Antimicrobials: Folic Acid Inhibitors and Beta Lactams Flashcards
Explain the mechanism of sulfonamides
They inhibit folic acid synthesis by blocking PABA (para-aminobenzoic acid) - an enzyme in folic acid synthesis
It has the similar structure to PABA and it acts as a false substrate
blocking folic acid synthesis will block DNA replication
(folic acid is made by bacteria and not animal cells)
How can you tell a drug is a sulfonamide?
They all start with sulfa____
What are the characteristics of sulfonamide antibiotics
bacteriostatic
time dependent
What types of microbes are sulfonamides effective against? What are they not effective in treating?
Good for:
gram (+): strep/staph
gram (-): E. coli/kleibsiella/proteus (but there is more AMR)
protozoa/coccidia: eimeria/toxoplasma/sarcocystis
NOT
anaerobes or psuedomonas
abscesses
Can you use sulfonamides to treat abcesses? Why or why not?
No because there is a higher concentration of PABA in the abcess which makes sulfonamides wayyy less effective
Describe the relevant pharmacokinetics of sulfonamide drugs
Absorption:
- good except in ruminants
- enter CNS and prostate
- stays extracellular in the liver/kidney/lung
Metabolism: Liver
- horse/cow: oxidate and glucuronidate/acetylate
- dog: no N-acetyltransferase = slower
Eliminate: Kidney
- excrete drug unchanged and metabolite
How can you manipulate the excretion of sulfonamide drugs?
alkinizing the urine can increase excretion because sulfonamides are weak acids
What is one concern to consider when using sulfonamides
It is commonly used in LA as a food/water additive
Residues can remain in pork and cause allergy reactions in people consuming the meat
What is a potentiated sulfonamide?
diaminopyrimidine + sulfonamide
List 2 diaminopyrimidines
trimethoprim
ormetoprim
What is the mechanism of diaminopyrimidines? Why is it important
Inhibit dihydrofolate reductase
- another enzyme in the folic acid synthesis pathway
therefore with potentiated sulfonamides we are blocking folic acid synthesis in 2 places
Explain how diaminopyrimidines distribute in the body
They are organic lipi-soluble basic molecules
Distribution
- good at diffusing across cell membrane (sulfonamides cant)
- enter CNS/prostate/milk
What are the important characteristics of potentiated sulfonamides?
bacteriocidal
time dependent
- better BID
What types of microbes are potentiated sulfonamides effective against? What are they not effective in treating?
gram (+) and some (-) aerobes
Not: anaerobes or psuedomonas
What is trimethoprim sulfadiazine? What category drug is it?
a ratio of 1:5 (trimethoprim : sulfasiazine)
category 3 drug = good choice
What is trimethoprim sulfadiazine used for? In what species is it used mainly? How is it administered?
Horses
- respiratory infection
- wounds
- perioperative
- hepatitis
- labelled for strangles but +/- efficacy against abscesses
dogs
- skin/resp infection
- bite wounds
- prostatitis
labelled for SID but use BID
What are the adverse effects of trimethoprim sulfadiazine
crystalluria (not common anymore)
drug residues in food animals
keratoconjunctivitis sicca (dry eye) - dogs and rabbits
idiosyncratic toxicities - dogs
- blood dyscrasias/polyarthritis/hepatitis
drool - cat
diarrhea - horses
caution in pregnant and nursing animals
Why is the development of drug resistnace so important?
Resistnace to one drug in that category = resistance to all drugs in that category
List 3 mechanisms of drug resistnace against sulfanomide drugs
efflux transport
failure to penetrate the organism
changing target enzyme
these traits can be passed around via plasmids
What is the bacterial cell wall made of? Why is it so important?
peptidoglycan
without it = osmotic imbalance and lysis (wonderwall :( )
Explain the mechanism of beta lactam drugs
They bind penicillin binding proteins which are transpeptidases - they cross link the peptidoglycan cell wall.
Prevent cross linking = lysis
less effective against gram (-) because they have a smaller cell wall
What are the characteristics of beta lactam drugs
bacteriocidal
time dependent
post antibiotic effect only against gram (+)
What are the adverse effects of beta lactams
very few because mammalian cells do not have a cell wall
Explain the pharmacokinetics of beta lactams
Absorbtion: varied PO absorb
Distribution: wide
- eye and CNS only penetrated if there is inflammation
Metabolism: none
Excretion: kidney (unchanged)
- good for UTI
Explain the 3 mechanisms of AMR against beta lactam drugs
bacteria produce beta lactamase which cut the lactam ring in the abx
efflux pumps
reduce penetration of the outer membrane
What are 3 considerations to have when giving penicillin
synergistic with cephalosporin and aminoglycosides
NOT with bacteriostatic drugs
NEVER PO to a hindgut fermenter (horse/rabbit) - can give injectable
List 5 types of penicillin
penicillin G
aminopenicillins
penicillinase resistant penicillins
extended spectrus penicillins
potentiated penicillins
What microbes are targeted by penicillin G? What is not targeted?
