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93 Cards in this Set
- Front
- Back
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beta-lactams: mechanism of action
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kill bacteria by inhibiting or weakening cell wall (bactericidal)
penicillin binding proteins (PBPs): binding sites for β-lactam AB’s |
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beta-lactams: bacterial resistance mechanisms
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failure to penetrate outer bacterial cell layer (ex. gram neg. bacteria)
altered target: PBPs can mutate & ↓ their affinity for AB --> resistance production of β-lactamase: most common mechanism |
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beta-lactams
a. bactericidal or bacteriostatic? b. time or conc. dependent? |
a. bactericidal
b. time dep. |
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penicillins: spectrum
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primarily Gram positive, some obligate anaerobes
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penicillins: 3 formulations
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Penicillin G Potassium, Penicillin G Sodium: short lived plasma conc.
Procaine Penicillin G: lasts ~24 hrs Benzathine Penicillin G: can last up to 14 days (not used much d/t residues) |
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penicillins
a. oral absorption b. volume of distribution c. half life d. method of elimination e. routes of administration |
a. poor (<10%)
b. small (doesn't cross mems well) c. short (0.5-1.2 hrs) d. renal e. IM, IV, SQ only |
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penicillins: adverse effects
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allergic rxns
vomiting/diarrhea |
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penicillins: regulatory considerations
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high doses in cattle not approved --> extended withdrawal times
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aminopenicillins
a. 2 most common b. spectrum |
a. Amoxicillin, Ampicillin
b. same as Penicillin + some gram negative bacteria (acquired resistance common) |
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aminopenicllins
a. oral absorption b. volume of distribution c. half life |
a. poor in horses & ruminants, good in other animals (Amoxicillin 2x > Ampicillin)
b. low c. short |
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aminopenicillins: adverse effects
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allergy
vomiting/diarrhea |
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beta-lactamase inhibitors: 2 primary drugs added to aminopenicillins
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clavulanic acid (potassium clavulanate)
sulbactam |
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Clavamox
a. components b. species c. uses |
a. amoxicillin, clavulanic acid
b. dogs & cats c. used to tx infection in most tissues: UTI, skin infection, pneumonia, systemic infection |
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Unasyn
a. components b. species c. routes of administration |
a. sulbactam, ampicillin
b. dogs, horses, cattle c. IM, IV, SQ |
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advantages of beta-lactamase inhibitors
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low toxicity & good safety profile of other beta-lactams
may be useful for infections caused by β-lactamase producing bacteria (ex. Staph, Gram neg. bacilli, Gram neg. anaerobes) |
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cephalosporins: spectrum
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similar to aminopenicillins; have activity against:
Staph (β-lactamase positive) Strep Gram neg. bacteria (including E. coli, Proteus, Klebsiella), except Pseudomonoas anaerobic bacteria, except Bacteroides fragilis resistance common |
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cephalosporins:
a. routes of administration b. oral absorption c. metabolism d. elimination e. half life f. volume of distribution |
a. SC, IM, IV, oral, intramammary
b. good in small animals, poor in large animals c. liver (minimal) d. renal e. variable (short to long) f. small, but good distribution into ECF of most tissues |
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Cephalexin
a. generation b. uses |
a. 1st generation cephalosprin
b. commonly used for many infections, including pyoderma, UTI, pneumonia, soft tissue infection, & osteomyelitis |
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Cefazolin
a. generation b. uses |
a. 1st generation cephalosporin
b. most commonly used injectable cephalosporin in vet med |
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1st generation cephalosporins: spectrum
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Staph
Strep Anaerobes Gram neg. bacteria (may develop resistance) |
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3rd generation cephalosporins: spectrum
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Strep (variable)
Anaerobes Gram neg. bacteria (more active than other generations) greater CNS penetration |
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Cefpodoxime-proxetil
a. trade name b. generation c. activity d. uses e. dosing |
a. Simplicef
b. 3rd generation cephalosporin c. more active than many other 3rd generation cephalosporins against Staph - not active against Pseudomonas aeruginosa, Enterococcus, or MRSA d. tx of cutaneous infections e. SID; prodrug |
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Ceftiofur
a. generation b. uses c. Excede |
a. 3rd generation cephalosporin
c. tx respiratory infections in cattle, pigs, & horses d. crystalline free acid form: slow-releasing drug that is injected at base of ear of cattle & neck of pigs |
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cephalosporins: adverse effects
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allergy: less common than in penicillins
vomiting, diarrhea |
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carbapenems: spectrum
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broad spectrum: gram pos. & gram neg.
