pharmacology IV

Fluoroquinolones

Bacterial killing is concentration-dependent and
requires only short contact time (~20 minutes). A
postantibiotic effect is produced in a number of
bacteria and lasts at least 4-8 hours or longer.

Potent, broad spectrum antibacterial drugs.
– Limited activity against anaerobes and streptococci.
– Mycoplasma, Mycobacterium, Chlamydia.

Resistance: stepwise mutations of DNA gyrase
and topoisomerase IV genes, with cross
resistance.
• Efflux pumps.

Oral absorption of quinolones is rapid.
– May be impaired by food, antacids, and multivalent
cations (Al, Mg, Fe, Zn).
– Absorption after oral administration to ruminants is poor.

– Quinolones are rapidly and widely distributed to all
tissues, including CNS, bone, prostate, and intracellular
spaces (concentrate in macrophages and neutrophils).
All have high bioavailability (70-99%).
– Half-lives, concentration-dependent killing, and PAE of
some permit once-daily dosing.
• Half-lives in birds and mammals range from 3 to 10 hours. Halflives
in reptiles may extend up to 72 hours.
– Some hepatic metabolism occurs.

– Renal tubular active secretion results in high urinary
concentrations of active drug. Some of the parent drug
and metabolites are excreted in both urine (30-95%)
and bile (feces) (amount varies with each drug).
• Drug crystals may form in acidic urine but are of dubious
significance.
– Excreted in milk. Use with caution in lactating animals.

• Chondrotoxicity, erosion of articular cartilage.
• Vomiting and diarrhea.
• CNS toxicity – proconvulsant activity.
• Occulotoxicity.
• Tendonitis and tendon rupture.
• Hepatotoxicity.
• Injection-site injury.

Enrofloxacin (Baytril)
• Dosage range of 5-20 mg/kg, either as a single
daily dose or divided into two equal daily doses
for use in dogs and cats.
• Both oral and injectable formulations are
available.
• Focal alopecia may occur over sites of SC
injection.
• Injectable approved for treating bovine
respiratory disease associated with
Mannheimia haemolytica, Pasteurella
multocida or Haemophilus somnus (1998).

Orbifloxacin (Orbax)
• For treatment of dogs and cats at dosage of 2.5
mg/kg of body weight administered once daily
(orally).

Difloxacin (Dicural) -- for managing diseases in
dogs associated with bacteria susceptible to
difloxacin, once-a-day treatment. Efficacy
established for skin and soft tissue infections and
urinary tract infections.

Marbofloxacin (Zeniquin) -- for use in dogs and
cats to treat susceptible bacterial infections.

Danofloxacin (A180) -- for treatment of bovine
respiratory disease associated with Mannheimia
haemolytica and Pasteurella multocida. 48-hour
dose interval. Worldwide uses include swine,
poultry and cattle respiratory diseases.

Sarafloxacin and enrofloxacin in poultry have been
banned by FDA after being blamed for a rise in
drug-resistance.

• Norfloxacin and ciprofloxacin -- some of the
human formulations that have occasionally been
used in animals

Beta-lactam drugs, inhibit cell wall synthesis,
rapidly bactericidal.

• Effective against
gram-positive
aerobes and most
anaerobes.
– Broad spectrum,
semisynthetic
penicillins effective
against some gramnegative
bacteria.

– Many penicillins (e.g., penicillin G, ticarcillin) are
degraded by gastric hydrochloric acid and are poorly
absorbed orally.
– Acid-stable penicillins (e.g., penicillin V, ampicillin,
amoxicillin) are well absorbed orally.
– Most penicillins are available in parenteral formulations.
• Absorption/elimination after injection is also rapid unless the
compound is combined with a salt, such as procaine, that slows
its absorption.

– Penicillins are rapidly ionized and rapidly distributed
widely to tissues and extracellular fluids, except those of
the CNS and the eye. They have poor intracellular
penetration (low volume of distribution and short halflives).
– Metabolism is minimal.

– More than 90% of an administered dose is excreted
unchanged in the urine by glomerular filtration and
active tubular secretion.

