What is the difference

between an Antibiotic,
Antibacterial and
Antimocrobial?
* Antibiotic is a substance produced by a micro-organism
that kills or inhibits other micro-organisms
* Antibacterials are synthetic agents which have activity
against bacteria
* Antimicrobials are any substance (natural or synthetic)
that kills or inhibits growth of a micro-organism without
damaging the host.
What are the five
mechanisms of action for
microbials?
1) lnhibition of protein synthesis (at bacterial ribosome)
2) lnhibition of nucleic acid synthesis (DNA or RNA)
3) Disruption of cell walls
4) Disruption of cell membranes
5) lnterfere with metabolic pathways
What are the types of
resistance that micro-
organisms have to
antimicrobials?
* lnherent
* Chromosomal mediated
* Transferable drug resistance
Give three examples of the
inherent resistance of micro-
organisms to antimicrobials?
1) Mycoplasma resistance to Beta Lactams via
lack of cell wall
2) Anaerobic organisms (F. necrophorum)
resistance to aminoglycosides
3) Aerobic organisms resistance to
nitromidazole, which requite oxygen to function.
Describe how Chromosomal
Resistance takes place.
A mutation in one bacteria allows it to
survive and multiply when other non-
resistant bacteria have been killed off
with the antimicrobial.
How is transferable
resistance conferred?
Plasmid replicate autonomously and contact
genes which allow it to transfer from one
bacteria to another. These genes may encode
antimicrobial resistance for one or more drugs.
Name five mechanisms that
make micro-organisms
successful in resisting
antimicrobials.
1) Produce enzymes which inactivate the drug
2) Alter the drugs binding site on self
3) Reduce drug uptake
4) Develop enzymes with low drug affinity
5) lncrease production of competitive metabolites
(ex:PABA)
Define Minimal lnhibitory
Concentration (MlC).
The highest dilution at which there is no
growth of microorganisms after
incubation (in vivo). This is a
quantification that is used in determining
dosing.
Explain the difference between a
Time Dependant and a
Concentration Dependant
antimicrobial.
Time Dependant antimicrobial require that the hosts
plasma concentration of the drug remain above the MlC
for a specific period of time for effictiveness, where as
Concentration Dependent antimicrobials require that the
peak serum concentration of the drug exceed the MlC
for effectiveness.
Give three examples of
Time Dependent
antimicrobials.
1) Beta-lactams
2) Macrolides
3) Lincosamides
* Key that a dose is not missed as drugs
have short half-lives.
Give three examples of
Concentration Dependent
antimicrobials.
1) Aminoglycosides
2) Fluoroquinolones
3) Metronidazole
* lnfrequent, but HlGH dosing
What are the four major
groupings of Beta-Lactams?
1) Penicillins
2) Cephalosporins
3) Monocatams*
4) Carbapenems*
* Not used in vet med. Saved for
SERlOUS human situations.
What are the three types of
Penicillins and their Method
of action?
* Narrow Spectrum
* Broad Spectrum
* Antipseudomonal
Bactericidal
- lnhibits transpeptidase enzymes by irreversibly binding
to the active site. Halts cell wall production.
- Disrupt cross linking of glycopeptide polymer in
bacterial cell wall.
~Prevents cell wall formation
~Lyses cell wall of growing cells
What four things determine
Penicillins activity against a
bacteria?
1) Tranpeptidase
2) Ability to penetrate LPS cell wall (Gram -)
2) Resistance to Beta-lactamase
4) Amount of peptidoglycan in cell wall
What is Beta lactamase?
Where does it come from?
An enzyme produced by certain bacteria that can cleave
the betalactam ring of Betalactam antimicrobials.
Produced by:
- Staphylococci (Gram +)
* Plasma mediated
- E.Coli, Klebeisella (Gram -)
* Chromosomal mediated
What are the Pharmokinetics of
Penicillin? How does this effect its
activity?
