Pharmacology

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2 Pharmacology

OCULAR PHARMACOLOGY
ROUTES OF ADMINISTRATION
ANESTHETICS
AUTONOMIC SYSTEM
OCULAR HYPOTENSIVE (GLAUCOMA) MEDICATIONS
ANTI-INFLAMMATORY DRUGS
ANTIALLERGY MEDICATIONS
IMMUNOSUPPRESSIVE AGENTS
ANTI-INFECTIVE DRUGS
MISCELLANEOUS
OCULAR TOXICOLOGY

Ocular Pharmacology

Pharmacodynamics

the study of the biochemical and physiologic effects of drugs and their mechanisms of action.

Pharmacokinetics

the study of the factors that determine the relationship between drug dosage and the change in concentration over time in a biological system.

Bioavailability

amount of drug absorbed (penetration into ocular tissues)

Depends on concentration, rate of absorption, tissue binding, transport, metabolism, and excretion
Methods of improving bioavailability:

INCREASE CONCENTRATION: limited by solubility and tonicity (hypertonicity causes reflex tearing, which dilutes and washes drug from the eye)
SURFACTANTS: surface-active agents alter cell membranes, increasing permeability of the corneal epithelium
OSMOTICS: alter tonicity
INCREASE PH: increases nonionized (lipid-soluble) form of drug, increasing corneal penetration (pH of tears = 7.4)
INCREASE VISCOSITY: viscous additives (methylcellulose, polyvinyl alcohol) increase contact time and therefore penetration
INCREASE CONTACT TIME: gels and oil-based ointment formulations (mineral oil, petrolatum), polymer matrix (DuraSite); must be able to release drug

Therapeutic index

method of comparing potency of different antibiotics. A measure of relative effective (therapeutic) concentration of antibiotic at target site against a target organism.

Inhibitory quotient (IQ)

The most potent antibiotic has the lowest minimum inhibitory concentration (MIC) (or highest IQ).

Routes of Administration

Topical

absorption related to corneal penetration

1 drop =  50 µL (20–40 drops in most bottles)
Conjunctival cul-de-sac holds only 10 µL (20% of drop)
Drop diluted by reflex tearing and normal tear turnover: only ~50% of drug that reaches the cul-de-sac is present 4 minutes later (10% of drop)
Corneal barriers to penetration:

TIGHT JUNCTIONS (epithelium and endothelium): limit passage of hydrophilic drugs
STROMA (water rich): limits passage of lipophilic drugs

Methods of increasing absorption:

1 Add surfactants (disrupts epithelial integrity; e.g. benzalkonium chloride, topical anesthetic).
2 Promote punctal occlusion (decreases drainage).
3 Close eyelid after drops are placed.
4 Increase lipid solubility of drug (increases pH); more important than water solubility.
5 Increase frequency of drops.

Topical medications have systemic adverse effects because the drugs bypass hepatic ‘first-pass’ metabolism (cul-de-sac → nasolacrimal duct → mucosa → bloodstream)
Examples of other delivery systems:

PRODRUG: dipivalyl epinephrine (Propine; prodrug of epinephrine, less toxicity), nepafenac (Nevanac; prodrug of amfenac)
OINTMENT: drugs that have better uptake in ointment form, including tetracycline, chloramphenicol, and fluorometholone
SUSTAINED RELEASE GEL: pilocarpine (Pilopine HS; decreased dosing)
INSERT: pilocarpine (Ocusert; membrane-controlled system; slow release over 1 week); hydroxypropyl cellulose (Lacrisert; artificial tear slow-release pellet); collagen shield (bandage contact lens presoaked in antibiotic)

Subconjunctival / sub-Tenon’s

increases duration and concentration, bypasses conjunctival and corneal barriers, avoids systemic toxicity; useful if poor compliance

Retrobulbar / peribulbar

used for anesthesia; alcohol or chlorpromazine (to kill pain fibers and optic nerve [ON] in blind, painful eye)

Intraocular

direct ocular effects; beware toxicity (particularly from preservatives), retinal tear, retinal detachment (RD), endophthalmitis; used intraoperatively (intracameral, intravitreal) and in retinal diseases (intravitreal) including macular edema, choroidal neovascularization (CNV), endophthalmitis, cytomegalovirus (CMV) retinitis

Systemic

must cross blood–ocular barrier (blood–aqueous for anterior segment, blood–retinal for posterior segment); penetrance is improved with decreased molecular size, decreased protein binding, and increased lipid solubility

Concentration

1% solution = 1 g/100 mL = 10 mg/mL

Example: How much atropine is contained in 5 mL of a 2% solution?

image

Anesthetics

Mechanism

reversible blockade of nerve fiber conduction (block sodium channels); pH dependent (less effective at low pH [inflamed tissue])

Structure

2 classes; do not necessarily have allergic cross-reactivity

Ester: hydrolyzed by plasma cholinesterase and metabolized in liver; cocaine, tetracaine (amethocaine), proparacaine, procaine, benoxinate
Amide: longer duration and less systemic toxicity; metabolized in liver; lidocaine, mepivacaine, bupivacaine

Topical

disturb intercellular junction of corneal epithelium (increase permeability)

Proparacaine (Ophthaine): 10- to 30-minute duration, corneal toxicity; may cause allergic dermatitis (also common with atropine and neomycin); does not necessarily have allergic cross -reactivity with tetracaine
Tetracaine (Pontocaine): similar to proparacaine but longer duration and more toxic to corneal epithelium
Benoxinate: similar to proparacaine; combined with fluorescein (Fluress) for tonometry
Cocaine: greatest epithelial toxicity; excellent anesthesia, sympathomimetic effect (test for Horner’s syndrome)

Parenteral

may be used with epinephrine (1 : 100,000) to increase duration by preventing systemic absorption; also decreases bleeding; hyaluronidase (Wydase) 150 IU increases tissue penetration, but decreases duration. Side effect of retrobulbar anesthesia = respiratory depression, bradycardia

Toxicity: hypotension, convulsions, nausea, vomiting
Lidocaine (Xylocaine): 1-hour duration (2 hours with epinephrine); used for local anesthesia : akinesia
Procaine (Novocain): 30- to 45-minute duration
Mepivacaine (Carbocaine): 2-hour duration
Bupivacaine (Marcaine): 6-hour duration

General

all agents decrease IOP except ketamine, chloral hydrate, N2O, and ether

Malignant hyperthermia: rare, autosomal dominant condition that occurs after exposure to inhalation agents (most commonly halothane, also succinylcholine, haloperidol); more common in children and males; thought to be due to calcium-binding disorder in sarcoplasmic reticulum that causes increased intracellular calcium, which stimulates muscle contraction

