Antileprotic drugs - drdhriti
Download as PPT, PDF•115 likes•42,689 views
The document discusses leprosy, a disease caused by Mycobacterium leprae, and its treatment using various antileprotic drugs including dapsone, clofazimine, and rifampicin. It outlines the mechanism of action, pharmacokinetics, and possible adverse effects of these medications, as well as classifications of leprosy and treatment regimens recommended by the WHO. Leprosy is now curable, but it can lead to deformities if not treated in time.
Antileprotic drugs - drdhriti
- 1. ANTILEPROTIC DRUGS Dr. D. K. Brahma Associate Professor Department of Pharmacology NEIGRIHMS, Shillong
- 2. INTRODUCTION • Leprosy is caused by a slow-growing type of bacteria called Mycobacterium leprae (M. leprae) • Also known as Hansen's disease, after the scientist who discovered M. leprae in 1873 - Dr. Gerhard Henrik Armauer Hansen of Norway • Bears social stigma • It primarily affects the skin, mucous membrane and the peripheral nerves • Long Incubation period (3 – 5 years) • Curable now – deformities/defects – may not reverse
- 3. ANTILEPROTIC DRUGS Chaulmoogra oil Discovery of sulfonamides 1940 onwards 1. Sulfones – Dapsone ( DDS) 2. Phenazine derivative - Clofazimine 3. Antitubercular drugs - Rifampicin, Ethionamide 4. Other Antibiotics: Ofloxacin, Moxifloxacin, Minocycline and Clarithromycin
- 4. DAPSONE (DDS) • The simplest, oldest, cheapest, most active and most commonly used • Diamino diphenyl sulfone (DDS) • MOA: • Leprostatic even at low concentration – higher conc. Arrests growth of may other bacteria • Chemically related to Sulfonamides – same mechanism – inhibition of incorporation of PABA into folic acid (folic acid synthase) • Specificity to M leprae – affinity for folate synthase • Doses for acute infection – too toxic • Activity: • Used alone – resistance – MDT needed • Resistance – Primary and Secondary (mutation of folate synthase – lower affinity) • 2.5% to 40% Vs 20% Resistance • However, 100 mg/day – high MIC -500 times and continued to be effective to low and moderately resistant Bacilli (low % of resistant patient) • Persisters. Also has antiprotozoal action (Falciparum and T. gondii)
- 5. DAPSONE (DDS) • Pharmacokinetics: • Complete oral absorption and high distribution (less CNS penetration) • 70% bound to plasma protein – concentrated in Skin, liver, muscle and kidney • Acetylated and glucoronidae and sulfate conjugated – enterohepatic circulation • Half life 24-36 Hrs, but cumulative (1 – 2 weeks) • ADRs: Generally Well tolerated drug (100 mg /day) • Haemolytic anaemia (oxidizing property) - G-6-PD are more susceptible • Gastric - intolerance, nausea, gastritis • Methaemoglobinaemia, paresthesia, headache, mental symptoms and drug fever • Allergic rashes, FDE, phototoxicity, exfoliative dermatitis and hepatotoxicity etc.
