OPTH Lec07 and 08 Flashcards
Bioavailability
% of unchanged drug that is absorbed in the circulation; want to increase bioavailability of eye drops
Surfactants
increase solubility of hydrophilic drugs; Improves penetration through the cornea Benzalkonium Chloride = MC Emulsifies cell walls – improves penetration, but can cause ocular surface damage
How can we improve bioavailability
Osmotics – adjust tonicity of drops to prevent reflex tearing Non-ionized forms of drugs = lipid soluble, thus better penetration
How are eye drop measurements expressed
Parts per 100 1% = 1 gram per 100 cc How many mg of atropine in 5cc of a 1% solution? (1 gram/100 cc ) * 5 cc = .05 grams = 50 mg
Administration of Eye Drops
Drugs to Nasolacrimal duct to Mucosa No first pass effect through GI tract and liver
Anesthetic Eye Drops do what?
Prevents generation and conduction of nerve impulse Anesthesia impedes sodium access to the axon by blocking transmembrane sodium channels
Name the Anesthetic Eye Drops:
tetracycline, proparacaine
What does tetracaine do?
Onset: 15-20 seconds Duration: 15 – 20 minutes Corneal Toxicity, Never prescribe for home use
What does proparacrine do?
Better tolerated than tetacaine Onset: 12.9 seconds Duration: 20 minutes Allergic Dermatitis
What kind of neurons are there in the symp nervous system?
1st order - from in hypothalamus, descend to IML horn of lower cervical and upper thoracic spinal cord 2nd order - Pass through sympathetic chain and synapse in superior cervical ganglion 3rd order - Travel to the eye with branches of carotid artery to innervate smooth muscles and glands
What kind of receptors are there in the symp nervous system and where are they?
Alpha 1 – most vascular smooth muscle, pupillary dilator, heart Alpha 2 - adrenergic and cholinergic nerve terminals Beta 1 – heart, fat cells Beta 2 – respiratory and vascular smooth muscle, skeletal muscle
Name the alpha drugs that act on autonomics:
norepinephrine, epinephrine
Naem the beta drugs that act on autonomics:
epinephrine, isoproterenol
What are alpha blocking drugs?
thymoxamine
Which drugs do you use for Galucoma?
Beta blocking – timolol, betaxolol, levobunalol, etc. Alpha agonist – clonidine, apraclonidine, brimonidine
What does Epinephrine do?
Increases trabecular outflow; Small increase in aqueous production; Vasoconstriction; Mydriasis; Mostly alpha, slight beta effect
Describe Epinephrine Toxicity:
o Nervousness, anxiety, tachycardia, headache o May exacerbate CAD, HTN, Thyrotoxicosis o Corneal pigmentation, madarosis, turns contact lenses black o Rebound Hyperemia o Conjunctival Pigment Deposits
What does Phenylephrine do?
Direct acting, alpha agonist; Alpha-1 selective, little effect on Beta; Used for mydriasis; Onset 15-60 mins, duration 3.7 hours; No effect on ciliary muscle
What is the toxicity of phenylephedrine?
Acute Hypertension Seen with 10% solution Never use 10% in infants Hypersensitivity in patients with diabetic neuropathy Pulmonary Edema, arrhythmia
What does clonidine do?
– Central acting, even topically – Alpha 2, some alpha 1 agonist – Decreases aqueous production by vasoconstricting the ciliary body – Little effect on pupil. Accommodation, or vision – Multiple cardiovascular effects
What is apraclonidine?
– Alpha agonist, mostly alpha 2 – Lowers IOP by suppressing aqueous production – Vasoconstriction of the ciliary body may also play a role – Does not cross blood brain barrier in adults – Can cause somnolence in children – No effect on BP, almost no cardiac effects
What are the side effects of apraclonidine?
Transient dry nose, mouth (30-40%) Eye lid retraction Mydriasis Conjunctival blanching Do not use in kids!
