III. TREATMENT OF BACTERIAL INFECTIONS There are five main categories of antibiotics used in the treatment of bacterial infections.

These categories are based on how the drugs affect the target organism.

Antibiotic Drugs
Category Mode of Action 1 Inhibit bacterial cell wall formation Disrupt the bacterial cytoplasmic membrane Inhibit bacterial folic acid synthesis Inhibit bacterial protein synthesis Inhibit bacterial DNA synthesis Example Oral Drugs Penicillins, Cephalosporins, Vancomycin There are no oral antibiotics in this category Sulfonamides, Trimethoprim, Pyrimethamine Erythromycin, Clarithromycin, Azithromycin, Tetracycline, Doxycycline, Clindamycin, Chloramphenicol Fluoroquinolones (e.g., Norfloxacin, Ofloxacin, Ciprofloxacin)

Antibiotics That Inhibit Bacterial Cell Wall Formation

Augmentin (amoxicillin with clavulanic acid)

Augmentin 1. Useful treatment for ocular infections such as preseptal cellulitis, canaliculitis. 4. Clavulanic acid inactivates the penicillinase or beta-lactamase that organisms such as Staphylococcus, Haemophilus, and Neisseria gonorrheae produce, making the amoxicillin more efficacious in inhibiting cell wall formation for these bacteria.

Dicloxacillin

1. Penicillin antibiotic. 2. Its structure renders it resistant to penicillinases but not to beta lactamases. 2. It is useful for treating staphylococcal infections because these organisms produce penicillinase. 3. Ask the patient about any penicillin allergies such as rash, hives, itching, or difficulty breathing before prescribing either Augmentin or Dicloxacillin. 4. The most severe side-effects include anaphylaxis, anemia, pseudomembranous colitis, and StevensJohnson syndrome, as well as risk of secondary infection by non-susceptible bacteria or fungi. Any digestive problems such as diarrhea or unusual bleeding should be reported by the patient promptly.

Cephalosporins: Keflex (cephalexin) and cefaclor

1. Cephalexin and cefaclor are first and secondgeneration cephalosporins, respectively, that share similar ocular indications with Augmentin. 2. Although Keflex is a popular antibiotic, the secondgeneration Ceclor may be a better choice because its spectrum of activity includes many beta-lactamase producing bacteria. Ceclor is also approved for children as young as 1 month. 3. Cefadroxil (Duracef) another popular, but more expensive, cephalosporin antibiotic. 4. Potential serious side-effects associated with these drugs include hypersensitivity reactions, pseudomembranous colitis, hypoprothrombinemia, and reversible renal impairment. Elderly individuals who have decreased renal function should be prescribed an alternative medication if possible. 5. Patients who are allergic to penicillins may also react to cephalosporins (the incidence of cross allergies is estimated between 5-16%), so an alternative antibiotic class may be required.
Antibiotics That Inhibit Folic Acid Synthesis

Bactrim (trimethoprim/sulfamethoxazole) Trimethoprim/sulfamethoxazole (Bactrim)

1. The second-choice antibiotic for cases of preseptal cellulitis or lacrimal infections in patients who have contraindications to other antibiotics. 2. It is a combination of two antibiotics that each inhibit the bacterias intermediary metabolism of folic acid synthesis. 3. This medication is less effective against gramnegative organisms. 5. Serious side effects of Bactrim are comparable to the penicillins and cephalosporins. 6. Folinic acid supplement may need to be coprescribed to prevent the patient from developing folate deficient megaloblastic anemia. 7. As this antibiotic contains a sulfonamide (sulfamethoxazole), it is contraindicated in patients with sulfa allergies. Sulfonamides are also less effective in purulent infections because the pus contains breakdown products that reduce the bacterias need for folic acid.

. Daraprim (pyrimethamine) for malaria

1. Pyrimethamine is prescribed for cases of active ocular toxoplasmosis retinochoroiditis. It is typically used in conjunction with sulfadiazine, and like sulfadiazine it is a folic-acid inhibitor. Serious side effects are comparable to Bactrim, the penicillins, and cephalosporins, but might also include seizures. This medication is also used for malaria treatment and prophylaxis.