Interference with oxidative phosphorylation causes hypermetabolic crisis
FINDINGS: tachycardia (1st sign), elevated CO2 levels, tachypnea, unstable BP, arrhythmias, cyanosis, sweating, increased temperature (later sign), muscle contractions; later, heart failure and disseminated intravascular coagulation (DIC) develop; laboratory tests show respiratory and metabolic acidosis and increased K, Mg, myoglobin, creatine phosphokinase (CPK), hypoxemia, hypercarbia, myoglobinuria
SCREENING: elevated CPK, muscle biopsy / contracture test, platelet bioassay (decreased adenosine triphosphate [ATP] in platelet exposed to halothane)
TREATMENT: stop anesthesia, hyperventilate with 100% oxygen, give sodium bicarbonate, cool patient (iced saline IV and lavage; surface cooling), mannitol and furosemide (Lasix), IV dantrolene (prevents release of calcium from sarcoplasmic reticulum), procainamide, insulin (do not use lactated Ringer’s solution, which increases potassium)
PROGNOSIS: 50-60% mortality

Autonomic System

Sympathetic

Extensive system for mass response (‘fight or flight’) (Table 2-1)

Table 2-1 Autonomic system responses

Organ / Function Sympathetic (fight / flight) Parasympathetic (homeostasis)
HR Increase Decrease
BP Increase Decrease
GI motility Decrease Increase
Bronchioles Dilate Constrict
Bladder Constrict Dilate
Vessels Constrict Dilate
Sweat Decrease Increase
Pupils Dilate Constrict
Eyelids Elevate Normal

Synapses near cord (superior cervical ganglion)

Long postganglionic nerves

Adrenergic receptors

α1: smooth muscle contraction (arteries [decrease aqueous production by reducing ciliary body blood flow], iris dilator, Müller’s muscle)
α2: feedback inhibition, ciliary body (decreases production and / or increases outflow)
β1: cardiac stimulation
β2: pulmonary and GI smooth muscle relaxation, ciliary body / trabecular meshwork (increase aqueous production, increase outflow facility)

Neurotransmitter

acetylcholine (ACh) at preganglionic terminal, epinephrine and norepinephrine (NE) at postganglionic terminal

Monoamine oxidase (MAO) breaks down NE in nerve terminal; blocked by MAO inhibitors (avoid with phenylephrine, epinephrine, and pseudoephedrine-based cold remedies)
Catechol-O-methyltransferase (COMT) breaks down NE in effector cell
Reserpine prevents storage of NE in nerve terminal
Cocaine, tricyclics block reuptake of NE by nerve terminal (thus potentiate its action)
Hydroxyamphetamine increases release of NE from nerve terminal

Parasympathetic

More limited system for discrete response (homeostatic)

Synapses near end organ (ciliary ganglion)

Short postganglionic nerves

Cholinergic receptors

Nicotinic: somatic motor and preganglionic autonomic nerves (extraocular muscles, levator, orbicularis [outside eye])
Muscarinic: postganglionic parasympathetic nerves (iris sphincter, ciliary muscle [inside eye])

Neurotransmitter

ACh

Acetylcholinesterase (AChE) breaks down ACh

Cholinergic Drugs

Direct-acting agonists

act on end organ; therefore, do not need intact innervation; cause shallowing of anterior chamber (AC); disruption of blood–aqueous barrier, miosis, brow ache, and decrease in IOP

Acetylcholine (miochol: very short-acting, unstable, used intracamerally), methacholine, carbacholine (carbamylcholine, carbachol; direct and indirect acting), pilocarpine (less potent than ACh, but resistant to AChE; no miosis if IOP >40 mmHg)

Indirect-acting agonists

anticholinesterases (AChE inhibitor); strongest agents; cause miosis and decrease in IOP (contract longitudinal fibers of ciliary muscle = increased outflow of trabecular meshwork [TM]).

Reversible: carbacholine, physostigmine (eserine; treat lid lice), edrophonium (Tensilon; for diagnosis of myasthenia gravis): can cause bradycardia, treat with atropine
Irreversible: echothiophate (Phospholine Iodide; treat glaucoma and accommodative esotropia [ET]; may cause iris cysts and subcapsular cataracts), isofluorophate (very long-acting, not used clinically), demecarium
Adverse effects: cataract, RD, pupillary block, blocks metabolism of succinylcholine (prolonged respiratory paralysis) and ester anesthetics, can mimic acute abdomen (GI effects); antidote is pralidoxime (PAM) or atropine

Muscarinic antagonists

anticholinergics; cause deepening of AC, stabilization of blood–aqueous barrier, mydriasis, and cycloplegia

Atropine (1- to 2-week duration; most allergenic, supersensitivity seen in Down syndrome), scopolamine (hyoscine; 1-week duration; greater CNS toxicity than atropine), homatropine (1- to 3-day duration), cyclopentolate (Cyclogyl; 24-hour duration; beware CNS side effects with 2% solution, especially in children), tropicamide (Mydriacyl; 4- to 6-hour duration)
Toxicity: mental status changes, hallucinations, tachycardia, urinary retention, dry mouth / skin, fever
Antidote: physostigmine (1-4 mg IV)

Nicotinic antagonists

Nondepolarizing agents: gallamine, pancuronium; do not cause muscle contraction
Depolarizing agents: succinylcholine, decamethonium; cause muscle contraction and elevated IOP; contraindicated for ruptured globe (extraocular muscle [EOM] contraction can cause extrusion of intraocular contents)

Adrenergic Drugs

Sympathomimetics

may cause mydriasis, vasoconstriction, decreased IOP

Direct-acting α-agonists: epinephrine, phenylephrine, dipivefrin, clonidine, apraclonidine (iopidine), brimonidine, methyldopa, naphazoline (Naphcon), oxymetazoline (Afrin), tetrahydrozoline (Visine)
Direct-acting β-agonists: epinephrine, isoproterenol, terbutaline, dopamine, albuterol (salbutamol)
Indirect-acting agonists: cocaine, hydroxyamphetamine (Paredrine), ephedrine

Sympatholytics

may cause decreased IOP

General blockers: guanethidine, bethanidine, protriptyline, 6-hydroxydopamine
α-blockers: thymoxamine, dibenamine, phentolamine, prazosin, labetalol, dapiprazole (Rev-Eyes; miosis)
β-blockers: timolol, levobunolol, betaxolol, metipranolol, carteolol, propranolol, metoprolol, atenolol, nadolol, pindolol

Ocular Hypotensive (Glaucoma) Medications

β-Blockers

Mechanism

reduce aqueous production (inhibit Na+/K+ pump) by decreasing cyclic adenosine monophosphate (cAMP) production in ciliary epithelium; around 20% IOP reduction

Loss of effectiveness over time due to downregulation of β-receptors (long-term drift)

Adverse effects

dry eye syndrome (decreased corneal sensitivity), bradycardia, heart block, bronchospasm, impotence, lethargy, depression, headache, rarely diarrhea and hallucinations, alopecia, dermatitis; may mask hypoglycemia

Nonselective (β1 and β2)

timolol (Timoptic), levobunolol (Betagan), metipranolol (Optipranolol), carteolol (Ocupress)

