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126 Cards in this Set
- Front
- Back
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Why would you choose to use a beta-lactams?
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-safe
- efficacy - flexibility in drug dose - inexpensive |
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What is a penn made of?
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- four member b- lactam ring
- 5-member thiazolidine ring |
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Cephalopsorin?
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- four member b-lactam ring
- 6-member dihydrothiazine |
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What is the mechanism of action of the Betas?
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- act on enzymes called PBP- they bind covalently and irreversibly to the PBP and the cell wall is disprupted
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Why are they ineffective against gram neg?
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- they must diffuse through the cell wall before binding to PBP- cant get through gram - cell wall because of the lps layer decreases penetration
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What are the adverse effects of betas?
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immune mediated- autoimmune hemolytic anemia; immune mediated thrombocytopenia; anaphylaxis
- clostridium overgrowth -horses and procaine reactions |
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What is a negative aspect of using pen g?
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- low vd and VERY POOR at penetrating tissue
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What does it kill?
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- gram positive
-obligate anaerobes - some pasteurella |
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T/F aminopenicillins can penetrate the gram neg wall better than pen g, but resistance is easily acquired by gram neg
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true
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What is the major advantage of using aminopen over pen g?
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- they are oral bioavailable in small animals
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what are aminopenns inactivated by?
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beta-lactamases
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What are they available as?
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- ampicillin, amoxi, hetcillin
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why would you use a clavulanic acid or sulbactam?
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- they have very little antibacterial action of their own, but can inhibit b-lactamase
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What are the advantages of using a beta-lactamase inhibiting drug compound?
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-lower tox
-extension of antibacterial speectrum -retain activity against anaerobes |
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What is great about antistaph penn?
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- resistant to staph b-lact so great for staph but minimal for gram neg cant get past wall
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What is there resistant mechanism?
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- fail to bind to PBP- major problem for staph in humans
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True/ False- you can give this orally?
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-false
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What are antipsedomonas penn good for?
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- penetrate outer cell wall of pseudo and other gram neg but sus. to beta-lac inactivation
- retain anaerobic bact when given with aminoglycoside - no oral formulation, expensive |
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What are cephalosporins?
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- b-lactams that are resistant to the action of staph b-lactamases
- poor lipid soluble, limited intracellular and low vd - generations 1-4 gram neg spectrum increases and gram pos decreases the higher you go |
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Resistance?
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-fail to bind to PBP, or beta-lactamases
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What are the adverse effects?
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- similar to penn
- 3-7 people that are allergic to penn are allergic to this -GI irritation vomit in dogs - diarrhea in horses after ceftiofur -superinfection, alter gi flora |
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What bact can you treat 1st generation with?
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- usually gram pos cocci, inclding beta-lac producing staph, bc bind to PBP
- eclo, kleb, haemophilus, proteus, actino, pasteurella, and salm |
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What are the 3 first gen. used?
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- cefazolin
- cefadroxil -cephalexin |
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What do you use 2nd gen for?
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- gran neg bact resistant to 1st gen
- ecoli, kleb, proteus, enterobacter, less effective against gram pos - no approved vet products - cefoxitin can be used for intra-abdominal sepsis |
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What do you use 3rd for?
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- greater act against gram neg- often good against gram pos
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When would you use 3rd generation?
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- nosocomial pneumonia
- postop wound - UTI because cath |
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What are 2 3rd gen products?
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-ceftiofur
-convenia |
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When do you use ceftiofur?
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- wide spectrum for pos and neg
- widely used in cattle - uti in and small animals |
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What is converted to?
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-desfurolyceftiofur- which doesnt have same act against proteus and staph- misleading
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When do you use convenia?
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- cats and dogs, gram pos and neg, every 14 days SQ, has long 1/2 life 5 days in dogs, 6 in cats
- for pyoderma, ST and urinary infections in dogs and cats |
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What are carbapenems so strong?
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- highly resistant to most beta-lactamases
- have the post broadest spectrum of any drug |
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What are the importance of aminoglycosides?
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- bc of use against gram neg bact such as ecoli, pseduo
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What is there MOA?
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- used against aerobic bact gram neg pump drige inside cell by o2 dependent interation- must be pumped in cell wall and then create perm
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what are they good for?
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- low vd, poor distrbuted
-inefffective against gram neg - renal excretion and accumulates in kidneys for 14 months- bad in LA - no good for abcesses |
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What are the 3 top side effects?
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- nephrotoxicity
-ototoxicity -neuromuscular blockade |
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When do you use gentamicin?
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-part pseudo- also prot, kleb, e coli, staph
-dog/cat- gram neg genital and and UTRI, resp, septicemia, and ST infection, otitis externa and skin infections, opthalmic -horse/cattle- intrauterine use only but is used in horses for septicemia and before surg -swine- colibacillosis in neonates |
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What can you monitor to look for tox?