highly resistant to β-lactamase enzymes & penetrate most gram neg. bacteria readily more bactericidal than other β-lactam ABs against gram neg. bacteria produce post-antibiotic effect (PAE) not seen w/ other β-lactams |
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carbapenems
a. uses b. example drug |
a. use limited to serious infections caused by bacteria resistant to other ABs
b. Meropenem (Merrem): given IV or SQ to dogs & cats - not likely to cause seizures, as Imipenem, another drug in class, can |
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aminoglycosides: mechanism of action
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bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis
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aminoglycosides:
a. bactericidal or bacteriostatic? b. concentration or time dependent? c. dosing |
a. bactericidal
b. concentration dependent c. SID (long PAE) |
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aminoglycosides: spectrum
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effective against most gram neg. bacteria, including Enterobacteriaceae (E. coli, Klebsiella, Proteus, Enterobacter) & Pseudomonas aeruginosa
somewhat effective against Staph (resistance can occur) anaerobic bacteria are resistant |
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aminoglycosides: effects of tissue environ. on activity
a. pH b. cellular debris c. O2 tension d. cations |
a. activity is less at low pH (optimum: 6-8)
b. aminoglycosides are bound to & inactivated by cellular debris --> poor activity in abscesses c. low O2 tension, such as found in anaerobic tissue or decaying tissue --> ↓ activity d. divalent cations (ex. Ca2+, Mg2+) interfere w/ uptake into bacteria |
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aminoglycosides: bacterial resistance mechanisms
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anaerobic bacteria are intrinsically resistant
failure to penetrate cell wall altered target (ribosome) that resists binding synthesis of bacterial enzymes that inactivate drug |
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aminoglycosides
a. volume of distribution b. half life c. oral absorption d. elimination |
a. small: poor distribution into respiratory fluids, eye, prostate, CNS
-VD larger in young animals b/c of ↑ proportion of extracellular fluid --> higher doses need for neonates to maintain effective plasma concentrations b. short (1-2 hrs) c. poor d. renal |
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aminoglycosides: adverse effects
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renal toxicosis: toxicity most severe in proximal tubules b/c drug is actively taken up there
-animals that are dehydrated, have electrolyte imbalances, endotoxemia, or existing renal dz, or are taking the drug for longer than 7-10 days are at a higher risk for toxicity -assess renal function BEFORE beginning tx ototoxicity, vestibulotoxicity: may result from prolonged use neuromuscular blockade: rare (only at high doses) |
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aminoglycosides: clinical uses
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acute overwhelming sepsis
tx of resistant gram neg. organisms (ex. Pseudomonas, E. coli, Staph) topical preparations: skin infections, eyes, ears (no systemic absorption) |
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aminoglycosides: prototype & formulations
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Gentamicin
IV, SC, IM, topical (ears, eyes, skin) |
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aminoglycosides: regulatory status
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not registered for systemic use in food animals (very long withdrawal times for slaughter)
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tetracyclines: mechanism of action
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bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis
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tectracylines
a. bactericidal or bacteriostatic? b. time or conc. dependent? |
a. bacteriostatic (binding to ribosome is reversible)
b. time dependent |
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tetracyclines: spectrum
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BROAD
active against gram neg. & gram pos. bacteria, Chlamydia, rickettsia, spirochetes, mycoplasma, L-form bacteria, & some protozoa (Plasmodium, Entameba) Pseudomonas spp., Enterobacteracae usually resistant |
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tetracyclines: bacterial resistance mechanisms
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caused by failure in active transport required to enter bacterial cell
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tetracyclines
a. oral absorption b. half life c. volume of distribution d. elimination |
a. good in most species
- Ca2+ & other divalent cations chelate tetracyclines --> inhibit oral absorption b. moderately long c. well distributed to most tissues, except CNS - passively diffuse into cells --> effective for treating intracellular infections d. renal |
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tetracyclines: adverse reactions
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diarrhea (esp. horses)
-horses: oral administration of oxytetracycline has been assoc. w/ proliferation of Clostridium perfringens or Salmonella in colon (“Colitis X”) esophageal lesions: doxycyline hyclate capsule or broken tablet administered to cat can become lodged in esophagus --> esophageal lesions & stricture (try to give w/ water or food in cats) tooth discoloration in young animals renal tubular necrosis: high doses (rare) toxic hepatatis: rare |