Antibiotics That Inhibit Bacterial Protein Synthesis

Doxycycline

Doxycycline (Vibramycin) 1. long-acting tetracycline antibiotic commonly used for ocular rosacea, blepharitis, hordeola and meibomian gland dysfunction. It is also used in cases of ocular Chlamydia and certain protozoal infections such as toxoplasmosis. 2. This class of antibiotic inhibits protein synthesis by binding to the organisms ribosomes. Interestingly, there is also an anticollagenolytic activity in this class that may be useful in certain cases of sterile corneal ulcers. 4. Doxycycline is prescribed much more often than tetracycline because there are fewer dosages per day and doxycycline can be taken with meals. Tetracycline must be taken in higher dosages and on an empty stomach to allow absorption. There are usually fewer side effects with doxycycline than tetracycline.

5. Tetracycline-type antibiotics, such as doxycycline, can cause photophobia, pseudotumor cerebri, and blood dyscrasias, as well as decreased bone growth and teeth discoloration in children under 8 years of age, so avoid it with children, nursing mothers, or pregnant women.

Erythromycin

1. Erythromycin and similar drugs such as azithromycin and clarithromycin, is a macrolide antibiotic. 2. This class, like the tetracyclines, inhibits protein synthesis by ribosomal binding they simply bind to the larger ribosomal subunits while the tetracyclines bind to the smaller ribosomal subunit. 3. Erythromycin is typically indicted as a secondchoice treatment in Staphylococcus and other grampositive eyelid infections, as well as for chlamydial infections such as ophthalmia neonatorum and adult inclusion conjunctivitis.

Although erythromycin has a limited antibacterial spectrum (mainly gram-positive bacteria), it is one of the safest antibiotics to use. As such, it may be used more frequently with children and pregnant women, because side-effects are infrequent. Serious side-effects can include anaphylaxis, pseudomembranous colitis, and hepatotoxicity when the estolate form of erythromycin is prescribed.

Zithromax (azithromycin) 1. Azithromycin (Zithromax) is another macrolide antibiotic. 2. It is used primarily for chlamydial conjunctivitis, prescribed in a dose-pack as four 250 mg tablets PO in one day. 4. Zithromax has become known as the big gun in treating chlamydial infection, and has been used worldwide in an effort to eradicate Chlamydia caused trachoma. 5. Serious side effects of azithromycin include anaphylaxis, Stevens-Johnson syndrome,

pseudomembranous colitis, cholestatic jaundice. Fortunately, the short duration use of this medication may help reduce many side-effects that can occur with long-term antibiotic treatment. The antibiotic Chloramphenicol should be avoided due to the rare risk of potentially fatal bone marrow depression such as aplastic anemia (even with topical use), as well as numerous potential neurological complications.

Antibiotics That Inhibit Bacterial DNA Synthesis

1. Unlike other antibiotics that are bacteriostatic (bacteria-inhibiting) such as macrolides, the fluoroquinolones are bactericidal (bacteria-killing). 2. The fluoroquinolones blockage of bacterial DNA gyrase to produce more DNA causes bacterial death. As such, this drug may be preferred when other drugs are ineffective or are contraindicated.

Cipro (ciprofloxacin)

1. Ciprofloxacin is a common fluoroquinolone which is prescribed for numerous bacterial and urinary tract infections, gonorrhea, and anthrax. 3. Milk or any calcium-fortified products should be avoided when taking fluoroquinolones. 4. Serious side-effects include seizures, psychosis, allergy, pseudomembranous colitis, and phototoxicity. 5. Resistance to fluoroquinolones, particularly by staphylococci, has been growing, so newer-generation fluoroquinolones or other class antibiotics may need to be considered if the patient's infection is not resolving.

BASIC KNOWLEDGE ABOUT ANTIBIOTICS

ANTIBIOTICS Antibiotics are substances that inhibit the growth of or destroy bacteria that cause infection. Antibiotics do not work against viral diseases such as the common cold or influenza.

HOW ANTIBIOTICS WORK? The body's balance between health and illness is called homeostasis. Homeostasis largely depends on the relationship of the body to the bacteria with which it lives. For example, bacteria are always present on human skin. When the skin is cut, the bacteria are able to enter the body and may cause infection. The invading bacteria are usually destroyed by blood cells called phagocytes and by various actions of the immune system. However, when there are too many bacteria for the system to handle, illness results and antibiotics are needed to help restore homeostasis.