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- increase in GGT
- increase in GGT: Creat ration - proteinuria - increase BUN, creat |
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When do you use neomycin?
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- coliform enteritis in SA and LA
- can be used to in hepatic Enceph - usually topical bc nephro and ototox |
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What does chloramphenicol work?
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- bind to 50s subunit and blocker transfer of RNA stopping protein synethesis
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What does it kill?
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- broad spectrum - gram pos and anaerones, haemo, salm, pastr, myco, brucella
- high lipid soluable and low protein binding |
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Why is it bad to use in cats?
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- its eliminated by glucuronidation
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When do you use it?
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- chol is banned in LA do to ido aplastic anemia in humans
- used in SA for CNS - FLF: used for bovine resp complex |
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What are some adverse effects?
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chlor- inhibits cyp 450- decreases clearance of pheno and cyclo0 prolong anesthesia
- immunosupression - chlor- bone marrow tox- anemia: dose related and idiopathic - dont use flor n horses- causes muscle inflammation and diarrhea - cant use with other antbact- penn or amino |
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What is the MOA of sulfonamides?
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- block DPS in folic acid pathway- block folic acid production
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Where are they ineffective?
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- in pus or necrotic tissue ie abcess bc they have PABA
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What are some adverse effects?
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- crystalluria
- KCS - idosyncratic tox- bloox, polyarthritis, hepatopathies, dermatopathies in dogs- usually 7-14 after tx- so maybe dont treat more than 10 days? |
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Why are potentaited sulphonamides better?
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- synergistic so bacterialcidal
- really nontoxic to cells - resistance less likely |
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What do trimethoprin or ormetoprin do?
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- inhibit bacterial folic acid synthesis at the next step in the folic acid synthesis
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True/ Fasle- they are not lipid soluble or well distributed through the body
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false
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What are some uses?
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dog/cat- prostatitis, meningitis, toxo, pyoderma
cattle- infections with past, f. necro, corny, salm horses- strepy, salm, actino EPM |
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When would you use pyrimethamine?
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- to treat EPM myeloencephalitis in horses
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What is the MOA of tetracycline?
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- bind to 30s subunit and interfere with bact protein synthesis
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What are they good against?
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- gram pos, gram neg- chlam, myco, rickettsia, some protozoa
- doxy is good against anerobes |
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They are well distributed into most tissues except where?
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CNS- except when meninges are inflamed
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What is good/ bad about doxy?
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- not excreted renal
- but cant use for UTI |
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What do they interact with?
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- ca containing products
- interfer with GI absorption |
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What are the adverse effects?
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- GI- V/D
- renal tubular necrosis -neonates- discolored teeth -hypersen- in cats - alter gi flora in horses - rapid iv leads to hypotension and collapse- in horses causes tachycardia, hypertension, collapse and death - doxy can cause a neuromusc blockade |
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What are the clinical uses?
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cattle and sheep- oxy for past. pneumonia, mastitis, anaplasmosis, and listeria
swine- atrophic rhinitis, pneumonia from patr, and myco SA- oxy for UTI, resp infection, ophthalmic clam, rickettsial DZ birds- psittacosis horses- oxy for PHF and equine ehrlichiosis, used to treat contracted flexor tendons in calves and foals |
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What are the MOA of fluoroquinolones?
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- bind to DNA gryrase
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What are they effective against?
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- broad, gram neg and pos, myco, chlam, rickettsia
THE ONLY ONE AGAINST PSEUDO |
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What are the adverse drug effects?
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- GI most common
- arthropathy in young animals - teratogenicity - LOWER SEIZURE THRESHOLD - may increase theophylline conc in the body bc of interfering with met. -hallucinations - acute blindness in cats |
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When do you use it?
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SA- skin, resp, UTI from gram neg, staph
cattle- off label use is banned!!! enrofloxacin is only labelled for pneumonia in cattle horses- rhodococcus equi but can cause artropathies... |
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MOA of macrolides?
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- bind to 50s subunit and stop PS- bacteriostatic
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Why is clindamycin valuable?
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- act. against all anaerobic bact, toxo gondii and poss mycoplasma
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Lincomycin?
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- good against staph, aureus and anaerobes, not gram neg
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Adverse effects?
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-GI upset very common with erythromycin in SA
- IM is very painful, may causes carcass damage in LA - alter intestinal flora- FATAL DIARRHEA in humans, rabbits, horses, ruminants - tilmycosin injections can be fatal in swime horses and humans - IV tilmycosin is fatal in cattle, injection by another route in swim horses and humans is fatal |
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When would you use Draxxin?
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- long acting macrolide
-approved for beef cattle and swine - use to teat BRD |
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When do you use macrolines?
