Lecture 3 OcPharm AntiBiotics 2024 PDF

Pharm II_2024 Antibiotics Anti-infec tive Drugs Antibiotics Ocular Pharmacology Dia ne T. A da mc zyk, O D Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 1 Pharm II_2024 Antibiotics Anti-infective and Ba c teria l O verview Diane T. Adamczyk, OD, FAAO Copyright © 2024 2 2 Pharm II_2024 Antibiotics A...

Pharm II_2024 Antibiotics Anti-infec tive Drugs Antibiotics Ocular Pharmacology Dia ne T. A da mc zyk, O D Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 1 Pharm II_2024 Antibiotics Anti-infective and Ba c teria l O verview Diane T. Adamczyk, OD, FAAO Copyright © 2024 2 2 Pharm II_2024 Antibiotics Anti-infec tive Overview > Normal flora > Considerations for infection > Barriers: skin and mucous membranes > Immune status > Organism > Vira l, ba c teria , fungi Diane T. Adamczyk, OD, FAAO Copyright © 2024 3 -GI tract has normal flora and similar to that we have normal flora in our eyes to keep things in balance -when we disrupt normal flora from an infection there’s an abundance of bacteria and we can disrupt the normal flora by taking antibiotics to kill/suppressing bad bacteria but also has an effect on good bacteria -when prescribing antibiotics we have to think about the pt immune system status such as if they are immunocompromised -understand the organism that’s causing the infection bc antibiotics do nothing for viruses -oral use of antibiotics can help develop resistance to the antibiotic 3 Pharm II_2024 Antibiotics Normal Mic robial Flora > C a n va ry be twe e n ind ivid ua ls > C an becom e 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 4 Pharm II_2024 Antibiotics Normal Oc ular 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 oc c a siona lly re c ove re d from non-infe c te d e ye s Diane T. Adamczyk, OD, FAAO Copyright © 2024 5 5 Pharm II_2024 Antibiotics Bacteria > Bacteria: single celled microorganisms > Sub d ivid e d b y sha p e a nd g ra m sta in > Gram Positive > Staphylococcus (aureus, epidermidis) > Streptococcus (pneumonia, pyogenes, faecalis) > Gram Negative > Rods: Haemophilus influenzae, Pseudomonas a e ruginosa , Se rra tia ma rc e sc e ns > C oc c i: Ne isse ria gonorrhoe a e > Unique structural morphology includes > Chlam ydia (trachom a, inclusion conjunctivitis) > Tre p o ne ma p a lla d ium (syp hilis) > Mimic viruses Diane T. Adamczyk, OD, FAAO Copyright © 2024 6 6 Pharm II_2024 Antibiotics Anti-infec ti Overview Diane T. Adamczyk, OD, FAAO Copyright © 2024 7 -antibiotic goes after cell wall and being selective against what it is going after 7 Pharm II_2024 Antibiotics Antibac terial Drugs > Ba c te ric id a l: kills ba c te ria > Minimum bactericidal concentration (MBC) is the minimum concentration of drug which can kill 99.99%of the organism population > Ba c te riosta tic : inhibit ba c te ria 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 -bacteriostatic has to work with the immune system in order to to go after the microorganism and inhibit bacteria growth whereas bactericidal doesn’t need to work with the immune system bc the drug is going to do it -ex. Some drugs such as macrolides overlap and are bacteriostatic but at high concentrations its bactericidal 8 Pharm II_2024 Antibiotics Antibac terial Drugs > Ba c te ric id a l: kills ba c te ria > Ba c te riosta tic : inhibit ba c te ria growth Diane T. Adamczyk, OD, FAAO Copyright © 2024 9 9 Pharm II_2024 Antibiotics Antibac terial Drugs > Selec tive toxic ity (bac teria vs human) > Ba c te ria : c e ll wa ll (humans don’t) > Antibacterial drug:Inhibit synthesisof cell wall > C e ll me mbra ne > Similar between bacteria and humans > Ribosomes > Different size and composition > Inhibit bacterial protein synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 10 10 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 11 11 Pharm II_2024 Antibiotics Antibac terial Drugs Selec tive toxic ity (ba c teria vs huma n) Biosynthetic pa thways (intermediary meta bolism) Folic ac id:bac terial c ells synthesize Enzyme DNA gyrase à help reproduce the bacteria A n essential bacterial enzyme involved in DNA replication Diane T. Adamczyk, OD, FAAO Copyright © 2024 12 -fluroquinolone's go after the DNA gyrase 12 Pharm II_2024 Antibiotics Mec hanisms of Antibiotic Ac tion > Inhibition of cell wall synthesis > Penicillins > > > > > > Macrolides Tetracyclines > Chloramphenicol Inhibition of folic acid synthesis > > > Polymyxin B Gramicidin Inhibition of bacterial protein synthesis > Aminoglycosides > > > Cephalosporins Bacitracin > Vancomycin Increased bacterial cell membrane permeability Sulfonamides Trimethoprim Damage to bacterial DNA > Fluoroquinolones Diane T. Adamczyk, OD, FAAO Copyright © 2024 13 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 -summary chart 14 Pharm II_2024 Antibiotics Mec hanisms of Resistanc e > Bac teria l produc tion of enzymes tha t degrade/inactivate antibiotics > Pump mechanisms or decreased permeability antibiotics > Resista nc e genes > Alteration of bacterial ribosomes > C hromosomal mutation Diane T. Adamczyk, OD, FAAO Copyright © 2024 15 -resistance happens when the bacteria gets smart by producing enzymes that degrade the antibiotic or altering themselves genetically such as ribosomes and chromosomes -pump mechanism is when the bacteria pumps the antibiotic into themselves and then quickly pump it out so it doesn’t kill them but allows them to develop resistance -biggest way we are developing resistance to antibiotics is animal feed 15 Pharm II_2024 Antibiotics Mec hanisms of Resistanc e > C ross resistanc e > M isuse and overuse of antibiotic s > During the systemic use of antibiotics Inappropriate use Patient non-compliance > With the use of antibioticsin animal feed Diane T. Adamczyk, OD, FAAO Copyright © 2024 16 -biggest way we are getting resistance is bc of animal feed bc they put antibiotics in animal feed so animals eat them and we eat animals 16 Pharm II_2024 Antibiotics > C onc e rn for rising a ntibiotic re sista nt ba c te ria > FDA : limite d how a nd whe n a ntibiotic s use d for live stoc k > Use of a ntibiotic s to improve animal growth is prohibited > Use of a ntibiotic s for cattle/swine/poultry through fe e d stoc k or wa te r must c ome from dire c tive from ve te rina ria n Diane T. Adamczyk, OD, FAAO Copyright © 2024 17 17 Pharm II_2024 Antibiotics Oral Antibacterial Drugs > C linic a l Ind ic a tions > Meibomianitis > Inte rna l Hord e olum > Ocular Rosacea > Dacryocystitis > Preseptal Cellulitis > Chlamydial Conjunctivitis > Prophyla xis (orbita l fra c ture s,sinusitis) Diane T. Adamczyk, OD, FAAO Copyright © 2024 18 -topicals are good but if you need to get to deeper structures such as meibomian glands or sinus you need oral antibiotics 18 Pharm II_2024 Antibiotics Probiotic s > Probiotics are live nonpathogenic microorganisms administered to improve microbial balance, particularly in the GItract > De fine d : live mic ro o rg a nism tho ug ht to c o nfe r he a lth 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 exa mples:yogurt, sa uerkra ut, kimc hi à make probiotic > Timing: when to take (do not take with antibiotic ie space at least 2 hours before/after antibiotic doses) à making probiotic less effective > Generally safe, with flatulence and bloating most frequent side effect > Used cautiously with patients taking immunosuppressants (e.g. ta c rolimus, c hemothera py, proton inhibitors) or who a re immunoc ompromised– c a n c a use infec tion 19 -oral antibiotics will cause our GI normal flora to be out of balance and the end result can be diarrhea -don’t want to take the probiotic and the antibiotic at the same time bc it makes the probiotic less effective so wait at least 2 hours before or after so each can act the way they need to act 19 Pharm II_2024 Antibiotics > Probiotic s > Things to look for: > C olony Forming Units (C FU) – (ra nge c a n va ry 10 million to 1 billion to 50 billion C FUs) > Stra in Diversity – e.g. 8-12 sepa ra te stra ins > Stra ins – e.g. La c toba c illus a c idophilus > Prebiotics – fiber based to nourish good bacteria > Enteric c oa ted – survives stoma c h a c id > M a nufa c ture/expira tion da te – dec rea sed effec tivity with time Use Exa mples: > Dia rrhea l illness > Antibiotic-associated diarrhea > Infla mma tory bowel disea se > Irrita ble bowel syndrome > Allergic disease (atopic dermatitis, allergic asthma, allergic rhinitis, food allergies) > Atherosclerosis Diane T. Adamczyk, OD, FAAO Copyright © 2024 20 -the higher the number of colony forming units, the better the