- Vd
- pKa
- t1/2
- Exclusion
- Excretion
- Post antibiotic effect
* Vd 0.2-0.3L/Kg - Low
* pKa 2.7 - Acid
* t1/2=0.5-1.2 hrs (Short)
* Excluded from CSF & aqueous humor
* Renal excretion (good for UTl's)
* Time Dependent - maintain [high]
What are the three types of
Narrow Spectrum
Penicillins?
- Penicillin G
- Penicillin V
- Cloxacillin & Nafcillin
Which Narrow Spectrum Penicillin is
described by:
- Gram + only
- Acid labile (NOT orally available)
- Beta lactamase susceptible
Penicillin G
Which Narrow Spectrum Penicillin is
described by:
- Gram + only
- Acid stable (Orally available)
- Beta lactamase susceptible
Penicillin V
Which Narrow Spectrum Penicillins are
described by:
- Gram + only
- Acid stable (Orally available)
- Beta lactamase stable
Cloxacillin & Nafcillin
Often salts are combine with
Penicillins, why?
Salt change how long the
antimicrobial acts in the
body.
Benzylpenicillin is most commonly used in Vet.
Med.
* What type of Penicillin is it?
* Why is Procaine added to Benzylpenicillin to
make Procaine benzylpenicillin?
* Penicillin G
* Procaine is added to
reduce the pain of lM or SQ
injections
What bacteria is Methicillin and/or
Cloxacillin used to combat? Why?
Staphylococci
A Gram + bacteria that produces
Beta lactamase
Name two groups w/ two
examples Broad Spectrum
Penicillins.
Aminopenicillins
* Ampicillin
* Amoxycillin
Antipsuedomonals
* Carbenicillin
* Ticarcillin
Which Penicillin group is
described by:
- Targets Gram + & -
- Acid stable
- Beta lactamase susceptible
Broad Spectrum Aminopenicillins
* Ampicillin
* Amoxycillin
~Routinely Used
Which Penicillin group is described by:
- Targets Gram + & -
- Beta lactamase susceptible
- Effective against Pseudomonas
Broad Spectrum
Antipsuedomonals
* Carbenicillin
* Ticarcillin
Why is Clavulanic Acid
added to Amoxycillin?
Clavulanic Acid is a "suicide drug".
lt uses up the Beta latamase
freeing up the Amoxycillin to
attach the bacteria.
What is the function of
administering Aminopenicillins in:
- Sodium Salts
- Trihydrate salts
- Depot preparations?
Sodium Salts - Highly soluble for oral and lV
admin.
Trihydrate Salts - Longer acting for lV & SQ
admin.
Depot prep - Long acting in oily vehicle
Name the two groups/three
drugs or Antipseudomonal
Penicillins. How do the two
groups differ?
Dicarboxylic Acid derivative
- Ticarcillin
- Carbenicillin
*Synergistic with aminoglycodides
*Sensitive to Beta latamase from P. aueruginosa
*Sensitive to gastric acid (given parentrally)
Ureidopenicillins
- Piperacillin
*Broader spectrum that ticarcillin
Name three Beta lactamase
suicide inhibitors often
paired with penicillins. What
is their mechanism?
1) Clavulanic Acid
2) Tazobactam
3) Sulbactam
* lrreversibly bind to Beta lactamase enzymes.
~Weak antibiotics on their own
How toxic are penicillins?
What circumstances?
Very Safe
- occasional anaphylaxis/mild
hypersensitivity
- Fatal clostridial colitis in guiena pigs &
rabbits due to loss of normal gut flora
What is the big advantage
of Cephalosporins?
Resistant to Betalactamase
enzymes
What are the key differences
between the 4 generations of
Cephelosporins?
1st Gen
- Good Gram + and anaerobes
- Moderate Gram -
- Orally available
2nd Gen (Cefuroxime)
- Similar to 1st
- better w/ E.coli, Klebsiella, Proteus
3rd Gen (Cefovecin, Ceftiofur)
- Reduced Gram + activity
- Excellent Enterobacteriaceae
What are the key
Pharmacokinetics of
Ceftiofur?