• Penicillins are generally non-toxic.
• Hypersensitivity reactions can be seen; they can
be mild, i.e., urticaria and pruritis or severe, i.e.,
staggering, dyspnea, and collapse. [.2% to 5%]
– Cross-hypersensitivity reactions occur.
– Penicillin skin testing is safe and reliable method of
determining whether a person with a history of IgEmediated
penicillin allergy is actually at risk for an
immediate allergic reaction if given the drug.

Procaine salts of penicillin should not be used in
birds, snakes, turtle, guinea pigs, or chinchillas
because these species are susceptible to
procaine toxicity. Procaine is detectable in the
urine of horses for several days and some horses
are sensitive to procaine when receiving high
doses of procaine penicillin G, probably resulting
from inadvertent IV administration. Hyperkalemia
and cardiac arrhythmia may result from
intravenous administration of potassium penicillin.

Ampicillin is poorly absorbed (approximately
20-40% of dose) when administered orally to dogs
compared to amoxicillin (60-70% availability).

Penicillin G and Penicillin V.

Penicillinase-stable penicillins: methicillin, oxacillin

ampicillin, amoxicillin.

Penicillins act synergistically with
aminoglycosides.

Penicillin G (benzylpenicillin) is used in
various pharmaceutical forms in all species
for the treatment of infections caused by
gram-positive, non-penicillinase-producing
pathogens, anaerobes and a limited range
of gram-negative bacteria (e.g.,
Pasteurella, Haemophilus, Actinobacillus,
Moraxella spp.).

Procaine penicillin G is slowly absorbed
from intramuscular injection sites,
providing therapeutic levels for up to 24
hours from a single dose.

• Benzathine penicillin G is even
more slowly absorbed than procanie pen G, over 48-72
hours, but blood levels are
relatively low.

Sodium or potassium salts of
penicillin G may be administered
intravenously or intramuscularly
every 4-6 hours

Penicillin V is administered orally
for treatment of susceptible grampositive
bacterial infections.

infections caused by beta-lactamase producing
Staphylococcus spp.

Broad-spectrum penicillins: Ampicillin,
amoxicillin, and hetacillin are active
against many gram-negative aerobes
(e.g., E.coli, Proteus, Salmonella,
Pasteurella, Actinobacillus, Haemophilus
spp.) as well as gram-positive pathogens
(e.g., Staphylococcus, Streptococcus,
Corynebacterium, Erysipelothrix,
Clostridium spp.). They are acid-stable
(for oral administration), but not resistant
to beta-lactamase hydrolysis.

Carbenicillin and ticarcillin have extended
broad-spectra of activity against Pseudomonas
spp, but lack resistance to beta-lactamase
hydrolysis. To achieve and maintain effective
concentrations, they must be given parenterally,
usually in combination with an aminoglycoside.

Potentiated penicillins: Beta-lactamase inhibitors
• Some beta-lactam compounds with minimal
antibacterial activity bind and inactivate betalactamases.
When administered in combination
with a penicillin, it spares the active drug from
hydrolysis.
• Clavulanic acid is combined with amoxicillin or
ticarcillin in commercial preparations.
• Sulbactam is combined with ampicillin.

– Most cephalosporins are unstable in gastric acid and
must be administered parenterally. Cephalexin and
cefadroxil are acid-stable and are well absorbed orally.
– Oral absorption is poor and erratic in horses and
ruminants.

– Widely distributed to tissues and extracellular fluids,
except those of the CNS and the eye. Poor
intracellular penetration (low volume of distribution).
– Metabolism is variable. Some metabolites retain
antibacterial activity.
– Ceftiofur produces active metabolites with very long
half-lives, allowing 24 hour dosing.

– Renal excretion of the unchanged drug in urine is by
glomerular filtration and active tubular secretion.

• Hypersensitivity reactions may occur with some crosshypersensitivity
with penicillins.
• Organ toxicity is rare. Nephrotoxicity may develop with
prolonged administration. Dosages should be adjusted in
the presence of renal disease.
• Interactions: Cephalosporins act synergistically with
aminoglycosides.
• No pre-slaughter drug withdrawal or milk discard time is
required for ceftiofur.
• Empiric cephalosporin use is rarely justified: (1) short halflife
requires administration every 8-12 hours, and (2) they
tend to select for extended spectrum beta-lactamase
producing bacteria.

