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Pharm II_2024 Antibiotics / Anti-infective Drugs Antibiotics Ocular Pharmacology ↳ Antibiot , antiviral , antifungal.. Diane T. Adamczyk, OD Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 Pharm II_2024 Antibiotics Anti-infective and Bacterial Overview Diane T. Adamczyk, OD, FAAO Copyright © 2024 2 P...

Pharm II_2024 Antibiotics / Anti-infective Drugs Antibiotics Ocular Pharmacology ↳ Antibiot , antiviral , antifungal.. Diane T. Adamczyk, OD Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 Pharm II_2024 Antibiotics Anti-infective and Bacterial Overview Diane T. Adamczyk, OD, FAAO Copyright © 2024 2 Pharm II_2024 Antibiotics Anti-infective Overview  Normal flora  Considerations for infection  Barriers: skin and mucous membranes  Immune status  Organism  Viral, bacteria, fungi Diane T. Adamczyk, OD, FAAO Copyright © 2024 3 Pharm II_2024 Antibiotics Normal Microbial Flora  Can vary between individuals  Can become pathogenic in the right circumstances, such as  Debilitating disease  Immunosuppression  Helps to prevent the colonization of pathogenic species  Substances may be produced that inhibit the growth of other species Diane T. Adamczyk, OD, FAAO Copyright © 2024 4 Pharm II_2024 Antibiotics Normal Ocular Flora  Bacteria typically recovered from 80 to 90% of normal eyes include:  Coagulase-negative staphylococci  Propionibacterium acnes  Corynebacterium species  Staph aureus, Strep pneumoniae & H. flu are pathogens occasionally recovered from non-infected eyes Diane T. Adamczyk, OD, FAAO Copyright © 2024 5 Pharm II_2024 Antibiotics Bacteria  Bacteria: single celled microorganisms  Subdivided by shape and gram stain  Gram Positive  Staphylococcus (aureus, epidermidis)  Streptococcus (pneumonia, pyogenes, faecalis)  Gram Negative  Rods: Haemophilus influenzae, Pseudomonas aeruginosa, Serratia marcescens  Cocci: Neisseria gonorrhoeae  Unique structural morphology includes  Chlamydia (trachoma, inclusion conjunctivitis)  Mimic viruses  Treponema palladium (syphilis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 6 Pharm II_2024 Antibiotics Anti-infective Overview Diane T. Adamczyk, OD, FAAO Copyright © 2024 7 Pharm II_2024 Antibiotics Antibacterial Drugs  Bactericidal: kills bacteria  Minimum bactericidal concentration (MBC) is the minimum concentration of drug which can kill 99.99% of the organism population  Bacteriostatic: inhibit bacteria growth  May do this for example by interfering with bacterial protein production or bacterial cellular metabolism  Must work together with the immune system to remove the microorganisms from the body  Minimum inhibitory concentration (MIC) is the minimum concentration of drug which can inhibit the growth of the microorganism Note: not always a precise distinction between static and cidal antibiotics  High concentrations of some bacteriostatic agents are also bactericidal  For example: macrolides can be bactericidal in high doses  Certain antibiotics may be cidal to certain pathogens and static to others Diane T. Adamczyk, OD, FAAO Copyright © 2024 8 Pharm II_2024 Antibiotics Antibacterial Drugs  Bactericidal: kills bacteria  Bacteriostatic: inhibit bacteria growth - Perent from growing -kill Diane T. Adamczyk, OD, FAAO Copyright © 2024 9 Pharm II_2024 Antibiotics Antibacterial Drugs  Selective toxicity (bacteria vs human)  Bacteria: cell wall  Antibacterial drug: Inhibit synthesis of cell wall  Cell membrane  Similar  Ribosomes  Different size and composition  Inhibit bacterial protein synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 10 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 11 Pharm II_2024 Antibiotics Antibacterial Drugs Selective toxicity (bacteria vs human) Biosynthetic pathways (intermediary metabolism) Folic acid: bacterial cells synthesize Enzyme DNA gyrase An essential bacterial enzyme involved in DNA replication Diane T. Adamczyk, OD, FAAO Copyright © 2024 12 Pharm II_2024 Antibiotics Mechanisms of Antibiotic Action  Inhibition of cell wall synthesis  Penicillins  Cephalosporins  Bacitracin  Vancomycin  Increased