24. Sulphonamides and diaminopyrimidines

Question 1

Sulphonamides. Drugs

Answer 1

• sulfaDIMIDINE
• sulfaDIAZINE
• sulfaCHLORPYRAZINE
• sulfaMETHOXAZOLE
• sulfaSALAZINE
• sulfaCHLORPYRIDAZINE
• sulfaDOXINE
• sulfaQUINOXALINE

Question 2

Diaminopyrimidines. Drugs

Answer 2

• trimethoprim
• baquiloprim

Question 3

Sulphonamides. Diaminopyrimidines. Mode of action

Answer 3

• SAs: broad spectrum bacteriostatic activity (gram—, gram+, many protozoan organisms)
• DAP: bacteriostatic, used only in combination with SAs in vet medicine. Alone resistance develops rapidly
• together DAPs and SAs -> sequential blockade of microbial enzyme occur with bactericidal consequences

Question 4

SAs, DAPs. Structure

Answer 4

SAs:
- bad solubility in acidic environment
- Na-salt is used, highly alkaline

DAPs:
- weak base, poorly soluble in water

Question 5

SAs for local use

Answer 5

• silver sulfaDIAZINE

Question 6

SAs. Mechanism of action

Answer 6

SAs compete with PABA for the enzyme dihydropteroate synthetase, preventing incorporation PABA into the folic acid

Mammals dont have this step -> selective action

Question 7

DAPs. Mode, mechanism of action

Answer 7

Inhibit tetrahydrofolic (THF) acid synthesis from dihydrofolic (DHF) acid by combining with the enzyme dihydrofolate reductase

Affinity to bacterial enzyme is much greater than to mammalian -> selective toxicity

Bacteriostatic on their own, bactericidal together with SAs

Question 8

SAs. Spectrum

Answer 8

Broad!
Good susceptibility:
- Bacillus, Brucella, Streptococcus, Chlamydophilia, Nocardia, Erysipelothrix rhusiopathiae, Listeria monocytogenes
- Coccidia, Toxoplasma, Sarcocystis, Pneumocystis, Cryptosporidium

Moderate susceptibility:
- Staphylococci, Enterococci, E. coli, Klebsiella, Proteus, Actinobacillus, Haemophilus, Pasteurella, Pseudomonas, Bacteroides, Fusobacterium

Question 9

SAs. Resistant species. Resistance

Answer 9

• Mycobacterium, Mycoplasma, Coxiella, Clostridium, Rickettsia, Pseudomonas, Spirochetes, Leptospira
  Anaerobic cocci
• Resistance is very frequent
• cross-resistance among SAs
• decreased penetration, PABA-specific dihydropteroase-synthetase, overproducing of PABA

Question 10

Antimicrobial activity of combination SAs + DAPs. Advantages of combination

Answer 10

NOT ACTIVE against Mycoplasmas, Mycobacteria, Rickettsias, Spirochaetes, Leptospira, Pseudomonas

Less frequent resistance, broadened spectrum, increased activity, bactericidal effect `