narrow spectrum
anaerobes: fusobacterium/clostridium
gram (+) and (-)
- arcanobacterium/listeria/pasturella
spirochetes: leptosporosis/borrelia
NOT:
staph (gram (+) aerobe)
enteric gram (-) aerobes
- proteus/klebsiella/e. coli/pseudomonas
B. fragilis (gram (-) anaerobe)
What are 3 types of penicillin G? How are they administered
penicillin G sodium or potassium
- IV/IM + short duration
procaine penicillin G (depocillin)
- SC/IM (not IV) - give SID or BID
benzathine penicillin G
- IM only q3-5d + long duration
give dose above the labelled dose
List 2 examples of aminopenicillins and explain the difference
amoxicillin - PO
ampicillin - SC/IM/IV
route of administration is the only difference
How do amino penicillins compare the penicillin G
aminopenicillins are better at penetrating gram (-) cell membranes
Can be effective against enteric gram (-) aerobes
- proteus/klebsiella/e. coli
NOT:
staph (gram (+) aerobe)
- gram (-) aerobe - bordatella/pseudomonas
B. fragilis (gram (-) anaerobe)
List 2 types of penicillinase resistant penicillins? What microbes are they for
methicillin
cloxacillin: intramammary S. aureus
tx staphylococcus
You recieve a culture and sensitivity that indicated resistance to penicillinase resistant penicillin? What does this tell you?
methicillin resistant staph aureus or pseudointermedius is the causative agent
cannot use a beta lactam drug
What are extended spectrum penicillins
similar to aminopenicillins
rare
What are potentiated penicillins? Give one example
clavulinic acid + amoxicillin (aminopenicillin)
clavamox
What is clavulinic acids?
it is a beta lactamase inhibitor
- similar structure to beta lactam and will act as a false substrate
it is unstable and needs to be protected from moisture
PO absorbed with no effect on amoxicillin’s PK
What microbes are potentiated penicillins used to treat?
All except pseudomonas (gram - aerobe)
List the types of penicillin in order of human importance
category 1: carbapenems
category 2: potentiated aminopenicillin
category 3: aminopenicillin/penicillin
What are the characteristics of cephalosporins
bacteriocidal
time dependent
beta lactam
What microbes are 1st generation cephalosporins effective against? What are they not effective against?
GOOD:
gram (+) aerobe
- beta-lactamase staphylococcus
- strep
gram (-) aerobe
- pasturella/manheimmia/histophilus
NOT
methicillin resistant staphylococcus
anaerobes
gram + aerobe = enterococcus
gram - aerobe = bordatella/pseudomonas
What microbes are 3st generation cephalosporins effective against? What are they not effective against?
GOOD:
gram (+) aerobe
- beta-lactamase staphylococcus
- strep
gram (-) aerobe
- resp: pasturella/manheimmia/histophilus
- enteric (e. coli/klebsiella/proteus)
some efficacy against gram (-) anaerobes
NOT
methicillin resistant staphylococcus
gram (+) anaerobes
gram + aerobe = enterococcus
gram - aerobe = pseudomonas
Explain the pharmacokinetics of cephalosporins
Absorption: good PO
Distribution: wide
- NOT prostate/CNA/intracellular
Excretion: Renal (good for UTI)
- potentially nephrotoxic if giving with other nephrotoxic drugs or if dehydrated
List 2 types of 1st generation cephalosporins
cephalexin
cephazolin
What is cephalexin for? How is it administered? What type of drug is it?
Staphylococcal pyoderma in dogs
PO
category 2 drug (cephalosporin)
What is cephazolin for? How is it administered?
perioperative prophylactic with good bone distribution
SC/IM/IV
What are 2nd generation cephalosporins
similar to 1st generation but better for anaerobes
ex. cefoxitin
List 2 types of 3rd generation cephalosporins
ceftiofur
cevovecin
What is ceftiofur used for? In what animals is it used?
UTI in dogs
also used in horses and production animals
What are the 2 types of ceftiofur? What are their brand names? How do you administer them?
ceftiofur sodium aka excenel
- SC/IM/IV + short acting
ceftiofur crytalline free acid aka exceed
- SC or IM
What is the brand name for cevovecin? How do you administer?
convenia
long acting - highly protein bound drug
give as an injectable - lasts for 14d at therapeutic levels
What are some drawbacks of cevovecin
wide spectrum of action but less anaerobe activity
not a first line of defense drug because it has a higher risk of AMR (due to long duration)
What are the main characteristics of carbapenems
bactericidal
broadest spectrum beta lactam
What are carbapenems used for?
only for severe infection
lots of AMR =it is a last resort drug
