Lecture 3 OcPharm AntiBiotics54.pdf

Pharm II_2024 Antibiotics Anti-infec tive Overview > Drug c onsid e ra tions > Selective toxicity > Spectrum of activity > Spec ies whic h drug shows intrinsic a c tivity > Na rrow vs broa d > Resistance Diane T. Adamczyk, OD, FAAO Copyright © 2024 28 28 Pharm II_2024 Antibiotics > Accurate diagnosi...

Pharm II_2024 Antibiotics Anti-infec tive Overview > Drug c onsid e ra tions > Selective toxicity > Spectrum of activity > Spec ies whic h drug shows intrinsic a c tivity > Na rrow vs broa d > Resistance Diane T. Adamczyk, OD, FAAO Copyright © 2024 28 28 Pharm II_2024 Antibiotics > Accurate diagnosis Guidelines: Effective Antimic robial Therapy > M ic roorga nism se nsitive to a nti-infe c tive > Le a st toxic d rug > Adequate drug levels > Optimum route of administration > Appropriate dosage > Appropriate treatment time > A ugme nt d rug tx with physic a l proc e d ure s Diane T. Adamczyk, OD, FAAO Copyright © 2024 29 -how do you know which antimicrobial to pick à based on the right diagnosis -you want to pick least amount of drug, least amount of time, greatest effect -root of administration is also impt -augment the drug à so if pt has blepharitis you prescribe antibiotic with steroids along with proper lid hygiene 29 Pharm II_2024 Antibiotics > Ina c c ura te d ia gnosis Antimic robial Failure > Resistance > Inadequate drug dosage > Noncompliance > Inadequate supplemental physical procedures > Ina d e qua te immune syste m re sponse Diane T. Adamczyk, OD, FAAO Copyright © 2024 30 -static drug à won’t be effective if pt has inadequate immune system 30 Pharm II_2024 Antibiotics Antibac terial:Affec ting C ell Wall Synthesis Diane T. Adamczyk, OD, FAAO Copyright © 2024 31 31 Pharm II_2024 Antibiotics Antibacterial: Affec ting Cell Wall Synthesis Penicillins Cephalosporin Vancomycin Bacitracin Diane T. Adamczyk, OD, FAAO Copyright © 2024 32 -vancomycin à think of MRSA and it’s a very toxic drug and that’s why its not used frequently 32 Pharm II_2024 Antibiotics > Inhibition of c e ll wa ll synthe sis Antibacterial: Affec ting Cell Wall Synthesis > Penicillins > Amoxic illin a nd c la vula na te (Augmentin) > Dicloxacillin > Cephalosporins > C epha lexin (Keflex) > C efa c lor (C ec lor=bra nd d/c US) > Bacitracin à comes in an ointment not solution bc the stability is better in an ointment > Vancomycin Diane T. Adamczyk, OD, FAAO Copyright © 2024 33 33 Pharm II_2024 Antibiotics Antibacterial: Affec ting C ell Wa ll Synthesis Penicillins Bacterial Cell W all Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 34 -cell wall of the bacteria is going after the cross linked peptides that are part of bacterial cell wall -penicillin is preventing the bonding of the two cross linked peptides 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 > Nec essa ry for biologic a l a c tivity > Sid e c ha in > Determines a ntiba c teria l spec trum > Susceptibility to bacterial degradative enzymes (B-la c ta ma se enzymes) > Pha rma c okinetic properties > Bactericidal > Effec tive:Gram +, Gram – Lippincott’s Illustrated Reviews. Pharmacology. Diane T. Adamczyk, OD, FAAO Copyright © 2024 35 -penicillin contains thiazoline ring beta lactam ring and the side chains -slight variations in the side chain -for bacteria resistance à makes an enzyme called penicillinase and this goes after the penicillin so it becomes inactive 35 Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Penic illins: Use > Penic illins Use: Hordeolum Preseptal cellulitis Dacryocystitis Dacryoadenitis Diane T. Adamczyk, OD, FAAO Copyright © 2024 36 36 Pharm II_2024 Antibiotics Antibacterial: Affecting Cell Wall Synthesis Penicillins > A dve rse Re a c tions > Hypersensitivity response > GI irritation: Nausea, vomit, diarrhea > Superinfection Diane T. Adamczyk, OD, FAAO Copyright © 2024 37 -diarrhea à common side effect but doesn’t mean the pt is allergic to penicillin -people who are truly allergic produce an anaphylactic reaction and could possibly die -superinfection à you think you are suppressing the infection but in turn it overpowers the infection 37 Pharm II_2024 Antibiotics Penic illin Allergy > ~10%report allergy to penicillin (higher in older and hospitalized patients > However, hypersensitivity uncommon ( Cross-react penicillin and cephalosporin ~2%(vs 8%previously reported) Diane T. Adamczyk, OD, FAAO Copyright © 2024 38 -allergic reactions are not high as they used to be 38 Pharm II_2024 Antibiotics > Low risk history > Nonallergic symptoms (e.g. GI symptoms) > Direct amoxicillin challenge > M ode ra te risk history > Urticaria or other pruritic rashesàwant to get the pt skin tested > Penicillin skin testing > High risk history à do not give penicillin > Anaphylaxis, +penicillin skin testing, recurrent penicillin reactions, or hypersensitivitiesto multiple B-lactam antibiotics Diane T. Adamczyk, OD, FAAO Copyright © 2024 39 -person should get tested if they truly are allergic to penicillin 39 Pharm II_2024 Antibiotics Antibac terial:Affec ting C ell Wall Synthesis Penic illins:Classific ation > Penic illin C la ssific ation: 1. Penic illins effec tive Gram + > Penic illin G (IV, IM), Penic illin V (PO) 2. Penic illins resistant to penic illinase > Dic loxac illin:PO 3. Penic illins with extended spec tra of ac tivity, with improved ac tivity against Gram > Amoxicillin, Amoxicillin and clavulanate (Augmentin): PO 4. Penicillin with antipseudomonal activity Diane T. Adamczyk, OD, FAAO Copyright © 2024 40 -bacteria that developed the enzyme penicillinase à dicloxacillin is used for that bacteria 40 Pharm II_2024 Antibiotics Drugs:Affec ting C ell Wall Synthesis Penicillins Inhibition of cell wall synthesis Penicillins Amoxicillin and clavulanate (Augmentin) Dicloxacillin Diane T. Adamczyk, OD, FAAO Copyright © 2024 41 41 Pharm II_2024 Antibiotics Drug Penicillins: Amoxicillin and Clavulanate > Penicillins with extended spectra of activity (Amoxicillin/clavulanate) > Modification of basic penicillin structure > Inactivated by penicillinase > Clavulanate: > B-lactamase inhibitor that protects penicillin component from inactivation by penicillinase or B-lactamase > Wea k a ntimic robia l a c tivity > Amoxicillin and clavulanate (Augmentin) Diane T. Adamczyk, OD, FAAO Copyright © 2024 42 -amoxicillin can be inactivated by penicillinase so clavulanate is added -purpose of the clavulanate is to protect the amoxicillin from the smart bacteria that have the enzyme beta lactamase thinking it has to break down the amoxicillin -virtually has no antimicrobial activity -augmentin is the combination of the two drugs 42 Pharm II_2024 Antibiotics Penic illins: : Amoxic illin/C la vula na te > Am oxicillin/Clavulanate (Augmentin) > M a y b e use d d uring p re g na nc y a nd b re a stfe e d ing > C linic a l use s: > Hordeolum > Pre se p ta l c e llulitis > Dacryocystitis > Dacryoadenitis Tre a tme nt Exa mp le : Pre se p ta l c e llulitis: Adult: Amoxicillin/clavulanate 875/125 mg q12h (with or without meal, better with food to lessen stomach upset) Children: Amoxicillin/clavulanate: 25-45mg/kg/day in 2 divided doses (q12h) Diane T. Adamczyk, OD, FAAO Copyright © 2024 43 -won’t ask specifics in this instance for prescribing 43 Pharm II_2024 Antibiotics Epocrates Diane T. Adamczyk, OD, FAAO Copyright © 2024 44 -from epocrates 44 Pharm II_2024 Antibiotics Presepa tC l eu ls itl(Chd liren): Amoxiciln/clavulanate: 25-45mg/kg/dayn i2dv id ieddoses(q12h) -56 lb child = 25.4 kg -Rx: 30 mg/kg/day divided q12h (use amoxicillin mg dose) -Calculated: 762 mg(total per day)/2(bid)=381mg bid -AvailableChewable:200mg/28.5or400mg/57mg Use: 400mg/57mg po BID -vailableSusp:125mg/31.25mg/5mLsusp