Antimicrobials: Folic Acid Inhibitors and Beta Lactams

Question 1

Explain the mechanism of sulfonamides

Answer 1

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)

Question 2

How can you tell a drug is a sulfonamide?

Answer 2

They all start with sulfa____

Question 3

What are the characteristics of sulfonamide antibiotics

Answer 3

bacteriostatic

time dependent

Question 4

What types of microbes are sulfonamides effective against? What are they not effective in treating?

Answer 4

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

Question 5

Can you use sulfonamides to treat abcesses? Why or why not?

Answer 5

No because there is a higher concentration of PABA in the abcess which makes sulfonamides wayyy less effective

Question 6

Describe the relevant pharmacokinetics of sulfonamide drugs

Answer 6

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

Question 7

How can you manipulate the excretion of sulfonamide drugs?

Answer 7

alkinizing the urine can increase excretion because sulfonamides are weak acids

Question 8

What is one concern to consider when using sulfonamides

Answer 8

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

Question 9

What is a potentiated sulfonamide?

Answer 9

diaminopyrimidine + sulfonamide

Question 10

List 2 diaminopyrimidines

Answer 10

trimethoprim

ormetoprim

Question 11

What is the mechanism of diaminopyrimidines? Why is it important

Answer 11

Inhibit dihydrofolate reductase
- another enzyme in the folic acid synthesis pathway

therefore with potentiated sulfonamides we are blocking folic acid synthesis in 2 places

Question 12

Explain how diaminopyrimidines distribute in the body

Answer 12

They are organic lipi-soluble basic molecules

Distribution
- good at diffusing across cell membrane (sulfonamides cant)
- enter CNS/prostate/milk

Question 13

What are the important characteristics of potentiated sulfonamides?

Answer 13

bacteriocidal

time dependent
- better BID

Question 14

What types of microbes are potentiated sulfonamides effective against? What are they not effective in treating?

Answer 14

gram (+) and some (-) aerobes

Not: anaerobes or psuedomonas

Question 15

What is trimethoprim sulfadiazine? What category drug is it?

Answer 15

a ratio of 1:5 (trimethoprim : sulfasiazine)

category 3 drug = good choice

Question 16

What is trimethoprim sulfadiazine used for? In what species is it used mainly? How is it administered?

Answer 16

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

Question 17

What are the adverse effects of trimethoprim sulfadiazine

Answer 17

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

Question 18

Why is the development of drug resistnace so important?

Answer 18

Resistnace to one drug in that category = resistance to all drugs in that category

Question 19

List 3 mechanisms of drug resistnace against sulfanomide drugs

Answer 19

efflux transport

failure to penetrate the organism

changing target enzyme

these traits can be passed around via plasmids

Question 20

What is the bacterial cell wall made of? Why is it so important?

Answer 20

peptidoglycan

without it = osmotic imbalance and lysis (wonderwall :( )

Question 21

Explain the mechanism of beta lactam drugs

Answer 21

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

Question 22

What are the characteristics of beta lactam drugs

Answer 22

bacteriocidal

time dependent

post antibiotic effect only against gram (+)

Question 23

What are the adverse effects of beta lactams

Answer 23

very few because mammalian cells do not have a cell wall

Question 24

Explain the pharmacokinetics of beta lactams

Answer 24

Absorbtion: varied PO absorb

Distribution: wide
- eye and CNS only penetrated if there is inflammation

Metabolism: none

Excretion: kidney (unchanged)
- good for UTI

Question 25

Explain the 3 mechanisms of AMR against beta lactam drugs

Answer 25

bacteria produce beta lactamase which cut the lactam ring in the abx efflux pumps reduce penetration of the outer membrane

Question 26

What are 3 considerations to have when giving penicillin

Answer 26

synergistic with cephalosporin and aminoglycosides NOT with bacteriostatic drugs NEVER PO to a hindgut fermenter (horse/rabbit) - can give injectable

Question 27

List 5 types of penicillin

Answer 27

penicillin G aminopenicillins penicillinase resistant penicillins extended spectrus penicillins potentiated penicillins

Question 28

What microbes are targeted by penicillin G? What is not targeted?

Answer 28

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)

Question 29

What are 3 types of penicillin G? How are they administered

Answer 29

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

Question 30

List 2 examples of aminopenicillins and explain the difference

Answer 30

amoxicillin - PO ampicillin - SC/IM/IV route of administration is the only difference

Question 31

How do amino penicillins compare the penicillin G

Answer 31

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)

Question 32

List 2 types of penicillinase resistant penicillins? What microbes are they for

Answer 32

methicillin cloxacillin: intramammary S. aureus tx staphylococcus

Question 33

You recieve a culture and sensitivity that indicated resistance to penicillinase resistant penicillin? What does this tell you?

Answer 33

methicillin resistant staph aureus or pseudointermedius is the causative agent cannot use a beta lactam drug

Question 34

What are extended spectrum penicillins

Answer 34

similar to aminopenicillins rare

Question 35

What are potentiated penicillins? Give one example

Answer 35

clavulinic acid + amoxicillin (aminopenicillin) clavamox

Question 36

What is clavulinic acids?

Answer 36

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

Question 37

What microbes are potentiated penicillins used to treat?

Answer 37

All except pseudomonas (gram - aerobe)

Question 38

List the types of penicillin in order of human importance

Answer 38

category 1: carbapenems category 2: potentiated aminopenicillin category 3: aminopenicillin/penicillin

Question 39

What are the characteristics of cephalosporins

Answer 39

bacteriocidal time dependent beta lactam

Question 40

What microbes are 1st generation cephalosporins effective against? What are they not effective against?

Answer 40

GOOD: gram (+) aerobe - beta-lactamase staphylococcus - strep gram (-) aerobe - pasturella/manheimmia/histophilus NOT methicillin resistant staphylococcus anaerobes gram + aerobe = enterococcus gram - aerobe = bordatella/pseudomonas

Question 41

What microbes are 3st generation cephalosporins effective against? What are they not effective against?

Answer 41

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

Question 42

Explain the pharmacokinetics of cephalosporins

Answer 42

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

Question 43

List 2 types of 1st generation cephalosporins

Answer 43

cephalexin cephazolin

Question 44

What is cephalexin for? How is it administered? What type of drug is it?

Answer 44

Staphylococcal pyoderma in dogs PO category 2 drug (cephalosporin)

Question 45

What is cephazolin for? How is it administered?

Answer 45

perioperative prophylactic with good bone distribution SC/IM/IV

Question 46

What are 2nd generation cephalosporins

Answer 46

similar to 1st generation but better for anaerobes ex. cefoxitin

Question 47

List 2 types of 3rd generation cephalosporins

Answer 47

ceftiofur cevovecin

Question 48

What is ceftiofur used for? In what animals is it used?

Answer 48

UTI in dogs also used in horses and production animals

Question 49

What are the 2 types of ceftiofur? What are their brand names? How do you administer them?

Answer 49

ceftiofur sodium aka excenel - SC/IM/IV + short acting ceftiofur crytalline free acid aka exceed - SC or IM

Question 50

What is the brand name for cevovecin? How do you administer?

Answer 50

convenia long acting - highly protein bound drug give as an injectable - lasts for 14d at therapeutic levels

Question 51

What are some drawbacks of cevovecin

Answer 51

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)

Question 52

What are the main characteristics of carbapenems

Answer 52

bactericidal broadest spectrum beta lactam

Question 53

What are carbapenems used for?

Answer 53

only for severe infection lots of AMR =it is a last resort drug