bacterial cell membrane permeability  Polymyxin B  Gramicidin  Inhibition of bacterial protein synthesis  Aminoglycosides  Macrolides  Tetracyclines  Chloramphenicol  Inhibition of folic acid synthesis  Sulfonamides  Trimethoprim  Damage to bacterial DNA  Fluoroquinolones Diane T. Adamczyk, OD, FAAO Copyright © 2024 13 Pharm II_2024 Antibiotics Bactericidal Antibiotics Inhibit Cell Wall Penicillins Cephalosporins Bacteriostatic Antibiotics Affect Intermediary Metabolism (Folic Acid) Sulfonamides Trimethoprim (may be cidal from synergy when combo drug) Vancomycin Bacitracin Affect Cytoplasmic Membrane Polymyxin Gramicidin Affect Protein Synthesis Aminoglycosides Pyrimethamine Affect Protein Synthesis Tetracyclines Macrolides Chloramphenicol (some cidal activity) Affect DNA Synthesis Fluoroquinolones Note: Some antibiotics may have bactericidal and bacteriostatic activity dependent on dose or specific bacteria Diane T. Adamczyk, OD, FAAO Copyright © 2024 14 Pharm II_2024 Antibiotics Mechanisms of Resistance  Bacterial production of enzymes that degrade/inactivate antibiotics  Pump mechanisms or decreased permeability antibiotics  Resistance genes  Alteration of bacterial ribosomes  Chromosomal mutation Diane T. Adamczyk, OD, FAAO Copyright © 2024 15 Pharm II_2024 Antibiotics Mechanisms of Resistance  Cross resistance  Misuse and overuse of antibiotics  During the systemic use of antibiotics  Inappropriate use  Patient non-compliance  With the use of antibiotics in animal feed Diane T. Adamczyk, OD, FAAO Copyright © 2024 16 Pharm II_2024 Antibiotics  Concern for rising antibioticresistant bacteria  FDA: limited how and when antibiotics used for livestock  Use of antibiotics to improve animal growth is prohibited  Use of antibiotics for cattle/swine/poultry through feedstock or water must come from directive from veterinarian Diane T. Adamczyk, OD, FAAO Copyright © 2024 17 Pharm II_2024 Antibiotics Oral Antibacterial Drugs  Clinical Indications  Meibomianitis  Internal Hordeolum  Ocular Rosacea  Dacryocystitis  Preseptal Cellulitis  Chlamydial Conjunctivitis  Prophylaxis (orbital fractures,sinusitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 18 Pharm II_2024 Antibiotics Probiotics  Probiotics are live nonpathogenic microorganisms administered to improve microbial balance, particularly in the GI tract  Defined: live microorganism thought to confer health benefits  Broadly describes various strains of bacteria and yeast  Consist of yeast or lactic acid bacteria  They are regulated as a dietary supplement and food Diane T. Adamczyk, OD, FAAO Copyright © 2024  Used for a variety of conditions including up to 30% on antibiotics experiencing antibiotic associated diarrhea  Food examples: yogurt, sauerkraut, kimchi  Timing: when to take (do not take with antibiotic ie space at least 2 hours before/after antibiotic doses)  Generally safe, with flatulence and bloating most frequent side effect  Used cautiously with patients taking immunosuppressants (e.g. tacrolimus, chemotherapy, proton inhibitors) or who are immunocompromised– can cause infection 19 Pharm II_2024 Antibiotics  Things to look for:  Colony Forming Units (CFU) – (range can vary 10 million to 1 billion to 50 billion CFUs)  Strain Diversity – e.g. 8-12 separate strains  Strains – e.g. Lactobacillus acidophilus  Prebiotics – fiber based to nourish good bacteria  Enteric coated – survives stomach acid Probiotics  Manufacture/expiration date – decreased effectivity with time  Use Examples:  Diarrheal illness  Antibiotic-associated diarrhea  Inflammatory bowel disease  Irritable bowel syndrome  Allergic disease (atopic dermatitis, allergic asthma, allergic rhinitis, food allergies)  Atherosclerosis Diane T. Adamczyk, OD, FAAO Copyright © 2024 20 Pharm II_2024 Antibiotics Probiotics  Effects through:  Lowering intestinal pH (suppress growth of pathogenic bacteria, reestablishing gut flora balance)  Enhance mucin from gut epithelial cells (serve as antibacterial barrier prevent binding of pathogens)  Promote secretory IgA (that binds to pathogens)  Interfere with quorum sensing (a mechanism by