CHAPTER 10

Medications

General

PHARMACOKINETICS Average drop ¼ 50 mL; however, the tear lake holds only 10 mL. Tear turnover is 16% per minute; thus, approximately 50% remains at 4 minutes. Most drops act by Þrst-order kinetics: a constant fraction is absorbed and eliminated (e.g., 100 ! 50 ! 25 ! 12.5, etc.).

DRUG PERMEABILITY Penetration into the eye is dependent on

Lipid solubility: characterized by the partition coefÞcient; a higher coefÞcient indicates more lipid solubility and thus greater permeability. Partition coefÞcient ¼ (drug in lipid phase) (drug in aqueous phase).

Corneal permeability: cornea structure is soluble to fat (epithelial layer), then water (stroma), then fat (endothelial layer). Thus, the more lipid that is soluble, the greater the permeability, up to a point. Surfactants and increased concentration of the drug (up to the point of increased tearing) increase corneal permeability.

Ionization status: Henderson-Hasselbach equation demonstrates that a substance with higher pH is more nonionized or uncharged and is more lipid soluble.

Antibacterials: Aminoglycosides

PROPERTIES Bind 30S bacterial ribosomal subunit, irreversible and thus bactericidal. Active against many gram-negative and staphylococcal organisms.

AMIKACIN 20Ð50 mg/mL fortiÞed topical, 0.4 mg intravitreal.

GENTAMICIN (Garamycin) 1 drop every 4 hours or ½ inch ribbon of ointment bidÐtid (solution 0.3%, ointment 0.3%).

NEOMYCIN SigniÞcant topical hypersensitivity.

TOBRAMYCIN (Tobrex) 1 drop every l to 4 hours or ½ inch ribbon of ointment every 3 to 4 hours or bidÐtid (solution 0.3%, ointment 0.3%), or

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374 MEDICATIONS

fortiÞed topical 14 mg/mL solution, 0.1Ð0.2 mg intravitreal. Slightly more active against Pseudomonas than gentamicin.

Antibacterials: Cephalosporins and Penicillins

PROPERTIES Beta-lactam antibiotics that inhibit bacterial transpeptization enzymes necessary for cell wall synthesis; bactericidal.

CEFAZOLIN (Ancef) 50 mg/mL fortiÞed topical solution or 100 mg subconjunctival injection. First-generation cephalosporin that is active against most gram-positive cocci.

CEFTAZIDIME 2.25 mg intravitreal. Third-generation cephalosporin with greater activity against gram-negative organisms, including Pseudomonas.

PENICILLIN G 200,000 units/mL fortiÞed topical, 1 million units subconjunctival, 2 million to 18 million units intravenous every 4 to 6 hours. Active against most streptococci, gonococci, and anaerobes. Most staphylococci produce beta-lactamase and are resistant. Hypersensitivity in 3 to 10%.

Antibacterials: Fluoroquinolones

PROPERTIES Inhibits bacterial DNA gyrase, thus interfering with DNA replication; bactericidal and inhibitory. Active against most gram-negative organisms, staphylococci, and many streptococci. Avoid ßuoroquinolones in children, as they may inhibit cartilage and growth plate development.

GATIFLOXACIN (Zymar) 1 gtt every 1 to 6 hours (solution 0.3%). Fourthgeneration ßuoroquinolone.

LEVOFLOXACIN (Levoquin, Quixin) 1 gtt every l to 6 hours (solution 0.5%). Third-generation ßuoroquinolone.

MOXIFLOXACIN (Vigamox) 1 gtt every 1 to 6 hours (solution 0.5%). Fourth-generation ßuoroquinolone.

NORFLOXACIN (Chibroxin) 1 drop every 2 to 6 hours (solution 0.3%).

OFLOXACIN (Ocuflox) 1 drop every l to 6 hours (solution 0.3%).

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Antibacterials: Inhibitors of Cell Wall Function

BACITRACIN Ointment every 3 to 4 hours or bidÐqid. Polypeptide that inhibits early steps in peptidoglycan synthesis. Treats Neisseria, H. flu, Actinomyces, and most gram-positive bacteria.

POLYMYXIN B AND GRAMICIDIN Detergent-like action to increase cytoplasmic membrane permeability. Polymyxin B is mixture of basic peptides that dissolve cell membranes with greatest activity against gram-negative bacteria.

VANCOMYCIN FortiÞed topical 50 mg/mL, 1 mg in 0.1 mL intravitreal, 2 g every 6 to 12 hours intravenous. Inhibits early steps in peptidoglycan synthesis. High level of activity against most gram-positive cocci and bacilli.

Antibacterials: Inhibitors of Nucleic Acid Synthesis

PYRIMETHAMINE Inhibits conversion of dihydrofolic acid into tetrahydrofolic acid, but also more active against host cell and thus more toxic than trimethoprim; bacteriostatic.

RIFAMPIN Binds to bacterial DNA-dependent RNA polymerase.

SULFACETAMIDE (Sulamyd, Bleph-10, Sulf-10, Isopto Cetamide) 1 drop every 2 to 6 hours (solution 10, 15, 30%) or ½ inch ribbon of ointment every 3 to 8 hours (ointment 10%). Bacteriostatic inhibition of folic acid synthesis by competing with PABA for conversion into dihydrofolic acid. Active against many gram-positive, gram-negative, Chlamydia, Actinomyes, and Nocardia organisms.

TRIMETHOPRIM Inhibits conversion of dihydrofolic acid into tetrahydrofolic acid; bacteriostatic.

Antibacterials: Inhibitors of Protein Synthesis

CHLORAMPHENICOL (Chloroptic) 1 drop every 4 to 6 hours (solution 0.5%), or small amount of ointment up to every 3 hours (ointment 1%), or make 5 mg/mL fortiÞed topical drops from 100 mg subconjunctival solution. Binds to the 50S ribosomal subunit; bacteriostatic. Active against many gram-positive, gram-negative, and anaerobic organisms. Idiosyncratic fatal aplastic anemia occurs with similar frequency to that of fatal anaphylaxis following penicillin therapy (about 1 in 50,000); also, can cause doserelated bone marrow suppression.

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376 MEDICATIONS

CLINDAMYCIN 50 mg/mL fortiÞed topical. Binds the 50S subunit of bacterial ribosomes.

ERYTHROMYCIN (Ilotycin, AK-Mycin) ½ inch ribbon of ointment every 3 to 4 hours or bidÐqid (ointment 0.5%). Binds ribosomal 50S subunit. Similar activity to penicillin against gram-positive bacteria; also active against

Hemophilus, Neisseria, and Chlamydia.

TETRACYCLINE Binds 30S bacterial ribosomal subunit like aminoglycosides but has reversible binding and is thus bacteriostatic. Active against many gram-positive, gram-negative, Chlamydia, Actinomyes, and Mycobacterium organisms.

Antibacterials: Combinations

NEOSPORIN (neomycin þ bacitracin þ polymyxin B) 1 drop every l to 6 hours for 7 to 10 days or ½ inch ribbon of ointment every 3 to 4 hours for 7 to 10 days.

TOBRADEX (tobramycin þ dexamethasone) 1 drop every 2 to 6 hours or

½ inch ribbon of ointment bidÐqid.

Antifungal Agents

AMPHOTERICIN B (AMB) 0.15% topical every 30 to 60 minutes initially for fungal corneal ulcers (mix AMB powder with sterile water), 5Ð10 mg intravitreal or 1 mg/kg/day intravenous for fungal endophthalmitis (limited by renal toxicity). Highly effective polyene antibiotic against a broad range of fungi.

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