First-generation cephalosporins are active
against gram-positive aerobes and a modest
spectra of gram-negative aerobes. Cephalexin
and cefadroxil are available for oral
administration. Cephapirin, cephalothin, and
cefazolin are parenteral formulations.

Second-generation cephalosporins have a
broader spectrum of activity, including more
gram-negative pathogens and some anaerobes,
but ineffective against Enterococcus and
Pseudomonas spp. Cefoxitin is occasionally used
in veterinary medicine.

Third-generation cephalosporins
have an extended spectrum of
activity against gram-negative
pathogens (e.g., Pseudomonas,
Proteus, Enterobacter, and
Citrobacter spp.), are more resistant
to beta-lactamases and penetrate
the blood-brain barrier better.

Ceftiofur is used to treat respiratory
disease of cattle, sheep, swine, and
horses and urinary tract infection of
dogs.

• Imipenem and ertapenem are atypical beta-lactams with
very broad-spectrum activity.
• Bactericidal: carbapenems inhibit synthesis of bacterial
cell wall. Causes a 2-4 hour post-antibiotic effect, inhibiting
bacteria from resuming growth.

– Carbapenems are active against gram-positive and gram-negative
aerobes and anaerobes. They have the widest spectrum of any
single antibacterial.

– Resistant to most bacterial beta-lactamases (no cross-resistance
with penicillins or cephalosporins). Rare bacterial resistance is due
to altered cell wall target protein or lack of an outer membrane porin
protein.

Absorption / Administration:
– Currently available carbapenems are not absorbed
orally because of instability at gastric pH. Adminstered
IV, IM or SC.
– Oral carbapenems are currently in development.

Distribution and metabolism:
– Carbapenems are distributed widely but enter CSF only
in the presence of inflammation.
– Imipenem is rapidly hydrolyzed in the renal tubules by a
dihydropeptidase to nephrotoxic compounds.

Excretion:
– Eliminated by glomerular filtration and tubular
secretion. Metabolism decreases urine concentration of
active drug.
– Imipenem is combined with cilastatin, a renal
dihydropeptidase inhibitor, to decrease nephrotoxicity
and increase active urine concentration.

• Nausea, vomiting, diarrhea, phlebitis at infusion
site, fever, seizures, allergic reactions to vehicle.
• Neurotoxicity by interaction with GABA receptor A.

• Imipenem-cilastatin is indicated primarily for
treatment of serious infection caused by
cephalosporin-resistant Enterobacteriaceae and
some anaerobes when a single agent is needed.
Requires 3-4 doses per day.
• Ertapenem is proposed as a first-line drug for
complicated community-acquired mixed
aerobic/anaerobic polymicrobial infections. Longer
half-life allows once-daily dosing.

Tetracyclines
• Broad-spectrum, bacteriostatic by inhibiting
protein synthesis.
– Activity against gram-positive and gram-negative
aerobes and anaerobes, mycoplasmas, rickettsiae,
chlamydiae, spirochetes, and even some protozoa
(amoebae).
– Prevent elongation of polypeptide chain.
• Most resistance is plasmid mediated efflux pumps
and provides cross resistance.
• Cross resistance among the tetracycline
analogues.

– Oral absorption results in systemic therapeutic levels of all
tetracyclines except chlortetracycline. Divalent or trivalent
cations impair absorption; thus milk, antacids, or iron salts
should be not be administered concurrently. Doxycycline is
less affected.
– Buffered solutions can be administered IV, IM or SC.
Chemical manipulation (choice of carrier and high
magnesium content) can delay the absorption of
oxytetracycline from IM sites and produce a long-acting
effect. They can cause tissue necrosis at IM injection sites in
which residues may remain for several weeks.
– Absorption of tetracyclines also may occur from the uterus,
though plasma levels remain low, resulting in residual levels
of drug in milk.

– Tetracyclines distribute rapidly and extensively in the
body, particularly after parenteral administration. They
enter almost all tissues and body fluids at high
levels. The more lipid-soluble tetracyclines (doxycycline
and minocycline) readily penetrate intracellularly as well
as crossing the blood-brain barrier.
– Metabolism is minimal in domestic animals.
– Increased magnesium content of the formulation delays
absorption from SC or IM injection depots.

