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

1. Dr. D. K. Brahma
Associate Professor
Department of Pharmacology
NEIGRIHMS, Shillong

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 - 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.  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.  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.  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: 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.  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.  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.  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. 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.  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. 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. Photo Courtesy: Dr. Anju R. Marak,
SM&HO cum DLO and DMO-MCH,
Ri-Bhoi District, Meghalaya

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 (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
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

15. New Case detection Report

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