Antibiotics can be bacteriostatic (prevent bacteria from multiplying) or bactericidal (kill bacteria). For most infections, these two types of antibiotics appear to be equally effective, but if the immune system is impaired or the individual has a severe infection, a bactericidal antibiotic is usually more effective. Bactericidal drugs, however, may be bacteriostatic against certain microorganisms, and vice versa.

Each of the various types of antibiotics kill microorganisms in a unique way. Some disturb the structure of the bacterial cell wall; others interfere with the production of essential proteins; and still others interfere with the transformation (metabolism) of nucleic acid (substances found in the cells of all living things).

Classes of Antibiotics The following are the most commonly used types of antibiotics: Penicillins Cephalosporins Fluoroquinolones Aminoglycosides Tetracyclines Macrolides Polypeptides

Penicillins encompass a large group of bactericidal agents. They include: Penicillin G Penicillin V Cloxacillin Nafcillin Oxacillin Ampicillin Amoxicillin Ticarcillin

Penicillins work by damaging the cell walls of the invading bacteria as the bacteria are in the process of reproduction. Penicillin G and V, for example, are widely used for streptococcal infections as well as for other types of bacterial infection.

Antibiotics are classified as narrow-spectrum drugs when they work against only a few types of bacteria. Broad-spectrum antibiotics, on the other hand, attack many types of bacteria. However, the danger with broad-spectrum

antibiotics is that they are more likely to promote antibiotic resistance. For that reason, narrow-spectrum antibiotics, which often cost less, are used whenever possible. Broadspectrum antibiotics are generally reserved for infections that are unresponsive to narrowspectrum drugs.

Broad-spectrum penicillins, such as ampicillin and amoxicillin, are used on infections caused gram-negative organisms. Hypersensitivity reactions (such as rash or fever) to penicillin are relatively common side effects. However, severe life-threatening allergic reactions (such as anaphylactic shock) are rare. Penicillins are often given in combination with other types of antibiotics.

Cephalosporins are broad-spectrum antibiotics. They include: Cefadroxil Cefazolin Cephalexin Cephalothin Cephapirin Cephradine

Like penicillins, the cephalosporins work by interfering with bacterial cell wall formation. The cephalosporin cefotaxime sodium is particularly effective in treating deep infections such as those occurring in bones or resulting from surgery. The cephalosporins are often administered when sensitivity to penicillin is known or suspected. Occasionally, however, individuals allergic to penicillins will also be allergic to the cephalosporins. Adverse side effects of the cephalosporins may include rash or fever.

Fluoroquinolones are the newest class of antibiotics. They include: Ciprofloxacin Enoxacin Levofloxacin Norfloxacin Ofloxacin

The fluoroquinolones are well absorbed, have a broad spectrum of attack, and are considered relatively safe. These antibiotics interfere with bacterial enzymes and are most often used for treating urinary tract infections. Since fluoroquinolones may affect bone growth, however, the use of this class of antibiotics is not recommended in children or pregnant women.

Aminoglycosides work by impeding the protein formation of bacteria in invading cells. This class of antibiotics includes: Gentamicin Streptomycin Neomycin

The aminoglycosides are effective against a wide variety of bacteria and other organisms and are believed to prevent the production of proteins in the invading bacterial cells. These drugs are effective against pneumonia, typhus, and other bacteria-caused illnesses but can impair liver and kidney function. Thus they are usually administered with caution..

MACROLIDES: The macrolides interfere with the protein formation of invading bacteria. The macrolides are often used in patients who are known or suspected to be sensitive to penicillin. Some of the side effects of the macrolides are gastrointestinal discomfort. The macrolides include: Azithromycin Clarithromycin Erythromycin

Polypeptides are a class of antibiotics that is quite toxic and is used primarily on the skin surface. These drugs include: Bacitracin Colistin Polymyxin B

Choosing an Antibiotic Physicians are usually able to determine the type of organism responsible for causing the most commonly seen infections and know which class of antibiotic will be the most effective in combating it. If the agent causing illness is not known, a culture from the infection is usually examined under a microscope to identify the invading organism. However, even when the bacteria have been identified and their sensitivity to antibiotics have been determined, the choice of antibiotic is not always an easy one.