What is brimonidine and what is it used for?
– Alpha agonist, primarily alpha-2 – Decreases aqueous production – Increases uveoscleral outflow – Less allergy than apraclonidine – No heart rate/BP effects – Can cause sedation by stimulating central alpha-2 receptors
What are the side effects of Brimonidine?
10-30% dry mouth, burning, fatigue, redness Visual Disturbance Contraindicated in young children due to somnolence
What is Thymoxamine (0.5%)
– Alpha blocker – Inhibits pupillary dilator muscle of the eye – Competes against NE – Constricts Pupil – No effect on IOP, Aqueous production – No effect on accommodation
What are clinical uses for Thymoxamine?
Reverse phenylephrine dilation Treatment of angle closure glaucoma Treatment of lid retraction from thyroid disease (sympathetic innv to Muller’s muscle) Maintain position of IOL
What are the side effects of Thymoxamine?
Burning, Conjunctival Hyperemia
What is Timolol?
– Nonspecific Beta Blocker (β -1 and β -2 receptors) – Antagonizes circulating catecholamines at the β -1 and β -2 receptors at the ciliary epithelium – Decreases aqueous production/ No influence on outflow – No change in vision, pupil, or accommodation – IOP decrease seen in 30-60 minutes – Short term increase in weeks with upregulation of beta receptors – No effect on optic nerve blood flow
What are the contraindications of Timolol?
Asthma, COPD, Bradycardia, Arrhythmias
What is the toxicity/side effects of Timolol?
Depression, decreased pulse, GI irritation Anxiety, confusion, decreased sexual function, hair loss Exacerbation of Myasthenia Gravis Decreased response to hypoglycemic episodes
What is Betaxolol?
– β -1 selective blocker – Decreases aqueous production by 32-47%/No effect on outflow or pupil – Less potent than timolol, but safer to use in lung disease
What are the side effects fo Betaxolol?
Local: Burning, spk, conjunctivitis Systemic: Less than timolol, Decrease pulse, BP, arrhythmia
What is Carteolol?
– Non selective Beta Blocker – Intrinsic Sympathomimetic activity = Transient beta agonist activity – Similar efficacy in IOP lowering – Less ocular irritation – Similar Side Effect Profile to Timolol
Describe the effect of Beta blockers on Lipids:
– Beta Blockers inhibit lipoprotein lipase and lecithin cholesterol acetyltransferase – Timolol decreases HDL by 8-11% – Carteolol decreases HDL by 3% – Oral nonselective Beta Blockers decrease HDL by 19%
Where do cholinergic medications act?
– Muscarinic- affect smooth muscle and glands; Blocked by Atropine; found in the eye; Iris sphincter muscle – Nicotinic – affect skeletal muscle and autonomic ganglia; found outside the globe; Extra Ocular muscles
How is acetylcholine administered?
– Cannot use topically bc corneal cholinesterase destroys it – Injected intracamerally (into anterior chamber) during cataract surgery to cause miosis
What is methacholine?
– More resistant to cholinesterase – Can administer topically – 2.5% used to diagnose Adie’s tonic pupil
What is Carbachol?
– Combination of acetylcholine and physostigmine – Can administer topically, more effective intracamerally – Causes Miosis – Increases trabecular outflow
What are the side effects of Carbachol?
Accommodative spasms, conjunctival hyperemia
What is physostigmine?
cholinesterase inhibitor
What is pilocarpine?
– Direct acting; ONLY on muscarinic receptors – Effective even on denervated structures – Penetrates cornea well
What are the side effects of pilocarpine?
Salivation; Lacrimation; Sweating; N/V/D; Bronchiolar spasm/ pulmonary edema
What are the uses of pilocarpine?
Angle Closure Glaucoma; Reversal of pupillary dilation
What are the effects of pilocarpine?
Miosis; Pupillary block in high concentrations; Induces myopia; Increase trabecular outflow; Decrease uveoscleral outflow
What type of medication is physiostigmine?