– Renal excretion by glomerular filtration is major route
of elimination of active drug. Tetracyclines are active in
acidic urine.
– Intestinal elimination (bile) is always significant (approx.
10-20%), resulting in enterohepatic cycling.
– Doxycycline is unique, being excreted primarily in the
digestive tract by nonbiliary secretion of inactive
compounds.

Superinfections of fungi, yeast, or resistant bacteria may
occur with prolonged administration of broad-spectrum
antibiotics such as tetracyclines. Oral therapeutic doses
may disrupt ruminal microflora in adult ruminants or colonic
microflora in horses.
• Tetracyclines (except doxycycline) are potentially
nephrotoxic and should be avoided if renal function is
compromised. Administration of outdated tetracycline
products may lead to acute tubular necrosis.
• Tetracyclines chelate calcium in teeth and bones as they
are forming: as they become incorporated into these
structures, they inhibit calcification (hypoplastic dental
enamel) and cause yellowish-brownish discoloration. At
high, prolonged concentrations, the healing process in
fractured bones is impaired.
• Phototoxicity and hepatotoxicity are rare side effects in
animals.
• Rapid IV injection can produce hypotension and sudden
collapse. This appears to be related to the ability of
tetracyclines to chelate ionized calcium, and possibly a
depressant effect by the propylene glycol carrier. Undiluted
propylene glycol-based formulations can cause
intravascular hemolysis, leading to hemoglobinuria,
hypotension, ataxia, and CNS depression.
• Doxycycline -- Esophagitis and esophageal stricture
reported in cats.
• Cats may show a "drug fever" reaction often accompanied
by vomiting, diarrhea, depression, inappetence, and
eosinophilia.

Tetracycline, chlortetracycline, and
oxytetracycline are used in the treatment of local
and systemic bacterial, mycoplasma, rickettsial,
chlamydia, and protozoal infections in cattle,
sheep, horses, goats, and swine. Specific
conditions include chlamydiosis, anaplasmosis,
ehrlichiosis, hemoplasmosis as well as general
organ infections. They are also used as feed
additives and growth promoters in cattle and
swine.

Doxycycline and tetracycline are used in the treatment of
respiratory and urinary tract infections in dogs and cats and
as specific therapy for infections caused by Borrelia,
Brucella, Mycoplasma, and Ehrlichia species. They are
also effective in the treatment of psittacosis in birds.
• Minimal dosage adjustment of doxycycline is needed with
hepatic or renal failure.
• Doxycycline recently (1998) approved for topical treatment
and control of periodontal disease in dogs. (Do not use in
less than 1-yr-old or in pregnant bitches).
• Doxycycline inhibits T-cell proliferation and production of
cytokines and chemokines by human peripheral blood
mononuclear cells. These results suggest that the antibiotic
doxycycline has anti-inflammatory effects.

Tetracyclines

Oxytetracycline inhibits tractional structuring of
collagen fibrils by equine myofibroblasts through a
matrix metalloproteinase-1 mediated mechanism.
This may explain the results of treatment of
flexural deformities in foals resulting in elongation
of ligaments and tendons.

• Broad-spectrum, bacteriostatic by inhibiting
protein synthesis.
• Most resistance is plasmid mediated
chloramphenicol acetyltransferases.

– Chloramphenicol is rapidly absorbed from the
gastrointestinal tract and from topical administration.
– Injectable formulations.

Distribution and metabolism:
– Chloramphenicol is rapidly and widely distributed to
all tissues, including those of the CNS and eye.
– Chloramphenicol undergoes extensive hepatic
metabolism, primarily by glucuronide conjugation.
• Cats, very young animals, and animals with liver disease
frequently do not have full microsomal enzyme capabilities to
biotransform chloramphenicol to inactive metabolites.
– Florfenicol and thiamphenicol -- have significantly
altered distribution and metabolism.

– Free chloramphenicol is eliminated by glomerular
filtration whereas the glucuronide metabolite is
eliminated by tubular secretion. Only 5-15% of
chloramphenicol present in urine is in the active form.

