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62 Cards in this Set
- Front
- Back
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What are the three beta lactams? |
Penicillins Cephalosporins Carbapenems |
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What is the MOA of beta lactams? |
Inhibit call wall synthesis by blocking the final step of cell wall synthesis by inhibiting transpeptidation or cross linking of peptidoglycans in the cell wall by covalently binding penicillin binding protein |
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What is penicillin's antimicrobial spectrum of activity? |
Gram positives esp. Streptococcus
Corynebacterium Listeria Clostridium and Staphylococcus often resistant Gram-negatives usually resistant Anaerobes |
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What causes Beta-lactam resistance usually? |
•Mostcommon is beta-lactamaseenzymes that hydrolyze beta lactams •Plasmidencoded gene •Moststaphylococcus species areresistant to penicllindue to this mechanism |
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What are the PK properties of penicillin? |
•Poororal bioavailability, inactivated by gastric pH •Notlipid soluble, does not penetrate well •Vd low, extracellular fluids only •Weakacid so ionized in plasma •Durationof action short acting and manipulated by formulation •Renalclearance by active tubular secretion–Probenecid blocks |
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What are Penicillin properties? |
•Bactericidal •Littleto no PAE •Timedependent PK/PD activity |
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What is Concentration-dependent killing? |
•Dependentupon theintensity of the exposure. •peak serum concentration correlates best with efficacy (i.e, aminoglycosides) •totaldrug exposure, correlates best with efficacy (i.e., fluoroquinolones) Area Underthe Curve (AUC) isthe measure of total drug exposure |
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What is peak serum concentration? |
Concentration dependent killing where peak serum concentration correlates best with efficacy Aminoglycosides |
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What is total drug exposure? |
Concentration dependent killing where total drug exposure correlates best with efficacy Fluoroquinolones Area under the curve (AUC) is the measure of total drug exposure |
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What is time dependent killing? |
The duration of exposure of the microbe to the antibiotic is the critical parameter Serum concentrations of these antibiotics should be above MIC for at least 40-60% of the dosing interval, with a higher percentage of coverage of the dosing interval being preferred |
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What are the agents that exhibit time dependent killing? |
beta lactams, macrolides, clindamycin, glycopeptides, tetracylines, trimethoprim |
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What are the adverse reactions for penicillins? |
Hypersensitivity both anaphylaxis and AIHA, thromocytopenia and urticaria Not dose dependent Procaine reactions and residues Meat residues/ injection site Clostridial overgrowth in rabbits, guinea pigs and hamsters |
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What are the reactions related to giving potassium penicillin? |
Reactions frequent, esp. when administration is rapid Head shaking/ rubbing, lip smacking, teeth grinding, salivation, lacrimation, increased borborygmus, mild colic/agitation, passage of soft/liquid feces Signs can usually be eliminated by slow IV administration of the drug Similar reactions have not been reported with rapid IV administration of sodium penicillin G or sodium ampicillin |
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What are the formulations for penicillin? |
IV in a potassium or sodium salt, water soluble, give 4X/day IM or SQ Procaine penicillin Benzathine penicillin long acting Most long acting do not maintain therapeutic concentrations at the bottle recommended dose |
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What are the two Aminopenicillins? |
Amoxicillin (oral) Ampicillin (IV, IM) |
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What are the characteristics of Aminopenicillins? |
•Amoxicillin(oral) and ampicillin (IV, IM) •Oral(especially amoxicillin) •Notinactivated in gastric pH •Better penetrationof outer layer of gram negative bacteriathan penicillin •Still sensitiveto beta lactamases •Broaderactivity than penicillins •Broadspectrum, especially when combined with a beta-lactamase inhibitor |
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What are four other penicillins and beta lactams? |
Carbapenem (imipenem) Anti-pseudomonas penicillins (Ticarcillin) Anti-staphylococcalpenicillins(oxacillin,methicillin, cloxacillin) Monobactams (aztreonam) |
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What is carbapenem (imipenem) |
Beta lactam Very broad spectrum Used as last resort in resistant life threatening infections |
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What is anti-pseudomonas penicillins (ticarcillin)? |
Beta lactam Penetrate outer wall of gram negatives B-lactamase sensitive Gram negative uterine infections |
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What is Anti-staphylococcalpenicillins(oxacillin,methicillin, cloxacillin)? |