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SA- ( clin, eryth and linco) pyodermas, bact enteritis, osteomyelitis, and ST infection
Horse- use erythromycin andrifampin for rhod. equi infection cattle- BRD from past/myco- but resistance develops quick swine-linco, tylosin and tiamulin- bact enteritis and pneumonia rabbits- tilmicosin for snuffles |
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MOA of Rifampin?
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-inhibits DNA dependent RNA polymerase so supress RNA synthesis
- effective against variety of of mycobacterum and gram pos, high conc gets pox virus and adenovirus can also get antifungal when combined with outher drug |
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Why is it usually given with another antimicrobial?
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- resistance develops fast
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Why are the phamokinetics of the drug good?
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- very lipophilic and penetrates most tissues
- conc. in neutro and macrophages so gets intracellular pathogens - good for spetic foci and gran. infections |
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What are adverse effects?
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- turns everything red it touches!!!!- animal has red tears, urine, saliva, sweat- but not harmful
- induces cyp 450 so may shorten half life of other drugs |
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When do you use it?
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SA- use with amp-b and 5-flu in the treatment of histroplasmosis or aspergillosis with CNS involvement
horses- pulm. abcesses from rhod. equi in foals- so with erythromycin or another macrolide calves- use with another drug to tx umbillical infections- not labelled for food animals DONT USE IN ANIMALS GOING INTO FOOD CHAIN |
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MOA of flagyl?
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- met by bact to produce cytotoxic derivites that damage DNA and other critical intracellular macromolcules
- aerobic bact lack this pathway |
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What do they kill?
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-anaerobic bact
- protozoa - can penetrate bone, abcess and CNS good VD and lipophillic!! |
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adverse effects?
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- carinogenicity and teratogenic in lab animals, illegal in FA
-neutotoxicosis in dogs chronic tx |
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WHen do you use it clinically?
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SA- anaerobic infections- bacterial stomatitis, ostemyelitis, pneumonia and lung abcess, clostridial enteritis, and peritonitis, giardia
horses- pleuropneumonia and lung abcess DO NOT USE IN FOOD ANIMALS |
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When do we use a first line antibiotics and give examples?
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- initial tx of known or suspected infection - no C/S
- penn, most ceph, TMS, tetraS |
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2nd line?
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- when c/s and patent factors 1st wont work
- fluroquinolones, 3rd or later ceph |
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3rd line?
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- life threatening conditions when c/s indicate first or 2nd wont work
- carbapenems |
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Restricted?
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- use only when life- threatening and no other options
- vancomycin |
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Name 5 mechanisms by which bacteria develop resistance?
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- enzymatic inactivation of drug- produce enzymes
- target modification or replacement- alter target binding site decreases drugs affinity active drug efflux- may increase the transport of a drug out of a cell -reduced drug uptake- decrease perm available to that drug - development of alternative metabolic or synthetic pathways- to bypass or repair damage from antimicrobials |
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What does the WHO define adverse drug reactions as?
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noxious or unintended effects of a drug that occur at appropriate doses used for prophylaxis, diagnosis or therapy
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Dose related A is caused by what?
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- pharm tox
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B?
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idiosyncratic, intrinsic tox
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How do you explain type a?
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- predictable, dose dependent, the higher the dose the more patients affected and more severe the reaction- can reproduce experimentally and are seen in drug trial
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What should you do when you have a reaction?
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- stop drug, tx side effects, can reintroduce at lower dose
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What is A subcategorized into?
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- pharm based
- chem based |
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What do you see with a pharm reaction?
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-mechanism based
- are an undesired pharm effect on a specific target or receptor- can be exaggerated primary response |
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What do you see with a chemical based dose dependent ADR?
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-occur due to intrinsic chemical properties of a drug and its metabolites
- toxicity involves- nonspecific binding of a drug or its metabolites to nearby proteins, NA, lipids or oxidative damage |
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What are idiosyncratic reactions?
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- dose-independent, unpredictable that occur at normal dose
- cant reproduce exp. - usually immune mediated do to drug- mod. proteins or autoantigens - anaphylaxis - never use drug again |
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What questions should you ask to DX ADR?
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1- is the time appropriate for adr?
2- has adr been reported before 3-other possible explanations for CS? 4- has patient taken drug before what happened? 5- do signs disappear when drug stops and recur with exposre 6- is there incorrect dosing error or elevated plasma levels 7- are there predisposing factors such as breed or other drugs |
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What is prudent use?
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-responsible use of antimicrobials with the overall goal of decreasing antimicrobial usage to decrease resistance
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When might you do a C and S?
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- unpredictable pathogen
-sever infection -failure in ind. case -failure in multiple cases in env - other variables such as farm/kennel |
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What is MIC?