which bacteria enhance their virulence)  Exert anti-inflammatory effect in gut  Decreasing colonization (by competitively blocking their adhesion to the epithelium)  Decreasing invasion by pathogenic organisms (production of various substances that are toxic to pathogenic microorganism)  Modifying host immune response  May activate opioid and cannabinoid receptors in gut (ameliorate visceral pain) Diane T. Adamczyk, OD, FAAO Copyright © 2024 21 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 22 Pharm II_2024 Antibiotics Probiotics (Food) Diane T. Adamczyk, OD, FAAO Copyright © 2024 23 Pharm II_2024 Antibiotics Oral Contraceptive and Antibiotics  Failure rate associated with OCs are typically 1-3% *  Various hypothesis:  Decreased enterohepatic circulation, increased liver degradation, contraceptive displacement from receptor site  Antibiotic-induced diarrhea  Increased liver p450 enzyme induction  However - Inconsistencies in study findings over time if OC failure with oral antibiotics *Oral contraceptive failure rates and oral antibiotics. JAmAcadDermatol 1997;36:705-10 Diane T. Adamczyk, OD, FAAO Copyright © 2024 24 Pharm II_2024 Antibiotics BMJ Evidence-Based Medicine; 2020-111363  Non-enzyme inducing antibacterial drugs e.g.: cephalexin, ciprofloxacin, erythromycin, trimethoprim  Enzyme-inducing drug e.g.: carbamazepine, topiramate, rifampicin  Risk of unintended pregnancies:  Enzyme-inducing drugs: 13 fold increase  Antibacterial drugs: 7 fold increase  Many groups (WHO, US Center for Disease Control and Prevention) do not advise any additional precautions  This article however based on the uncertainties advised precautions Diane T. Adamczyk, OD, FAAO Copyright © 2024 25 Pharm II_2024 Antibiotics Antimicrobial Drug Interaction and Warfarin  Considerations:  Cephalosporins  2nd and 3rd generation might increase warfarin effect by inhibiting production of vitamin Kdependent clotting factors, and other mechanisms  Consider monitoring INR  Fluoroquinolones  Increased response possibly due to  inhibition of warfarin metabolism,  displacement of warfarin from protein binding sites or  disruption of intestinal flora affecting vitamin K synthesis  Monitor INR  Macrolides (e.g. azithromycin, erythromycin)  Increase effect of warfarin through inhibition of hepatic metabolism of warfarin  Monitor INR  Increased INR reported with all macrolides. (including ophthalmic erythromycin)  Considerations:  Penicillins  IV=inhibit platelet function  Oral = increase risk of bleeding  Monitor INR  Sulfonamides  Increased effect from  reduced warfarin clearance,  displacement of warfarin from protein binding sites,  alterations in gut flora  Avoid if possible  Tetracyclines  Increased response due to unknown mechanisms  Monitor INR Pharmacist’s Letter. August 2012 Diane T. Adamczyk, OD, FAAO Copyright © 2024 26 Pharm II_2024 Antibiotics Topical Antibiotic Drugs Anterior Segment Infection Conjunctivitis Corneal Ulcer Blepharitis Prophylaxis Diane T. Adamczyk, OD, FAAO Copyright © 2024 27 Pharm II_2024 Antibiotics Anti-infective Overview  Drug considerations  Selective toxicity  Spectrum of activity  Species which drug shows intrinsic activity  Narrow vs broad  Resistance Diane T. Adamczyk, OD, FAAO Copyright © 2024 28 Pharm II_2024 Antibiotics  Accurate diagnosis Guidelines: Effective Antimicrobial Therapy  Microorganism sensitive to anti-infective  Least toxic drug  Adequate drug levels  Optimum route of administration  Appropriate dosage  Appropriate treatment time  Augment drug tx with physical procedures Diane T. Adamczyk, OD, FAAO Copyright © 2024 29 Pharm II_2024 Antibiotics  Inaccurate diagnosis Antimicrobial Failure  Resistance  Inadequate drug dosage  Noncompliance  Inadequate supplemental physical procedures  Inadequate immune system response Diane T. Adamczyk, OD, FAAO Copyright © 2024 30 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 31 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins Cephalosporin Vancomycin Bacitracin Diane T. Adamczyk, OD, FAAO Copyright © 2024 32 Pharm II_2024 Antibiotics  Inhibition of cell wall synthesis