The effectiveness of the treatment depends on a variety of factors: 1. How well the drug is absorbed into the blood stream. 2. How much drug reaches various body fluids. 2. Drugs selection must take into account the nature and seriousness of the illness, the side effects of the drug, the possibility of allergies or other serious reactions, how quickly the body eliminates the drug as well as the cost of the drug.

Administering Antibiotics For severe bacterial infections, antibiotics are usually given by injection first (typically intravenously). When the infection is under control, antibiotics can be taken orally. Antibiotics must be taken until the infecting organism is eliminated from the body, which may be days after the symptoms disappear. Thus, stopping treatment too soon may result in a relapse or may encourage the development of resistant bacteria. For this reason, the antibiotics usually taken for several days after all evidence of the infection are gone.

Preventive Antibiotics Antibiotics are used not only to treat infections but to prevent them (prophylactically). To be effective and to avoid the development of resistance in bacteria, preventive antibiotic therapy must be used for only a short duration, and the antibiotic must be potent against the particular type of bacteria involved.

One example of preventive therapy is taking antibiotics before or during travel to foreign countries to prevent diarrhea. Also, preventive antibiotics are often used in people exposed to someone with meningitis (caused by meningococcus bacteria) because of the risk of infection.

Antibiotics are also used to prevent infections before, during, and after surgery. People with heart valve disorders routinely take antibiotics before surgery, including dental surgery (or even dental procedures such as cleaning).These people have increased risk of endocarditis from bacteria normally found in the mouth and other parts of the body. Such bacteria may enter the blood stream during the dental procedure and travel to the damaged heart valve.

Preventive antibiotics may also be taken by people whose immune system is not fully functional, such as people with leukemia, people receiving chemotherapy for cancer, or people with AIDS.

Healthy people undergoing those types of surgery that carry a high risk of infection (such as major orthopedic or intestinal surgery) may also take preventive antibiotics.

Side Effects Allergic reactions to antibiotics are usually observed as skin rashes, but severe anemia (too few red blood cells), stomach disorders, and deafness can occasionally result. People who have certain medical conditions may experience side effects when taking antibiotics. In addition, when people take antibiotics with certain foods or medications, the effects of the antibiotic or the risk of side effects may increase. After taking an antibiotic, any unusual symptoms should be reported to the physician immediately.

Antibiotic Resistance An antibiotic limits or stops the growth of a specific microorganism by interfering with the wall of the bacterial cell at which it is targeted, while simultaneously having little effect on the body's normal cells.

When an individual takes an antibiotic for a long period of time, such as for an illness like rheumatic fever, the targeted bacteria may develop their own defense against the drug. An enzyme (a complex protein capable of inducing chemical changes without being changed itself) that can destroy the drug may be produced by the bacteria, or the cell wall may become resistant to being broken by the action of the antibiotic. When this resistance occurs, as it does most often in response to long or frequent treatment with penicillin or streptomycin, an individual is said to be "fast" against the drug. For example, a person may be penicillin-fast, meaning penicillin is no longer able to help fight the infection and another type of antibiotic must be administered.

Health experts are particularly concerned about antibiotic resistance in bacteria that cause certain serious infections. For example, some strains of Staphylococcus aureus, that may cause pneumonia or blood stream infections, are resistant to almost all antibiotics, make those conditions very difficult to treat. Many strains of tuberculosis also are now resistant to one or more of the agents used to control tuberculosis.

Summary Tables on Antimicrobials Drugs contraindicated in children & pregnancy Tetracycline (retardation of bone growth; stains teeth) Fluoroquinolones (cartilage toxicity) Thalidomide (severe birth defects) Metronidazole (mutagenic and carcinogenic potential)

Chloramphenicol is contraindicated in infants (Gray baby syndrome because infants dont produce enough glucoronyl transferase)

Alternative drugs in patients with a history of severe (anaphylactic) penicillin allergy Aztreonam (a monobactam; primarily indicated for Gram organisms and is not a drug of first choice) Macrolides Vancomycin

Clindamycin

Synergistic drug combinations (& their mechanisms) Cell Wall Synthesis Inhibitor (CWSI) + Aminoglycoside increases permeability of organism to aminoglycosides)