- No milk withdrawal, as it binds to acute phase
proteins and doesn't readily cross into milk
- Highly protein bound -> increased t1/2
- Rapidly metabolize to active compound
Cephalosporins
- Mechanism of Action
- Post antibiotic effect & t1/2
- Vd
- Exclusions
- Excretion
- Same as penicillins (Bactericidal)
- None - Time dependent; short t1/2, frequent
dosing required
- Same as penicillins
- Prostate, CSF, aqueous humor (except later
generations)
- High concentration in urine & bile
How have the
Pharmacokinetics of
Cephalosporins changed in
subsequent generations?
- Less oral bioavailability
- Glomerular excretion and tubular secretion
- Some de-acetylated in liver -> to active
metabolites (ex: Cephalothin>>ceftiofur
Name a Cephalosporin that is
good for UTl's, and skin and soft
tissue infections in companion
animals? What generation is it?
Cefovecin - 3rd generation
* Parentral Admin. only
* Tx every 14 days (long t1/2)
* Must keep refrigerated
Name two Cephalosporins
used in Food Producing
species and their key
difference.
Good Gram - activity
* Ceftiofur (3rd gen) - highly PPB, hepatic
metabolism
* Cefquinome (4th gen)
What antimicrobials were
developed to deal with Beta
lactase producing Gram -
organisms? What are they used
for?
* Carbapenems
* Monbactams
*** Saved for human medicine ***
Name five Aminoglycosides.
1) Streptomycin
2) Dihydrostrptomycin
3) Neomycin
4) Gentamicin
5) Amikacin
What are the structural properties
and associated pharmokinetics of
the Aminoglycosides?
- Big Bulky Sugars
- Polar
* Poorly absorbed from Gl tract (Great for
treating Gl infection)
* Well absorbed with lM or SQ admin.
* Small Vd
Aminoglycosides
- Mechanism of action
* lnhibits protein synthesis
- Penetrates through bacterial cell membrane (requires
02)
- Binds to a non-enzymatic site on ribosome
- Alters codon/anticodon recognition
- defective bacterial protein is produced
* lnduces RNA breakdown
* Damages cell membranes
* Effects DNA metabolism
Aminoglycosides
- Post antibiotic effect
Concentration Dependent
Why are Aminoglycosides
synergistic with Beta lactams?
Beta lactams interfer with cell wall
synthesis allowing the
Aminoglycoside easier penetration
into the cell.
Why do the Aminoglycosides bind
to the non-enzymatic site on the
bacterial ribosome?
lncreases drug movement
into the cell
Why is Aminoglycoside activity
decreased by pus, inflamed tissue
and abscesses?
The low oxygen environment blocks the oxygen
dependent active transport of the drug into the
bacterial cell.
Other factors include - low pH, divalent cations
& hyperosmolar conditions
What is the spectrum of
Aminoglycosides
antimicrobial activity?
Narrow to Moderate Spectrum
- Some Gram +
- Mycoplasma
- Some mycobacteria (not Strep)
Relative Activity
Amikacin> Toramycin> Gentamicin> Neomycin>
Streptomycin
Aminoglycosides
Pharmacokinetics
- t1/2
- Vd
- PPB
- Excretion
* t1/2 - short (1-3hr)
* Small (<0.35l/kg)
* Low PPB (25%)
* Renal excretion unchaged
Why is alteration of dosing for
Aminoglycosides more important
that Beta lactams?
Aminoglycosides are excreted via
Glomular filtration only. lmpaired
renal function will decrease rate of
excretion - dose must be adjust for
toxicity.
What type of bacterial
resistance currently occurs
for Aminoglycosides?
* Plasmid mediate resistance - coding for
enzymes that deactive Aminoglycosides and
prevent ribosomal binding
* Chromosomal mutation that alters binding site
(Streptomycin)
Which Aminoglycoside is
relatively free of resistance
issues and why?
Amikacin
- infrequent use
What are the toxicity issues
associated with
Aminoglycosides?