10% do not show a therapeutic effect; inhibit lipoprotein lipase (break down chylomicrons and VLDL) and cholesterol acyltransferase (incorporate cholesterol into HDL); may cause decreased HDL levels
Carteolol has intrinsic sympathomimetic activity

Cardioselective (β1 image β2)

betaxolol (Betoptic)

Fewer pulmonary adverse effects

Indications: patients with pulmonary problems who cannot tolerate nonselective β-blockers; often used for normal tension glaucoma; may not cause as much vasoconstriction of vessels supplying ON

α2-Agonists

Apraclonidine (Iopidine), brimonidine (Alphagan P)

Mechanism: reduce aqueous production by decreasing episcleral venous pressure
Adverse effects: allergy, superior lid retraction, dry mouth, blanching of conjunctival vessels, miosis, lethargy, headache, stomach cramps; avoid in children especially <3 years of age: increased risk of somnolence, seizures, apnea due to CNS penetration

Dipivefrin (Propine)

prodrug of epinephrine (converted into epinephrine in cornea by esterases), lower concentration and increased solubility vs epinephrine (penetrates cornea 17× better); thus less toxicity and fewer adverse effects

Mechanism: improves aqueous outflow, slightly reduces aqueous production
Adverse effects: allergy, cystoid macular edema (CME) in aphakia, hypertension, tachycardia (fewer systemic adverse effects than epinephrine)

Epinephrine

1–2% is equivalent to Propine 0.1%; 3 salt forms: hydrochloride, borate, bitartrate (1st two are equivalent, 2% bitartrate is equivalent to 1% hydrochloride or borate)

Mechanism: improves aqueous outflow, slightly reduces aqueous production
Adverse effects: allergy, CME in aphakia (reversible), hypertension, tachycardia, arrhythmias, adrenochrome (black) deposits in conjunctiva

Miotics

Mechanism

increase aqueous outflow (contraction of ciliary muscle opens trabecular meshwork), decrease uveoscleral outflow

Pilocarpine

only direct cholinergic agonist; peak action at 2 hours, 8-hour duration

Beware for treatment of angle closure: causes shallowing of AC and narrowing of angle, but miosis pulls peripheral iris away from angle, balancing out the other effects
Adverse effects: headache, brow ache, accommodative spasm, increased range of accommodation, miosis (dimming, reduction of vision), induced myopia (forward shift of lens–iris diaphragm), pupillary block, follicular conjunctivitis, dermatitis, nyctalopia, rarely retinal tear or even RD
Other effects: breakdown of blood–aqueous barrier, reduction of uveoscleral outflow

Carbachol

direct and indirect cholinergic agonist; stronger effect and longer duration of action; poor corneal penetration; needs corneal surface disrupter (benzalkonium chloride); intraocular formulation (Miostat) used during surgery for pupillary miosis

Echothiophate (phospholine iodide)

indirect cholinergic agonist (cholinesterase inhibitor); 3-week duration; also used in accommodative esotropia

Adverse effects: greater orbicularis, ciliary, and iris muscle spasm; cataracts in adults (therefore, use only in aphakic or pseudophakic patients); iris cysts in children (proliferation of iris pigment epithelium; phenylephrine prevents cyst formation); decreased serum pseudocholinesterase activity (can accentuate succinylcholine effects during general anesthesia)

Carbonic Anhydrase Inhibitors (CAIs)

Mechanism

decrease bicarbonate formation in ciliary body epithelium; bicarbonate formation is linked to Na+ and fluid transport, so CAIs reduce aqueous production

Carbonic anhydrase catalyzes the reaction

CO2 + H2O ↔ H2CO3

Amount of carbonic anhydrase is 100× that needed for aqueous production; so, >99% must be inhibited to achieve IOP decrease

Sulfonamide derivative (do not administer to patients with sulfa allergy)

Oral

acetazolamide (Diamox; PO / IV), methazolamide (Neptazane, PO; more lipid soluble, less toxicity)

Adverse effects: dry eye syndrome (decreased tear production), metabolic acidosis (IV administration causes greater metabolic acidosis), kidney stones (reduced excretion of urinary citrate or magnesium), hypokalemia (especially when used with other diuretics; very dangerous with digoxin), paresthesias (hands / feet / lips), GI upset, diarrhea, lethargy, loss of libido, weight loss, metallic taste, aplastic anemia, Stevens-Johnson syndrome; transient myopia

Topical

dorzolamide (Trusopt), brinzolamide (Azopt)

Adverse effects: metallic taste, paresthesias, malaise, weight loss, depression, skin rash, corneal endothelial decompensation / toxicity (consider stopping prior to cataract surgery)

Prostaglandin Analogues / Prostanoids

Mechanism

increase uveoscleral outflow, around 30% IOP reduction

Latanoprost (Xalatan), bimatoprost (Lumigan), travoprost (Travatan), unoprostone isopropyl (Rescula)

prostaglandin F2α analogues

Adverse effects: flu-like symptoms, hyperemia, eyelash growth, periocular skin and iris pigmentation (increases number of melanosomes, but not melanocytes), CME, reactivation of herpes simplex virus (HSV) keratitis

Hyperosmotic Agents

Mechanism

low-molecular-weight substances that increase serum osmolality to draw fluid out of eye (reduces vitreous volume)

Adverse effects: headache, thirst, nausea, vomiting, diarrhea, diuresis, dizziness, and rebound IOP elevation; IV agents can cause subarachnoid hemorrhage

Urea (IV; 30% solution)

not commonly used; extravasation causes tissue necrosis

Mannitol (Osmitrol; IV; 20% solution)

most potent; may exacerbate congestive heart failure

Glycerin (Osmoglyn; PO; 50% solution)

may cause hyperglycemia in diabetics (metabolized by liver into glucose)

Isosorbide (Ismotic; PO)

not metabolized (can be used in diabetics); secreted 95% unchanged in urine

Other hyperosmotic agents

used topically for corneal edema

Glycerin (Ophthalgan; topical; 100% solution): used to clear corneal edema for examination or laser procedure
Muro 128 (hypertonic saline; topical; drops or ointment; 2.5% or 5% strength): used to reduce epithelial edema of cornea, especially in treatment of recurrent erosions

Order of Allergy

Greatest to least

iopidine > epinephrine > Propine > brimonidine > β-blocker > pilocarpine

Anti-Inflammatory Drugs

The Inflammatory Pathway (Figure 2-1)

image

Figure 2-1 The inflammatory pathway. NSAIDs, nonsteroidal anti-inflammatory drugs; PG, prostaglandin; 5-HPETE, 5-hydroperoxyeicosatetraenoic acid.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Mechanism

inhibit cyclooxygenase pathway

Classes

Salicylates: acetylsalicylic acid (ASA), diflunisal, salicylamide
Acetic acids: indomethacin (indometacin), diclofenac (Voltaren), sulindac, etodolac, ketorolac (Acular, Toradol), nepafenac (Nevanac), bromfenac (Xibrom, Bromday)
Phenylalkanoic acids: ibuprofen, suprofen (Profenal), flurbiprofen (Ocufen), naproxen, fenoprofen, ketoprofen
Cyclooxygenase-2 inhibitors: celecoxib (Celebrex)

