## Mechanism of Dapsone in Leprosy **Key Point:** Dapsone is a sulfone that inhibits bacterial dihydrofolate reductase, blocking the synthesis of dihydrofolate and ultimately preventing nucleotide synthesis. This makes it bacteriostatic against *Mycobacterium leprae*. ### Comparison of Antileprotic Drugs | Drug | Class | Mechanism | Bactericidal/Static | Speed of Action | |------|-------|-----------|-------------------|------------------| | Dapsone | Sulfone | Inhibits DHFR | Bacteriostatic | Slow | | Rifampicin | Rifamycin | Inhibits RNA polymerase | Bactericidal | Rapid | | Clofazimine | Phenazine | Generates ROS, DNA intercalation | Bacteriostatic | Very slow | | Ofloxacin | Fluoroquinolone | Inhibits DNA gyrase | Bactericidal | Moderate | **High-Yield:** Dapsone is the backbone of multidrug therapy (MDT) for both tuberculoid and lepromatous leprosy. It is given for 12 months in lepromatous leprosy as part of WHO-MDT regimens. **Clinical Pearl:** Dapsone is also used in *Pneumocystis jirovecii* prophylaxis in HIV patients, leveraging the same DHFR inhibition mechanism. **Warning:** Do not confuse dapsone's mechanism with trimethoprim (which also inhibits DHFR but is not used in leprosy). Dapsone is sulfone-specific and has unique pharmacokinetics in mycobacterial infections.
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