Trimethoprim + Sulfa drug (blocks two steps in the synthesis of folic acid, which bacterial cells need to survive)

Mechanisms for drug resistance Intrinsic resistance (gram- bacteria have outer membrane impermeable to penicillin) Escape from antibiotic effect (cell membranes become permeable to folic acid to escape the effect of sulfonamides and trimethoprim) Penicillinase production (previously penicillinase- can become penicillinase+ and be resistant to some penicillins and cephalosporins) Methylase gene (50S subunit receptor gets methylated so macrolides and strepogramins no longer work) Plasmid mediated phosphorylation, acetylation, and adenylation (affects aminoglycosidesat the amine group on the drug, or methylation of the S12 protein to which they bind; remember, amikacin is the least likely aminoglycoside to which bacteria become resistant, so it may keep on truckin while streptomycin has fallen by the wayside)

Decreased drug uptake (tetracyclines & aminoglycosides)

Drugs with unusual types of toxicity Aminoglycosides have vestibular & auditory toxicity, nephrotoxicity & NMJ blockade Vancomycin -if not administered slowly enough by IV, hypotension and the Red Man Syndrome may result Sulfonamides can cause StevensJohnson (erythema multiforme) Metronidazole causes metallic taste and disulfiram-like reaction (antabuse) Fluoroquinolones causes cartilage toxicity Erythromycin & Clarithromycin IV erythromycin or high concentrations of these two macrolides, and/or concomitant administration with other drugs that prolong the QT interval (e.g. pimozide, astemizole, terfenadine) can result in potentially fatal arrhythmias Chloramphenicol causes major fatal aplastic anemia (rare but fatal) Tetracyclines cause yellowing of the teeth and can inhibit bone growth Rifampin and Clofazimine can cause reddened urine Ethambutol can cause red-green colorblindness

Drugs which can cause Hemolytic Anemia (particularly in G-6-P Dehydrogenase deficient individuals) and incidentally are also metabolized by acetylation (so their dosing needs to be adjusted in fast acetylators): o Isoniazid (INH) o Dapsone and Sulfonamides Drug Interactions Erythromycin, clarithromycin & ketoconazole - inhibit P-450 enzymes Rifampin - induces P-450 enzymes

Drugs cleared by the kidney (drugs potentially useful for kidney tract infections if the bacteria are also sensitive; drugs requiring dosage adjustment with renal dysfunction) Penicillins and Cephalosporins (with a few exceptions shown in the next table) Aminoglycosides *** Must figure out Creatinine clearance before maintenance dosing *** Tetracyclines (except doxy & mino) Chloramphenicol Fluroquinolones (80% excreted through kidney) Sulfonamides & Trimethoprim Pyrazinamide Clindamycin (is excreted by both kidney and via bile tract) Nitrofurantoin Cleared by the kidney, but not used for UTI:

Isoniazid (INH) & Pyrzinamide (primarily used for M. tuberculosis) Vancomycin Metronidazole

Primarily biliary excretion: Nafcillin Ceftriaxone Both biliary & renal clearance:

Oxacillin, Coxacillin & Dicloxacillin Ampicillin (however, dosage adjustment required in renal failure)

If a patient has complete renal failure and allergic to penicillin. Now what can a patient take for his infection? Macrolides Rifampin (antimycobacterial)

Clofazimine (for Mycobacterium species)

Which drugs work on anaerobes?*

Clindamycin (drug of choice against B. fragilis) Metronidazole (drug of choice against B. fragilis & Clostridium species) Penicillin G (Clostridium perfringens) Ticarcillin (somewhat effective against Bacteroides fragilis) Piperacillin & Mezlocillin (more effective against B. fragilis) Imipenem (effective against anaerobes) Cefoxitin (also some other cephalosporins) Chloramphenicol

*Note: Bacteroides is the most frequent anaerobic pathogen in man (80% of anaerobic infections). Bacteroides species are common in the terminal ileum & colon and are a major component of fecal matter.