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- LOWEST level that will inhibit bact growth
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Why isnt MIC perfect?
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- host defence differnt
- drug distribution - growth rates and size of inoculums -mixed infections - topics arent tested - env - in vivo synergism of some antimicrobials |
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What is vitro MIC based on? Breakpoint?
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-in vitro MIC is based on specific organism of drug whereas on animal clinical trials but is often human data
- breakpoint- is based on the host and drug, NOT specific organism |
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What is MBC?
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- lowest concentration that kills 99.9% of bact.
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Name 4 patients you would get bacterialcidal?
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- neonates
- immunosuppressed -bact. endocarditis, meningitis - surgical prophylaxis |
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What gets intracellular?
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-fluoro, tetra, macrolides, chloramphenicol, rifampin
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Cerebral spinal fluid?
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- pot. sulf., chloramphenicol, metron, rifampin, cefotaxime
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What gets prostate?
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- pot. sulph, fluoro, chloramphenicol, imipenem
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UTI?
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-amp/ amoxi, cephalosporin and oxy
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What is very effective in abscesses?
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- the abscess wall doesnt let non-lipid soluable drugs penetrate
-the acidic env. encourages weak bases to accumulate, but the low PH and presence of cellular debris within the abscess may interfere with the act of drug very effective- rifampin, chlor, tetra, metron moderate- erythyromycin, fluori cant use- amino, beta lact, tms |
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Why use combinations?
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- increase spectrum ( quinolone plus metron/clin/b-lactam)
- synergism, increase efficacy and decrease tox by decreasing dose- tms, beta and aminogly, aminopenn with clavulanic acid or sulbactam - prevent or ovoercome resistance- erythromycin and rifampin, amino and clav |
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What is the difference between concentration- dependent antimicro. and time- dependent?
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- concentration- high plasma conc. levels relative to the MIC of the pathogens determine the clinical efficacy
-time- the time during which the antimicr concentration exceeds the MIC of the pathogen determines clin efficacy |
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How long should you tx for?
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- 2-3 days beyond acute infection
- 7-10 days beyond resolution of chronic infection |
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What is antimicrobial resistance?
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- the ability of a microorganism to withstand the effect of a normall active concentration of an antimicrobial agent
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What is intrinsic resistance
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- organism with intrinsic resistance have an inherent structural or functional train in all members that withstands a type of drug
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What are 2 ways to get acquired resistance?
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- vertical transmission of random chromosomal mutations
- horizontal transer of plasmid genes |
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Horizontal occurs by what 3 ways?
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- conjugation
- transduction -transformation |
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what is cross selection?
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single gene mutation coferring resistanct to 2 or more agents, usually in the same class
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what is co-selection?
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- co existence of distinct genes or mutations in the same bacterial strain, each conferring resistance to a different class of AB
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what are the resistance mechanisms to beta-lactams?
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inherent- failure to penetrate outer cell wall : gram neg with lps
acquired: 1- beta lacs are 50 b-lactamases that hydrolyze the amide bond in the beta lactam ring, breaking it open and destroying its effect 2- altered penn binding proteins |
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What are the resistance mechanisms to aminoglycosides?
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intrinsic- all anaerobes lack 02 cant move AG into cell
acquired- have a unique first exposure adaptive resistance! |
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Sulfonamides?
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-if bact are resistant to one sulf resistance to all~
1- increased paba 2- altered or increased prod of dihydropteroate or dihydrofolate 3- decreased ability to penetrate cell |
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Chloramphenicol, Florfenicol?
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- most R due to preoduction fo acetyltransfer enzymes tjat acetylate the OH group
- also possible increased efflux |
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Tetracycline?
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-- R due to widespread use
- reistance genes, most increase drug efflux |
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Fluoroquinolones?
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1- altered DNA gyrase--> high level R
2- decreased cell wall perm 3- increased efflux- only seen with staph aureus |
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Macrolides?
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1- decrease binding to 50s by modifying ribosomes
2- increased efflux |
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Lincosamides?
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- almost always because gene erm that alter ribosomes that decrease binding to 50s
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Rifampin?
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- from altered RNA polymerase
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Metronidazole?
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intrinsic- aerobic bact cant reduce these antimicrobials
acquired- rare and due to decreased reduction to the derivatives |
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What are 2 ways that resistance can be given to humans?
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food-borne
direction transmission |
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What are 4 factors affecting resistance?
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- insufficient drug concentration at infection site
b- potency and efficacy of the drug against the organism c- compliance by the owner or producer with recc. dosage d- the hosts immune system |
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What is mutant selective window?
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- selection process are most intense in narrow concentration termed this
- this is when the antimicrobial inhibits the growth of one or more subpopulations while it has no effect on other subpopulations |