Indications

Prevent miosis during intraocular surgery: Profenal, Ocufen
Allergic conjunctivitis, corneal pain, postsurgical inflammation, CME: Voltaren, Acular, Nevanac, Xibrom, Bromday
Scleritis, uveitis: oral agents

Steroids

Mechanism

anti-inflammatory and immunosuppressive by inhibiting release of arachidonic acid, inhibiting release of lysosomal enzymes, preventing macrophage migration, interfering with lymphocyte function, decreasing fibroblast activity, inhibiting neovascularization, and reducing capillary permeability

Classes

Ester: loteprednol
Ketone: all others

Preparations (ketones)

Phosphate: hydrophilic; poor penetration of intact corneal epithelium (improved penetration with epithelial defect)
Alcohol: biphasic; penetrate intact cornea
Acetate: more biphasic; best corneal penetration

Potency

increased by 1–2 double bond(s), 9 fluorination, 6 methylation, O at C11; IOP elevation from deoxygenation at C21 (Table 2-2)

Derivatives of progesterone (weaker): FML, medrysone

Table 2-2 Relative potencies of steroids

Steroid Relative potency
Hydrocortisone 1 (the standard)
Cortisone 0.8
Triamcinolone 4
Prednisone 4
Prednisolone 5
Dexamethasone 25–30
Betamethasone 25–30
Fluorometholone 40–50
Fluocinolone 240

Subconjunctival / sub-Tenon’s injection (Table 2-3)

produces higher ocular concentration and longer duration; beware in IOP responder

Table 2-3 Common ophthalmic steroids

Generic name Trade name
Topical  
Prednisolone acetate 1% Pred Forte, Omni Pred
Fluorometholone acetate 0.1% Flarex
Dexamethasone alcohol 0.1% Maxidex
Fluorometholone alcohol 0.1% FML
Prednisolone phosphate 1% Inflamase
Dexamethasone phosphate 1% Decadron
Difluprednate 0.05% Durezol
Loteprednol etabonate 0.5% Lotemax
Loteprednol etabonate 0.2% Alrex
Subconjunctival  
Dexamethasone phosphate Decadron
Methylprednisolone acetate Solumedrol, Depomedrol
Prednisolone acetate Durapred
Triamcinolone acetonide Kenalog
Betamethasone Celestone
Intravitreal  
Triamcinolone acetonide Kenalog, Triesence

Other routes of administration

oral, IV, intraocular

Oral dose of 7.5 mg dexamethasone results in intravitreal concentration of therapeutic levels

Indications

conjunctivitis, keratitis, scleritis, uveitis, hyphema, CME, macular edema, CNV, endophthalmitis

Adverse effects

Systemic: adrenal insufficiency, hyperglycemia, hypertension, hypokalemia, peptic ulcers, delayed wound healing, superinfection, emotional lability, psychosis, growth retardation, muscle atrophy, osteoporosis, aseptic necrosis of the hip, hirsutism, weight gain, cushingoid appearance, pseudotumor cerebri
Ocular: posterior subcapsular cataract (PSC), elevated IOP, delayed wound healing / corneal re-epithelialization, secondary infections (e.g. HSV, fungal)

IOP-elevating potential

dexamethasone > prednisolone > fluorometholone  > hydrocortisone > tetrahydrotriamcinolone > medrysone (after 6 weeks of dexamethasone therapy, 42% have IOP >20 mmHg; 6% have IOP >31)

Steroids with less IOP-elevating potential

rimexolone (Vexol), loteprednol (Lotemax, Alrex)

Antiallergy Medications

Antihistamines / Vasoconstrictors (over-the-counter)

Naphazoline hydrochloride/pheniramine maleate

(OcuHist, Opcon-A, Naphcon-A), naphazoline hydrochloride / antazoline phosphate (Vasocon-A): vasoconstrictor naphazoline temporarily removes redness, but can cause rebound redness with chronic use

Mast Cell Stabilizer

Cromolyn (cromoglicate; Crolom; Opticrom)

reduces permeability of mast cell plasma membrane, preventing release of histamine; reduces phosphodiesterase activity (facilitator of mast cell degranulation); inhibits activation of neutrophils, monocytes, and eosinophils; does not interfere with binding of antigen to previously sensitized cells; no antihistamine activity therefore useful for chronic allergies, not for acute symptomatic relief

Mast Cell Stabilizer + Eosinophil Suppressor

Lodoxamide (Alomide)

2500 times more potent than cromolyn; also inhibits eosinophil activation

H1-Blockers (Antihistamines)

Levocabastine (Livostin), emedastine (Emadine)

pure H1-specific receptor antagonists; bind to histamine receptors (inhibit itching and hyperemia)

H1-Blockers + Mast Cell Stabilizers

Nedocromil (Alocril), pemirolast (Alamast), ketotifen (Zaditor, Alaway), olopatadine (Patanol, Pataday), azelastine (Optivar), epinastine (Elestat), bepotastine (Bepreve), alcaftadine (Lastacaft)

stabilize mast cells and binds to H1 receptors (inhibits itching); binds to H2 receptors at low level (inhibits hyperemia)

Immunosuppressive Agents

Cytotoxic Antimetabolites

Inhibit purine ring biosynthesis

Methotrexate

folate analogue; inhibits folate metabolism; inhibits synthesis of deoxythymidine monophosphate nucleotide; inhibits enzyme dehydrofolate reductase; inhibits T-cell function

Adverse effects: leukopenia, thrombocytopenia, hepatotoxicity, lung or renal toxicity; teratogenic; periorbital edema, hyperemia

Azathioprine (Imuran)

purine analogue that inhibits purine synthesis

Cytotoxic Alkylating Agents

Create cross linkage between DNA strands, resulting in inhibition of transcription of mRNA and prevention of DNA synthesis

Chlorambucil (Leukeran)

interacts with 7-guanine of DNA, resulting in strand breakage or cross linkage

Adverse effects: sterility, bone marrow suppression

Cyclophosphamide (Cytoxan)

Adverse effects: hemorrhagic cystitis (oral > IV), renal transitional cell cancer, sterility, bone marrow suppression

Prevent hemorrhagic cystitis with high water intake (IV or oral)

Cytostatic Anti-Inflammatories

Steroids

(see earlier)

Immunomodulator

Cyclosporine

blocks production of interleukin-2 (IL-2) and IL-2 receptors, inhibits proliferation of lymphocytes, inhibits T-cell activation and recruitment, interferes with production of IL-2 by T cells, prevents formation of IL-2 receptors by T cells; natural product of fungi

Indications:

TOPICAL: necrotizing scleritis, Sjögren’s syndrome / dry eye syndrome, ligneous conjunctivitis, atopic keratoconjunctivitis
SYSTEMIC: Mooren’s ulcer, uveitis in Behçet’s or sympathetic ophthalmia, prevention of corneal transplant rejection; also used in ocular cicatricial pemphigoid (OCP) and thyroid-related ophthalmopathy