– Depression, anorexia, dysphagia, salivation, nausea,
vomiting, sporadic diarrhea reported in dogs and cats.
– Dose-related bone marrow suppression and anemia
may occur in animals and humans.
– Non-dose-related bone marrow suppression and
aplastic anemia in humans is irreversible and often
appears after the drug has been discontinued.
Florfenicol and thiamphenicol, lacking the nitro group,
do not produce aplastic anemia.
• Various disturbances of eukaryotic protein
synthesis and function have been described:
– GI disturbances.
– Delayed wound healing.
– Suppressed anamnestic responses.
• Chloramphenicol is a potent noncompetitive
microsomal enzyme inhibitor that can
substantially prolong the duration of action of a
number of co-administered drugs (e.g., propofol,
pentobarbital, codeine, phenytoin, nonsteroidal
anti-inflammatory drugs, and coumarins) by
inhibiting hepatic mixed function oxidase enzymes
(cytochrome P450s).

Preparations and therapeutic uses
• Chloramphenicol is used in dogs, cats, horses,
and birds for local and systemic infections,
including respiratory, CNS, and ocular infections,
and infections caused by anaerobes.
• Chloramphenicol use in food animals has been
banned in the USA. [It is a criminal offense to use
chloramphenicol, not an extra-label discretion.]

Florfenicol
• Approved for use in food animals.
• Reduced number of sites for bacterial acetylation,
possibly making it more resistant to bacterial
inactivation.
• More water soluble and less lipid soluble than
chloramphenicol, resulting in slower diffusion
through lipid membranes, longer tissue distribution
times, less penetration into CSF, brain and
aqueous humor of the eye.
• Most of the dose is found unchanged in the urine
(no significant hepatic metabolism).

Aminoglycosides
• Gentamicin, amikacin, neomycin, streptomycin.
• Bactericidal by interfering with protein synthesis.
– Inhibit rate of synthesis and cause misreading of mRNA.

Aminoglycosides
• Uptake requires oxygen-dependent, active
transport into bacterial cell.

Primarily used for treatment of serious gramnegative
infections. Limited gram-positive activity.
– Obligate anaerobes are resistant.
– E. coli, Proteus, Klebsiella, Pseudomonas,
Campylobacter, Leptospira, etc.
– Poor cell wall penetration, used in combination with
beta-lactam.

Aminoglycosides
• Acquired resistance primarily by plasmid-mediated
enzymatic modification (acetylation,
phophorylation, adenylation) with incomplete
cross-resistance.

Absorption / Administration:
– Aminoglycosides are NOT efficiently absorbed from
the gastrointestinal tract.
– Oral administration is effective only as topical treatment.
– Systemic therapeutic levels are achieved only by
parenteral administration (IV, IM, SC)

– Aminoglycosides are distributed to the extracellular
fluid volume (small volume of distribution and short
half-life). Penetration of the CNS is minimal.
– Metabolism does not occur.

– Aminoglycosides are excreted unchanged in the urine
by glomerular filtration, but not active in acidic pH.

• Ototoxicity results from progressive damage to
cochlear sensory cells (causing deafness),
vestibular cells (causing ataxia), or both.
– Aminoglycosides are potentially ototoxic when instilled
directly into the external ear canal of dogs and cats if
the tympanic membrane has been ruptured.
– Decreasing order of ototoxicity: streptomycin,
dihydrostreptomycin, gentamicin, tobramycin, netilmicin.
• Nephrotoxicity is
caused by damage to
the membranes of
proximal tubular cells,
resulting in a loss of
brush border enzymes,
impaired absorption,
proteinuria, and
decreased glomerular
filtration rate.

• Dosages must be adjusted for animals with
decreased renal function.
• Factors that increase the risk of nephrotoxicosis
include: age (young and old), compromised renal
function, total dose, duration of treatment,
dehydration and hypovolemia, aciduria, acidosis,
severe sepsis or endotoxemia, concurrent
administration of loop-acting diuretics
(furosemide), and exposure to other nephrotoxins

Once a day dosing reduces risk of toxicity.
Decreasing order of nephrotoxicity: neomycin,
kanamycin, gentamicin, tobramycin, amikacin,
streptomycin.

Gentamicin is effective against
Pseudomonas, Proteus, and other
gram-negative aerobes involved in
septicemia. Resistance is
emerging and limiting the
effectiveness of this drug.

