glaucoma
II. Sympathomimetic drugs
Mechanisms of action
• Decreased aqueous secretion due to stimulation of alpha receptors in the ciliary body
• increased aqueous outflow due to stimulation of alpha and beta receptors.
• POAG – Preferred in the presence of systemic contraindication to beta-blocker
• Secondary glaucomas – Useful in most
III. Beta adrenergic blockers
Mechanism of action
• Timolol and levobunolol reduce aqueous secretion by blockade of beta-2 receptors in the ciliary processes
• Mechanism of action of betaxolol (cardioselecti ve beta blocker) is unknown.
• In POAG and secondary glaucomas, it is the drug of first choice unless contraindicated due to systemic diseases
• In PACG, it is useful as a temporary adjunct.
Commonly used preparations
• Non selective beta-1 and beta-2 blocker
• Available as 0,25 and 0.5 percent eye drops
• Efficacy is very good; however, the phenomenon of ‘short-term escape’ (marked initial fall, followed by a transient rise with continued moderate fall in IOP) and ‘long term-drift’ (slow rise in IOP after well controlled with months of therapy) are seen.
• Relative cardioselecti ve beta-I blocker (10 times more affinity for beta-1 than beta-2 receptors), so can be used in patients with bronchial asthma.
• Available as 0.25% and 0.5% eye drops
IV. Carbonic anhydrase inhibitors (CAI)
Mechanism of action
Reduce aqueous secretion by inhibitng the enzyme carbonic anhydrase.
• Used as additive therapy for short term in all types of acute glaucomas
• Long-term use is reserved for patients with high risk of visual loss, not responding to other modes of therapy.
V. Hyperosmotic agents
Mechanism of action
Increase the osmotic pressure gradient between the blood and vitreous and thus draw sufficient water out of the eye ball, therapy lowering IOP.
• For rapidly lowering of the acutely raised IOP as in primary acute congestive glaucomas or secondary acute glaucomas.
• As a prophylactic measure prior to intraocular surgery
• Cardiovascular overload
• Headache and backache
• Urinary retention
• Mental confusion
• An oral hyperosmotic agent with sweet and sickening taste
• Dose: 1-1.5 gm/kg body weight, used as 50% solution, therefore, dose is 50-80 ml mixed with equal amount of lemon juice
• Action peaks in 1 hour and lasts for 4-6 hours
• Metabolised to glucose and so repeated use in diabetes is not recommended.
• Dose: 1-2 gm/kg body weight or 5 to 10 ml/kg body weight of 20% solution in water
• Should be administered intravenously very rapidly over 20-30 minutes
• Action peaks in 30 minutes and lasts for 6 hours.
Antiglaucoma drugs: Mechanism of lowering IOP at a glance
Drugs which increase trabecular outflow
• Miotics (e.g., pilocarpine)
• Epinephrine, Dipivefrine
Drugs which increase uveoscleral outflow
• Prostaglanalins (latanoprost)
• Epinephrine, Dipivefrine
Drugs which decrease aqueous production
• Carbonic anhydrase inhibitors (e.g., acetazola- mide, dorzolamide)
• Alpha receptor stimulators in ciliary process (e.g., epinephrine, dipivefrine, clonidine, brimonidine, apraclonidine.
• Beta blockers (e.g., timolol, betaxolol, levobunolol)
Hyperosmotic agents (e.g., glycerol, mannitol, urea)
LASERS IN OPHTHALMOLOGY
|Type of laser||Atomic environment used||Effects produced||Clinical uses|
|Argon||Argon gas||Photocoagulation||• Diabetic retinopathy|
|Krypton||Krypton gas||Photocoagulation||• Peripheral retinal vascular abnormalities such as Eales’ disease, proliferative sickle cell disease, Coat’s disease and. retinopathy of prematurity,|
|Diode||Diode crystal||Photocoagulation||• Intraocular tumours such as retinobla toma, malignant melanoma and choroidal haemangioma|
|nd-YAG||A liquid dye, or a solid compound of yttrium- aluminium garnet and neodymium||Photodisruption||• Capsulotomy
|Excimer||Helium and flourine gas||Photoablation||• Refractive corneal surgery (LASIK)
• Phototherapeutic Keratectomy (PTK)
CRYOSURGERY IN OPHTHALMOLOGY
Principle. Working of cryoprobes is based on the Joule-Thompson principle of cooling.
Cryounit and probe.The cryounit uses freon, nitrous oxide or carbondioxide gas as cooling agent. Temperature produced depends upon the size of the cryoprobe tip, duration of freezing process and the gas used.
• Temperature produced at the tip of cryoprobe
– for intracapsular cataract extraction is about -40°C
– for cyclocryopexy is about -80°C
– for cryoretinopexy in retinal detachment surgery is about -70°C
1. Lids: (i) Cryolysis for trichiasis, (ii) Cryotherapy for warts and molluscum contagiosum, (iii) Cryotherapy for basal cell carcinoma and haemangioma.
2 Conjunctiva: Cryotherapy is used for hypertrophied papillae of vernal catarrh
3. Lens: Cryoextraction of the lens is the best intracapsular technique.
4. Ciliary body: Cyclocryopexy for absolute glaucoma and neovascular glaucoma.
5. Retina: (i) Cryopexy is widely used for sealing retinal holes in retinal detachment, (ii) Prophylactic cryopexy to prevent retinal detachment in certain pronecases. (iii) Retinal cryopexy for neovascularization, (iv) Cryo-treatment of retinoblastoma and angioma.
• Tropicamide is the fastest acting cycloplegic drug.
• Sulfonamides are most commonly known to cause Stevens Johnson syndrome.
• Topical steroids are contraindicated in superficial viral keratitis, bacterial corneal ulcer, fungal corneal ulcer.
• Intraocular permeability of the topically instilled drugs is mainly determined by the epithelium of cornea.
• Phenylephrine (10%) drops should not be used in neonates, cardiac patients and patients receiving antidepressants.