OcPharm Antibiotics Lecture 3 2024 PDF

Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Bacitracin Diane T. Adamczyk, OD, FAAO Copyright © 2024 54 54 Pharm II_2024 Antibiotics Drugs: Affec ting C ell Wa ll Synthesis Bacitracin > Spectrum: Gram + > Bactericidal > Ointment > Single Entity =Bacitracin alone (no longer a...

Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Bacitracin Diane T. Adamczyk, OD, FAAO Copyright © 2024 54 54 Pharm II_2024 Antibiotics Drugs: Affec ting C ell Wa ll Synthesis Bacitracin > Spectrum: Gram + > Bactericidal > Ointment > Single Entity =Bacitracin alone (no longer available US) > Combination Formulations: > Polyc in = Ba c itra c in+Polymyxin B > M a y be used pregna nc y a nd breastfeeding > Indication: Blepharitis > Dosage: q3-4h Diane T. Adamczyk, OD, FAAO Copyright © 2024 55 -not a family of drugs -comes in ointment form and can be in combination with other drugs -biggest use is for blepharitis 55 Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Vancomycin Diane T. Adamczyk, OD, FAAO Copyright © 2024 56 -think MRSA 56 Pharm II_2024 Antibiotics Drug Vanc omyc in > Pharmacology > Bactericidal > Dosa ge c onsidera tions > Use during pregna nc y: > > > Highlyactive gram positive Solution for injection, capsule, dry powder (for fortified) > Drugs.com:use only if clearly needed > Epocrates: Inj-avoid 1st and 2nd trimesters; weigh risk/benefit 3rd trimester > Epocrates: Other formulations: may use during pregnancy and breastfeeding Highly toxic > Anaphylaxis, vasculitis, nephrotoxicity, ototoxicity, neutropenia, others Diane T. Adamczyk, OD, FAAO Copyright © 2024 57 -biggest use is for MRSA -highly toxic systemically -highly active against the gram pos -can also be fortified 57 Pharm II_2024 Antibiotics Drug Vanc omyc in > Use: > Bacterial endophthalmitis > Methic illin/penic illin resistant infec tions > Bac terial keratitis – vision threatening > Ruptured globe > Orbital cellulitis Treatment example: > Bacterial keratitis (resistant/vision threatening): fortified vancomycin (25 mg/mL) q1h Diane T. Adamczyk, OD, FAAO Copyright © 2024 58 58 Pharm II_2024 Antibiotics Ototoxic ity and Drug Therapy > Ototoxic ity is typic ally assoc iated with bilateral high-frequenc y sensorineural hearing loss and tinnitus. > Hearing loss can be temporary but is usually irreversible with most agents. > Generally, antibiotic-induced ototoxicity is bilaterally symmetrical, but it c an be asymmetric al. > The usual time of onset is often unpredictable, and marked hearing loss c an oc c ur even after a single dose. > Additionally, hearing loss may not manifest until several weeks or months after completion of antibiotic or antineoplastic therapy. Medscape Diane T. Adamczyk, OD, FAAO Copyright © 2024 59 -a lot of drugs cause ototoxicity but is seen more in vancomycin -hearing loss is temporarily and can be reversible but sometimes its not and can be unilateral or bilateral -ototoxicity with vancomycin is unpredictable meaning you can be off of the drug and it will still have an effect or you can take one dose and notice hearing loss 59 Pharm II_2024 Antibiotics Antibac terial: Affecting C ytoplasmic Membrane Diane T. Adamczyk, OD, FAAO Copyright © 2024 60 60 Pharm II_2024 Antibiotics Drugs Affec ting: Cytoplasmic Membrane 2-Polymyxin Gramicidin Diane T. Adamczyk, OD, FAAO Copyright © 2024 61 -drug is going after the cytoplasmic membrane causing an imbalance in osmotic gradient between the internal aspect of the bacteria and the external environment 61 Pharm II_2024 Antibiotics Mec hanisms of Antibiotic Action Diane T. Adamczyk, OD, FAAO Copyright © 2024 > Increased bacterial cell membrane permeability > Polymyxin B > Gramicidin 62 62 Pharm II_2024 Antibiotics Antibacterial: Affecting Cytoplasmic Membrane: Polymyxin B Diane T. Adamczyk, OD, FAAO