Sulfonamides Flashcards
What is unique about prescribing sulfa drugs?
typically all are used the same
dont need to know all the names
What are the different potentiated sulfa drugs?
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
What are some other sulfas?
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)
What sulfa drug can be used as a uterine bolus for retained placenta?
what else is it used for?
sulfanilamide (other)
+ oral bolus
+ topical cream for pyoderma
What is the MOA of sulfonamide?
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
Why are sulfa drugs used together?
synergism! more potent
alone will not kill 99.9%
What is the spectrum of activity for sulfas?
effective
- some gram +, some gram -, many anaerobes, some protozoa and coccidia
less/not effective
- strep equi, e.coli, salmonella isolates
- pseudomonas
- enterococcus
What is important to considering clinically regarding SOA and sulfa?
high variable with individual isolates
What is the mechanism of resistance of sulfas?
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
What patterns of resistance is noted within sulfa drugs?
cross resistance between
emerges slower in potentiated sulfas
Although PK is not uniform between what is the F of sulfas?
generally good oral F
What is the distribution like in sulfas?
into many tissues
- CSF, synovial, urine
- more inflammation more penetration
Are there consistencies with protein binding between sulfa drugs?
differences between sulfas and species
- differences in elimination half life
Where are sulfas metabolized and excreted?
hepatic metabolism (to inactive metabolites)
renal excretion (glomerular) - tubular reabsorption can occur
What makes optimal dose regime challenging for sulfas?
diaminopyrimadines (Trimethorpim) and sulfas have very different PK
What is the PK-PD relationship for sulfas?
not well established but probably time dependent?
Why do clinicians use BID>SID?
old dose regime outdated
What are the adverse events of sulfas?
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
What drug interactions should be considered when giving sulfas?
procaine penicillin G is PABA analogue so will inhibit
