Sulfonamides

Question 1

What are the Sulfonamides?

Answer 1

• Sulfamethoxazole

- Sulfadiazine

Question 2

How do the Sulfonamides work?

Answer 2

Competitive inhibitors of dihydropteroate synthase (Bacteriastatic and Bacteriacidal)

 - Analogs of para-aminobenzoic acid (PABA)
 - Bacteria that form their own folic acid- works
 - Bacteria that don’t form their own folic acid- doesn’t work
 - You? Doesn’t affect your cells - Need to be paired with Trimethoprim for good blockage!

Question 3

What are the Absorption Characteristics of the Sulfonamides?

Answer 3

Rapid (70-100%) absorbed in GI tract

Absorption site: small intestine

Question 4

What are the Distribution Characteristics of the Sulfonamides?

Answer 4

All tissues including central nervous system

Placental transfer notable

Question 5

What are the Metabolism Characteristics of the Sulfonamides?

Answer 5

Liver

Metabolite loses antibacterial activity but retains toxicity potential

Question 6

What are the Excretion Characteristics of the Sulfonamides?

Answer 6

Renal

Question 7

What are the Characteristics of Sulfamethoxazole?

Answer 7

• Slower in; slower out
• Only available in combination in U.S.
• Crystalluria more likely

Question 8

What is Trimethoprim/sulfamethoxazole active against?

Answer 8

• Chlamydia diphtheriae
• N. meningitidis
• Staphylacoccus aureus
• S. Pyogenes
• E. coli

Question 9

What are the Kinetics for Trimethoprim/sulfamethoxazole?

Answer 9

• Absorption
  - Trimethoprim in faster than sulfamethoxazole
• Distribution
  
  • Trimethoprim distribution greater than sulfamethoxazole
• Excretion
  - Renal so dose adjusted in renal impairment

Question 10

What are the Oral Sulfonamides used for?

Answer 10

• Urinary tract infections due to E. coli, Klebsiella and Enterobacter sp, M. morganii, P. mirabilis and P. vulgaris
• Acute otitis media in children
• Acute exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or S. pneumoniae
• Treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP)
• Traveler’s diarrhea due to enterotoxigenic E. coli
• Treatment of enteritis caused by Shigella flexneri or Shigella sonnei

Question 11

What are the IV Sulfonamides used for?

Answer 11

• Documented PCP
• Empiric treatment of PCP in immune compromised patients
• Treatment of documented or suspected shigellosis, typhoid fever, or other infections caused by susceptible bacteria

(Done By ID consult because Trimethoprim is dosed by weight)

Question 12

What are potential drug interactions with the Sulfonamides?

Answer 12

Potentiation through inhibition of metabolism

• Alternative involves plasma protein displacement of the interacting drug
• Warfarin sodium
• Sulfonylurea hypoglycemic agents
• Phenytoin

All drugs become more potent

Question 13

What are side effects of the Sulfonamides?

Answer 13

• The folic acid “dilemma”
  - Won’t deplete you but what about in a deficient state? (Megaloblastosis, leukopenia, thrombocytopenia)
• Dermatologic (rash)
• Gastrointestinal (nausea)
• *Central nervous system
  - headache, depression, and hallucinations
• Crystalluria (Why need to take each dose with 6 oz. water)
• Blood
  - Acute hemolytic anemia
  - Agranulocytosis
  - Aplastic anemia
• Hypersensitivity
  - Variable incidence
  - Fatalities reported (Necrosis of the liver)

Question 14

Prescription for Trimethoprim/

sulfamethoxazole?

Answer 14

160/800 mg
One tablet every 12 hours

IV is every 6 hours
Uncomplicated UTI: 3-5 days
Complicated UTI: 7-10 days