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93 Cards in this Set

  • Front
  • Back
beta-lactams: mechanism of action
kill bacteria by inhibiting or weakening cell wall (bactericidal)

penicillin binding proteins (PBPs): binding sites for β-lactam AB’s
beta-lactams: bacterial resistance mechanisms
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

a. bactericidal or bacteriostatic?

b. time or conc. dependent?
a. bactericidal

b. time dep.
penicillins: spectrum
primarily Gram positive, some obligate anaerobes
penicillins: 3 formulations
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)

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
penicillins: adverse effects
allergic rxns
penicillins: regulatory considerations
high doses in cattle not approved --> extended withdrawal times

a. 2 most common
b. spectrum
a. Amoxicillin, Ampicillin
b. same as Penicillin + some gram negative bacteria (acquired resistance common)

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
aminopenicillins: adverse effects
beta-lactamase inhibitors: 2 primary drugs added to aminopenicillins
clavulanic acid (potassium clavulanate)


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

a. components
b. species
c. routes of administration
a. sulbactam, ampicillin
b. dogs, horses, cattle
c. IM, IV, SQ
advantages of beta-lactamase inhibitors
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)
cephalosporins: spectrum
similar to aminopenicillins; have activity against:
Staph (β-lactamase positive)

Gram neg. bacteria (including E. coli, Proteus, Klebsiella), except Pseudomonoas

anaerobic bacteria, except Bacteroides fragilis

resistance common

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

a. generation
b. uses
a. 1st generation cephalosprin
b. commonly used for many infections, including pyoderma, UTI, pneumonia, soft tissue infection, & osteomyelitis

a. generation
b. uses
a. 1st generation cephalosporin
b. most commonly used injectable cephalosporin in vet med
1st generation cephalosporins: spectrum
Gram neg. bacteria (may develop resistance)
3rd generation cephalosporins: spectrum
Strep (variable)
Gram neg. bacteria (more active than other generations)
greater CNS penetration

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

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
cephalosporins: adverse effects
allergy: less common than in penicillins
vomiting, diarrhea
carbapenems: spectrum
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

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
aminoglycosides: mechanism of action
bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis

a. bactericidal or bacteriostatic?
b. concentration or time dependent?
c. dosing
a. bactericidal
b. concentration dependent
c. SID (long PAE)
aminoglycosides: spectrum
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
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
aminoglycosides: bacterial resistance mechanisms
anaerobic bacteria are intrinsically resistant

failure to penetrate cell wall

altered target (ribosome) that resists binding

synthesis of bacterial enzymes that inactivate drug

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
aminoglycosides: adverse effects
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)
aminoglycosides: clinical uses
acute overwhelming sepsis

tx of resistant gram neg. organisms (ex. Pseudomonas, E. coli, Staph)

topical preparations: skin infections, eyes, ears (no systemic absorption)
aminoglycosides: prototype & formulations

IV, SC, IM, topical (ears, eyes, skin)
aminoglycosides: regulatory status
not registered for systemic use in food animals (very long withdrawal times for slaughter)
tetracyclines: mechanism of action
bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis

a. bactericidal or bacteriostatic?
b. time or conc. dependent?
a. bacteriostatic (binding to ribosome is reversible)
b. time dependent
tetracyclines: spectrum

active against gram neg. & gram pos. bacteria, Chlamydia, rickettsia, spirochetes, mycoplasma, L-form bacteria, & some protozoa (Plasmodium, Entameba)

Pseudomonas spp., Enterobacteracae usually resistant
tetracyclines: bacterial resistance mechanisms
caused by failure in active transport required to enter bacterial cell

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
tetracyclines: adverse reactions
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

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
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
chloramphenicol: mechanism of action

-bactericidal or bacteriostatic?
binds 50-S ribosomal subunit --> inhibits bacterial protein synthesis

chloramphenicol: spectrum
good activity against Gram neg., Gram pos., anaerobes, Rickettsia, Chlamydia, Mycoplasma

poor activity against Pseudomonas, unpredictable activity against Enterobacteracae (resistance common)
chloramphenicol: bacterial resistance mechanisms
inactivation by bacterial enzymes, inhibited entry into bacteria