–B-lactamaseresistant –Cellulitis,intramammaryinfusion mastitis |
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What is Monobactams (aztreonam? |
–Gram-negativesand Pseudomonas –Secondof third choice drug –Littleveterinary experience |
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What are Beta LactamaseInhibitor? |
•Clavulanic acid •Sulbactam •Noteffective antimicrobials alone, but they inactive b-lactamase activity makingco-administered beta lactam more active •Clavamox™ (amoxicillinand clavulanicacid) •Unasyn ™ (ampicillin and sulbactam) |
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What are Cephalosporins? |
•B-lactamattached to a 6 member ring •Mechanismof action, resistance mechanisms, sameas penicillin, but different PBP •Oraland parenteral |
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What are the cephalosporin generationsbased on spectrum of activity? |
–1st : good against gram + and anaerobes –2nd : some gram – ,still gram + and anaerobes –3rd : gm -, gm+, anaerobes; broad spectrum, but uniqueto each drug –4th : gram -, gram +, some anaerobes; more resistantto beta-lactamases |
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What are theCephalosporinPrototype 1st generation? |
•: Cefazolin(IV) Ancef™ Cephalexin(oral) Keflex™ Cefadroxil(oral) approved Cefa-tabs™ orCefa-drops™ |
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What are theCephalosporinPrototype 2nd generation? |
•Cefoxitin (IV, SQ, IM) |
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What are theCephalosporinPrototyp 3rd generation? |
•Ceftiofur (IM, IV)Excede™ Naxcel™ Excenel™ Cefovecin(SC) Convenia™ Cefpodoxime(oral) Simplicef™ Ceftazidime |
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What are theCephalosporinPrototype 4th generation? |
•Cefepime (IV) |
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What are the Adversereactions for cephalosporins? |
•Hypersensitivity,both anaphylaxis and AMHA, thrombocytopenia and urticaria –Mostcommon drug allergy in people –Notdose dependent |
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What are the cephalosporinsin food animals rules? |
–Extralabel cephalosporins arebanned in cattle, swine, chickens, turkeys unless approved dosing regimen isused. –Human and companion animal cephalosporinsbanned in food animals. |
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What are the characteristics for FirstGeneration Cephalosporins? |
•Bothoral and parenteralformulations •Ingeneral, good activity against gram + and anaerobes •Cefazolin–IVdrug commonly used in small animal surgery –Rapidlyeliminated, need to administer frequently •Cephalexin, Cefadroxil –Orallyadministered drug–Commonlyused in small animals for pyoderma, UTI |
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What are the characteristics for SecondGeneration Cephalosporins? |
•Ingeneral, good activity against gram + and anaerobes, better activity againstgram negatives than first generation cephalosporins •Activeagainst Bacteroides •Cefoxitin–(IV,SQ, IM) drug sometimes used for in hospital care of small animalpatients/foals. –Mustbe given parenterally |
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What are the characteristics for ThirdGeneration Cephalosporins? |
•Diversegroup, but popular in vet med •Ingeneral, good activity against gram + plus gram - and some activity againstanaerobes •Ceftiofur HCl, Na, or CFA (IV, IM, SC) •Cefovecin (SC) •Cefpodoxime (oral) •Ceftazidime (IV, IM) |
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What is Ceftiofur HCl, Na, or CFA (IV, IM, SC) |
-ThirdGeneration Cephalosporin –Approvedfor use in cattle, swine, horses –Mustbe given parenterally –Depotformulation available (ceftiofurcrystalline free acid) |
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What is Cefovecin (SC)? |
-ThirdGeneration Cephalosporin –Approvedfor use in dogs and cats for skin infections –Longacting (given weekly) due to slow elimination of drug -Gm +and gm – infections. |
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What is Cefpodoxime (oral)? |
-ThirdGeneration Cephalosporin –Approvedfor use in dogs –Usedprimarily in dogs and cats with soft tissue infections |
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What is Ceftazidime (IV, IM)? |
–Unusualin that it is active against Pseudomonas –Usedoccasionally in small animals, popular in reptiles |
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What is Ceftiofur? |
•Naxcel™ •Licensedfor respiratory disease in food animals, horses, dogs •Goodagainst gram negative and streptococcus •E.coli has higher MIC than respiratorypathogens- need higher dose •CattleSQ or IM q24 |
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What are the characteristics of FourthGeneration Cephalosporins? |
•Rarelyused in Vet Med •Generallyreserved for life-threatening infections •Ingeneral, good activity against gram + plus gram - , with enhanced stability tobeta-lactamases. •Ascompared to third generation, better activity against Pseudomonas, limited activity against anaerobes •Cefepime (IV)–Noveterinary approval–Usedin small animal patients and foals with life-threatening infections–Mustbe given IV– |
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What are the characteristics of Carbepenem beta lactams? |
