8b – Sulfonamides Flashcards
1
Q
Sulfa formulations (potentiated and non-potentiated)
A
- Companies use different components based on what is available and will depend on the formulation they want
- NO crazy big differences
- *sometimes use a human generic TMS tablet formulation
- *some NOT used as an antibiotic
- Medicated feed, boluses, water preparations
2
Q
Used in large animal
A
Trimidox
Borgal
*IM or SC
3
Q
What are sulfas mechanism of action?
A
- Structure is similar to para-aminobenzoic acid (PABA)
o Competitive inhibition for enzyme dihydropteroate synthase (PABA incorporation into folate pathway - *not going after bacterial cell wall, or bacterial protein synthesis
- **BLOCK SYNTHEISIS OF dihydrofolate (pre-cursor steps): bacteriostatic
4
Q
Diaminopyrimidines (what is added to potentiated sulfas): things ending in ‘oprim’
A
- Trimethoprim, ormetoprim, pyrimethamine
- *inhibits dihydrofolate reductase (next step in folate synthesis)
- **do not get tetra-hydrofolic acid=NO DNA synthesis
- **BOTH: block DNA synthesis (more bacteriocidal)=A LOT MORE POTENT
5
Q
So why aren’t sulfa drugs toxic to us?
A
- Utilize dietary folate (Vitamin B9)
o *don’t need to SYNTHESIZE IT - SAFE for us in terms of folate production
6
Q
What are some implications with sulfas being a competitive inhibitor of PABA?
A
- If lots of PABA available in local environment, bacteria will be RESISTANT to sulfa drugs
o Ex. abscess=sulfas NOT effective
7
Q
What is generally susceptible to sulfonamides?
A
- Some gram + isolates
- Some gram – isolates
- Many anaerobes: likely NOT the best choice (penicillin’s or cephalosporins used more likely)
- *Some protozoa and coccidia (ex. in poultry)
8
Q
What is generally NOT/LESS effective to sulfonamides?
A
- Resistance emerges RAPIDLY in many bacterial species
o Many/most Strep equi, E. coli, Salmonella - Pseudomonas
- Enterococcus
9
Q
Synergism of sulfas and trimethoprim
A
- Makes them very potent when used together
o POTENTIATION - *sum of both drugs together is much GREATER than if you just ‘added’ them
10
Q
Sulfas spectrum of activity
A
- Many of the labels are OLD and are labelled for lots of infectious condition
- *highly variable for individual isolates
11
Q
What are some mechanisms of resistance against sulfonamides?
A
- Chromosomal or plasmid-mediated
- Hyper-production of PABA (or in environment)
- Altered dihydropteroic synthase or FHFR (trimethoprim) ENZYMES
- Increased production of DHFR
- Reduced drug penetration into bacteria
12
Q
What are some important notes with resistance?
A
- Cross resistance between sulfas is typical
o If resistant to one=likely RESISTANT to the OTHERS - *emerges more slowly with potentiated sulfas then with sulfas alone
13
Q
Sulfas oral bioavailability, distribution, elimination half life)
A
- *not uniform between drugs and species
- Generally good oral bioavailability
- Distributes into many tissue
- *difference in protein binding=subsequent differences in elimination half-lives
14
Q
Sulfas elimination
A
- Hepatic metabolism (to inactive metabolites)
o NOT worried about hepatic disease - Renal excretion (glomerulation filtration)
o Tubular reabsorption can occur
o Decrease reabsorption with ALKALINE URINE (ion-trapping of acidic sulfa)
o *worried about renal disease
15
Q
Sulfonamides when potentiate and PK
A
- DIFFERENCES
o Makes optimizing the sulfa:TMP ratio challenging
o Makes C&S results more difficult to interpret (test may have used a different ratio to the drug formulation we will use)
o Differences between vet and human formulations - Ex. TMP eliminated quickly and sulfa eliminated slowly=sulfa is hanging around for longer by itself
