Sulfonamides

Question 1

What is unique about prescribing sulfa drugs?

Answer 1

typically all are used the same

dont need to know all the names

Question 2

What are the different potentiated sulfa drugs?

Answer 2

sulfadaizine (with trimethoprim) - aka TMS
tribrissen (injectable) and uniprim (powder/granules
- for horses with resp/soft tissue
- tribrissen for salmon feed

Sulfadimethozine (with ormetoprim)
- romet 30 (furunculosis in salmon)

Sulfadozine (with trimethoprim) - TMS

• Bordal, trimodox (IM or slow IV)
• indicated for numerous pig and cattle

human generic

Question 3

What are some other sulfas?

Answer 3

sulfaguanidine (calf scour boluses)
sulfamerizine, sulfamethazone (electrolyte powders)
- resp and GI
sulfamethazine (oral triple sulfa bolus)
- common course of drug residues (sticks to equipment)

sulfapyridine (medicated water)

sulfaquinoxaline (oral cocciostat for poultry)
- quinnoxine-S with pyrimtheamine

sulfathizole (water, bolus, cream)

Question 4

What sulfa drug can be used as a uterine bolus for retained placenta?
what else is it used for?

Answer 4

sulfanilamide (other)
+ oral bolus
+ topical cream for pyoderma

Question 5

What is the MOA of sulfonamide?

Answer 5

structure like PABA

• competitive inhibitor of PABA incooperation into folate synthesis pathway
• if lots of PABA in environment = not effective (e.g. abscesses)

diaminopyrimideins (trimethoprim, ormetoprim, pyrimethamine)
- inhibits dihydrofolate reductave

block two steps in pathway = cant make DNA
- not enough to kill 99.9% alone (use together) SYNERGISM

not toxic to us (diet folate)

competitive

Question 6

Why are sulfa drugs used together?

Answer 6

synergism! more potent

alone will not kill 99.9%

Question 7

What is the spectrum of activity for sulfas?

Answer 7

effective
- some gram +, some gram -, many anaerobes, some protozoa and coccidia

less/not effective

• strep equi, e.coli, salmonella isolates
• pseudomonas
• enterococcus

Question 8

What is important to considering clinically regarding SOA and sulfa?

Answer 8

high variable with individual isolates

Question 9

What is the mechanism of resistance of sulfas?

Answer 9

common

chromosomal or plasmid mediated

hyperproduction of PABA (or environment)

altered dihydropteroic synthase (sulfas) or DHFR (trimethoprim) enzymes

increased production of DHFR (increased folate in bacteria)

reduced drug penetrates into bacteria

Question 10

What patterns of resistance is noted within sulfa drugs?

Answer 10

cross resistance between

emerges slower in potentiated sulfas

Question 11

Although PK is not uniform between what is the F of sulfas?

Answer 11

generally good oral F

Question 12

What is the distribution like in sulfas?

Answer 12

into many tissues

• CSF, synovial, urine
• more inflammation more penetration

Question 13

Are there consistencies with protein binding between sulfa drugs?

Answer 13

differences between sulfas and species

- differences in elimination half life

Question 14

Where are sulfas metabolized and excreted?

Answer 14

hepatic metabolism (to inactive metabolites)

renal excretion (glomerular)
- tubular reabsorption can occur

Question 15

What makes optimal dose regime challenging for sulfas?

Answer 15

diaminopyrimadines (Trimethorpim) and sulfas have very different PK

Question 16

What is the PK-PD relationship for sulfas?

Answer 16

not well established but probably time dependent?

Question 17

Why do clinicians use BID>SID?

Answer 17

old dose regime outdated

Question 18

What are the adverse events of sulfas?

Answer 18

hypersensitivity

• type 1 (IgE)
• forms reactive metabolites that casue direct cytotoxicity or stim immunologic response
• blood dyscrasias (hemolytic anemia in horses, thrombocytopenia and epistaxis)
• arthritis (non-septic)
• skin eruptions (dobermans)
• hepatic necrosis

keratoconjuctivitis sicca (KCS)

• dry eye from lack of tear proudction
• sulfa toxic to lacrimal acinar cells
• 15% of dogs (more in small buldgy eye dogs)
• resolve when sulfa stops

Renal damage

• sulfa are poorly soluble (precipitate in urine with dehydration or acidic urine)
• crystallura, hematuria, and tubule blockage
• less problem with TMS (lower dose sulfas when used with trimethoprim
• keep them hydrated

Hypothyroidism

• inhibition of thyroid enzyme activity
• reversible

GI
- diarrhea, vomiting, salivation

Anemia from chronic use (rare)

• folate related (not hypersensitivity)
• decrease folate rpoduction from intestinal bacteria
• supplement folic acid (b-vits)

injection reactions

• IM lesions
• rapid IV cause thrombophlebitis or anaphylaxis in horses

Question 19

What drug interactions should be considered when giving sulfas?

Answer 19

procaine penicillin G is PABA analogue so will inhibit