A -Note: 30.48 mL=762mg -30.48 mL (total per day)/2(BID)=15.24mL BID or 1 tablespoon BID (15.24mL~3.1 teaspoon=1 tablespoon) Diane T. Adamczyk, OD, FAAO Copyright © 2024 45 45 Pharm II_2024 Antibiotics Drugs: Affec ting C ell Wa ll Synthesis Penic illins: Dic loxa c illin > Penic illins resistant to penic illinase: Dic loxac illin > A penicillinase resistant penicillin that is NOT inactivated by bacterial penicillinase enzyme (that would otherwise destroy the beta-lactam ring o f the a ntib io tic ) > M a y b e use d d uring p re g na nc y a nd b re a stfe e d ing > C linic a l use s: > Internal Hordeolum > Preseptal c ellulitis > Tre a tme nt Exa mp le : Inte rna l Ho rd e o lum Dic lo xa c illin: 250mg q 6h (1-2w ks) (e mp ty sto ma c h)(1 hr b e fo re , 2 hr a fte r me a ls) Diane T. Adamczyk, OD, FAAO Copyright © 2024 46 -summary slide 46 Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Cephalosporins Diane T. Adamczyk, OD, FAAO Copyright © 2024 47 47 Pharm II_2024 Antibiotics > Mechanism of action similar to Penicillins > Spectrum: Gram(+), Gram(-) > Classified as first, second, third, fourth generations drugs Cephalosporins Diane T. Adamczyk, OD, FAAO Copyright © 2024 > 1st to 4th generation: > G rea ter gra m(-) a c tivity with subsequent genera tions > Less efficacy against gram positive with subsequent generations > Greater efficacy against resistant organisms with subsequent genera tions 48 -as you get go up a generation, it’s going to have a greater effect on gram neg and the lower generations have a greater efficacy on gram pos 48 Pharm II_2024 Antibiotics Antibac terial:Affec ting C ell Wall Synthesis Cephalosporins > Pharmacology > B lactam ring > Similarpenicillin/similar mechanism > Addition of different side chains modify and create 1,2,3 generations > Broad spectrum > Bactericidal > Resistance > Drug inactivation by B lactamases Diane T. Adamczyk, OD, FAAO Copyright © 2024 49 49 Pharm II_2024 Antibiotics Antibac terial:Affec ting C ell Wall Synthesis Cephalosporins > Adverse reactions > Hypersensitivity reactions > Cross sensitivity > 20%penicillin allergy with cross sensitivity was historic thinking, but probably much less– approximately 1% > More likely see with 1st generation cephalosporins > Vitamin K deficiency > Nausea, vomit, diarrhea Diane T. Adamczyk, OD, FAAO Copyright © 2024 50 -vit k plays a role in blood clotting so cephalosporins can cause bleeding with vit k deficiency 50 Pharm II_2024 Antibiotics Antibac terial:Affec ting C ell Wall Synthesis Cephalosporins > Clinical Conditions: > Preseptal cellulitis > Dacryocystitis > Dacryoadenitis > Orbital fracture > Other (fortified use) à specially made in a special pharmacy to give a higher concentration Diane T. Adamczyk, OD, FAAO Copyright © 2024 51 51 Pharm II_2024 Antibiotics Cephalosporins: Cephalexin > First G e ne ra tio n: C e p ha le xin (Ke fle x) > M a y be used during pregna nc y a nd brea stfeeding > C linic a l use:à allthesedrugs are oral > Preseptal cellulitis > Dacryocystitis > Dacryoadenitis Trea tment Exa mple: Dacryoadenitis: Cephalexin 250-500 mg QID(or q6h) (with orwithout meals) Preseptal Cephalexin 500 mg TID or 875 mg BID (with orwithout meals) Diane T. Adamczyk, OD, FAAO Copyright © 2024 52 52 Pharm II_2024 Antibiotics Drug Cephalosporins:Cefazolin > First G e ne ra tion: C e fa zolin > Dosage form: injection > May be used during pregnancy and breastfeeding > Fortified: > Sterile water and 500 mg of cefazolin dry powder to form 10 mL of solution =strength of 50 mg/mL Treatment Example: > Bacterial keratitis: fortified cefazolin (50 mg/mL) Diane T. Adamczyk, OD, FAAO Copyright © 2024 53 -understand the concept of a fortified solution 53 Pharm II_2024 Antibiotics Antibacterial:Affecting Cell Wall Synthesis Bacitracin Diane T. Adamczyk, OD, FAAO Copyright © 2024 54 54