Antibacterial: Affecting Cell Wall Synthesis  Penicillins  Amoxicillin and clavulanate (Augmentin)  Dicloxacillin  Cephalosporins  Cephalexin (Keflex)  Cefaclor (Ceclor=brand d/c US)  Bacitracin  Vancomycin Diane T. Adamczyk, OD, FAAO Copyright © 2024 33 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins Bacterial Cell Wall Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 34 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins  Pharmacology:  Contain common nucleus composed of: B-lactam Antibiotic  Thiazolidine ring  B-lactam ring  Necessary for biological activity  Side chain  Determines antibacterial spectrum  Susceptibility to bacterial degradative enzymes (B-lactamase enzymes)  Pharmacokinetic properties  Bactericidal  Effective: Gram +, Gram – Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 35 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins: Use  Penicillins Use: Hordeolum Preseptal cellulitis Dacryocystitis Dacryoadenitis Diane T. Adamczyk, OD, FAAO Copyright © 2024 36 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins  Adverse Reactions  Hypersensitivity response  GI irritation: Nausea, vomit, diarrhea  Superinfection Diane T. Adamczyk, OD, FAAO Copyright © 2024 37 Pharm II_2024 Antibiotics Penicillin Allergy  ~10% report allergy to penicillin (higher in older and hospitalized patients  However, hypersensitivity uncommon (>>disrupting the cell’s osmotic integrity  Bactericidal  Gram negative bacteria  Especially pseudomonas  Clinical Use:  Conjunctival and lid infections  ADR (rare) Diane T. Adamczyk, OD, FAAO Copyright © 2024 64 Pharm II_2024 Antibiotics Drugs: Affecting Cytoplasmic Membrane Polymyxin B Combos  Combo Drugs:  With other antibiotics (various)  Polymyxin B/Neomycin/Gramicidin (Neosporin)  Polymyxin B/Trimethoprim (Polytrim)  Polymyxin B/Bacitracin (Polycin)  Polymyxin B/Bacitracin/Neomycin (Neo-Polycin)  With steroids  Polymyxin B/bacitracin/neomycin/hydrocortisone Diane T. Adamczyk, OD, FAAO Copyright © 2024 65 Pharm II_2024 Antibiotics Antibacterial: Affecting Cytoplasmic Membrane: Gramicidin Diane T. Adamczyk, OD, FAAO Copyright © 2024 66 Pharm II_2024 Antibiotics Drugs: Affecting Cytoplasmic Membrane: Gramicidin  Gramicidin  Interacts with the bacterial cell membrane>>>disrupting the cell’s osmotic integrity (like polymyxin B)  Bactericidal (?some static activity?)  Gram positive  Combination:  Polymyxin B/Neomycin/Gramicidin (Neosporin)  May use during pregnancy and breastfeeding Diane T. Adamczyk, OD, FAAO Copyright © 2024 67 Pharm II_2024 Antibiotics Antibacterial: Affecting Protein Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 68 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 Aminoglycosides Macrolides Tetracyclines Chloramphenicol Clindamycin 69 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis  Inhibition of bacterial protein synthesis  Aminoglycosides  Neomycin  Gentamicin  Tobramycin  Macrolides  Erythromycin  Azithromycin  Clarithromycin  Tetracyclines  Tetracycline  Doxycycline  Minocycline  Chloramphenicol  Clindamycin Diane T. Adamczyk, OD, FAAO Copyright © 2024 70 Pharm II_2024 Antibiotics Antibacterial: Affecting Protein Synthesis Aminoglycosides Diane T. Adamczyk, OD, FAAO Copyright © 2024 71 Pharm II_2024 Antibiotics Antibacterials: Affecting Protein Synthesis Aminoglycosides Pharmacology Inhibit bacterial protein synthesis: By binding to bacterial ribosome Bactericidal Gram negative and positive Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 72 Pharm II_2024 Antibiotics Antibacterials: Affecting Protein Synthesis Aminoglycosides Pharmacology Resistance (Gram negative bacilli) Alteration of bacterial ribosomes Decreased antibiotic uptake Enzymatic inactivation of the drug Cross resistance (e.g. Gentamicin and tobramycin) Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 73 Pharm II_2024 Antibiotics  Neomycin Drugs Affecting Protein Synthesis Aminoglycosides Diane T. Adamczyk, OD, FAAO Copyright © 2024  Gentamicin  Tobramycin  Amikacin 74 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Aminoglycosides: Neomycin  Neomycin Ophthalmic  Broad spectrum antibacterial  Gram positive and Gram negative bacteria  Ineffective P. aeruginosa  Neomycin In combination with various drugs:  Polymyxin B/gramicidin  Polymyxin B/bacitracin  Polymyxin B/bacitracin/hydrocortisone  Polymyxin B/dexamethasone  Polymyxin B/hydrocortisone  Neomycin ADRs  Drug sensitization (contact dermatitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 75 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Aminoglycosides: Gentamicin  Gentamicin Ophthalmic  Spectrum: ↳  Gram(+), Gram(-), Pseudomonas a.  