– Indirect parasympathomimetic – Temporarily inactivates cholinesterase – Improves ciliary contraction – Miosis Lasts 12-36 hours – Antidote for anticholinergic overdose (atropine, scopolamine, cyclopentolate) – Careful with use, very potent, high doses dangerous
What are the toxic effects of physiostigmine?
death
What are the cholinergic side effects?
Diarrhea, salivation, bradycardia, diaphoresis, bronchial constriction, nausea, vomiting, coma, loss of reflexes
What are the anticholinergic drugs?
Atropine, Homatropine, Scolpolamine, Cyclopentolate, Tropicamide
What is atropine?
Competitive antagonist of acetylcholine Causes: Mydriasis and cycloplegia
What are the uses of atropine?
Iritis – relaxes the ciliary body; mblyopia – alternative to patching; hyphema; Reverses oculocardiac reflex
What is the toxicity of atropine?
100 mg fatal in adults, 50 mg fatal in children Hot as a hare, red as a beet, dry as a bone, blind as a bat, mad as a hatter
What is the duration of use for atropine, homatropine, scolpolamine, cyclopenotolate, and tropicamide?
Atropine = 14 days, Homatropine = 2-4 days, Scolpolamine = 6 dasy, Cyclopentolate = 24 hours, Tropicamide = 4-6 hours
What are the signs of anticholinergic toxicity?
Decrease GI motility, increase gastric secretion; Dry mouth; Urinary retention; Decreased sweating; Tachycardia; Bronchial dilation; Confusion; Treat toxicity with Physostigmine; Mydriasis; Cycloplegia
What is glaucoma?
Death of the optic nerve; Elevated IOP is a risk factor
What causes glaucoma?
Decreased Production of Aqueous Humor; Increase Outflow of Aqueous Humor via Trabecular Outflow or Uveoscleral Outflow -treatment by decreasing IOP
How do you treat galucoma?
Decrease aqueous production using Beta blockings, alpha agonists, Carbonic Anhydrase Inhibitors; or; Increase outflow via Adrenergics, Prostaglandin Analogues, Cholinergics
Name the medications that are Beta Blockers:
Timolol, Betaxolo, Carteolol
Name the medications that are alpha agonists:
Apraclonidine, Brimonidine
Name the medications that are Carbonic Anhydrase Inhibitors:
– Topical: Dorzolamide, Brinzolamide – Systemic: Acetazolamide
How do Carbonic Anhydrase Inhibitors work?
– HCO3 + H- à H2CO3 à Co2 + H20 – Carbonic anhydrase catalyzes this reaction in the ciliary process to make aqueous – CAIs are sulfonamide derivatives – avoid in sulfa allergies – CAI’s reduce Aqueous production by 32% – Must inhibit 90% of carbonic anhydrase before you see a decrease in IOP
Describe CAI Toxicity:
GI side effects; Malaise; Depression; Weight Loss; Kidney Stones; Metabolic Acidosis; Do not use in sickle cell pts
What is Diamox?
– Can also be used to decrease elevated ICP in pseudotumor cerebri – Increases rate of subretinal fluid absorption between retina and pigment epithelium (Used to treat CME) – Coadministration of ASA and Diamox may lead to acid base abnormalities
What are contraindications to administering CAIs?
– Adrenal Insufficiency – Kidney and Liver Disease – Addison’s Disease – Hyperchloremic acidosis – Severe Pulmonary Obstruction
How do prostaglandin analogs work?
– Increase uveoscleral outflow – Causes relaxation of the ciliary muscle and changes in the extracellular matrix between muscle fiber bundles – Upregulates matrix-metalloproteinases – Lowers IOP 33%, no effect on aqueous production
Name the prostaglandin analogs:
– Latanoprost (Xalatan) – Travoprost (Travatan) – Bimatoprost (Lumigan / Latisse)
What are the side effects of prostaglandin analogs?