•Imipenem: formulated with cilastatin,inhibits breakdown of imipenem by the kidney. •Verybroad spectrum of activity (includingPseudomonas spp) •Veryresistant to beta lactamases. •PoorCNS penetration unless meningitis. •Rapidlycidal-less endotoxinrelease •Usedrarely in vet med due to expense and need for parenteral administration •Generallyreserved for multi-drug resistant gram negative infections. •IVonly, slowly to prevent seizures |
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What is Glycopeptides:Vancomycin MOA? |
•Bindsto the terminal portion of the amino acid side chain preventing cross-linking |
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What is Glycopeptides:Vancomycin spectrum of activity? |
•Grampositives, including multi-drugresistant (MDR), methicillin resistant staphs (MRSA), Clostridium |
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What is Glycopeptides:Vancomycin mechanism of resistance? |
requiresseveral gene alterations but may be plasmid mediated |
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What is Glycopeptides:Vancomycin used for? |
•THISIS A DRUG RESERVED FOR MDR, LIFE THREATENING INFECTIONS ONLY |
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What is Bacitracin? |
•Intopical ointments, extremely nephrotoxic no systemic administration, topicalonly •Bacitracin interferes with the dephosphorylation of the CC55-isoprenylpyrophosphate, a molecule which carriesthe building blocks of the peptidoglycan bacterialcell wall outsideof the inner membrane |
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What are the Primarypathogens of UTI? |
•Mostlikely pathogens –E.coli, enterics –Staph |
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What are the potentialantimicrobials for enterics in the urine? |
–Aminopenicillins –Cephalosporins –Tetracycline –Fluoroquinolones –Aminoglycosides –Potentiated sulfonamides |
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•Whatantimicrobials do you not use for enterics in the urine? |
Doxycycline Chloramphenicol Difloxacin Macrolides Rifampin Metronidazole |
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What is the OverallGoal of Antibiotic Therapy? |
•Achieveeffective concentrations of an appropriate drug at the site of infection toeradicate the pathogen while avoiding adverse effects due to toxicconcentrations of the drug in the patient |
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What are the Aminoglycosides? |
•Gentamicin •Amikacin •Neomycin •Streptomycin •Tobramycin •Dihydrostreptomycin |
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How is Gentamicinadministered? |
•IVor IM |
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How is Amikacinadministered? |
IVor IM, more resistant to enzyme inactivation |
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How is Neomycinadministered? |
topical or oral to “sterilize” the gut |
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How isTobramycin administered? |
parental,ophthalmic more active against Pseudomonasspp |
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How is Dihydrostreptomycinadministered? |
•lotsof resistance, still in some dry period mastitis meds |
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What are the Primaryclinical indicationsAminoglycosides? |
•Amikacin and gentamicin are used as powerful parentralantimicrobials against gram negatives •Equineneonatal sepsis and equine gastrointestinal disease •Not used extralabel in Food Animal •Systemicaminoglycosides used infrequently in SA |
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What is the MOA of aminoglycosides? |
Bindto 30S subunit of the ribosome, preventsprotein synthesis Prevent initiation, prevent elongation, causemisread •Diffusesthrough outer membrane through porins •Transportthrough inner membrane is energy dependent/ oxygen dependent –Requires electrochemical potential –Reduced efficacy in anaerobic environment –Reduced efficacy in acidic environment |
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What is the Antimicrobialspectrum of activity for aminoglycosides? |
–Gramnegatives –Staphylococcusintermedius –Aerobesonly –Notstreptococcus |
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What is the mechanism of resistance for aminoglycosides? |
•Enzymeinactivation- plasmid mediated •Mutationof cell membrane structure, failure to penetrate (change in porin),minor mechansim •Anaerobes:drug fails to get into bacteria •Firstexposure adaptive resistance |
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What is Adaptiveresistance in aminoglycosides? |
•Reversiblerefractiveness to bactericidal action –protective phenotype alteration. –susceptibility returnswhen drug removed for a sufficiently long period •Cantake up to 15-20 half-lives to completely return to baseline susceptibility •If asecond dose is administered too early, resistance may be sustained |
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What are the PKproperties of aminoglycosides? |
•Charged(weak base), low Vd, distributed to extracellular space •Pooractivity in acidic environment •Poororal absorption •Eliminationexclusively by glomerular filtration. Drug accumulates in kidneys •Withdrawaltime for food animals VERY long, not an approved drug |
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What are the Properties of aminoglycosides? |
•Bactericidal •Post-antibioticeffect–Durationdepends on initial concentration •Concentrationdependent •Adaptiveresistance For all of the reasons above,parental administration of aminoglycosides aretypically once daily |