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tetracyclines
a. large animal drug b. small animal drug |
a. oxytetracycline (parenteral)
- IM absorption delayed by addition of “viscosity excipient” --> long acting forms b. doxycycline hyclate - can be given orally or IV - drug of choice for rickettsial infections |
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tetracyclines: clinical uses
a. cattle & sheep b. swine c. small animals d. birds e. horses |
a. oxytetracycline used to tx lung infections assoc. w/ bovine respiratory dz (BRD)
b. Mycoplasma, atrophic rhinitis, pneumonic pasteurellosis c. Ehrlichiosis, Rickettsia, Mycoplasma, Chlamydia, UTIs, respiratory infections d. tx of choice for psittacosis caused by Chlamydophila psittaci (oral, add doxycline to drinking water) e. oxytetracycline has been used to tx Potomac Horse Fever (Neorickettsia risticii) - IV administration of doxycycline in horses has caused acute death |
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chloramphenicol: mechanism of action
-bactericidal or bacteriostatic? |
binds 50-S ribosomal subunit --> inhibits bacterial protein synthesis
-bacteriostatic |
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chloramphenicol: spectrum
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good activity against Gram neg., Gram pos., anaerobes, Rickettsia, Chlamydia, Mycoplasma
poor activity against Pseudomonas, unpredictable activity against Enterobacteracae (resistance common) |
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chloramphenicol: bacterial resistance mechanisms
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inactivation by bacterial enzymes, inhibited entry into bacteria
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chloramphenicol
a. oral absorption b. volume of distribution |
a. good oral absorption in most animals, except ruminants
b. high volume of distribution: penetrates some tissues, such as eye & CNS, better than many other ABs |
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chloramphenicol: regulatory status
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banned for use in cattle b/c of risk of residues in treated animals
very few preparations currently on market |
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chloramphenicol: adverse reactions
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bone marrow toxicity
- dose relation anemia & pancytopenia: dogs & cats - ↓ in protein synthesis in bone marrow may be assoc. w/ chronic tx - reversible if discontinued - idiosyncratic aplastic anemia: described only in humans (rare, but severe) - irreversible - not dose related - led to ban in food animals WEAR GLOVES WHEN HANDLING |
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Florfenicol
a. class b. spectrum c. uses |
a. newer analogue of chloramphenicol that does NOT produce aplastic anemia in people
b. similar spectrum to chloramphenicol, but more active c. cattle, swine: tx of respiratory infections |
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macrolides: mechanism of action
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bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis
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macrolides
a. bactericidal or bacteriostatic? b. time or conc. dependent? |
a. bacteriostatic (bactericidal for some Gram pos. bacteria)
b. time dependent |
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macrolides: spectrum
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NARROW
good activity against Gram pos. bacteria, Rhodococcus, Mycoplasma, Chlamydia poor activity against most Gram neg. bacteria, except some Pasteurella & Mannheimia haemolytica |
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macrolides: bacterial resistance mechanisms
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gram neg. bacteria inherently resistant
other bacteria can develop resistance w/ repeated exposure ↓ entry into bacteria, altered target site on ribosomal RNA, inactivation by bacterial enzymes |
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macrolides
a. oral absorption b. volume of distribution |
a. good in monogastrics, 15-20% in horses
b. good tissue distribution -concentration in most tissues are higher than in plasma -drugs concentrate in WBCs --> WBCs carry drug to infected tissues -high concentrations in tissues persistent for much longer than plasma concentrations |
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macrolides: prototype, routes of administration
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Eryhtromycin: clinical use has ↓ in recent years
oral, IM (painful infection) |
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macrolides: adverse rxns
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serious changes in bacterial intestinal flora --> diarrhea in rodents, horses
- DO NOT give orally to rodents ↑ upper GI motility - can cause vomiting & regurgitation in small animals - at small doses, can be used as a motility-stimulating drug - mechanism: ↑ activation of motilin receptors via release of endogenous motilin or via cholingeric mechanisms in upper GI tract |
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macrolides: clinical uses
a. small animals b. horses c. cattle, pigs |
a. pyoderma, respiratory infections, osteomyelitis, soft tissue infections
b. resp. infections (esp. w/ Rhodococcus equi) c. respiratory infections |
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Tilmicosin
a. class b. species c. precaution |
a. macrolide (injectable: SQ only)