Amikacin is more effective than all
other aminoglycosides for the
treatment of gram-negative aerobic
infections. Resistance rarely
occurs. It causes less
nephrotoxicity than other
aminoglycosides.

gentamicin.

Apramycin is administered orally to calves and
piglets to control gram-negative enteric infections,
particularly E. coli and Salmonella.

Spectinomycin is also an aminocyclitol, but is
bacteriostatic rather than bactericidal. It is active
against a wide range of gram-negative bacteria
and Mycoplasma causing enteric and respiratory
disease.

Aminoglycosides
Penicillins
Cephalosporins
Quinolones
Bacitracin
Vancomycin
Polymyxins
Potentiated sulfonamides

Chloramphenicol
Tetracyclines
Sulfonamides
Macrolides
Lincosamides

penicillins, cephalosporins, macrolides, tetracyclines, aminoglycosides, and quinolones

Carbapenems are active against gram-positive and gram-negative aerobes and anaerobes. They have the widest spectrum of any single antibacterial

rapidly growing microorganisms. The antibacterial spectrum of potentiated sulfonamides includes most bacteria except Pseudomonas and Mycobacterium spp.

Most sulfonamides are well absorbed orally. A few enteric formulations are also available. Intravenous administration is occasionally used. Frequency of dosing varies considerably with the individual sulfonamides.
Trimethoprim is rapidly absorbed following oral administration. Trimethoprim is inactivated in the rumen.

Sulfonamides are rapidly distributed throughout all body tissues. Trimethoprim diffuses extensively into tissues and body fluids.
The type and extent of metabolism vary with the sulfonamide and the animal species. Metabolism by acetylation and glucuronide conjugation occurs in most species; however, acetylation does not occur in dogs. Oxidation also occurs, especially in dogs.
Trimethoprim metabolism in the liver varies between animal species

Renal excretion of the unchanged sulfonamides and metabolites is via glomerular filtration, active secretion, and passive tubular reabsorption.
Trimethoprim is largely excreted in the urine by glomerular filtration and tubular secretion. A substantial amount may also be found in feces and milk.

sulfonamides

1.Renal crystalluria
2.Keratoconjunctivitis sicca
3.Immune-mediated polyarthritis, retinitis, glomerulitis, vasculitis, serum sickness, anemia, thrombocytopenia, urticaria, erythema multiforme, toxic epidermal necrolysis, facial swelling and conjunctivitis occur rarely
4.Hepatotoxicity -- cholestatic hepatitis
5.Folic acid deficiency anemia may occur in cats after several weeks; large doses and longer treatment will affect dogs
6.Hypothyroidism

Macrolides

Macrolides have anti-inflammatory properties as well, reduce bronchial responsiveness, sputum purulence, levels of IL-8, etc. Effectively treat steroid-dependent asthma and COPD

gram-positive aerobes, mycoplasmas, and anaerobes. Some strains of Pasteurella and Haemophilus may be susceptible. In vitro synergism occurs with rifampin against Rhodococcus equi.

the drug can not pentrate their cell walls

Macrolides are variably absorbed from the GI tract if not inactivated by gastric acid. Oral preparations are often enteric-coated or stable esterified salts are used.
IV or IM administration results in rapid absorption, but pain and swelling occur at the injection sites

Macrolides are widely distributed in tissues except those of the CNS, and concentrations are about the same as in plasma, or even higher particularly in lungs (8-60 times plasma levels).
Active transportation by phagocytic cells.
Metabolic inactivation of the macrolides is drug dependent.

Erythromycin and tiamulin are metabolized by the liver and excreted in bile.
Tylosin and tilmicosin are excreted unchanged in bile and urine.

1.Mild gastrointestinal upset (nausea and vomiting) may result from oral doses of erythromycin
2.Pain and irritation at intramuscular injection sites may occur
3.Tilmicosin produces cardiovascular toxicity in species other than cattle and swine
4.Severe diarrhea may occur if erythromycin is administered orally to adult ruminants or if tylosin is administered orally or parenterally to adult horses
5.Erythromycin and tiamulin diminish the activity of some cytochrome P450 enzymes. Clarithromycin does not inhibit cytochrome P450. Azithromycin is excreted through a biliary process, not by cytochrome P450.

