Drug acting on Leprosy, Antileprotic drugs

1. DRUGS ACTING ON LEPROSY
Presented by
Mr. Kundan Sable
(Pharmacology)
Institute Of Pharmaceutical
Education And Research,
Wardha

2. INTRODUCTION :
• Antileprotic drugs Leprosy is a chronic infectious disease caused
by Mycobacterium leprae
• A leprostatic agent is a drug that interferes with proliferation of
the bacterium that causes leprosy.
• Leprosy is characterized by depressed cell-mediated immunity
Mycobacterium leprae is a bacterium that causes leprosy, also
known as “Hansen’s disease which is a chronic infectious disease
that damages the peripheral nerves and targets the skin, eyes,
nose, and muscles

3. Mycobacterium leprae
• In size and shape, it closely resembles Mycobacterium
tuberculosis
• Microphotograph of Mycobacterium
leprae, the small brick-red rods in
clusters, M. leprae is an aerobic
bacillus (rod-shaped bacterium) with
parallel sides and round ends,
surrounded by the characteristic
waxy coating unique
to mycobacteria
Fig: Mycobacterium leprae

4. • Due to its thick waxy coating, M. leprae stains with a carbol
fuchsin Growth and drug susceptibility testing are done by
injecting into animal models
• Optical microscopy shows M. leprae in clumps, rounded
masses, or in groups of bacilli side by side, and ranging from
1–8 μm in length and 0.2–0.5 μm in diameter
• Mucroscopical examinations be used as a diagnostic test for
the presence of bacilli in body lesions of suspected leprosy
patients.

5. SYMPTOMS :
• Skin discoloration
• Skin lesions. ( The skin lesions result in decreased
sensation to touch, temperature, or pain)
• Skin nodules
• Skin plaques
• Thickened skin
• Nasal congestion

6. CLASSIFICATIONS :
1.Sulfone
Dapsone (DDS)
2. Phenazine derivative
Clofazimine
3. Antitubercular drugs
Rifampin,
Ethionamide
4. Other antibiotics Ofloxacin,
Minocycline,
Clarithromycin

7. Dapsone
Brand Name : Aczone
• Dapsone also known as diaminodiphenyl sulfone,
• Dapose is an antibiotic commonly used in combination
with rifampicin and clofazimine for the treatment of
leprosy
• Dapsone is a synthetic derivative of diamino-sulfone with
anti-inflammatory and anti-bacterial properties.

8. Mechanism of Action
• As a structural analog of p-aminobenzoic acid
(PABA)
• Dapsone inhibits dihydropteroate synthase
(DHPS).
• This enzyme important in folate synthesis,
resulting in a depletion of the folate pool and a
reduction in the amount of thymidylate available
for DNA synthesis

10. Pharmacokinetics
• Absorption: Bioavailability is 70 to 80% following oral
administration. Oral administration, the drug is
slowly absorbed, the maximum concentration in
plasma being reached at about 4 hours.
• Metabolism : Dapsone is metabolized by the
Cytochrome P450 system.
• Elimination : By Renal route,
• DOSE : 100 mg daily

11. Adverse effects.
Most Commom Adverse effects Nausea,Vomiting,Loss
of appetite,Dizziness,Blurred vision,Ringing in the
ears,Headache, Insomnia, Increased sensitivity of the
skin to sunlight.
Serious side effects of dapsone including:
Unusually fast heartbeat, Unusually fast breathing,
Bluish lips or skin,

12. Contraindications
Contraindications Dapsone should not be used in
patients with severe anaemia with Hb < 7g%,G-6-PD
deficiency and in those showing hypersensitivity
reactions.
Sufone syndrome
It is the reaction which Develops 4–6 weeks after
dapsone treatment Consists of fever, lymph node
Enlargement, desquamation of skin, jaundice and
Anaemia

13. Rifampin
• Rifampin Is bactericidal to M. tuberculosis and many
Other gram-positive and gram-negative bacteria
Mechanism of action —
• Rifampin is thought to inhibit bacterial DNA-dependent
RNA polymerase, which appears to occur as a result of
drug binding in the polymerase subunit deep within the
DNA/RNA channel, facilitating direct blocking of the
elongating RNA

14. Pharmacokinetics :
• It is well absorbed orally,Widely distributed in the body:
penetrates cavities, placenta and meninges.
• It is Metabolized in liver to an active deacetylated Metabolite
which is excreted mainly in bile, some In urine also.
• Rifampin and its desacetyl derivative undergo enterohepatic
circulation.
• The t½ Of rifampin is variable (2–5 hours).

15. Interactions:
• Rifampin is a microsomal enzyme Inducer—increases several
CYP450 isoenzymes, Including CYP3A4, CYP2D6, CYP1A2 and
CYP2C subfamily. It thus enhances its own Metabolism as well as
that of many drugs Including warfarin, oral contraceptives, cortico
Steroids, sulfonylureas, digitoxin, steroids, HIV Protease inhibitors,

16. Clofazimine
Brand name : Lamprene
Mechanism of Action :
• Clofazimine works by binding to the guanine bases of bacterial
DNA, thereby blocking the template function of the DNA and
inhibiting bacterial proliferation.
• It also increases activity of bacterial phospholipase A2, leading
to release and accumulation of lysophospholipids, which are
toxic and inhibit bacterial proliferation.