* 8th Cranial Nerve Toxicity
- Vestibular
- Cochlear
* Nephrotoxicity
* Neuromuscular blockage (non-depolarizing)
* Collapse (lV lnjection)
* Hypersensitivity
How does 8th Cranial Nerve
Toxicity occur in
Aminoglycosides and how
does it manifest itself?
* Vestibular Toxicity (Reversible)
- damage to sensory cells of the labyrinth
- lssues with balance, ataxia, incoordination, nystagmus
* Cochlear Toxicity (irreversible)
- damage to sensory cells in the cochlea
What two drugs are most
commonly associated with
Vestibular Toxicity?
Aminoglycosides
1) Streptomycin
2) Dihydrostreptomycin
What four drugs are most
commonly associated with
Cochlear Toxicity? What can
potentiate this?
Aminoglycosides
1) Streptomycin
2) Neomycin
3) Kanamycin
4) Amikacin
* Loop diuretics and other diuretics (Avoiding
using together)
What four drugs are most
commonly associated with
Nephrotoxicity?
Aminoglycosides
1) Neomycin
2) Gentamicin
3) Kanamycin
4) Amikacin
What are the clinical signs
of Nephrotoxicity?
- Acute tubular necrosis
- Proteinuria
- Hyaline & granular cast in urine
***Reversible lF caught early on via blood/urine
sampling***
What causes collapse
during lV administration of
Aminoglycosides? How can
this be avoided?
Decreased heart rate
Decrease cardiac output
* Administer slowly
How does the potential for
Nephrotoxicity of Aminoglycosides
affect the dosing regime of the
drug?
A single injectable daily does will
expose the kidneys to drug once a
day. lnterim time allows them to
"recover" before next dose.
What are three important
uses for Neomycin? Why is
it not given parentrally?
Mastitis - lntramammary
Skin infection - Topical
GlT infection - Orally
* Too toxic for pareteral use
What drug is typically used
to treat Actinobacillosis
(TB)?
Streptomycin
Name two Aminocyclitols.
Apramycin
Spectinomycin
Apramycin
- Type of drug
- Active against
- Resistance
- Common use
Aminocyclitol Aminoglycoside
* Gram - (S. Aureus), some mycoplasma
* resist R-plasma mediated degradative
enzymes
*Treatment for Gram - infections in
calves/piglets
Spectinomycin
- Type of drug
- Mechanism of action
- Resistance
- Common use
Aminocyclitol Aminoglycoside
* lnhibition of protein synthesis at translocation
step
* Chromosomal mutation confers resistance in
bacteria
* Common Use - diarrhea in piglet, mycoplasma
in poultry
Sulphonomides
- Mechanism of Action
- Spectrum
- Competitive inhibition of PABA,
which inhibits the folic acid
cascade. (Bacteriostatic)
- Broad Spectrum
What types of microbials do
Sulphonmides cover?
- Gram +
- Gram -
- Chlamydophila
- Protoza
* NO Activity against Mycoplasma, enterococci,
& Pseudomonas
Describe the three ways in
which microorganisms have
become resistant to
Sulphonmides.
1) Chromosomal mutation
- impair penetration
- enzyme in folic acid cascade (Dihydropteroate)
becomes insensitive to drug
- increase PABA production to out compete
2) Plasmid mediated
- impaired penetration
- Dihydropteroate becomes insensitive to drug
3) R Factor resistance (similar to streptomycin)
How are Sulphonamides
administered? How can you
improve their effectiveness
in the lower Gl tract?
- They can be administered in ANY way
- Being weak acids they are easily absorbed from the
upper Gl tract. A bulky amino nitrogen group can be
substituted on the drug, which must be hydrolysed in the
lower Gl before being absorbed.
Sulphonamides
- Vd
- Penetration ability
- PPB ability
* Good Vd - can reach significant
level in CSF
* Penetrate milk & synovial fluid
* Low PPB
How do Sulphonomides differ from
Aminoglycosides & Beta Lactams
in metabolization?
Sulphonomides are metabolized to less soluble,
inactive compounds via acetylation (except
dogs), glucuronidation & hydroxylation in the
liver. Aminoglycosides & Beta Lactams are not
metabolized.