Erythromycin

Azithromycin and clarithromycin are newer macrolides with better enteral absorption, increased resistance to gastric acid, and they achieve high concentrations in phagocytic cells from which they are released over several days.

Tulathromycin (Draxxin) is a long-acting, single-dose injectable (derived from azithromycin) for treatment of respiratory disease in cattle and swine. Plasma half-life >70 hr., half-life in lung 6-8 days, volume of distribution 10 L/kg.

Lincosamides

gram-positive aerobes, mycoplasmas, and anaerobes. Toxoplasma sp. is susceptible to clindamycin.
(narrow sepctrum)

Lincomycin is incompletely absorbed. About 90% of an oral dose of clindamycin is absorbed and effective plasma levels are rapidly obtained.
Clindamycin is also administered IM

Lincosamides are widely distributed, with excellent penetration of bone and soft tissues, including tendon sheaths. CNS levels are low.
Metabolism of lincosamides in the liver is extensive

Unchanged drug and metabolites are excreted in the urine, bile, and feces. Levels remain high in the feces for some days, and growth of susceptible organisms in the large intestine may be suppressed for up to 2 weeks. Prolonged enterohepatic circulation of lincosamides

In horses, rabbits, hamsters, and guinea pigs, lincosamides are contraindicated because they may produce severe, often fatal, necrotizing enterocolitis (usually associated with overgrowth of toxigenic clostridia). Oral administration to ruminants can be fatal.
Neuromuscular blockage may occur at high doses or when lincosamides are administered with anesthetics

Vancomycin

Vancomycin is only effective against gram-positive bacteria, particularly the cocci

Vancomycin is not absorbed orally. IV administration is used.

Vancomycin is distributed in the extracellular fluids.
Metabolism does not occur

The active form of the drug is excreted by glomerular filtration in the urine. In renal insufficiency, striking accumulation may occur.

Ototoxicity and nephrotoxicity occur with large dosages or prolonged administration, but are becoming more infrequent with purified formulations.
Hypersensitivity reactions are observed infrequently

severe methicillin-resistant staphylococcal and enterococcal infections of bone and soft tissue.
Effective August 20, 1997, FDA announced that extralabel use of glycopeptides is prohibited in food animals

Polymyxins are used only as topical antibiotics

Polymyxin activity is limited to gram-negative bacteria

Polymyxin is not absorbed orally or from topical application. It is too nephrotoxic for systemic use.
Polymyxin B, administered at low, nontoxic doses, is an investigational treatment used to neutralize systemic endotoxin. Polymyxin binds bacteria-free LPS and neutralizes the endotoxic activity. Effective doses do NOT have antibacterial activity.

tuberculosis

mycobacteria and gram-positive pathogens.

Rifampin is readily but incompletely absorbed from the GI tract.

Rifampin is widely distributed in body tissues and fluids and because of its high lipid solubility, it is effective against intracellular infections.
Rifampin is biotransformed into several metabolites, some of which are active. Metabolites may impart an orange-red color to the urine, feces, and saliva.

It is primarily excreted in bile and to a lesser degree in urine. Enterohepatic cycling commonly occurs

Rifampin is usually well tolerated and produces few side effects.

Rifampin is combined with erythromycin in the treatment of Rhodococcus equi infections in foals.

most obligate anaerobes and is active against protozoa, including Giardia and Trichomonas species.

Metronidazole is rapidly and readily absorbed from the GI tract with peak serum levels within 1-2 hours.

Metronidazole is widely distributed to all tissues, penetrating the blood-brain barrier and attaining therapeutic concentrations in abscesses and empyema fluid.
One-third to one-half of the drug dose is metabolized by oxidation and conjugation in the liver

Both metabolites and the unchanged drug are excreted in the urine and feces

Profuse salivation, anorexia, weight loss has been reported when administered to cats.
High or prolonged doses may induce signs of neurotoxicity in dogs, such as tremors, muscle spasms, ataxia, and even convulsions. Injury with degenerative changes in Purkinje's cells and associated cerebellar and vestibular axons. May take several days to months to resolve while some dogs develop uncontrollable seizures and fatal encephalopathies.
Metronidazole should NOT be used in pregnant animals, particularly during the first trimester. In vivo evidence for carcinogenicity and mutagenicity is still tenuous.