Adverse effects (systemic administration only): renal toxicity (renal tubular atrophy, interstitial fibrosis), hypertension, paresthesia, peripheral neuropathy, elevated erythrocyte sedimentation rate (ESR), hypertrichosis, hepatotoxicity, hyperuricemia

Others

Colchicine

inhibits leukocyte migration; prevents recurrence of Behçet’s

Oncolytic agents

Antineoplastics: bleomycin, dactinomycin, mitomycin (topically in glaucoma, corneal and pterygium surgery), daunorubicin (daunomycin), doxorubicin (hydroxydaunorubicin, Adriamycin)

ADVERSE EFFECTS: anemia, Stevens-Johnson syndrome (SJS), decreased vision, conjunctivitis, tearing

Alkylating agents: busulfan, carmustine, chlorambucil, cyclophosphamide

ADVERSE EFFECTS: rare

Vinca alkaloids: vincristine, vinblastine

ADVERSE EFFECTS: diplopia, nystagmus, ptosis, CN palsies

Antiestrogen: tamoxifen

ADVERSE EFFECTS: corneal opacities, retinopathy

Heavy metals: cisplatin

ADVERSE EFFECTS: papilledema, optic neuritis

Antimetabolites: methotrexate, 5-fluorouracil (5-FU; topically in glaucoma surgery)

ADVERSE EFFECTS: periorbital edema, conjunctival hyperemia, photophobia, tearing; corneal epithelial erosions

Anti-Infective Drugs

Antibiotics

Inhibitors of Intermediary Metabolism

Sulfonamides

static; sulfacetamide, sulfadiazine, sulfisoxizole, sulfamethoxazole; resistance is problem

Mechanism: inhibit folic acid synthesis
Spectrum: Gram-positives and Gram-negatives; also, toxoplasmosis, Chlamydia, Actinomyces, Pneumocystis
Indications: blepharitis, conjunctivitis, toxoplasmosis
Adverse effects: allergy (SJS syndrome), transient myopia
Pyrimethamine (Daraprim):

ADVERSE EFFECTS: bone marrow depression (anemia, thrombocytopenia; prevent with use of folinic acid [Leucovorin])

Dapsone:

INDICATIONS: OCP, leprosy
CONTRAINDICATIONS: patients allergic to sulfa or with G6PD deficiency

Trimethoprim

blocks next step in folate metabolism; often combined with sulfamethoxazole (Bactrim)

Spectrum: Gram-positives and Gram-negatives (Staphylococcus, Streptococcus, Serratia, Proteus, Haemophilus, Enterobacter, Escherichia coli, Klebsiella)
Indications: conjunctivitis

Inhibitors of Cell Wall Synthesis

β-Lactams (cidal)

Penicillins (PCN)

least toxic; variable protein binding

Adverse effects: allergy, diarrhea
Penicillin G:

SPECTRUM: Streptococcus and non–penicillinase-producing Staphylococcus, Neisseria, Treponema pallidum
INDICATIONS: syphilis

Isoxazolyl PCNs: penicillinase-resistant; methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin

SPECTRUM: extended to Staphylococcus aureus

Amino PCNs: broader spectrum; ampicillin, amoxicillin

SPECTRUM: Gram-positives (except staph), Neisseria, Haemophilus, Proteus, Shigella, Salmonella, Listeria, E. coli
INDICATIONS: preseptal cellulitis

Carboxy PCNs: antipseudomonal; carbenicillin, ticarcillin

SPECTRUM: extended to Gram-negatives (Pseudomonas and Enterobacteriaceae) and anaerobes (Bacteroides)

Ureido PCNs: antipseudomonal; piperacillin, mezlocillin, azlocillin

SPECTRUM: extended to Gram-negatives (Pseudomonas and Enterobacteriaceae) and anaerobes (Bacteroides)

β-Lactamase Inhibitors: combined with PCNs to increase spectrum of activity; clavulanate (amox / clavulanate = Augmentin), sulbactam (amp / sulbactam = Unasyn)

Cephalosporins

more resistant to β-lactamases; 20% cross react with PCN-allergic patients

1st generation: cefazolin (Ancef, Kefzol), cefalexin (cephalexin, Keflex), cephalothin (Keflin), cefaclor (Ceclor)

SPECTRUM: Gram-positives (staph, strep) and some Gram-negatives
INDICATIONS: cefazolin for keratitis, endophthalmitis

2nd generation: cefamandole (cephamandole, Mandol), cefonicid (Monocid), cefotetan (Cefotan), cefoxitin (Mefoxin), cefuroxime (Zinacef)

SPECTRUM: better Gram-negative but less Gram-positive, anaerobic (cefoxitin, cefotetan), Haemophilus influenzae and Neisseria (cefuroxime)

3rd generation: cefoperazone (Cefobid), cefotaxime (Claforan), ceftazidime (Tazidime), ceftizoxime (Cefizox), ceftriaxone (Rocephin), moxalactam (Moxam)

SPECTRUM: even better Gram-negative, Pseudomonas (ceftazidime)

Monobactams (aztreonam)

aerobic Gram-negatives

Carbapenems (imipenem)

β-lactamase resistant; very broad activity (almost all Gram-positives, Gram-negatives, and anaerobes); does not cover methicillin-resistant S. aureus (MRSA)

Non β-Lactams (cidal)

Polymyxin B

basic peptides; act as detergents and disrupt cell membrane

Spectrum: Gram-negatives (Haemophilus, Enterobacter, E. coli, Klebsiella, Pseudomonas)
Indications: conjunctivitis (combined with trimethoprim [Polytrim])

Bacitracin

polypeptides; often used in combination with neomycin or polymyxin to broaden activity

Spectrum: Gram-positives, Neisseria, Haemophilus, Actinomyces
Indications: blepharitis, conjunctivitis

Vancomycin

glycopeptide

Spectrum: very good for Gram-positives; staph (including MRSA), strep (including PCN- resistant strains), Bacillus, Propionibacterium acnes, Clostridium difficile
Indications: keratitis, endophthalmitis
Adverse effects: systemic administration is associated with ototoxicity and nephrotoxicity

Inhibitors of Protein Synthesis

Aminoglycosides

cidal; inhibit 30S ribosome; poor GI absorption

Gentamycin (gentamicin [better for Serratia]), tobramycin (Tobrax [better for Pseudomonas]), amikacin (best for Pseudomonas and Mycobacterium; less nephrotoxic than gent), streptomycin (TB, Streptococcus viridans), neomycin (Acanthamoeba; allergy common), paromomycin (Acanthamoeba), kanamycin
Spectrum: Gram-negative bacilli and some staph (gent and tobra are active against S aureus and Staphylococcus epidermidis)
Indications: conjunctivitis, keratitis, endophthalmitis
Adverse effects: systemic administration is associated with ototoxicity and nephrotoxicity, allergy