Copyright © 2024 63 63 Pharm II_2024 Antibiotics Drugs:Affec ting Cytoplasmic Membrane Polymyxin B > Polymyxin B: > Pharmacology > Interactswith the bacterial cell membrane >>>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 -bactericidal and goes against pseudomonas which is bacteria relatively seen in CL wearers -ex. Pt comes in and the have a corneal ulcer secondary to CL wear. Fluroquinolone helps with going after the corneal ulcers and would be used during the day and at night you would use polymyxin b bc fluroquinolone goes against the DNA gene and polymyxin b goes after cytoplasmic membrane -this is a way to attack the corneal ulcer bc instead of going after one mechanism the combination of 2 drugs with 2 different mechanisms helps better fight the infection 64 Pharm II_2024 Antibiotics Drugs: Affecting Cytoplasmic Membrane Polymyxin B C ombos > Com bo Drugs: > With other antibiotics(various) > Polymyxin B/Neomyc in/G ra mic idin (Neosporin) > Polymyxin B/Trimethoprim (Polytrim) > Polymyxin B/Ba c itra c in (Polyc in) > Polymyxin B/Bacitracin/Neomycin (Neo-Polycin) > With steroids > Polymyxin B/ba c itra c in/neomyc in/hydroc ortisone Diane T. Adamczyk, OD, FAAO Copyright © 2024 65 -polytrim is the most popular drug used in kids who get pseudomonas or conjunctivitis or bacitracin - 65 Pharm II_2024 Antibiotics Antibacterial: Affecting Cytoplasmic Membrane: Gramicidin Diane T. Adamczyk, OD, FAAO Copyright © 2024 66 66 Pharm II_2024 Antibiotics Drugs: Affecting Cytoplasmic Membrane: Gramicidin > Gramicidin > Inte ra c ts with the ba c te ria l c e ll me mbra ne >>>disrupting the c e ll’s osmotic inte grity (like polymyxin B) > Bactericidal (?some static activity?) > G ra m positive > Combination: > Polymyxin B/Neomycin/Gramicidin (Neosporin) > M a y use during pregna nc y a nd brea stfeeding Diane T. Adamczyk, OD, FAAO Copyright © 2024 67 -goes after cell membrane and gram pos whereas polymyxin b goes against gram neg -used in combination with drugs such as neomycin 67 Pharm II_2024 Antibiotics Antibacterial: Affecting Protein Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 68 68 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 Aminoglyc osides Macrolides Tetracyclines C hlora mphenic ol Clindamycin 69 69 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis > Inhibition of bacterial protein synthesis > Aminoglycosides à big antibiotic used ocular conditions > Neomycin > Gentamicin > > > Tobramycin Macrolides > Erythromycin > Azithromycin > Clarithromycin Tetracyclines > Tetrac yc line > Doxyc yc line > Minoc yc line > > Chloramphenicol Clindamycin Diane T. Adamczyk, OD, FAAO Copyright © 2024 70 -chloramphenicol à causes aplastic anemia which is why it isn’t commonly used in US 70 Pharm II_2024 Antibiotics Antibacterial: Affec ting Protein Synthesis Aminoglycosides Diane T. Adamczyk, OD, FAAO Copyright © 2024 71 71 Pharm II_2024 Antibiotics Antib a c teria ls: Affec ting Protein Synthesis Aminoglycosides Pharmacology Inhibit bacterial protein synthesis: By binding to bacterial ribosome Bactericidal G ram negative and positive Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 72 -bacteria and humans both have ribosomes but have different forms of ribosomes -binds to the 30s ribosome subunit and interferes with the protein synthesis -bacteria changed their ribosome leading to resistance 72 Pharm II_2024 Antibiotics Antib a c teria ls: Affec ting Protein Synthesis Aminoglycosides Pharmacology Resistance (Gram negative bacilli) Alteration of bac terial ribosomes Dec reased antibiotic uptake Enzymatic inac tivation of the drug Cross resistance (e.g. Gentamicin and tobramycin) Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 73 -resistance have developed with the aminoglycosides esp with gram neg 73 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Aminoglyc