Sulphonamides

Question 1

Chemistry:

Answer 1

Bad solubility in acidic enviroment

Question 2

Local drugs:

Answer 2

Sulfacetamide
Mafenide
Silver sulfadiazine
Sulfatthiazine

Question 3

“Intestinal disinfectant”

Answer 3

Sulfaguanidine

Question 4

Systemic drugs:

Answer 4

Frequently used:
Sulfadimidine
Sulfachlorpyridazine
Sulfadoxine
Sulfadiazine
Sulfamethoxasole

Less frequent, Eimeria, Isospora
Sulfaquinoxaline, Sulfachlorpyrazine

Long acting:
Sulfadimethoxine, sulfamethoxypyrazine

Question 5

Diaminopyrimidines, active substances:

Answer 5

Trimethoprim, Diaveridine, Pirimethamin, Ormethoprim.

Long acting: Aditoprim, Baquiloprim.

Question 6

Mechanism of action:

Answer 6

Compete with PABA for the enzyme dihydropteroate synthetase- prevents PABA incorporation into folic acid.
Trimethoprim inhibits dihydrofolate reductase.
Selective toxicity: greater affinity to bacterial enzyme, than mammalians.

Question 7

Mode of action:

Answer 7

Bacteriostatic on their own.

Bactericidal when administrated together.

Question 8

Spectrum of SUA:

Answer 8

Wide spectrum:
Gram+, Gram-.
Aerobic, ANAEROBIC
Chlamydophilia.

Anti-protozol effect: coccidia, Toxoplasma.

Question 9

Resistance SUA:

Answer 9

Very frequent- used for over 70 years.

Chromosomal mutation.
Plasmid- and integron- mediated resistance.

Cross-resistance in SUA.

Decreased penetration, PABA- dihyrdopteroate- synthetase.
Overproduction of PABA- purulent tissue debris.

Question 10

Spectrum of DAP:

Answer 10

Bacteriostatic.
Gram+, Gram-
Antiprotozoal effect.

Negligible activity againts: anaerobes, Chlamydophilia, Mycobacterium, Mycoplasma.

Question 11

Resistance DAP:

Answer 11

Plasmid-and integron- mediated resistance, Chromosomal.

Cross restance with sulphonamides.

Question 12

Antimicrobial activity of combinations:

Answer 12

Mode of action: bactericidal

Wide antibacterial spectrum: gram+, gram-,

Antiprotozoal effect- Toxoplasma gondii, coccidia. Pneumocystis carinii, some Malarias.

NOT active against:
Mycobacteria, Rickettsia, Spirochaetes, Leptospira, Pseudomonas.
In vivo: NO ANAEROBE.

Question 13

Advantages of the combinations:

Answer 13

Synergistic interaction- POTENTIATED SUAs.
Two bacteriostatic= bactericidal effect.
10x increased DAPs component, 100x of the SUAs.
Broadened spectrum.
Resistance less frequent.
SUA-restistant strains become susceptible.

Question 14

Pharmacokinetics of SUA:

Answer 14

Aborption: Good- oral, except sulfaguanidine.

Distribution: Good in tissue and EC fluid. Inhibited by purulent material. Meningitis- cross BBB.

Metabolism: Acetylation- badly soluble metabolites. Glucuronic acid conjugation, soluble molecules, quick excretion.

Elimination: kidney- active and metabolites. Acidic pH, bad solubility.
Free axcess to drinking water! Can lead to crystals in kidney.

Question 15

Pharmacokinetics properties of DAPs:

Answer 15

Absorption: Well absorbed PO.

Distribution: Excellent, high Vd. Good penetration through special barriers. Therapeutic drug level in liquor, prostate and milk.

Metabolism: partly in the liver, kidney- mainly in active form.

Question 16

Mupirocin:

Answer 16

Category A
Fermentation product of Pseudomonas fluorescens
tRNA synthetase inhibition- gram+ cocci.

Treat S. aureus- topical
Intranasal MRSA.

Question 17

Bacitracin- Zn

Answer 17

Mixture of related cyclic peptides.
Product of Bacillus subtilis.

Mechanism of action: Inhibition of cell wall synthesis

Spectrum: Narrow. Gram+- Staph, Strep, Clostridia, Haemophilus.

Clinical use: NOT systematically= nephrotoxic.
Topical and local infection- mouth, nose, eye, skin and mammary gland.
Ointments often combined with polymyxin, neomycin.
Suppress mixed bacterial flora.
Oral premix: prevetion of necrotic enteritis- Cl. perfringens in rabbit.