IMMUNOSUPPRESSIVES: NONCYTOTOXIC

thrombocytopenia) and cause nausea, sterility (thus, bank sperm or eggs prior to use), hemorrhagic cystitis, increased risk of infection and malignancy. Has slow onset. Check CBC weekly for Þrst month, then every other week for 2 months, then monthly, and check liver function tests occasionally.

Immunosuppressives: Noncytotoxic

LEFLUNOMIDE (ARAVA) Decreases T cells; used in RA and chronic uveitides.

MYCOPHENALATE MOFETIL (CellCept) Decreases T and B cells.

COLCHICINE Decreased PMN response; inhibits leukocyte migration.

CYCLOSPORINE (Neoral) 2.5Ð5.0 mg/kg/day in two doses for many diseases, such as uveitis, WegenerÕs granulomatosis, and corneal melts, to delay rejection in high-risk corneal grafts (91% success if cyclosporine begun 2 days before surgery), severe vernal or ligneous keratoconjunctivitis, and RA. Topical cyclosporine (Restasis) is available for inßammatory dry eye syndrome.

Action: affects cell-mediated (T-cell) immunosuppression. Binds intracellular receptor (cyclophilin), like FK-506, altering gene regulation and decreasing many modulators, especially interleukin-2. Metabolized by cytochrome P-450.

Side effects: nephrotoxic; may cause hypertension and infection.

DAPSONE 25 mg bid; adjust to clinical response and to keep the hematocrit about 30%. Used for immune complex disease and diseases mediated by PMN (OCP has a 70% response). May cause hemolytic anemia, especially with G-6-PD deÞciency; avoid in patients with sulfa allergy.

ETANERCEPT (Enbrel) Soluble tumor necrosis factor (TNF)-alpha receptor, which decreases the levels of TNF.

FK-506 Like cyclosporine but more potent; inhibits T-cell function. Cytoplasmic receptor inhibits genes for interleukin-2, -3, and -4, interferon gamma, TNF-alpha, granulocyte colony stimulating factor, and c-myc gene that is normally responsible for early T-cell activation.

INFLIXIMAB (Remicade) Decreased TNF (bound by monoclonal AB), may be effective in chronic uveitis.

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390 MEDICATIONS

Miotics: Cholinergic, Indirect Reversible

(See also Glaucoma: Miotics)

EDROPHONIUM (Tensilon) Reversible indirect nicotinic (parasympathomimetic) agonist that competitively inhibits acetylcholinesterase by binding to the active site of ganglia and skeletal muscle. Used in diagnosis of myasthenia gravis with 2 mg IV rapidly injected followed in 1 minute by 8 mg if Þrst dose had no effect. May have muscarinic side effects (cholinergic crisis: sweating, nausea, vomiting, salivation, and fever) unless atropine 0.5 mg is coadministered.

NEOSTIGMINE (Prostigmin) Reversibly carbamylates acetylcholinesterase. Used to treat myasthenia gravis.

PHYSOSTIGMINE (Eserine) Parasympathomimetic indirect-acting cholinesterase inhibitor that reversibly carbamylates acetylcholinesterase. Used to treat atropine overdose 0.25 mg SQ every 15 minutes up to 4 mg. Also is a louse respiratory poison.

Mydriatics and Cycloplegics: Anticholinergic

ATROPINE (Isopto Atropine) 1 drop before procedure or qd, or ointment qd (solution 0.5, 1.0%, ointment 1.0%). Muscarinic antagonist. Used for cycloplegia, lasts 5 to 10 days; mydriasis lasts 7 to 14 days. Also used to treat ciliary block (malignant) glaucoma and to block oculocardiac bradycardia during surgery with 1 gtt of 1% solution ¼ 0.5 mg (same as ACLS for bradycardia). Treat atropine overdose with physostigmine 0.25 mg every 15 minutes until symptoms resolve. See Table 10Ð5 for anticholinergic precautions.

CYCLOPENTOLATE (AK-Pentolate, Cyclogyl, Pentolair) 1 drop in 1Ð2 doses before procedure or examination (solution 0.5, 1.0, 2.0%]. Cycloplegia lasts 6 to 24 hours; mydriasis lasts up to l day.

TABLE 10–5

Anticholinergic Precautions

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HOMATROPINE (Isopto Homatropine) 1 drop before procedure or bidÐtid (solution 2.0, 5.0%). Cycloplegia and mydriasis can persist 1 to 3 days.

TROPICAMIDE (Mydriacyl) 1 drop before procedure (solution 0.5, 1.0%). Cycloplegia and mydriasis effects last up to 6 hours.