Amphotericin B, nystatin, and natamycin (pimaricin) are polyene antifungal drugs currently used in veterinary medicine.
Amphotericin B is used primarily for systemic treatment, rarely for topical application

Fungistatic: Imidazoles inhibit the synthesis of ergosterol in fungal cytoplasmic membranes resulting in altered cell membrane permeability.

Most imidazoles used as antifungal drugs have a wide antifungal spectrum of activity, including activity against Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, Cryptococcus neoformans, Aspergillus spp., and Candida spp., other yeasts and dermatophytes

Fungicidal: 5-FU inhibits thymidylate synthetase, thereby inhibiting DNA and RNA synthesis in susceptible fungi.
Spectrum of antimicrobial activity:

Flucytosine is effective against Cryptococcus, Candida, Torulopsis. Filamentous and other systemic mycotic agents are resistant.

Fungistatic: Griseofulvin is actively taken up by growing dermatophytes, binds to microtubules to inhibit spindle formation and mitosis. Its action is slow -- infected cells must be shed and replaced with uninfected cells.
Spectrum of antimicrobial activity:

Griseofulvin is effective against dermatophytes (e.g., Microsporum and Trichophyton spp.). Other fungi are unaffected.

Amantadine inhibits replication of influenza A virus, influenza C virus, Sendai virus

Idoxuridine(IDU) is effective for the treatment of herpesvirus infection of the superficial layers of the cornea (herpesvirus keratitis) and of the skin, but is toxic when administered systemically.

Trifluridine, an analog of deoxythymidine, is currently the agent of choice for the treatment of herpesvirus keratitis in humans

Vidarabine, or ara-A, is used topically for ocular herpes and systemically for herpetic encephalitis as well as for neonatal herpesvirus infections

Acyclovir is relatively safe and is useful against a variety of infections caused by DNA viruses, especially the herpesvirus family. However, resistance can occur

Ribavirin is a synthetic triazole nucleoside (an analog of guanosine) with a broad spectrum of activity against many RNA and DNA viruses, both in vitro and in vivo

old dewormer not used much
Hosts:dog,cats,swine,poultry
spectrum:ascarides

(pyrantel)
Hosts:dogs, cats, horses, swine
spectrum:ascarides, hooks, strongyles, and pinworms in horses, some activity for equine tapeworms
Safe, Nicotinic agonist, antidote is atropine

Hosts:dogs, cats, cattle, sheep, goats, horses, swine, zoo animals
spectrum:all adult GI nematodes, immature and arrested nematode larvae, some activity for flatworms
safe, mode of action prevents glucose uptake
no antidote

hosts:cattle, sheep, swine
route:oral subcutaneous, topical
spectrum:adult intestinal nematodes and lungworms in ruminants, no activity for inhibited stage
2x the dose is toxic
depolarinzing neuromuscular blocker
antidote:atropine

hosts:cattle, sheep, horse, swine, dogs, cats
spectrum:endectocides, nematodes, some arthropods, no activity for tapes and flukes

(praziquantel)
Hosts:dogs, cats, horses
spectrum:tapes, flukes
safe

praziquantel (droncit)

spectrum:giardia
anaerobic bacteria
other protozoans

ronidazole

clindamycin

sulfa drugs and others

azithromycin

nitazoxinide
ponazuril

clindamycin plus sulfas

old melarsomine, now use thiacetarsamide

ectoparasitcide
some repellent activity

synthetic pyrethrins
ectoparasites
ear tags
sprays
shampoos
pour ons

organophsospate for the treatment of fleas and ticks

organoposphates aliphatic derivative used as a spray and in flea collars

organophsphate aliphatic dervative used in ear tags

organophosphate phenyl derivate
used in pour ons, ear tags for horn and face fly control

organophsphates phenyl derivative feed through insecticides

chlorpyrifos, coumaphos, diazinon, and phosmet

formamide effecting CNS of parasites
used for treatment of demodex and tick control(collars)
anitdote: yohimibine

frontline, top spot
effective against fleas, ticks, and sarcoptic mange
GABA regulated chloride channel blocker

advantage
control of fleas

treatment of adult fleas

active against flea eggs and larvae inhibits chitin synthesis

ocicidal and larvalcidal agianst fleas