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
chloramphenicol: regulatory status
banned for use in cattle b/c of risk of residues in treated animals

very few preparations currently on market
chloramphenicol: adverse reactions
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


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
macrolides: mechanism of action
bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis

a. bactericidal or bacteriostatic?
b. time or conc. dependent?
a. bacteriostatic (bactericidal for some Gram pos. bacteria)

b. time dependent
macrolides: spectrum

good activity against Gram pos. bacteria, Rhodococcus, Mycoplasma, Chlamydia

poor activity against most Gram neg. bacteria, except some Pasteurella & Mannheimia haemolytica
macrolides: bacterial resistance mechanisms
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

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
macrolides: prototype, routes of administration
Eryhtromycin: clinical use has ↓ in recent years

oral, IM (painful infection)
macrolides: adverse rxns
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
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

a. class
b. species
c. precaution
a. macrolide (injectable: SQ only)
b. cattle, sheep
-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

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

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)
lincosamides: mechanism of action
bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis

a. bactericidal or bacteriostatic?
b. time or conc. dependent?
a. bacteriostatic
b. time dependent
lincosamides: spectrum

-good activity against Gram pos. bacteria, Mycoplasma, most anaerobic bacteria
-little activity against Gram neg. bacteria

a. oral absorption
b. volume of distribution
a. good
b. good tissue distribution
lincosamides: adverse effects
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

a. prototype
b. uses in small animals
a. Clindamycin
b. oral cavity infections, pyoderma, osteomyelitis, soft tissue infections, Staph infections
trimethoprim-sulfonamide combinations: mechanism of action
inhibit formation of tetrahydrofolic acid (active form of folic acid): step in synthesis of nucleotides
trimethoprim-sulfonamide combinations: how it targets bacteria
- 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
trimethoprim-sulfonamide combinations: spectrum

good activity against Gram pos., Gram. neg., & some protozoa (Toxoplasma, intestinal coccidian, Sarcocystis neurona)

resistance common
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)
trimethoprim-sulfonamide combinations: bacterial resistance mechanisms
mutation of dihydrofolate reductase enzyme to become resistant to trimethoprim

utilization of other pathways by bacteria to make folic acid
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
trimethoprim-sulfonamide combinations: adverse effects
hypersensitivity rxns: DOGS
- 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

-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

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
fluoroquinolones: mechanism of action
inhibit DNA gyrase (topoisomerase II) or topoisomerase IV, which catalyze conversion of circular DNA to superhelical form

a. bactericidal or bacteriostatic?
b. time or conc. dependent?
a. bactericidal
b. conc. dependent
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)
fluoroquinolones: spectrum

good activity: Gram neg. (esp. E. coli, Salmonella, Enterobacter, Klebsiella), Gram pos., Chlamydia, Mycoplasma, Rickettsia

moderate activity: Pseudomonas aeruginosa

poor activity: Strep, Enteroccocus, anaerobes
fluoroquinolones: bacterial resistance mechanisms
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

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
fluoroquinolones: prototype & formulations
Enrofloxacin (Baytril)

tablets, injectable, otic preparations
fluoroquinolones: adverse effects
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
fluoroquinolones: drug interactions
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)
fluoroquinolones: clinical uses in small animals
soft tissue infections, skin infections, pneumonia, osteomyelitis, prostatitis, UTIs

commonly used in many species, esp. exotics
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)
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

metronidazole: spectrum

highly effective against anaerobes

good activity against many protozoa (incl. Giardia), Helicobacter

a. oral absorption
b. volume of distribution
a. rapid & complete oral absorption in small animals & horses

b. high: distributes well into all tissues
metronidazole: adverse effects
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
metronidazole: clinical uses
-rational choice for anaerobic bacterial infections, incl. oral infections, osteomyelitis, pneumonia, intra-abdominal infections
metronidazole: regulatory status
food animals: prohibited b/c it is considered a potential carcinogen