17. Pharmacokinetics
Absorption : Orally active (40–70% absorbed), widely
Distributed in body and body fluids but Clofazimine has very
long plasm half life about 70 days. Metabolized by liver and
Eliminated in urin
It accumulates in many tissues, especially in fat, in crystalline
form. However, entry in CSF is poor.

18. Adverse effects :
Clofazimine produces pink to brownish skin pigmentation
in 75-100% of patients within a few weeks, as well as
similar discoloration of most bodily fluids and secretions
discoloration of the eyelid.Tear discoloration. Irritation of
the stomach or intestines. Discolored sweat. A skin rash.
Decreased appetite. Sputum discoloration. Nausea.

19. Ethionamide
Brand name : Trecator
Mechanism of Action
• Ethionamide is a prodrug which is activated by the enzyme
ethionamidase mono-oxygenase in Mycobacterium leprae
and then binds NAD+ to form an adduct which inhibits InhA
(Inha is an NADH dependent trans enoyl-acyl ACP carrier
protein) in the same way as isoniazid. The mechanism of
action is thought to be through disruption of mycolic acid.

20. Pharmacokinetic :
Absorption : Essentially completely absorbed following oral
administration. Bioavailability approximately 100%.
Protein binding: Approximately 30% bound to proteins.
Metabolism: Hepatic and extensive. Metabolized to the active
metabolite sulfoxide, and several inactive metabolites.
Route of elimination
Less than 1% of the oral dose is excreted as ethionamide in
urine. Ethionamide is extensively metabolized to active and
inactive metabolites.
Half-life: 2 to 3 hours

21. Contraindications :
Ethionamide may worsen the adverse effects of other
antituberculous drugs being taken at the same time. It boosts
levels of isoniazid when taken together and can lead to
increased rates of peripheral neuropathy and hepatotoxicity.
When taken with cycloserine, seizures have been reported. High
rates of hepatotoxicty have been reported when taken with
rifampicin. The drug’s labeling cautions against excessive alcohol
ingestion as it may provoke a psychotic reaction.

22. Adverse Effects:
Gastrointestinal intolerance is by far the major
problem with ethionamide – nausea is common and
vomiting may occur. Hepatocellular injury is possible
with ethionamide but is not common. Various CNS
effects have been reported. Hypothyroidism,
gynecomastia, alopecia, impotence also have been
reported.
Dosage:
Usual dose: 250-500 mg once or twice daily, rarely
exceeding 1000 mg.

23. Moxifloxacin
Trade Name : Avelox, Vigamox, Moxiflox
Moxifloxacin is used to treat a variety of bacterial infections. This
medication belongs to a class of drugs called quinolone
antibiotics. It works by stopping the growth of bacteria. This
antibiotic treats only bacterial infections. It will not work for virus
infections (such as common cold, flu).

24. Mechanism of Action
Moxifloxacin is a broad-spectrum antibiotic that is active against
both Gram-positive and Gram-negative bacteria. It functions by
inhibiting DNA gyrase, a type II topoisomerase, and
topoisomerase IV, enzymes necessary to multiplication of
bacterial DNA, thereby inhibiting cell replication.

25. Common side effects
It include diarrhea, dizziness, and headache.
Severe side effects
It may include spontaneous tendon ruptures, nerve damage
Rare but serious adverse effects that may occur as a result
of moxifloxacin therapy include irreversible peripheral
neuropathy, spontaneous tendon rupture and tendonitis,
hepatitis, psychiatric effects (hallucinations, depression),
Stevens–Johnson syndrome

26. Minocycline
Brand name : Minocin, Minomycin, Akamin
It is a tetracycline antibiotic used to treat a number of
bacterial infections such as pneumonia.
Mechanism of action :
Tetracycline antibiotics are protein synthesis inhibitors. They
inhibit the initiation of translation in variety of ways by
binding to the 30S ribosomal subunit, which is made up of
16S rRNA and 21 proteins. They inhibit the binding of
aminoacyl-tRNA to the mRNA translation complex.

27. Pharmacokinetic
Absorption : Minocycline is quickly and nearly completely
absorbed from the upper part of the small intestine. Taking it
together with food, including milk,
Elimination half-life: 14–22 (11–26) hours
Metabolism: Liver
Excretion: Mostly fecal, 10–15% renal
Protein binding: 70–75%
Solubility in water: Low
Minocycline is inactivated by metabolization in the liver to
about 50%.

28. Common side effects
it include nausea, diarrhea, dizziness, allergic
reactions, and kidney problems.
Serious side effects
it may include anaphylaxis, a lupus-like syndrome,
and easy sunburning.Use in the later part of
pregnancy may harm the baby and safety during
breastfeeding