– Hyperemia – Irreversible darkening of irides – Periorbital skin hyperpigmentation – Hypertrichosis/ eyelash growth (Bimatoprost marketed as Latisse) – Reversible CME cystoid macular edema (Use controversial with patient undergoing cataract surgery)
What are the anti-inflammatory corticosteroids?
o Hydrocortisone o Cortisone o Prednisone o Prednisolone o Dexamethasone o Betamethasone o Triamcinolone o Flucinolone
What are the anti-inflammatory NSAIDS?
o Diclofenac o Bromfenac o Nepafanac
How do corticosteroids work?
– Inhibition of degranulation of mast cells, basophils, neutrophils – Inhibits release of inflammatory mediators - histamines, bradykinins, platelet activating factor – Stabilization of intracellular and lysosomal membranes – Suppresses lymphocyte proliferation – Inhibits phospholipase A synthesis à decreased synthesis of prostagladins and leukotrienes – Inhibits cell mediated immune response – Prolonged use decreases antibody production
What are the uses for corticosteroids?
Uveitis, Corneal Edema, Hyperemia, Conjunctivitis, Macular Edema
What are the contraindications of corticosteroids?
Acute epithelial HSV, fungal eye disease; prevent’s healing after removal of superficial corneal foreign body; Acute, untreated eye infections
What are the ocular side effects of corticosteroids?
Cataracts (Posterior Subcapsular Cataract); Ptosis/mydriasis; Delayed wound healing; Enhanced microbial proliferation; Ischemia; Punctate keratopathy; Elevation in IOP
What are the systemic side effects of corticosteroids?
Peptic Ulcer; Bone resorption/Calcium loss; Immunosuppression; Growth suppression/muscle atrophy; Euphoria/psychosis; Pseudotumor cerebri; Aggravates DM/HTN; Edema/weight gain/hirsutism
What are the formulations of corticopsteroids?
Phosphates, Acetates, Alcohols; Acetate and Alcohol are biphasic and have better corneal penetration
How do NSAIDS work and when are they used?
– Inhibition of cyclooxygeenase à inhibit synthesis of prostaglandins – Unlike corticosteroids, leukotriene synthesis unaffected – Uses: Post-Op CME
What are the side effects of NSAIDS?
– Stinging/burning, No increase in IOP seen – Inhibit platelet aggregation - caution in patient with bleeding tendency or on ASA therapy – Increased incidence of corneal melting in generic NSAIDS
What is the treatment for Allergic Conjunctivitis?
– Mast Cell Stabilizers – H-1 Receptor Antagonists – Combo drugs – NSAIDS – Hallmark of Allergic Conjunctivitis = “Itching”
Name the Mast Cell Stabilizers:
– Cromolyn sodium – Lodoxamide – Nedocromil – Pemirolast
What is Cromolyn Sodium?
– Blocks cellular influx of calcium, therefore stabilizing mast cell membrane – Almost no side effects
What is Lodoxamide Tromehtamide?
– Blocks degranulation of mast cells – Inhibits type I hypersensitivity – Indirectly prevents antigen stimulated release of Histamine – Takes several days to work
Name the H-1 Receptor Antagonists?
– Bepotastine – Emedastine – Levocabastine – Pheniramine
What is Levocabastine?
– Blocks H1 receptor sites – Not for use with Contact Lenses – Works in minutes
Name the Mast Cell Stabilizers with H1 antagonist combination use:
– Ketotifen – Olopatidine – Azelastine – Epinastine
What are the categories of antibiotic eye drops?
– Fluoroquinolones – Aminoglycosides – Macrolides – Others
Name the Fluoroquinolones:
– Ciprofloxacin – Ofloxacin – Levofloxacin – Gatifloxacin – Moxifloxacin – Besifloxacin
What do fluoroquinolones do?