Spectinomycin

cidal; inhibits 30S ribosome; not an aminoglycoside; used for Neisseria

Tetracyclines

static; inhibit 30S ribosome; take on empty stomach (chelates calcium, antacids; iron, causing decreased absorption); use with caution in woman of childbearing age; also decreases efficacy of oral contraceptive medications

Tetracycline, doxycycline, minocycline, meclocycline
Spectrum: Gram-positive and Gram-negative, Chlamydia, Rickettsia, Mycoplasma
Indications: prophylaxis and treatment of ophthalmia neonatorum, Chlamydia; also rosacea, meibomianitis, scleral melting (due to anti-inflammatory and anticollagenolytic properties)
Adverse effects: GI upset, phototoxic dermatitis, tooth discoloration in children <8 years of age, teratogenic, nephrotoxicity and hepatotoxicity, decreased prothrombin activity (potentiates warfarin sodium [Coumadin])

Macrolides

static; inhibit 50S ribosome

Erythromycin, azithromycin (Zithromax), clarithromycin (Crixan, Biaxin)
Spectrum: Gram-positives and a few Gram-negatives, Chlamydia, Mycoplasma, Legionella
Indications: blepharitis, conjunctivitis, Chlamydia
Adverse effects: GI upset

Chloramphenicol

static; inhibits 50S ribosome

Spectrum: Gram-positives and Gram-negatives, anaerobes, Chlamydia, Rickettsia, Mycoplasma, spirochetes
Adverse effects: aplastic anemia and reversible bone marrow suppression

Clindamycin

static; inhibits 50S ribosome

Spectrum: Gram-positives and anaerobes, toxoplasmosis
Indications: toxoplasmosis
Adverse effects: may cause pseudomembranous colitis (due to overgrowth of C difficile; treat with oral vancomycin or metronidazole [Flagyl])

Others

Fluoroquinolones

cidal; analogues of nalidixic acid; inhibitors of genetic replication; inhibit DNA gyrase (topoisomerase II) and topoisomerase IV

2nd generation: ciprofloxacin (Ciloxan), ofloxacin (Ocuflox), norfloxacin (Chibroxin)
3rd generation: levofloxacin (Quixin, Iquix)
4th generation: gatifloxacin (Zymar, Zymaxid), moxifloxacin (Vigamox, Moxeza), besifloxacin (Besivance)
Spectrum: aerobic Gram-negatives and some Gram-positives (H. influenzae, Pseudomonas, Enterobacteriaceae, S aureus); also, Chlamydia, Rickettsia, Mycoplasma, and Mycobacterium. 4th generation agents have extended spectrum with enhanced activity against Gram-positives, fluoroquinolone-resistant organisms, and atypical mycobacteria
Indications: conjunctivitis, keratitis, surgical prophylaxis; prophylaxis in penetrating trauma (oral cipro achieves high levels in vitreous)
Adverse effects: GI upset; cartilage damage in children

Anti-TB Agents

Isoniazid

cidal; inhibits cell wall synthesis of mycobacteria

Adverse effects: hepatotoxicity, vitamin B6 deficiency

Rifampin

inhibits RNA polymerase of mycobacteria

Adverse effects: hepatotoxicity, turns body fluids orange-red

Pyrazinamide

unknown mechanism; analogue of nicotinamide

Adverse effects: hepatotoxicity, gout

Ethambutol

chelates metals

Adverse effects: optic neuropathy

Fumagillin

treatment of microsporidia keratoconjunctivitis

Antivirals

Mechanism

static; inhibit genetic replication; most are nucleotide analogues

Topical

treatment of HSV keratitis

Idoxuridine (IDU, Stoxil): can cause follicular conjunctivitis, corneal epitheliopathy, punctal stenosis
Vidarabine (Vira-A): adverse effects less severe than IDU
Trifluorothymidine (Viroptic): inhibits thymidylate synthetase (virus-specific enzyme)
Ganciclovir (Zirgan): guanosine analogue; activated only by thymidine kinase (virus-specific enzyme) and selectively interferes with viral DNA replication. Similar efficacy as topical acyclovir (not available in US); more effective than Viroptic, and less toxic to cornea; best tolerated

Systemic

Acyclovir (acycloguanosine, Zovirax; guanosine analogue; activated only by thymidine kinase (virus-specific enzyme)), valacyclovir (Valtrex; prodrug of acyclovir), penciclovir, famciclovir (Famvir; prodrug of peniclovir)

INDICATIONS: treatment of HSV and varicella zoster virus (VZV)
ADVERSE EFFECTS: may cause GI upset; high doses can cause nephrotoxicity and neurotoxicity

Ganciclovir (Cytovene): treatment of CMV

ADVERSE EFFECTS: bone marrow suppression (cannot use with azidothymidine [AZT])

Foscamet (Foscavir): treatment of CMV

ADVERSE EFFECTS: nephrotoxicitiy, less myelosuppression, electrolyte abnormalities

Antifungals

Mechanism

disrupt cell membranes

Classification

Yeasts: form pseudohyphae; Candida, Cryptococcus
Molds: filamentous; form hyphae

SEPTATE: Fusarium, Aspergillus, Penicillium, Curvularia, Paecilomyces, Phialophora
NONSEPTATE: Phycomycetes, Rhizopus, Mucor

Dimorphic fungi: grow as yeast or mold; Histoplasma, Blastomyces, Coccidioides

Polyenes

bind to ergosterol; damages fungal membranes

Amphotericin B: systemic

SPECTRUM: broad (especially Candida; also, Cryptococcus, Blastomyces, Histoplasma, Coccidioides, mucormycosis; not as good for Aspergillus, Fusarium)
INDICATIONS: keratitis, endopthalmitis (intravenous drug abuse [IVDA], immunosuppression, hyperalimentation)
ADVERSE EFFECTS: fever, hypotension, headache, phlebitis, GI upset, nephrotoxicity, anemia

Natamycin (pimaricin): topical only; too toxic for IV use, toxic to retina intravitreally

SPECTRUM: filamentous fungi (especially Aspergillus, Fusarium), not as good for Candida; not effective against Mucor (nonseptate, branching hyphae)
INDICATIONS: keratitis (removal of epithelium improves penetration)

Azoles

inhibit ergosterol synthesis; second-line agents to amphotericin; also used for Acanthamoeba

Adverse effects: GI upset, headache, rash
Imidazoles:

MICONAZOLE (topical, IV, intravitreal): broad spectrum (filamentous fungi and yeast)

ADVERSE EFFECTS: may cause corneal erosions, anemia

KETOCONAZOLE (topical, oral): broad spectrum

ADVERSE EFFECTS: reversible hepatotoxicity

CLOTRIMAZOLE (oral): good for Aspergillus

ADVERSE EFFECTS: hepatotoxicity

Triazoles: safer

ITRACONAZOLE (oral): broad spectrum
FLUCONAZOLE (oral): broad spectrum

Antimetabolites

most fungi are resistant, except Cryptococcus and some Candida

Flucytosine: converted to 5-FU, disrupts DNA synthesis

ADVERSE EFFECTS: myelosuppression, nausea, vomiting, diarrhea

Antiamoebics

Mechanism

cidal (amoebae and cysts); cationic surface-active properties; interfere with cell membranes and inhibit enzymes

