SN3 SHORT NOTE 5M ★ High-yield

Describe the antileprotic drugs and WHO multidrug therapy. Add a note on lepra reactions.

Pharmacology · 2nd Professional — Para-Clinical

Drugs and Their Properties

Drug	Mechanism	Distinctive features
Dapsone	A sulphone inhibiting dihydropteroate synthase and so folate synthesis	Bacteriostatic; cheap; the backbone of treatment for decades. Causes haemolysis (dose-related, marked in G6PD deficiency), methaemoglobinaemia, agranulocytosis, and the dapsone hypersensitivity syndrome with fever, rash, hepatitis and lymphadenopathy
Rifampicin	RNA polymerase inhibition	The most potent bactericidal antileprotic — a single dose renders the patient non-infectious within days, which is why it is given monthly under supervision
Clofazimine	Binds mycobacterial DNA; also anti-inflammatory	Causes reddish-black skin pigmentation and ichthyosis, which is cosmetically distressing and a cause of poor adherence, particularly in fair-skinned patients; its anti-inflammatory action is useful in erythema nodosum leprosum
Ofloxacin, minocycline, clarithromycin	Alternative bactericidal agents	Used where a first-line drug cannot be given, and in single-dose regimens for single-lesion disease

WHO Multidrug Therapy

Type	Regimen	Duration
Paucibacillary (1–5 lesions)	Rifampicin 600 mg monthly (supervised) + dapsone 100 mg daily	6 months
Multibacillary (more than 5 lesions)	Rifampicin 600 mg monthly + clofazimine 300 mg monthly (both supervised), with clofazimine 50 mg and dapsone 100 mg daily	12 months
Single-lesion disease	Single dose of rifampicin, ofloxacin and minocycline (ROM)	Single dose
Post-exposure prophylaxis	Single-dose rifampicin for contacts	Single dose

CLINICAL PEARL

Multidrug therapy was introduced because dapsone monotherapy created resistance on a global scale. Dapsone alone was used for decades and, being bacteriostatic and given as a single agent, selected resistant organisms worldwide by the 1970s. The combination regimen introduced in 1981 reversed that, and has since treated many millions — a demonstration, at population scale, of why single-drug treatment of a chronic mycobacterial infection cannot work.

Lepra Reactions

Feature	Type 1 (reversal)	Type 2 (erythema nodosum leprosum)
Immunology	Delayed hypersensitivity — a shift in cell-mediated immunity	Immune complex deposition (type III)
Occurs in	Borderline forms	Lepromatous and borderline lepromatous
Features	Existing lesions become red, swollen and tender; acute nerve pain and sudden loss of function — the chief cause of permanent deformity	Crops of tender subcutaneous nodules with fever, arthralgia, iritis, orchitis and neuritis
Treatment	Corticosteroids, promptly and in adequate dose, to save nerve function	Corticosteroids; clofazimine in high dose; thalidomide is highly effective but absolutely contraindicated in women of childbearing potential
Antileprotic drugs	Continued throughout	Continued throughout

Applied Aspects

Reactions are not drug allergy and not treatment failure; multidrug therapy must be continued while the reaction is treated separately
Type 1 reaction is a neurological emergency — nerve function can be lost within days and steroids must be started immediately; delay causes permanent disability
Assess and record nerve function at every visit, since disability, not the infection, is what determines the patient’s life
India accounts for a large share of the global case load, and although elimination as a public health problem has been achieved nationally, transmission continues and new cases with visible deformity are still detected
Stigma remains the greatest obstacle; treatment is free and effective, and the main barriers to early presentation are social
Screen and give single-dose rifampicin prophylaxis to household contacts, which reduces their risk substantially

All questions in Antimicrobials: TB, Fungal, Viral & Antiparasitic

Every Pharmacology chapter →