Antiepileptic drugs - drdhriti

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A Power Point presentation on ANTI EPILEPTICS suitable for Medical undergraduate level students

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  • the name was anti epileptics but the content is different it is showing anti leprotic drugs
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Antiepileptic drugs - drdhriti

  1. 1. Dr. D. K. Brahma Associate Professor Department of Pharmacology NEIGRIHMS, Shillong
  2. 2.  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  It primarily affects the skin and the peripheral nerves  Long Incubation period (3 – 5 years)
  3. 3. 1. Sulfones – Dapsone ( DDS) 2. Phenazine derivative - Clofazimine 3. Antitubercular drugs - Rifampicin, Ethionamide 4. Other Antibiotics: Ofloxacin, Moxifloxacin, Minocycline and Clarithromycin
  4. 4.  The simplest, oldest, cheapest, most active and most commonly used  MOA:  Leprostatic even at low concentration  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  Activity:  Used alone – resistance – MDT needed  Resistance – Primary and Secondary (mutation of folate synthase – lower affinity)  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. 5.  Pharmacokinetics:  Complete oral absorption and high distribution (less CNS penetration)  70% bound to plasma protein – concentrated in Skin, liver, muscle and kidney  Acetylated and glucoronidated and sulfate conjugated – enterohepatic circulation  Half life 24-36 Hrs, but cumulative  ADRs: Generally Well tolerated drug  Haemolytic anaemia (oxidizing property) - G-6-PD are more susceptible  Gastric - intolerance, nausea, gastritis  Methaemoglobinaemia, paresthesia, allergic rashes, FDE, phototoxicity, exfoliative dermatitis and hepatotoxicity etc.
  6. 6.  Symptoms: Fever, malaise, lymph node enlargement, desquamation of skin, jaundice and anemia  Starts after 4- 6 weeks of therapy, more common with MDT  Management: stopping of Dapsone, corticosteroid therapy  Dapsone contraindications: Severe anaemia and G-6-PD deficiency
  7. 7.  Phenazine dye – antileprotic, anti-inflammatory and Bacteriostatic  MOA:  Interference with template function of DNA  Alteration of membrane structure and transport  Disruption of mitochondrial electron transport  Monotherapy causes resistance in 1 – 3 years  Dapsone resistants respond to Clofazimine  Kinetics: absorbed orally (70%) and gets deposited in subcutaneous tissues – as crystals  Half life – 70 days
  8. 8.  ADRs: well tolerated  Skin: Reddish-black discolouration of skin, discolouration of hair and body secretions  Dryness of skin and troublesome itching, phototoxicity, conjunctival pigmentation  GIT: Nausea, anorexia, abdominal pain and loose stool (early and late) – dreaded enteritis  Contraindication: Early pregnancy, liver and kidney diseases
  9. 9.  Rifampicin: Cidal. 99.99% killed in 3-7 days, skin symptoms regress within 2 months  Included in MDT to shorten the duration of treatment and also to prevent resistance  No toxic 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  Minocycline: Lipophillic - enters M leprae. Less marked effect than Rifampicin
  10. 10.  Monotherapy - 1982 and since then MDT  Elimination achieved in India in 2005 (prevalence rate ?) - “< 1 case per 10,000”  Leprosy classified as LL, BL, BB, BT and TT  For operational purposes:  Paucibacillary: few bacilli and non-infectious – TT and BT  Multibacillary: large bacilli load and infectious – LL, BL and BB types  Single lesion Paucibacillary: single lesion
  11. 11. Paucibacillary (PB) - TT and BT 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
  12. 12. Photo Courtesy: Dr. Anju R. Marak, SM&HO cum DLO and DMO-MCH, Ri-Bhoi District, Meghalaya
  13. 13. Drug Paucibacillary (PB) Multibacillary (MB) Rifampici n 600 mg once a month Supervised 600 mg once a month Supervised Dapsone 100 mg daily self administered 100 mg daily self administered Clofazimi ne - 300 mg once a month Supervised 50 mg daily self administered Duration 6 Months 12 Months MBL: FDT-24 introduced in India in 1990, but not continued Alternative regimens: are used only in case of Rifampicin resistance or when it is impossible to employ standard MDT.
  14. 14. 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 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 2. 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

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