osides Diane T. Adamczyk, OD, FAAO Copyright © 2024 > Neomycin > G e nta mic in > Tobramycin > Amikacin 74 -first 3 are commonly used ocularly 74 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Aminoglyc osides:Neomyc in > Ne o myc in O p htha lmic > Bro a d sp e c trum a ntib a c te ria l > G ra m p o sitive a nd G ra m ne g a tive b a c te ria > Ine ffe c tive P. a e rug ino sa > Ne o myc in In c o mb ina tio n w ith va rio us d rug s: > Po lymyxin B/g ra mic id in > Po lymyxin B/b a c itra c in > Po lymyxin B/b a c itra c in/hyd ro c o rtiso ne > Polymyxin B/dexam ethasone > Po lymyxin B/hyd ro c o rtiso ne > Ne o myc in A DRs > Drug sensitization (contact dermatitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 75 -not the best to use against psudomonas à think CL wearer -can also be combined with steroids 75 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Aminoglyc osides:Gentamic in > Gentamicin Ophthalmic > Spectrum: > Use: > ADRs: (rare) > Dosa ge: Solution or O intment – q4h > Gram(+), Gram(-), Pseudomonas a. > In General NOT Effective against Streptococcus > Anterior segment infec tions > Corneal and c onjunc tival toxic ity > Allergic rx (50%of those allergic to neomyc in) Diane T. Adamczyk, OD, FAAO Copyright © 2024 76 -50% of people who are allergic to neomycin are also allergic to gentamicin 76 Pharm II_2024 Antibiotics Drugs Affecting Protein Synthesis Aminoglycosides:Tobramycin > Tobra myc in O phtha lmic > Spec trum: G ra m(+), G ra m(-), Pseudomona s A. > Simila r to genta mic in > Except: > sensitive to some genta mic in resista nt Pseudomona s stra ins > more potent a ga inst P. aeruginosa > Indications: Anterior segment infections > Also in c ombina tion with dexa metha sone (Tobra Dex) > ADRs > Less tha n with other Aminoglycosides Diane T. Adamczyk, OD, FAAO Copyright © 2024 77 -don’t get the same sensitivity response you get with neomycin -effective against gram pos neg and pseudomonas so better option if someone is allergic to gentamicin -less adverse effects than the other aminoglycosides and is better drug in the aminoglycosides for anterior segment infections -tobradex is the most commonly prescribed ocular medication by ER docs when a pt comes in with a red eye 77 Pharm II_2024 Antibiotics Drugs Affec ting Protein Synthesis Aminoglyc osides:Amikac in > Amikacin > Good fortreating 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 -can be specially formulated in times such as a pt has endophthalmitis or bacterial keratitis 78 Pharm II_2024 Antibiotics Antimic robia l Affec ting Protein Synthesis Tetracycline Diane T. Adamczyk, OD, FAAO Copyright © 2024 79 79 Pharm II_2024 Antibiotics Antimic robia ls Affec ting Protein Synthesis Tetracycline Overview > Pharmacology > Block protein synthesis > Bacteriostatic > Broad spec trum: > Gram positive and negative > Used for Chlamydia > Resistanc e developed towards (S. aureus) > Short, intermediate, long acting Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 80 80 Pharm II_2024 Antibiotics Antimicrobials Affecting Protein Synthesis Tetracycline: Overview > Oral Use: > Chlam ydia (inclusion conjunctivitis or trachom a) > A c ne ro sa c e a , me ib o mia nitis 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 -goes after and into the glands to do its job by going after the free fatty acids -bacteria are releasing the sebum and the free fatty acids are irritated and inflamed -tetracycline go after the bacteria but its major job is going after the irritation and inflammation -thinning of the cornea is a noninfected corneal ulcer and the cornea is thinning not bc of a bacteria but due to the enzymes that are breaking down the collagen -collagenolytic à break down of collagen and tetracycline is a anti collagenolytic so its against breaking down collagen 81