- 6. SULFONE SYNDROME • Sulfone syndrome: Starts after 4- 6 weeks of therapy, more common with MDT • Symptoms: Fever, malaise, lymph node enlargement, desquamation of skin, jaundice and anemia – malnourished patients • Management: stopping of Dapsone in severe cases, corticosteroid therapy • Corticosteroids (prednisolone 40 – 60 mg/day) – severe cases – till reaction controlled – tapered over 8-12 weeks • Dapsone contraindications: Severe anaemia and G-6-PD deficiency and hypersensitivity
- 7. CLOFAZIMINE • A dye - Leprostatic and anti-inflammatory • MOA: Interferes with template function of DNA in M. leparae • Activity: Used alone resistance (1 -3 years) – but Dapsone resistance cases responds in 2 months (lag period) • Kinetics: orally effective – accumulates in fat in crystalline form – entry to CSF poor – half life 70 days • Used as component of MDT • ADRs: - well tolerated • Reddish-black discolouration of skin – exposed parts • Discolouration of hair and body secretions, dryness of skin and itching, acneform eruptions and phototoxicity – conjunctival pigmentation • GI symptoms: Enteritis with intermittent loose stool, abdominal pain, anorexia and weight loss – early and late symptoms • Should be avoided in pregnancy and liver & kidney disease
- 8. OTHER DRUGS • Rifampicin: Cidal. 99.99% killed in 3-7 days, skin symptoms regress within 2 months • Not satisfactory if used alone – persisters even prolonged treatment • Included in MDT to shorten the duration of treatment and also to prevent resistance • Not toxic and no induction of hepatic enzyme - dose as single dose only • Should not be used in ENL and Reversal phenomenon • Ofloxacin: all fluoroquinolones except ciprofloxacin are active. Used as alternative to Rifampicin – 22 daily doses • Minocycline: Lipophillic - enters M leprae. Less marked effect than Rifampicin
- 9. TYPES OF LEPROSY • Granulomatous infection – skin,, mucous membrane and nerves • Systems of Classification: • 1st (Based on immune system of the patient): Mainly two types: lepromatous (sore on skin, nerves, and other organs) and tuberculoid (sore on skin) • 2nd (Ridley-Jopling system – based on symptoms): Borderline tuberculoid leprosy (BL), Borderline lepromatous (BL), Borderline leprosy (BB) and Intermediate leprosy (I) • For operational purposes: WHO • Paucibacillary (>5 lesions): few bacilli and noninfectious – TT and BT and I • Multibacillary (<5 lesions): large bacilli load and infectious – LL, BL and BB types • Single lesion Paucibacillary: single lesion
- 10. NLEP 2009 CLASSIFICATION Paucibacillary (PB) - TT and BT and I Multibacillary (MB) - LL, BL and BB • 1- 5 skin lesions • No nerve/only one nerve involvement +/- 1-5 skin lesions • Skin smear negative at all sites • 6 or more skin lesions • More than one nerve involved irrespective of skin lesions • Skin smear positive at any one of the sites
- 11. MDT LEPROSY – CONTD. • Initially (1982) – PBL Dapsone + Rifampicin for 6 Months and MBL – Dapsone + Rifampicin + Clofazimine – 2 years or till disease inactivity/smear negative – with added 5 years surveillance for MBL cases • However, 12 years study (in 1994) – fixed duration for 6 months and 2 years was recommended – 12 million to 2.7 million and no resistance • In 1999 – 6 months and 1 year recommended
- 12. WHO (1997) GUIDELINE – MDT (FDT-12) – 1999 INDIA Drug Paucibacillary (PB) Multibacillary (MB) Rifampicin 600 mg once a month Supervised 600 mg once a month Supervised Dapsone 100 mg daily self administered 100 mg daily self administered Clofazimine - 300 mg once a month Supervised 50 mg daily self administered Duration 6 Months 12 Months
- 13. LEPROSY PATIENTS IN MEGHALAYA Photo Courtesy: Dr. Anju R. Marak, SM&HO cum DLO and DMO-MCH, Ri-Bhoi District, Meghalaya
- 14. REACTIONS ? 1. Lepra Reaction : Occurs in LL type (Type – III HSR) – coincides with institution of chemotherapy or intercurrent infection • Arthus type of reaction – release of antigens from killed bacilli - may be mild, moderate and severe (ENL) • Symptoms: enlarged lesions, become red (inflamed nodules and papules) and painful, new lesions – fever and other constitutional symptoms • Treatment: • Mild analgesics • Mild: Clofazimine - 200 mg daily • Moderate to severe-Steroids: 60 mg/day-Prednisolone - taper off in 2-3 months 1. Reversal reaction Occurs in TT and BL cases (Type II HSR) – delayed hypersensitivity to M. leprae antigens • Symptoms: Cutaneous ulceration, multiple nerve involvement with swollen and tender nerves – occurs suddenly even after completion of therapy …… Treatment: same as above
- 15. 2005 VS 2015 New Case detection Report
- 16. BLISTER PACKS
- 17. “The biggest disease today is not leprosy or tuberculosis, but rather the feeling of being unwanted, uncared for, and deserted by everybody.” – Mother Teresa Thank you