TREATMENT OF VIRAL INFECTIONS

Zovirax (acyclovir) pills 1. Acyclovir (Zovirax) was the first oral antiviral approved for herpetic infections. Acyclovir disrupts viral DNA synthesis in infected host cells while leaving uninfected host DNA replication alone. 2. It is indicated for varicella zoster virus (VZV) and certain herpes simplex virus (HSV) infections. 4. Because of acyclovirs short half-life, it must be taken five times a day for initial infections. 6. Before prescribing, determine if a patient has hypersensitivity to acyclovir, or if there are any renal or hepatic problems, neurological problems (rare seizures have been reported), or hypoxia. However, this medication is relatively safe to use, and is recommended for children (at pediatric dosages) who

develop herpetic infections including chicken pox. One study suggests that children with epithelial herpetic infection may be better treated with oral acyclovir than topical antivirals.

Valtrex (valcyclovir) and Famvir (famciclovir) 1. Famciclovir (Famvir) and valcyclovir (Valtrex) are anti-herpetic drugs that have a longer half-life than acyclovir. 2. Famvir is usually prescribed for herpes simplex infections and for varicella/zoster infections. Valtrex is typically prescribed at double the dosage of Famvir. 3. Use caution with these medications, just as you would with acyclovir.

Thymidine analogs Idoxuridine (Herplex )

Anti-viral, anti-Herpes Simplex Virus (HSV) Mechanism of Action: Iodinated thymidine analog, activated intracellularly to tri-phosphate which can inhibit DNA

polymerases required for incorporation of thymidine into viral DNA. Idoxuridine, instead of thymidine, is incorporated into viral DNA, resulting in faulty DNA and the inability of the virus to infect tissue or reproduce Clinical Indications: Alternate drug for topical use against HSV keratitis. Contraindications: Hypersensitivity, severe systemic toxicity Side Effects: irritation, pruritis, inflammation Pharmacokinetics: Administered in eye drops, no systemic absorption Major drug Interactions: boric-acid containing solutions Notes: Poorly selective and can affect host DNA polymerases. The methyl (CH3) group of thymine is replaced by iodine (-I).

Trifluridine (Viroptic )
Anti-viral, anti-Herpes Simplex Virus (HSV-1 and -2) and antivaccinia virus. Mechanism of Action: Tri-fluoro thymidine analog, activated intracellularly to tri-phosphates which then inhibit DNA polymerases. Clinical Indications: A DOC for topical treatment of HSV keratitis. Also effective in treating cutaneous infections by acyclovir resistant strains of HSV. Contraindications: Hypersensitivity and chemical intolerance. Side Effects: Severe systemic toxicity.

Pharmacokinetics: used topically in eye drops and ophthalmic preparations. No systemic absorption. Major drug Interactions: None known Notes: Poorly selective and can affect host DNA polymerases. The methyl (CH3) group of thymine is replaced by a trifluoromethyl (-CF3) moiety.

Purine analog Vidarabine (Vira-A )

Antiviral, anti-herpes simplex virus (HSV types 1 and 2) Mechanism of Action: A purine analog, phosphorylated and activated intracellularly which then inhibits DNA polymerase activity. Clinical Indications: Acute keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 and HSV-2. Recommended for herpes encephalitis as an alternate drug. Contraindications: Hypersensitivity to vidarabine Side Effects: Causes bone marrow suppression and hepatic toxicity if given systemically. Pharmacokinetics: Ocular (topical) administration with no systemic absorption. Can be given i.v. (w/ significant side effects). Major drug Interactions: Corticosteroids

Notes: Ocular side effects such as glaucoma or cataract can be seen when coadministered with corticosteroids

natamycin (Natacyn)
NATACYN (natamycin ophthalmic suspension) 5% is a sterile, antifungal drug for topical ophthalmic administration. Mechanism of action: The mechanism of action appears to be through binding of the molecule to the sterol moiety of the fungal cell membrane. The polyenesterol complex alters the permeability of the membrane to produce depletion of essential cellular constituents. Natamycin is indicated for the treatment of fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms. Natamycin is contraindicated in individuals with a history of hypersensitivity to any of its components. For topical ophthalmic use only NOT FOR INJECTION. Failure of improvement of keratitis following 7-10 days of administration of the drug suggests that the infection may be caused by a microorganism not susceptible to natamycin. Continuation of therapy should be based on clinical reevaluation and additional laboratory studies. Rare cases of conjunctival chemosis and hyperemia thought to be allergic in nature, has been reported.