How are Sulphonomides
excreted? What is the main
concern surrounding
excretion?
* Sulphonomides are excreted by filtration & active
tubular secretion, unchanged in the urine. Gut active
sulphonomides are excreted in the feces.
Sulphonomides are capable of crystallizing in urine
(especially acidic urine from carnivores) when solubility
is exceeded. Alkalinisation of the urine enhances
elimination & decreases ppt.
How can Renal Crystalluria
be reduced in patients
receiving Sulphonomides?
- Use of longer acting compounds
- Use of more potent drugs
- Using combinations of Sulphonomides as they
have independent solubility properties.
What types of toxicity issues
are associated with
Sulphonomides?
1) Diarrhoea in ruminants (decreased flora)
2) Hemorrhagic Syndrome (Vit K antagonist)
3) Reversible non-spec. polyarthritis (Dobermans)
4) Keratoconjunctivitis sicca (Small breeds susceptible;
10-15% of animals develop dry eye)
5) Fatal arrhythmias w/ alpha2 agonists (horses) AVOlD
6) Shoft shelled eggs (CaCl3 interference)
7) Diuresis
What local factors can affect
to efficacy of
Sulphonomides?
* Pus - Free thymidine & purines produce
PABA
* Local Anesthetics (procaine) are PABA
esters which can compete with
Sulphonomides
There are five different
Sulphonomide preparations
that can be created, what
are they?
1) Rapid onset, short duration
2) Rapid onset, long duration
3) Ocular
4) Lower Gl (require hydrolysis)
5) Upper Gl
Name four
Diaminopyrimidines. Which
one is most significant in
Veterinary Medicine?
1) Trimethoprim ***
2) Ormetoprim
3) Baquiloprom
4) Pyrimethamine
Diaminopyrimidines
- Mechanism of Action
- Spectrum
- lnhibits dihyrofolate reductase (DHFR) in the
folic acid cascade. (Baterioscidal)
- Spectrum varies on drug - some are better
against bacteria, others against protozoa.
Trimethoprim
- Spectrum of activity
- Administration
* Broad Spectrum Bacteriostatic (via
DHFR inhibition)
* Can be given orally, except with
ruminants (drug degraded by flora)
What is the Vd for
Diaminopyrimidines? Do
they experience ion
trapping?
* Vd good - lipid soluble
* lon trapping readily occurs in the
mammary gland and prostate are they
are acidic and the drug is a weak base.
Why is Baquiloprim a better
Diaminopyrimidines to give
ruminants than
Trimethoprim?
* Baquiloprim is not degraded by rumen flora
and has a longer half-life than Trimethoprim.
* ls often give as a bolus to cattle in
combination with Sulfonamide.
What known toxicities are
there to
Diaminopyrimidines?
Uncommon, but
Erythrocyte dysfunction due to folic acid
deficiency. More common in humans and
treated with folic acid.
Why is it advisable to use
Diaminopyrimidines with
Sulphonamides?
By using a combination it is possible to use 1/8
of the usual dose of Sulphonamides, reducing
toxicity risks. Drugs are synergistic and
bacteriacidal and resistance is lower.
What is the newest class of
antibiotics? Name two.
Fluoroquinolones
- Enrofloxacin (Baytril)
- Ciprofloxacin
Nalidix Acid is a Quinolone
like Fluoroquinolone. Why is
Fluoroquinolone better?
Nalidix Acid is a narrow spectrum
bacterialcidal with limited
distribution and serious CNS side
effects.
What are the positive
qualities of
Fluoroquinolones?
- Broad spectrum Bactericidal
- Good oral bioavailability
- Large Vd (lipid soluble)
- No plasma mediated resistance
Are there any toxic effects
to Fluoroquinolones?
Arthropathy can occur in growing
animals. Modification of use can
avoid side effects.
Are Fluoroquinolones an
acid or base?
Can be either, depending on
environment. (Amphoteric)
Each group of the molecule
provides a function, what are
they?