– Inhibit DNA Gyrase – Broad Spectrum – effective against gram positive and negative, including Pseudomonas – Not effective against anaerobes
What are fluoroquinolones used for?
– Used to treat bacterial conjunctivitis, corneal ulcer – Useful in CL wearers due to increased Psuedomonas coverag
Name the aminoglycosides:
– Gentamicin – Tobramycin – Amikacin – Neomycin
What do the aminoglycosides do?
– Bind to 30-S ribosome unit to disrupt protein synthesis – Bactericidal – Treatment of gram negative ocular aerobic bacteria (including Pseudomonas) – Not effective alone vs. Gram positive
Where do aminoglycosides have an effect on toxicity?
– Vestibular – Auditory – Renal – Neuromuscular blockade – Skin Rashes – Retinal infarction with intravitreal use
Name the macrolides:
– Erythromycin – Azithromycin – Clrithromycin
How do the macrolides work and what are they effective for?
– Binds to 50S Ribosome to inhibit protein synthesis – Effective against most gram + cocci and gram – bacilli – Not effective against pseduomonas – Low serious side effects/allergies – Useful in treatment of blepharitis and bacterial conjunctivitis
How does vancomycin work?
– Interferes with cell wall synthesis – Fortified solution used topically in serious corneal ulcers – Used intravitreally in treatment of endophthalmitis
How do penicillins work?
– Act through inhibition of peptidoglycan (mucopeptide) synthesis in the bacterial cell wall – Bactericidal – Rarely used topically – Concern over allergic reaction – Increasing resistance
How does bacitracin work?
inhibits the synthesis of the cell wall
How does polymyxin work?
alters the bacterial cytoplasmic membrane permeability
How do sulfonamides work?
inhibit the nucleic acid synthesis
How is Bacterial Conjunctivitis treated?
– Caused by Staph Aureus – Choose antibiotics with gram positive coverage – Gentamicin commonly prescribed, but has poor gram positive coverage – Need Pseudomonas coverage in Contact Lens wearers
How is endophthalmitis treated?
– Endophthalmitis Vitrectomy Study – Treated with intravitreal antibiotics – 60% are coagulase negative staph – 10% gram negative – Vancomycin + Amikacin or Caftazidime
Name the antivirals and what they are used for:
– Trifluridine - Fluorinated pyrimidine nucleoside analog; Treatment of HSV Keratitis (Dendritic lesion of cornea); 1 drop 9x/day for 10-14 days
What are the side effects of tirfluridine?
burning, spk, hypersensitivity, hyperemia, epithelial erosions, scarring of puncta
What is a Cyclosporine used for and what are the side effects?
– Topical immunomodulator with anti-inflammatory effects – Treatment of Keratoconjunctivitis Sicca – Improves tear production – Takes 3-6 months before see effects – SE: burning
What are ocular side effects of Phenothiazines (systemic medications)?
(Chlorpromazine, Thioridazine): Binds to Melanin -> Pigmentary changes in retina – Deposits on lens, then cornea – Digitalis - Changes in visual perception; Snowy, green, white yellow
What are the side effects of estrogen/progesterone?
Optic Neuritis, papilledema, contact lens intolerance
What are the side effects of tamsulosin?
floppy iris syndrome; Caution during cataract surgery; take once = lifelong ris
What are the side effects of amiodarone?
Accumulates in cornea; Vortex Keratopathy after 1 month
What are the side effects of tamoxifen?
Whorl like subepithelial opacities; White refractile intraretinal deposits
What are the side effects of hydroxychloroquine?
Corneal deposits (verticillata); Retinal Toxicity; Bilateral Pigmentary Retinopathy; Drug binds to melanin; Bulls Eye Maculopathy
What are the side effects of topamax?
Acute myopia; Bilateral acute angle closure; Ciliary body swelling and choroidal effusions
What are the side effects of sidenafil?
Blue Haze in vision; Light sensitivity; Pupil sparing 3rd nerve palsy
