Nucleic Acid Synthesis Inhibitors (Sulfonamides)

Question 1

Properties of Sulfonamides

Answer 1

All are bacteriostatic, except the synergism combination of SMZ-TMP, which is bactericidal

Question 2

RoA of Sulfamethoxazole

Answer 2

Oral

Question 3

MoA of Sulfonamides

Answer 3

Sulfonamides mimic the structure of PABA, making them competitive inhibitors of Dihydropteroate synthase (DHPS)

Question 4

A.D.M.E of Sulfamethoxazole

Answer 4

E: excreted unchanged in the urine

Question 5

Indications of Sulfamethoxazole

Answer 5

1. Nocardiosis → N. asteroides
2. PCP → Pneumocystis carinii
   - oral Co-trimoxazole: 1 double-strength daily OR 2 single-strength 3 times weekly
3. Listeriosis meningitis → L. monocytogenes
   - IV Co-trimoxazole in patients who can’t take ampicillin
4. Prophylaxis of recurrent UTI in women → E. coli

Question 6

RoA of Sulfasalazine

Answer 6

Oral

Question 7

A.D.M.E of Sulfasalazine

Answer 7

A: it doesn’t get absorbed orally; as it acts locally in the colon
M: sulfasalazine gets catabolized by intestine microflora into a
carrier (Sulphapyridine) and an anti-inflammatory (5-aminosalicylate)
E: excreted unchanged in the urine

Question 8

Indications of Sulfasalazine

Answer 8

“Autoimmune diseases”
1. Chron’s disease
2. Ulcerative colitis
3. Rheumatoid arthritis

Question 9

RoA of Silver Sulfadiazine

Answer 9

Crème

Question 10

A.D.M.E of Silver Sulfadiazine

Answer 10

E: excreted unchanged in the urine

Question 11

Indications of Silver Sulfadiazine

Answer 11

1. Wound infections in 2nd & 3rd degree burns → S. aureus
2. Bed ulcers/sores → S. aureus

Question 12

RoA of Sulfacetamide

Answer 12

Eyedrop

Question 13

A.D.M.E of Sulfacetamide

Answer 13

E: excreted unchanged in the urine

Question 14

Indications of Sulfacetamide

Answer 14

Conjunctivitis → S. aureus

Question 15

Trimethoprim-Sulfamethoxazole (Combination/MoA/RoA/Dosages)

Answer 15

→ the combination of both drugs is called Co-Trimoxazole, it yields 20-folds the
efficacy of using them individually
→ MoA: when combined, the SMZ will inhibit DHPS and TMP will inhibit DHFR, providing a sequential block in the THF synthesis pathway
- it is given oral or IV with 2 dosages:
* Single-Strength 80 mg : 400 mg of TMP : SMZ
* Double-Strength160 mg : 800 mg of TMP : SMZ

Question 16

Sulfonamide-Pyrimethamine Synergism (What’s Pyrimethamine/MoA/Indication)

Answer 16

→ Pyrimethamine is antiprotozoal drug, with
the ability to inhibit DHFR enzyme
→ MoA: when combined, the sulfonamide will inhibit DHPS and pyrimethamine will inhibit
DHFR, providing a sequential block in the THF synthesis pathway.
→ This combination is used in the Eradication of Toxoplasmosis

Question 17

Adverse Effects of Sulfonamides

Answer 17

• Teratogenicity
  → never given during pregnancy before the 32nd week; as it
  has the chance to cause Cleft lip or neural tube defects
  like Spina bifida (Category C)
  → also, never given to neonates younger than 2 months old
• Crystalluria
  → Sulfonamides are insoluble in normal urine (pH=5), this
  will form crystals that damage nephrons
  → prevented by giving NaHCO3 to alkalize the urine and
  dilute sulfonamides
• Hemolytic anemia
  → the anemia caused by premature destruction of RBCs → rare and only occurs in G6PD deficiency patients
• Photosensitivity
  → sulfonamides increase the skin absorption to UV light,
  this increases the formation of ROS and sunburns
  → patients are advised to avoid sun and wear sunblock
• Hypersensitivity
  → this can vary from rash to angioedema to SJS
  → SJS (Stevens-Johnson Syndrome) is a fatal skin rash with
  blisters around eyes and mouth
  → in SJS, we should discontinue the sulfonamides and
  hospitalize the patient
• Kernicterus
  → sulfonamides displace bilirubin from albumin into blood - bilirubin crosses the underdeveloped BBB causing
  (Bilirubin-Induced Neurologic Dysfunction - BIND)
• Stomatitis “Dryness of mouth”
• Megaloblastic anemia
  → the anemia caused by abnormally enlarged RBCs due to impaired DNA replication due to folate (Vit 9) deficiency
• Hyperkalemia
  → trimethoprim will decrease K+ excretion; increasing its
  concentration in the blood, causing Arrhythmia