- 6 Fluoro Group
- 7 Piperazine Group
- a Alkyl or Ring Group
- 6 Fluoro Group(Broad Spectrum)
- 7 Piperazine
Group(Pseudomonas)
- a Alkyl or Ring Group (improved
distribution)
Fluoroquinolones
- Mechanism of Action
- Post Antibiotic Effect
* lnhibits bacterial DNA gyrase, but is less effective
against the analogous mammalian Topoisomerase
(enzyme that breaks DNA during negative supercoiling &
transcription).
* Concentration dependent (Once daily dosing)
What activity of Quinolones
have bacteria become
resistant to?
Fluoroquinolones enter bacterial cells via porins.
Bacteria have been seen to reduce porin permeability as
a form of resistance. Additionally, they can change the
DNA gyrase structure.
** Plasmid mediated resistance is no believed to occur.
Fluoroquinolones are known
as Broad Spectrum. What
do they cover?
- Gram negative aerobes
- Gram positive aerobes
- lntracellular bacteria (due to lipid soluble
nature)
- Mycoplasma
* Ciprofloxacin is good against mycobacteria
Fluoroquinolones are known
to concentrate in specific
tissues/areas. Which ones?
1) Lung & Bronchosecretions
2) Urine
3) Prostate
4) Bone
5) CSF
Name two antimicrobial groups
that are good for treatment of
prostate infections.
- Diaminopyrimadines
- Fluoroquinolones
What is meant by saying that a
drug concentrates in a tissue?
The tissue can achieve
higher concentrations than
plasma.
Fluoroquinolones
- Bioavailability
- PPB
- Excretion
- High oral bioavailability (except in rumenant,
perentral admin.)
- Low PPB
- Liver metabolism to active/inactive metabolite
& kidney
***Enterohepatic Recycling may occur**
Why should
Fluoroquinolones be
avoided in young animals?
Erosion of weight bearing cartilage
has been known to occur in dogs
& cats. Dog are more susceptible,
esp. Giant Breeds.
What toxicity concerns
surround Fluoroquinolones?
* Decrease dosing in animals with renal impairment
* Erosion of weight bearing cartilage
* Avoid with other drugs requiring liver clearance
(methylxanthines)
* Neurotoxicity - blindness in cat from Enrofloxacin
****Stick to recommended dose ranges*****
Name five Macrolides
licensed for use in
veterinary medicine.
1) Tylosin
2) Tilmicosin
3) Tiamulin
4) Spiramycin
5) Tulathromycin
Macrolide
- Mechanism of Action
lnhibits protein synthesis via
binding to 50S subunit and
inhibiting translocation..
What is the spectrum of
activity for Macrolides?
Moderate
- Gram +
- Some Gram -
- Anaerobes
- Mycoplasma
- Some Chlamydophila
- Non-tubercular mycobacterial orgs.
How are Macrolides similar
to narrow spectrum
Penicillins?
Both can cover:
- Gram +
- Some Gram -
- Anaerobes
What types of resistance
have come up against
Macrolides?
* Chromosomal - but bacteria can revert back to
sensitive if drug is removed.
* Plasmid mediated
- Change in drug binding site
- Decreased permeability
- Esterases which hydrolyse drug
Macrolides
- Solubility -> Metabolism
- Acid or Base -> Vd
* Which drugs have best Vd.
- Highly lipid Soluble
-> Hepatic Metabolism (to mostly
inactive metab.)
- Basic
-> Large Vd
* Spiramycin & Tilmicosin
Marcrolides have a high Vd,
how does this aid in their
antimicrobial activity?
They are able to achieve high
concentrations inside of Macrophages,
which aid in the killing of an organism
after phagocytosis.
What is the parent drug in the Macrolides
and what are the potential routes of
administration?
Are there any concerns surrounding
Administration?
Erythromycin
- Oral or parentral
- Highly irritant with any type of
administration.
What toxicity or side effects
occur with Erythromycin?
- Parasympathomemetic effects, which
induces vomiting in dogs.
- GlT disturbances in herbivores
What common diseases are
treated with Erythromycin?