Mydriatics: Adrenergic

PHENYLEPHRINE (Neo-Synephrine, Mydfrin, Relief) 1Ð2 drops before procedure or examination (solution 0.12, 2.5, 10.0%). No cycloplegic effect; mydriasis may last up to 5 hours.

Neurologic Medications

BOTULINUM TOXIN TYPE A (Botox) 2.5Ð10.0 units/10 mL (100 units/ bottle). Lyophilized (freeze dried) with human albumin (may cause antibodies to develop over years of use, causing increased resistance to Botox effects). Unopened preparation is stable for 2 years; keep refrigerated, with no light exposure. Unstable and should be used in about 2 hours once reconstituted with normal saline.

Action: binds presynaptic nerve terminals to block acetylcholine release. Neurologic toxins A through G serotypes, related to tetanus toxin. Activated by proteolytic cleavage by bacteria in human gut. Heavy chain responsible for cell entry; light chain gives toxicity. Binds preferentially at cholinergic nerve (i.e., striated muscle) membrane, internalizes (heavy chain), then intracellular poisoning by light chain by possible enzyme effect. Irreversible, but symptoms return due to new nerve growth (perhaps small effect from deactivation).

COCAINE Blocks norepinephrine reuptake and causes pupillary dilation normally, but not in HornerÕs syndrome.

HYDROXYAMPHETAMINE (Paredrine) Stimulates release of norepinephrine and thus causes pupillary dilation to conÞrm a third-order neuron lesion in HornerÕs syndrome.

LIDOCAINE Amide-type anesthetic hepatically inactivated, longer duration.

NEUROMUSCULAR BLOCKING AGENTS (NICOTINIC PARASYMPATHETIC ANTAGONISTS) Nondepolarizing (curare-like gallamine and pancuronium) or depolarizing (succinylcholine and decamethonium), which causes initial muscle contraction. Generally avoid depolarizing agents during

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392 MEDICATIONS

general anesthesia for open globe repair cases to avoid EOM contraction. Anticholinergic side effects (like mydriatics): ßushing, fever, tachycardia, and delirium

PROPARACAINE (Ophthaine, Ophthetic) 1Ð2 drops before procedure (solution 0.5%). Do not prescribe for unsupervised use, as corneal toxicity may occur with repeated use. Agent of choice for obtaining corneal cultures.

TETRACAINE (Pontocaine) 1Ð2 drops or ½Ð1 inch ribbon of ointment before procedure (solution 0.5%, ointment 0.5%]. Opens ion channels to prevent neuroconduction. Ester-type local anesthetic inactivated by serum cholinesterase (increased risk of systemic toxicity with cholinesterase deÞciency as with phospholine iodide, pesticide, exposure, and some congenital conditions). Increased hypersensitivity reaction versus amidetype. Do not prescribe for unsupervised use, as corneal toxicity may occur with repeated use. Disrupts intercellular tight junctions with increased epithelium permeability to topical agents.

TEGRETOL 200 mg bidÐtid. Used for seizures, also for chronic pain syndromes. May cause drowiness, nausea, vomiting, and aplastic anemia.

Other Agents

ARTIFICIAL TEARS (Tears Naturale, Hypotears, Lacrilube) 1Ð2 drops tidÐ qid prn. Lubrication ointment: Refresh PM Paralube.

BENZALKONIUM CHLORIDE Quaternary ammonium preservative in about 60% of ophthalmic solutions. Antimicrobial that also increases drug penetration by causing mild corneal epithelial disruption.

DAPIPRAZOLE (Rev-Eyes) AND THYMOXAMINE Alpha-blockers that compete with norepinephrine at alpha-1 receptors on the iris dilator muscle and thus reverse phenylephrine mydriasis with incomplete effect on cholinergic (tropicamine, etc.) mydriasis. Produces miosis without effect on accomodation or AC depth.

HYPERBARIC OXYGEN Used to treat arterial gas embolism, chronic CME, rhino-cerebro-orbital mucormycosis, radiation optic neuropathy, and potential reoxygenation following CRAO. Side effects include myopic shift, CWS, and cataract.

SERUM-DERIVED TEARS Two drops every 2 hours used for severe ocular surface disease and after limbal stem cell transplant. Prepare from eight vials whole blood, centrifuge, pipet off the top serum that contains growth

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factors, and put in bottles. Freeze whatever will not be used within the next couple of days.

THIMEROSAL Organic mercurial preservative found in about 15% of ophthalmic solutions. Allergic sensitivity common.

TISSUE PLASMINOGEN ACTIVATOR (TPA) 12.5 mg/0.1 mL, inject 0.05 mL in the AC or vitreous for Þbrin dissolution.

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