Chloramphenicol
Antibiotic: (wide spectrum & bacteriostatic) Mechanism of Action: Binds to 50S ribosomal subunit and inhibits peptidyl transferase and blocks protein synthesis Side Effects: Bone marrow suppression and idiosyncratic aplastic anemia. Gray baby syndrome. Superinfection.

Allergic Conjunctivitis What is meant by conjunctivitis? Inflammation of the conjunctiva, the delicate mucous membrane the lines the inner surface of the eye lids and covers the frontal part of white of the eye. What are the possible causes of conjunctivitis? 1. Viral or bacterial infection. 2. A chemical burn. 3. Mechanical injury. 4. May be a part of allergic reaction. Keratoconjunctivitis is a condition in which both conjunctiva and cornea are involved. What are the symptoms of conjunctivitis? 1. Light sensitivity. 2. Redness. 3. Itching. 4. A sensation of sand in the eye. 5. Eye discharge which can be either watery or thick and colored. What are organisms that can give rise to conjunctivitis?

Adenoviruses 1. May attack the conjunctiva and cornea. 2. Cause keratoconjunctivitis which is rapidly spread through direct and indirect contact with infected individuals. 3. Typically, a person is contagious for at least a week following onset of symptoms and treatment is mainly supportive with emphasis on strict hygiene to minimize spread of the virus. The majority of cases resolve without residual problems. Viruses causing cold sores, chickenpox and measles also may invade the conjunctiva. Treatment of these cases may include antiviral drops. Bacteria 1. Bacterial infection of the conjunctiva is less common than viral infection and occurs through direct contact with infected persons or through a person's own nasal or sinus mucosa. 2. Eye discharge is generally thick and colored as opposed to the watery discharge of viral conjunctivitis. 3. The organisms responsible for bacterial conjunctivitis in humans are staphylococcus, streptococcus and H.influenza. Chlamydia 1. Responsible for Trachoma (Chlamydia Trachomatis), a disease in which the conjunctiva and cornea become scarred, leading to blindness. (Trachoma is the leading cause of preventable blindness in the world. 2. Antibiotic treatment is usually effective. Conjunctivitis resulting from allergic reaction to topical eye medications or airborne allergens such as hay fever pollen. 1. Prominent symptoms include eyelid swelling, itchingeye redness and a mucoid discharge.

2. Cool compresses and artificial eye lubrication are of benefit and antiallergy medications are available. Vernal conjunctivitis 1. Allergic inflammation that tends to occur in the conjunctiva of susceptible usually male children. 2. Two types are available: In one, the lining of the upper eye lid is affected with a characteristic red, pebbled appearance. In the second type, the inflammation is manifested by separate yellowish elevations on the conjunctiva near the cornea. Treatment is similar to other cases of allergic conjunctivitis. Conjunctivitis accompanying erythema multiform A severe form of conjunctivitis that may culminate in blindness accompanies erythema multiform, an eruption on the skin and mucous membranes that sometimes occurs in association with a systemic infection or the use of certain medications. Drug treatment of inflammatory and allergic eye conditions: 1. Different forms of conjunctivitis are treated by: - Penicillin G drops or chloramphenicol for acute purulent conjunctivitis - Sulphacetamide eye drops for trachoma - Tetracycline eye ointement for chronic follicular conjunctivitis - Vidarabine or acyclovir for herpes simplex keratitis - Topical steroids for chronic papillary (atopic) conjunctivitis 2. Glucocorticoids to suppress inflammation and allergy 3. Topical antihistaminic as eye drops in allergic states 4. Sodium chromoglycate eye drops for treatment of spring catarrh or vernal keratoconjunctivitis 5. Astringents as zinic sulphate in angular conjunctivitis

Treatment of allergic conjunctivitis Can be treated with a variety of drugs: 1) Topical antihistaminics. 2) Mast cell stabilizers. 3) Nonsteroidal anti-inflammatory drugs (NSAIDs). 4) Corticosteroids. A) Topical antihistamines: Act by: A) Competitive inhibition of histamine at the H1 receptor. B) Block the effects of endogenously released histamine. Histamine is one of the main chemical mediators that trigger symptoms of ocular allergy. Ophthamic formulations are targeted directly to the involved site and usually providec rapid symptom relief without significant systemic side effects. Combinations of topical antihistamines with a topical vasoconstrictor may also be useful in short-term treatment of mild allergic conjunctivitis. Orally ingested antihistamines may partially relieve ocular symptoms and may be effective on nasal symptoms. Topical eye drops may be fastest and most effective in relieving ocular itch, redness and swelling. Eye drops allow the medication to get directly to the affected eyes. I. Emedastine difumarate 1. 0.05% ophthalmic solution contains 0.884mg/mL 2. Relatively selective H1-receptor antagonist for topical administration not for injection or oral use. 3. Contraindication: documented hypersensitivity.