Indications

topical for Acanthamoeba keratitis

Biguanides

polyhexamethylene biguanide (PHMB), chlorhexidine; first-line agents, less corneal toxicity

Diamidines

propamidine (Brolene), hexamidine; synergistic effect with biguanides, corneal toxicity

Antihelmintics

Mebendazole, thiabendazole, albendazole

inhibit glucose uptake and microtubule synthesis

Adverse effects: GI upset

Pyrantel pamoate

neuromuscular junction blocker

Adverse effects: nausea, vomiting, headache, rash

Diethylcarbamazine

enables phagocytosis of microfilaria

Ivermectin

increases gamma-aminobutyric acid (GABA) release paralyzing microfilaria

Adverse effects: fever, headache, rash

Praziquantel

causes calcium loss, paralyzing worm

Adverse effects: GI upset, fever

Miscellaneous

Aminocaproic acid (Amicar)

synthetic amino acid similar to lysine

Mechanism: antifibrinolytic; stabilizes blood clot, delays lysis, decreases secondary hemorrhages
Indications: hyphema
Contraindications: hypercoagulable states, pregnancy, renal disease, liver disease, patients at risk for myocardial infarction (MI), pulmonary embolism, cerebrovascular accident (CVA)
Adverse effects: nausea, vomiting, diarrhea, hypotension, rash

Botulinum toxin (Botox)

neurotoxin that blocks release of acetylcholine from nerve terminal; paralyzes muscle (1–3 months)

Indications: blepharospasm, hemifacial spasm, strabismus
Adverse effects: ptosis, diplopia, exposure keratopathy

Fluorescein dye

IV for fluorescein angiography

Adverse effects: nausea, vomiting, dizziness, headache, dyspnea, hypotension, skin necrosis, phototoxic reactions, anaphylaxis

Indocyanine green (ICG) dye

IV for ICG angiography; contraindicated in patients allergic to iodine

Adverse effects: GI upset, hypotension, urticaria, anaphylaxis

Ocular Toxicology (Table 2-4)

Anticholinergics (atropine, scopolamine, Donnatal)

toxicity causes flushing, agitation, tachycardia, somnolence, dry mouth, dry eye, mydriasis, cycloplegia, blurry vision, angle closure; increased sensitivity in albinism, Down syndrome, and neonates

Table 2-4 Ocular toxicology

Ocular structure Effect Drug
Extraocular muscles Nystagmus, diplopia Anesthetics, sedatives, anticonvulsants, propranolol, antibiotics, phenothiazines, pentobarbital, carbamazepine, MAO inhibitors
Lid Edema Chloral hydrate
  Discoloration Phenothiazines
  Ptosis Guanethidine, propranolol, barbiturates
Conjunctiva Hyperemia Reserpine, methyldopa
  Allergy Antibiotics, sulfonamides, atropine, antivirals, glaucoma medications
  Discoloration Phenothiazines, chlorambucil, phenylbutazone
Cornea Keratitis Antibiotics, phenylbutazone, barbiturates, chlorambucil, steroids
  Deposits Chloroquine, amiodarone, tamoxifen, indomethacin, gold
  Pigmentation Vitamin D
Increased IOP Open angle Anticholinergics, caffeine, steroids
  Narrow angle Anticholinergics, antihistamines, phenothiazines, tricyclic antidepressants, haloperidol, sulfonamides (Topamax)
Lens Opacities / cataract Steroids, phenothiazines, ibuprofen, allopurinol, long-acting miotics
  Myopia Sulfonamides, tetracycline, prochlorperazine, autonomic antagonists, duloxetine (Cymbalta)
Retina Edema Chloramphenicol, indomethacin, tamoxifen, carmustine
  Hemorrhage Anticoagulants, ethambutol
  Vascular damage Oral contraceptives, oxygen, aminoglycosides, talc, carmustine, interferon
  Pigmentary degeneration Phenothiazines, indomethacin, nalidixic acid, ethambutol, isotretinoin, chloroquine, hydroxychloroquine
Optic nerve Neuropathy Ethambutol, isoniazid, sulfonamides, digitalis, imipramine, streptomycin, busulfan, cisplatin, vincristine, chloramphenicol, disulfiram
  Papilledema Steroids, vitamin A, tetracycline, phenylbutazone, amiodarone, nalidixic acid, isotretinoin

Antihistamines

dry eye, mydriasis, cycloplegia, blurry vision, angle closure

Antibiotics

Aminoglycosides: intraocular administration may cause macular infarction (intravenous fluorescein angiography [IVFA]: pruned tree appearance of retinal vasculature)
Chloramphenicol: optic neuropathy; peripheral neuritis can precede visual complaints by 1–2 weeks
Penicillin and tetracycline: pseudotumor
Sulfonamides: conjunctivitis, transient myopia, angle closure, optic neuropathy
Isoniazid, rifampin, ethambutol: optic neuropathy

Antimalarials (chloroquine / hydroxychloroquine)

cornea verticillata, fine pigmentary macular changes (bull’s-eye maculopathy); patients may complain of halos around lights; visual acuity usually unchanged; dose related

Quinine

overdose can result in acute visual loss (to no light perception [NLP]), tinnitus, weakness, confusion

Barbiturates (phenobarbital)

nystagmus, diplopia, ptosis, conjunctivitis

Phenothiazines (chlorpromazine, thioridazine)

pigmentary retinopathy, corneal deposits, cataracts, angle closure

Tricyclic antidepressants

mydriasis, cycloplegia, dry eye, angle closure

Dilantin

diplopia, nystagmus, papilledema

Gold

deposits in inferior corneal stroma and anterior lens capsule (chrysiasis)

Talc

multiple tiny yellow-white glistening particles scattered through posterior pole with macular edema, venous engorgement, hemorrhages, arterial occlusion, retinal nonperfusion, and peripheral neovascularization (NV)

Amiodarone (Cordarone)

cornea verticillata, occasionally anterior subcapsular opacities

Digoxin

changes in color vision (xanthopsia [yellow vision]), optic neuropathy

Diuretics (hydrochlorothiazide)

xanthopsia, transient myopia, angle closure

Phosphodiesterase 5 inhibitors (Viagra, Cialis, Levitra)

decreased retinal blood flow by up to −30%; altered color and light perception; possibly ischemic optic neuropathy

Carmustine

retinal infarction, RPE changes, arterial occlusions, hemorrhages, macular edema, glaucoma, optic neuritis, INO

Narcotics (opiates)

miosis

NSAIDs (indomethacin)

corneal deposits, diplopia, optic neuritis, pigmentary macular changes; may have changes in vision, dark adaptation, and visual fields