- Staph. aureus infections with Penicillin
resistance
- R. equi pneumonia in foals (combine
with rifampicin)
- C. jejni enteritis
Tylosin
- Type of drug
- Primary use
- Concerns
- Macrolide
- Used in food production species (leptospirosis,
rickettsia, Mastitis, Bovine pneumonia)
- Similar toxicity to Erythromycin, irritant to
tissues, DO NOT use in horses
Spriamycin
- Type of drug
- Positive qualities
Macrolide
- Concentration and Long
persistence in tissues
Name a Macrolide that is
commonly used in the Pig
lndustry. How is it administered?
Tiamulin
- Orally in feed
Tiamulin
- Activity
- Contraindications
- Resistance
- Mycoplasma & Anaerobes
- DO NOT feed with ionophores in pigs & poultry as may
interfere with liver metabolism of ionophores, increasing
their concentration and toxicity. DO NOT use in
herbivores
- One way cross resistance with Tylosin (Resistance in
Tiamulin=Resistance in Tylosin)
What can be used to treat
Respiratory diseases like
Mycoplasma, Pasteurella,
Mannheimia, & Haemophilis
in pigs & poulty?
Tulathromycin (Macrolide)
Name two Lincosamide drugs and
their Mechanism of Action.
- Lincomycin (antibiotic)
- Clindamycin (Synthetic)
lnhibit bacterial protein synthesis
via 50S subunit binding.
Lincosamide
- Spectrum of Activity
- Gram +
- Anaerobes (Clindamycin is best)
- Mycoplasma
How do bacteria confer resistance
to Lincosamides? What other
antimicrobial group does
resistance effect?
* Chromosomal Mutation during
treatment (not common)
* Plasmid Mediated (Common)
- Methylate ribosomal drug binding site.
* Macrolides
Why are Lincosamides in
effective against Gram -
bacteria?
- lmpervious to drug entering
- Methylated ribosomal drug
binding site.
What are the Pharmokinetics of
Lincosamides?
- Acid/Base
- Adminstration
- PPB
- Vd
- Basic->ion trapping
- Oral & parentral admin.
- Highly PPB (as opposed to
macrolides)
- Lipid Soluble->High Vd
Where are Licosamides
likely to trap in the body?
- Udder
- Prostate
- Lung
- CSF (but not as high)
What areas are
Licosamides able to
penetrate in the body?
- CSF
- Bone
- Eye
- Synovial Fluid
Lincosamides
- Toxicity concerns for spp.
and administration
- Highly toxic to herbivores.
- Can cause Colitis X in horses
- Cat/Dog relatively non-toxic
* Give slowly lV to reduce incidence of myocardial
depression.
* Oral stricture from irritation via PO
Why are Lincosamides
given with food or a warm
water bolus to follow?
Oral stricture can occur from
tracheal irritation due to contact
with the drug.
What are three main interactions
(positive and negative) with
Lincosamides?
* Lincosamide/Spectinomycin - cattle respiratory disease
* Clindamycin synergistic with metronidazole against
anaerobes
* AVOlD use with macrolides or chloramphenicols as
they are antagonistic (compete for binding site)
What antimicrobial can be
used like Penicillin in
patients who are
hypersenstive to Penicillin?
Macrolides
Name two Tetracycline most
commonly used in Veterinary
medicine?
- Doxycycline
- Tetracycline
Tetracycline
- Mechanism of Action
- Unique characteristic
lnhibit bacterial protein synthesis by binding to
30S ribosomal subunit.
* Enters the bacterial cell two ways:
- Passive diffusion
- Active carrier-mediated transport
Tetracycline
- Spectrum
- Element that improves drugs
performance
Broad Spectrum
- Gram +
- Gram -
- Mycoplasma*
- Chlamydia*
- Rickettsia*
- Protozoa*
- Spirochaetes*
*Primary Use
- Acidic pH improves activity
Minocycline has a greater
activity that other
Tetracyclines, what
accounts for this?
- Higher Lipid solubility
which leads to greater Vd.