In General NOT Effective against Streptococcus =  Use: -  Anterior segment infections  ADRs: (rare) -  Corneal and conjunctival toxicity  Allergic rx (50% of those allergic to neomycin)  Dosage: Solution or Ointment – q4h Diane T. Adamczyk, OD, FAAO Copyright © 2024 76 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Aminoglycosides: Tobramycin  Tobramycin Ophthalmic  Spectrum: Gram(+), Gram(-), Pseudomonas A.  Similar to gentamicin  Except:  sensitive to some gentamicin resistant Pseudomonas strains  more potent against P. aeruginosa  Indications: Anterior segment infections  Also in combination with dexamethasone (TobraDex)  ADRs  Less than with other Aminoglycosides Diane T. Adamczyk, OD, FAAO Copyright © 2024 77 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Aminoglycosides: Amikacin  Amikacin  Good for treating resistant Pseudomonas aeruginosa  No ophthalmic  Solution for injection (nonocular) or extemporaneously prepared solution  Use:  Traumatic endophthalmitis: prepared for intravitreal injection  Bacterial keratitis (vision threatening): prepared for topical Diane T. Adamczyk, OD, FAAO Copyright © 2024 78 Pharm II_2024 Antibiotics Antimicrobial Affecting Protein Synthesis Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 79 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline Overview  Pharmacology  Block protein synthesis  Bacteriostatic  Broad spectrum:  Gram positive and negative  Chlamydia  Resistance (S. aureus)  Short, intermediate, long acting Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 80 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Overview  Oral Use:  Chlamydia (inclusion conjunctivitis or trachoma)  Acne rosacea, meibomianitis Free fatty acids Released from sebum by bacterial lipases Irritating and inflammatory Tetracycline: decrease lipase production  Nontuberculous phlyctenular keratoconjunctivitis  Noninfected corneal ulcers  Related to anticollagenolytic activity of systemic tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 81 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Oral Overview Oral Overview:  Antibiotic activity  Affect on free fatty acids- decreases bacterial lipase production  Anti-inflammatory effect  Anticollagenolytic activity Diane T. Adamczyk, OD, FAAO Copyright © 2024 82 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Overview Topical Use: Prophylaxis gonococcal ophthalmia neonatum (ophthalmic topical – no longer available US) Diane T. Adamczyk, OD, FAAO Copyright © 2024 83 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview  Adverse Reactions  Depress bone growth  Drug attracted to embryonic and growing bone tissue > form tetracycline-calcium complex > temporarily depressing bone growth  Intracranial hypertension (pseudotumor cerebri)  Mechanism: may be decrease cerebrospinal fluid absorption, at arachnoid villi Diane T. Adamczyk, OD, FAAO Copyright © 2024 84 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline Oral Overview  Absorption affected by:  Food (not doxycycline)  Iron containing tonics or antacids containing calcium, magnesium or aluminum  Sodium bicarbonate  Restriction with use of:  antacids,  iron,  zinc  dairy products,  vitamin-mineral preparations Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 85 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline Oral Overview  Adverse Reactions  Hypersensitivity reactions  Anaphylaxis, urticaria, rash, periorbital edema  Photosensitivity/toxic reactions  GI irritation  With food improve, but affect drug’s absorption (not doxycycline)  Epigastric distress (sore throat, glossitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 86 Pharm II_2024 Antibiotics Drugs and Photosensitivity Reactions  Drug induced photosensitivity may be result from:  Phototoxic reaction: damage to tissues is direct  Photoallergic reaction: damage to tissues is immunologically mediated  Usually reaction results from UV-A and UV-B  May result from various drugs for example:  Phenothiazines, amiodarone, NSAIDs, antimicrobials  e.g. tetracyclines, NSAIDs, sulfonamides (UV-A primarily) Diane T. Adamczyk, OD, FAAO Copyright © 2024 87 Pharm II_2024 Antibiotics Drugs and Photosensitivity Reactions  Drug induced photosensitivity: when exogenous molecules in the skin absorb normally harmless doses of visible and UV light >>> leading to acute inflammatory response  Can be topical or systemic drug  UV rays may be artificial or natural  Drug photosensitivity: foreign molecules (exogenous chromophores) absorb normally harmless doses of UV and visible radiation and create electronically excited state  Absorbed photons converted to chemical energy with the transfer of energy resulting in erythema, edema, blistering Diane T. Adamczyk, OD, FAAO Copyright © 2024 88 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview  Adverse Reactions  Changes during tooth development  Discoloration, dysgenesis, staining, caries Diane T. Adamczyk, OD, FAAO Copyright © 2024 89 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview  Adverse Reactions  Depress bone growth  Drug attracted to embryonic and growing bone tissue > form tetracycline-calcium complex > temporarily depressing bone growth  Intracranial hypertension (pseudotumor cerebri) Diane T. Adamczyk, OD, FAAO Copyright © 2024 90 Pharm II_2024 Antibiotics Tetracycline and Pseudotumor  Minocycline  May or may not have symptoms Symptoms may include headache, transient visual obscurations, diplopia, tinnitus, nausea/vomit  Pseudotumor resolves with d/c drug  May develop 2 months to year after use  Some may have residual disc pallor or swelling  Some may have residual visual field defect  Mechanism: may be decrease cerebrospinal fluid absorption, possibly by effect on cyclic adenosine monophosphate at arachnoid villi Diane T. Adamczyk, OD, FAAO Copyright © 2024 91 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview  Adverse Reactions  Blood dyscrasias  Potentiate coumarin type anticoagulant effect (affect blood clotting)  Vestibular toxicity (minocycline)  Lightheadedness, loss of balance, dizziness, nausea, tinnitus Pharmacology Lippincott’s Illustrated Reviews 4th Ed 2009 Diane T. Adamczyk, OD, FAAO Copyright © 2024 92 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Oral Overview  Contraindications  Avoid during pregnancy (prior Pregnancy Category D)  May use short-term while breastfeeding-theoretical risk of permanent infant bone and teeth discoloration with prolonged use  Children under 8 years Diane T. Adamczyk, OD, FAAO Copyright © 2024 93 Pharm II_2024 Antibiotics Tetracyclines: The Drugs Diane T. Adamczyk, OD, FAAO Copyright © 2024 94 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline : Tetracycline  Tetracycline (Generic)  Use:  Chlamydia  Acne Rosacea  Meibomianitis  Resistant sebaceous blepharitis *  Doxycycline > -  Tetracycline of choice for: morelikely to use blc WI  Chlamydia can take food  Acne rosacea  Meibomianitis  Ocular surface inflammatory disease Diane T. Adamczyk, OD, FAAO Copyright © 2024 95 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline : Tetracycline  Tetracycline (Generic) Dosage:  Spectrum: Gram(+), Gram(-); Chlamydia  Accumulate in Sebaceous Glands  Avoid pregnancy and lactation (prior Pregnancy category D)  Resistance can be a problem Diane T. Adamczyk, OD, FAAO Copyright © 2024 96 Pharm II_2024 Antibiotics Drugs.com 1-29-23 Epocrates 1-29-23 Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 97 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline : Tetracycline  Tetracycline (Generic) Dosage Considerations:  Should be taken on empty stomach (no food or dairy products 1 hr before/2 hr after)  250 mg & 500 mg capsules  Adults