4. Usually safe in pregnancy but benefits must outweigh the risks. 5. Contact lens should not be worn for 10 min after instillation of emedastine as the preservative, benzalkonium chloride, can be absorbed. 6. Caution in breastfeeding. II. Epinastine 1. Direct H1 receptor antagonist only for topical ophthalmic use. 2. Does not penetrate BBB and therefore should not induce adverse CNS effects. 3. Indicated for symptoms due to allergic conjunctivitis 4. Remove contact lenses before instillation. 5. Use caution when handling the container to avoid touch contamination. 6. May cause burning sensation, folliculosis, hyperemia or pruritus. III. Azelastine 1. Competes with H1-receptor sites on effector cells and inhibits release of histamine and other mediators involved in allergic resonse. 2. Caution: wait 10 min after instilling solution to insert soft contact lenses. Do not use contact lenses if eyes are red IV. Levocabastine 1. Selective histamine H1 receptor antagonist. 2. Shoul not be used in people wearing soft contact lenses, should not be used if discolored, not for syatemic use, should be shaken well before use. 3. Mast cell stabilizers have a slow onset of action, and may require several days of treatment before optimal symptom relief. Therefore, they are more suitable for prophylactic and long term treatment of chronic ocular allergies than in acute seasonal cases

B) Mast cell stabilizers: Inhibit sensitized mast cell degeneration when exposed to specific antigens by inhibiting the release of mediators from the mast cells. Block calcium ions from entering the mast cell. I. Lodoxamide tromethamine: mast cell stabilizer II. Olopatadine: relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cell. III. Ketotifen: noncompetitive H1-receptor antagonist and mast cell stabilizer. 4) Nedocromil: interferes with mast cell deregulation especially with release of leukotrienes and platelet activating factor. C) Dual or multiple-action agents 1. Combine the actions of antihistamines with those of mast cell stabilizers. 2. They provide effective relief from acute symptoms of the early-phase allergic reaction and inhibit the inflammatory processes triggered by the late-phase response. 4. These agents can inhibit eosinophil infiltration at the site of the allergic reaction. 5. These agents act on both the early- and the late-phase allergic response D) Corticosteroids 1. Have both anti-inflammatory (glucocorticoid) and saltretaining (mineralocorticoid) properties. 2. Have profound and varied metabolic effects in addition these agenta may modify the body's immune response to diverse stimuli. 3. They are effective but long-term use is associated with side effects as delay in corneal epithelium healing, local immunosuppression with consequent superinfection of cornea and conjunctiva, rise in IOP and cataract formation. 4. Example: Loteprednol *Topical ester steroid drop with decreased risk of glaucoma. * Monitor IOP if used for more than 10 days.

* Long-term use is associated with cataracts. * Caution in hypertension. * Suspect fungal invasion in any persistent corneal ulceration where a corticosteroid has been used or is in use (obtain fungal cultures when appropriate) E. NSAIDs as Ketorolac trimethamine * Topical NSAIDs do not alleviate all signs and symptoms associated with seasonal allergic conjunctivitis. * Their mechanism of action is believed to be through inhibition of COX enzyme that is essential in the biosynthesis of PGs, which results vasoconstriction, decrease in vascular permeability and leukocyte migration and a decrease in IOP. F. Allergen desensitization * May be indicated in selected cases. * The risk of anaphylaxis and other adverse reactions related to immunotherapy limits its use to specialists experienced in administering this kind. * Allergy shots or immunotherapy are sometimes used when other therapies do not help control the symptoms. These shots inject increasing amounts of the allergens that are affecting your eyes into your body to help curb your eyes' reaction. The treatment usually takes several months to achieve maximum results.

END OF THE LECTURE