b. cattle, sheep c. DON'T GIVE IV -IV administration has caused deaths in animals d/t negative inotropic effects on heart -do not give to any species other than cattle or sheep -accidental injection into humans has caused death by cardiovascular toxicity |
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Azithromycin
a. class b. comparative pharmacokinetics c. uses in dogs, cats, horses |
a. macrolide
b. better tolerated, better oral absorption, ↑ volume of distribution, ↑ half life, ↑ tissue concentrations compared to erythromycin - concentrations in WBCs may be 200x concentrations in serum --> allows intermittent dosing c. dogs: respiratory, skin, refractory infections -cats: respiratory, skin, Bartonella infections -horses: Rhodococcus equi infections |
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Tulathromycin
a. class b. uses c. comparative pharmacokinetics |
a. macrolide
b. used to tx respiratory infections in cattle & pigs c. improved gram neg. activity compared to other drugs in group -long half life in tissues --> long withdrawal times (cannot use in lactating dairy cows) |
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lincosamides: mechanism of action
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bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis
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lincosamides
a. bactericidal or bacteriostatic? b. time or conc. dependent? |
a. bacteriostatic
b. time dependent |
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lincosamides: spectrum
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NARROW
-good activity against Gram pos. bacteria, Mycoplasma, most anaerobic bacteria -little activity against Gram neg. bacteria |
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lincosamides
a. oral absorption b. volume of distribution |
a. good
b. good tissue distribution |
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lincosamides: adverse effects
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can cause bacterial overgrowth, particularly of Clostridium difficle, d/t activity against anaerobes
-serious & fatal diarrhea reported in humans, rabbits, ruminants, horses following oral administration --> DO NOT GIVE TO HORSES, RUMINANTS, RODENTS |
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lincosmaides
a. prototype b. uses in small animals |
a. Clindamycin
b. oral cavity infections, pyoderma, osteomyelitis, soft tissue infections, Staph infections |
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trimethoprim-sulfonamide combinations: mechanism of action
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inhibit formation of tetrahydrofolic acid (active form of folic acid): step in synthesis of nucleotides
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trimethoprim-sulfonamide combinations: how it targets bacteria
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- microorgs more selectively inhibited than animal cells
- sulfonamide serves as a “false substrate” for PABA, which is used by micro-orgs to synthesize folic acid - mammals use dietary folate, thus bypassing this step - bacterial form of enzyme dihydrofolate reductase has much higher affinity for trimethropin than does mammalian form |
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trimethoprim-sulfonamide combinations: spectrum
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BROAD
good activity against Gram pos., Gram. neg., & some protozoa (Toxoplasma, intestinal coccidian, Sarcocystis neurona) resistance common |
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trimethoprim-sulfonamide combinations
a. oral absorption b. volume of distribution c. elimination |
a. good in most animals
b. good: penetrates tissues, cells, CNS c. renal: high urine concentration (used to tx UTIs) |
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trimethoprim-sulfonamide combinations: bacterial resistance mechanisms
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mutation of dihydrofolate reductase enzyme to become resistant to trimethoprim
utilization of other pathways by bacteria to make folic acid |
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trimethoprim-sulfonamide combinations: clinical uses
a. horses b. small animals |
a. commonly used b/c of good oral absorption & inexpensive
- respiratory, joint, abdominal infections; EPM b. respiratory, skin, urinary tract infections; Toxoplasmosis, Coccidia |
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trimethoprim-sulfonamide combinations: adverse effects
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hypersensitivity rxns: DOGS
DO NOT GIVE SULFONAMIDE TO DOBERMANS!! - caused by sulfonamide component -lesions: polyarthritis, skin rash, fever, hepatitis, thrombocytopenia, pancytopenia, anemia -may be d/t inability of dogs to acetylate drugs --> most of drug directed to liver (cytochrome p450) for conversion to a toxic metabolite --> metabolites usually detoxified by glutathione conjugation (some patients may lack this ability) -toxic metabolites react w/ cell membranes --> cell injury KCS: DOGS -lacrimotoxic effect of sulfonamide -check tear production in dogs on these meds folate antagonism: HORSES (rare; --> anemia) diarrhea: HORSES UT obstruction, hepatitis, hypothyroidism, skin rxns |
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Pyrimethamine
a. structurally related to what drug? b. comparative spectrum c. uses |
a. trimethoprim (same mechanism of action)
b. more potent in terms of inhibition of dihydrofolate reductase of PROTOZOA than bacteria c. (w/ sulfonamide): EPM in horses, Neospora, Toxoplasma |
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fluoroquinolones: mechanism of action