probiotic is -pay attention to expiration date à drug loses effectivity 20 Pharm II_2024 Antibiotics Probiotic s > Effec ts through: > Lowering intestina l pH (suppress growth of pathogenic bacteria, reestablishing gut flora balance) > Enha nc e muc in from gut epithelia l c ells (serve a s antibacterial barrier prevent binding of pathogens) > Promote sec retory IgA (tha t binds to pa thogens) > Interfere with quorum sensing (a mec ha nism by whic h ba c teria enha nc e their virulenc e) > Exert a nti-infla mma tory effec t in gut > Dec rea sing c oloniza tion (by c ompetitively bloc king their a dhesion to the epithelium) > Dec rea sing inva sion by pa thogenic orga nisms (production of various substances that are toxic to pa thogenic mic roorga nism) > M odifying host immune response > May activate opioid and cannabinoid receptors in gut (a meliora te visc era l pa in) Diane T. Adamczyk, OD, FAAO Copyright © 2024 21 -does a wide variety things that are very positive and very good 21 Antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 22 -how probiotics work in the gut 22 Pharm II_2024 Antibiotics Probiotic s (Food) Diane T. Adamczyk, OD, FAAO Copyright © 2024 23 -some studies support taking nutritional probiotics are helpful but it is not as controlled but this is a good way to keep your natural flora in check 23 Pharm II_2024 Antibiotics Oral Contraceptive and Antibiotics > Failure rate associated with OCs are typically 1-3% * > Va rious hypothesis: > > Decreased enterohepatic circulation, increased liver degradation, contraceptive displacement from receptor site > Antibiotic -induc ed dia rrhea > Inc rea sed liver p450 enzyme induc tion à impt bc this enzyme breaks down the drug However - Inc onsistenc ies in study findings over time if O C fa ilure with ora l a ntibiotic s *Oral contraceptive failure rates and oral antibiotics. JAmAcadDermatol 1997;36:705-10 Diane T. Adamczyk, OD, FAAO Copyright © 2024 24 -if you take oral contraceptive with antibiotics it will diminish the effects of the oral contraceptive and are more likely to get pregnant 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, USCenter for Disease Control and Prevention) do not advise any additional precautions > Thisarticle howeverbased on the uncertainties advised precautions Diane T. Adamczyk, OD, FAAO Copyright © 2024 25 -enzyme looking at cytochrome p450 inducing drugs have a 13th fold in unintended pregnancy whereas antibacterial had a 7th fold increase -non-enzyme doesn’t have much of an effect on the cytochrome p450 -advise the pt to take precautions when pt is on oral antibiotics and oral contraceptives 25 Pharm II_2024 Antibiotics Antimic robia l Drug Intera c tion a nd Wa rfa rin > Considerations: > Cephalosporins > 2n d and 3rd generation might increase warfarin effect by inhibiting production of vitamin Kdependent clotting factors, and other mechanisms > Considerations: > > IV=inhibit platelet function > Oral =increase risk of bleeding > Considermonitoring INR > Fluoroquinolones > Increased response possiblydue to > inhibition of warfarin metabolism, > displacement of warfarin from protein binding sites or > disruption of intestinal flora affecting vitamin K synthesis > MonitorINR > > Increase effect of warfarin through inhibition of hepatic metabolismof warfarin > Increased INRreported with all macrolides. (including ophthalmic erythromycin) > reduc ed warfarin c learanc e, > displac ement of warfarin from protein binding sites, > alterations in gut flora > Avoid if possible M a c rolides (e.g. a zithromyc in, erythromyc in) > MonitorINR Sulfonamides > Increased effect from > MonitorINR > Penicillins > Tetracyclines > Increased response due to unknown mechanisms > MonitorINR Pha rma c ist’ s Le tte r. Aug ust 2012 Diane T. Adamczyk, OD, FAAO Copyright © 2024 26 -warfarin is a blood thinner has a lot of interactions -macrolides à have to monitor INR or clotting ability when taking warfarin, so you have to be concerned about it -if someone is on warfarin and you’re putting them on antimicrobial you have to monitor and call the primary doctor 26 Pharm II_2024 Antibiotics Topical Antibiotic Drugs Anterior Segment Infection Conjunctivitis Corneal Ulcer Blepharitis Prophylaxis Diane T. Adamczyk, OD, FAAO Copyright © 2024 27 27