Corticosteroids

posterior subcapsular cataracts, increased IOP, delayed wound healing, secondary infections, pseudotumor cerebri

Oral contraceptives

dry eye, vascular occlusions, perivasculitis, optic neuritis, pseudotumor cerebri

Tamoxifen

deposits in cornea and macula, may have macular edema

Isotretinoin

impairment of dark adaptation

Interferon

reversible vaso-occlusive disease

Review Questions (Answers start on page 357)

1 Which antibiotic results in the highest intravitreal concentration when administered orally?

a ciprofloxacin
b penicillin
c bactrim
d clindamycin

2 Which anesthetic agent would most interfere with an intraocular gas bubble?

a isoflurane
b propofol
c sodium thiopental
d nitrous oxide

3 Which of the following is not an adverse effect of CAIs?

a death
b paresthesias
c iris cysts
d Stevens-Johnson syndrome

4 Which β-blocker has the least effect on β2 receptors?

a levobunolol
b betaxolol
c carteolol
d timolol

5 Which drug has the least effect on uveoscleral outflow?

a atropine
b latanoprost
c pilocarpine
d dorzolamide

6 Which enzyme is inhibited by steroids?

a cyclooxygenase
b phospholipase A2
c lipoxygenase
d endoperoxidase

7 Which of the following steroid formulations has the best corneal penetrability?

a prednisolone acetate
b dexamethasone phosphate
c prednisolone phosphate
d dexamethasone alcohol

8 Adverse effects of foscarnet include all of the following except

a seizures
b infertility
c electrolyte abnormalities
d myelosuppression

9 Which glaucoma medication is not effective when IOP is >60 mmHg?

a acetazolamide
b timolol
c pilocarpine
d apraclonidine

10 Which medicine is not associated with OCP-like conjunctival shrinkage?

a phospholine iodide
b pilocarpine
c epinephrine
d timolol

11 Which β-blocker is β1-selective?

a carteolol
b timolol
c betaxolol
d levobunolol

12 The most appropriate treatment for neurosyphilis is

a penicillin G
b erythromycin
c penicillin VK
d tetracycline

13 The correct mechanism of action of botulinum toxin is

a it prevents release of acetylcholine
b it blocks acetylcholine receptors
c it inhibits reuptake of acetylcholine
d it is an acetylcholinesterase inhibitor

14 Fluoroquinolones are least effective against

a Klebsiella
b H. influenzae
c anaerobic cocci
d Serratia

15 Hydroxychloroquine toxicity depends most on

a patient age
b cumulative dose
c patient race
d daily dose

16 Calculate the amount of cocaine in 2 mL of a 4% solution

a 2 mg
b 8 mg
c 20 mg
d 80 mg

17 NSAIDs block the formation of all of the following substances except

a thromboxane
b leukotrienes
c prostaglandins
d prostacyclin

18 Systemic effects of steroids may include all of the following except

a papilledema
b hirsutism
c potassium depletion
d renal tubular acidosis

19 Which drug does not produce decreased tear production?

a pilocarpine
b diphenhydramine (Benadryl)
c timolol
d atropine

20 Natamycin is a

a diamine
b imidazole
c polyene
d aminoglycoside

21 Which glaucoma medicine does not decrease aqueous production?

a aproclonidine
b pilocarpine
c acetazolamide
d timolol

22 β-blockers may cause all of the following except

a constipation
b impotence
c alopecia
d depression

23 Idoxuridine may cause all of the following except

a filamentary keratitis
b punctal stenosis
c corneal hypesthesia
d nonhealing epithelial erosion

24 Which of the following antifungal agents has the broadest spectrum against yeast-like fungi?

a miconazole
b natamycin
c ketoconazole
d amphotericin

25 All of the following medications are combination antihistamine and mast cell stabilizers except

a Alomide
b Zaditor
c Optivar
d Patanol

26 The antidote for atropine toxicity is

a endrophonium
b physostigmine
c carbacholine
d pilocarpine

27 Which of the following agents is contraindicated for ruptured globe repair?

a gallamine
b halothane
c pancuronium
d succinylcholine

28 The duration of action of 1 drop of proparacaine is

a 5 minutes
b 20 minutes
c 45 minutes
d 1 hour

29 Which of the following medications is not commercially available as a topical formulation?

a ganciclovir
b azithromycin
c cyclosporine
d vancomycin

30 All of the following are complications of carbonic anhydrase inhibitors except

a hypokalemia
b aplastic anemia
c metabolic alkalosis
d kidney stones

31 Topiramate is associated with

a open-angle glaucoma
b normal tension glaucoma
c angle-closure glaucoma with pupillary block
d angle-closure glaucoma without pupillary block

32 A patient with ocular hypertension and an allergy to sulfonamides should not be treated with

a bimatoprost
b dorzolamide
c timolol
d brimonidine

33 Infectious keratitis due to Candida albicans is best treated with topical

a amphotericin B
b natamycin
c fluconazole
d clotrimazole

34 Which of the following oral agents should be used to treat a patient with ocular cicatricial pemphigoid?

a pyrazinamide
b 5-fluorouracil
c cyclophosphamide
d flucytosine

35 The glaucoma medication contraindicated in infants is

a timolol
b brimonidine
c latanoprost
d dorzolamide

36 Which systemic antibiotic is used to treat Chlamydia during pregnancy?

a doxycycline
b ceftriaxone
c penicillin
d erythromycin

37 The local anesthetic with the longest duration of action is

a mepivacaine
b procaine
c bupivacaine
d lidocaine

38 A 33-year-old man has had follicular conjunctivitis with a watery discharge for 5 weeks. Elementary bodies are present on a conjunctival smear, therefore, the most appropriate treatment is

a oral azithromycin
b oral acyclovir
c topical cromolyn
d topical prednisolone

39 The most appropriate treatment for Fusarium keratitis is topical

a tobramycin
b pimaricin
c chloramphenicol
d ciprofloxacin

40 All of the following are associated with vitamin A toxicity except

a CN 6 palsy
b retinal hemorrhages
c papilledema
d band keratopathy

Suggested Readings

Doughty M. Ocular Pharmacology and Therapeutics: A Primary Care Guide. Philadelphia: Butterworth-Heinemann; 2001.

Fraunfelder FT, Fraunfelder FW, Randall JA. Drug-Induced Ocular Side Effects, 5th edn. Philadelphia: Butterworth-Heinemann; 2001.

Fraunfelder FT, Roy FH. Current Ocular Therapy, 5th edn. Philadelphia: WB Saunders; 2000.

Grant WM, Schuman JS. Toxicology of the Eye, 4th edn. Springfield, IL: Charles C. Thomas; 1993.

Greenbaum S. Ocular Anesthesia. Philadelphia: WB Saunders; 1997.

2012 Physicians’ Desk Reference for Ophthalmic Medicines. Montvale, NJ: Medical Economics, 2012.

Zimmerman TJ. Textbook of Ocular Pharmacology. Philadelphia: Lippincott-Raven; 1997.

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