and children > 8 years old:  Use: rosacea, meibomianitis, resistant sebaceous blepharitis  Use weeks to months, taper with improvement Treatment Example: Meibomian Gland Dysfunction: tetracycline 250 mg qid x 3-4 wks Diane T. Adamczyk, OD, FAAO Copyright © 2024 98 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline : Tetracycline  Tetracycline Ophthalmic  No longer available in US  Use: ophthalmia neonatorum prevention  Replaced by erythromycin ophthalmic ointment Diane T. Adamczyk, OD, FAAO Copyright © 2024 99 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 100 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Doxycycline  Doxycycline (Vibramycin)  Use  Tetracycline of choice for:  Chlamydia infections (inclusion conjunctivitis, trachoma, etc.)  Acne rosacea  Meibomianitis  Ocular surface inflammatory disease  May have anti-inflammatory properties by suppressing interleukin activity  Various cap, tab, susp, inj  Depending on brand, may take with food  Note: ORACEA -Take on an empty stomach (1 hr before/2 hr after meal) immediat/sustained release of ↳ doxly cyclin  Pregnancy: avoid and Lactation: avoid if >3 wk tx (Category: D) - - - Diane T. Adamczyk, OD, FAAO Copyright © 2024 101 Pharm II_2024 Antibiotics Doxycycline Epocrates 1-29-23 Diane T. Adamczyk, OD, FAAO Copyright © 2024 102 Pharm II_2024 Antibiotics  Recalcitrant Recurrent Corneal Erosion:  Treatment:  Doxycycline (50 mg, BID) x 2 months AND  Topical steroid (e.g. prednisolone acetate 1% or fluorometholone) TID x 2-3 weeks  These meds decrease activity of metalloproteinase-9 in the corneal epithelium  This has been found to be increased in RCE and ocular rosacea patient  Rapid resolution and no further recurrences  Small sample size: 7 patients AmJOphthal 2001;132:8-13 Diane T. Adamczyk, OD, FAAO Copyright © 2024 103 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Doxycycline  Doxycycline (ORACEA) : approved for rosacea  40 mg capsule  Filled with 2 types of doxycycline beads =  30mg immediate release and  10 mg delayed release  Take QD in AM empty stomach Diane T. Adamczyk, OD, FAAO Copyright © 2024 104 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Doxycycline Ocular Rosacea:  Doxycycline: 100 mg bid x 2 wks (then taper) OR  Doxycycline (ORACEA)  40 mg capsule (30mg immediate release and 10 mg delayed release doxycycline)  40 mg qAM (empty stomach) OR  Erythromycin: 250 mg qid or Azithromycin 500 mg/day for 3 cycles with 7-day intervals Diane T. Adamczyk, OD, FAAO Copyright © 2024 105 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Tetracycline: Doxycycline  Doxycycline: Treatment Example: Rosacea: Doxycyline100mg BID x 1-2 weeks (then taper, maintain 20-100 mg/day or less than daily) Diane T. Adamczyk, OD, FAAO Copyright © 2024 106 Pharm II_2024 Antibiotics Tetracyclines and Pseudotumor  Purpose: determine use of tetracycline class antibiotic association with increased risk of developing pseudotumor cerebri syndrome  Results:  12-50 yo: incidence of tetracycline induced PTCS 63.9 per 100,000 person-years  vs incidence of idiopathic intracranial hypertension (IIH) < 1 per 1000,000 person-years  Conclusion:  Causative link not firmly established, study suggests PTC among tetracycline users significantly higher than incidence of IIH in general population Diane T. Adamczyk, OD, FAAO Copyright © 2024 107 Pharm II_2024 Antibiotics Tetracyclines and Pseudotumor Background:  PTCS characterized by increased intracranial pressure with normal brain parenchyma (no hydrocephalus, no mass, no underlying infection etc.)  Associated HA, transient visual obscurations, diplopia, pulsatile tinnitus  Causative link with use of tetracycline not firmly established  association based on onset and d/c of drug recognized  PTC-T in younger, those less likely to be obese, with shorter duration and lower recurrence vs IIH  In this study, almost all women, signs/symptoms within 30 days of starting drug and improved with d/c Diane T. Adamczyk, OD, FAAO Copyright © 2024 108 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Macrolides Diane T. Adamczyk, OD, FAAO Copyright © 2024 109