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inhibit DNA gyrase (topoisomerase II) or topoisomerase IV, which catalyze conversion of circular DNA to superhelical form
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fluoroquinolones
a. bactericidal or bacteriostatic? b. time or conc. dependent? |
a. bactericidal
b. conc. dependent |
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fluoroquinolones: factors affecting AB activity
a. pH b. cations |
a. less active in acid environ (pH ≤ 6)
- acid environ such as urine may ↓ effectiveness for treating UTIs b. activity may be inhibited by di- or tri- valent cations (ex. Mg, Fe, Ca, Al) |
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fluoroquinolones: spectrum
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BROAD
good activity: Gram neg. (esp. E. coli, Salmonella, Enterobacter, Klebsiella), Gram pos., Chlamydia, Mycoplasma, Rickettsia moderate activity: Pseudomonas aeruginosa poor activity: Strep, Enteroccocus, anaerobes |
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fluoroquinolones: bacterial resistance mechanisms
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chromosomal mutation of DNA gyrase or topoisomerase IV
efflux pump via outer membrane protein --> prevents accumulation of drug in bacteria (less common) - bacteria may also exclude other ABs --> multi-drug resistance |
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fluoroquinolones
a. oral absorption b. volume of distribution c. elimination d. PAE? |
a. good in all species
b. achieves high concentrations in most tissues & WBCs (exceeds plasma concentrations) - enrofloxacin converted to ciprofloxacin in liver - additive effect from both drugs (enrofloxacin is still active on its own) c. renal d. prolonged PAE |
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fluoroquinolones: prototype & formulations
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Enrofloxacin (Baytril)
tablets, injectable, otic preparations |
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fluoroquinolones: adverse effects
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GI effects: vomiting at high doses; transient diarrhea (rare d/t poor activity vs. anaerobes --> doesn’t alter gut flora as much as other ABs)
CNS effects: high doses can cause excitement, confusion, seizures (mostly reported in people) - avoid using in epileptic patients young animals: can produce arthropathy in dogs 8-28 wks old & foals 2-3 wks old - cats, calves appear resistant - joint damaged related to drug’s ability to chelate magnesium - may be reversible if recognized early enough blindness in cats - Enrofloxacin only: do not exceed 5 mg/kg in cats - mydriasis, acute blindness d/t retinal degeneration |
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fluoroquinolones: drug interactions
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di- & tri-valent cations may inhibit oral absorption
- ex. sucralfate, Fe supplements, oral antacids (contain Al, Mg) fluoroquinolones may inhibit hepatic metabolism of some drugs (ex. theophylline) |
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fluoroquinolones: clinical uses in small animals
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soft tissue infections, skin infections, pneumonia, osteomyelitis, prostatitis, UTIs
commonly used in many species, esp. exotics |
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fluoroquinolones: regulatory issues
a. food animals b. poultry |
a. cattle: Enrofloxacin, Danofloxacin approved ONLY for tx of respiratory dz
- all other use is ILLEGAL in food animals b. withdrawn by FDA d/t resistance possibly being transmitted to humans who eat poultry (ex. resistance of Campylobacter to fluoroquinolones in humans) |
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metronidazole: mechanism of action
bactericidal or bacteriostatic? |
rapidly taken up by bacteria --> metabolized by a reduction process --> cytotoxic derivatives
aerobic bacteria lack reductive pathway needed to produce the cytotoxic compounds bactericidal |
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metronidazole: spectrum
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NARROW
highly effective against anaerobes good activity against many protozoa (incl. Giardia), Helicobacter |
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metronidazole
a. oral absorption b. volume of distribution |
a. rapid & complete oral absorption in small animals & horses
b. high: distributes well into all tissues |
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metronidazole: adverse effects
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broken or crushed tablets have unpleasant taste
- Metronidazole benzoate is more insoluble & lacks unpleasant taste neurotoxicosis: at high doses only -inhibition of GABA --> ataxia, lethargy, proprioceptive deficits, nystagmus, seizure-like signs in dogs -dogs recover if drug administration is discontinued carcinogenicity & mutagenicity: some studies show that metronidazole causes mutations in bacteria -no reported problems in human or vet med |
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metronidazole: clinical uses
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-rational choice for anaerobic bacterial infections, incl. oral infections, osteomyelitis, pneumonia, intra-abdominal infections
-colitis -giardiasis |
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metronidazole: regulatory status
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food animals: prohibited b/c it is considered a potential carcinogen
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