Sulfonamides are one of the earliest antimicrobial drugs used in medicine. They work by blocking the bacterial pathway required for producing folic acid, an important compound bacteria need to grow and multiply. Humans do not make folic acid (we get it from food), which is why these drugs can selectively target bacteria without harming our own cells. Co-trimoxazole is a combination of two drugs—sulfamethoxazole and trimethoprim—that act together to give a stronger and more effective antibacterial response.
Mechanism of Action
Sulfonamides stop bacteria from making folic acid. They block an enzyme called dihydropteroate synthase that bacteria use to produce folic acid from PABA (para-aminobenzoic acid). Without folic acid, bacteria cannot produce DNA and cannot grow.
Trimethoprim acts at the next step in the same pathway by blocking the enzyme dihydrofolate reductase. This double blockage makes co-trimoxazole more powerful than sulfonamides alone.
Bacteriostatic or Bactericidal?
Individually, sulfonamides and trimethoprim are bacteriostatic (stop growth). But when combined as co-trimoxazole, they become bactericidal (kill bacteria).
Spectrum of Activity
Sulfonamides and co-trimoxazole work against a wide variety of microorganisms including:
- Gram-positive bacteria
- Gram-negative bacteria
- Some protozoa (e.g., toxoplasma)
- Pneumocystis jirovecii (fungus causing pneumonia in immunocompromised patients)
Common Sulfonamides
- Sulfadiazine
- Sulfisoxazole
- Sulfamethoxazole (component of co-trimoxazole)
- Sulfasalazine – used in ulcerative colitis and rheumatoid arthritis, not for infections
- Silver sulfadiazine – used for burns (topical)
Pharmacokinetics
- Sulfonamides are well absorbed when taken orally.
- Widely distributed into body tissues and body fluids.
- Cross the placenta—so they are avoided during late pregnancy.
- Mostly eliminated through urine.
Co-trimoxazole (Trimethoprim + Sulfamethoxazole)
Co-trimoxazole contains trimethoprim and sulfamethoxazole in a fixed ratio (1:5). They work synergistically, meaning the combined effect is stronger than either drug alone.
Advantages
- Broad antimicrobial coverage
- Bactericidal action
- Effective for many common infections
Uses of Sulfonamides
- Urinary tract infections
- Nocardiosis
- Toxoplasmosis (when combined with pyrimethamine)
- Chlamydial infections (rarely used now due to resistance)
Uses of Co-trimoxazole
- Urinary tract infections
- Respiratory infections like bronchitis
- Otitis media in children
- Traveler’s diarrhoea
- Pneumocystis jirovecii pneumonia (treatment and prophylaxis)
- Typhoid fever (alternative option)
Adverse Effects
Sulfonamides and co-trimoxazole may cause:
- Nausea, vomiting, loss of appetite
- Skin rashes (can be severe in some cases)
- Stevens–Johnson syndrome (rare but serious skin reaction)
- Photosensitivity
- Crystalluria (crystals in urine) — prevented by drinking plenty of water
- Blood disorders like anemia (due to folate deficiency)
- In newborns: risk of kernicterus — hence avoided in late pregnancy and neonates
Drug Interactions
- Increase effect of warfarin and other anticoagulants
- Increase toxicity of phenytoin
- May increase effect of methotrexate
Resistance
Bacterial resistance occurs through:
- Increased PABA production by bacteria
- Changes in target enzymes
- Decreased drug uptake
Resistance develops faster when sulfonamides are used alone. This is why co-trimoxazole is preferred in most infections.
Contraindications
- Pregnancy (especially near term)
- Breastfeeding
- Newborn infants
- Severe liver or kidney disease
Detailed Notes:
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