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Presented by
D.VIJAY KUMAR
09DG1R0013
T.K.R.COLLEGE OF PHARMACY

1

WHAT IS CHEMOTHERAPY

Chemotherapy can be defined as the
use of chemicals in infectious diseases
to destroy microorganisms without
damaging the host tissues

2

Basic principle of chemotherapy
The chemical agent should be toxic to
pathogenic micro organism and minimal
effect on host cell.
The selective toxicity is important for these
drugs.

3

BIOCHEMICAL REACTIONS OF ALL
BACTERIAL CELLS

Class 1:- Energy production
Class2:- Growth and servival
Class3:- Replication

 These reactions are potential targets
for attack by antibacterial drugs.
4

BIOCHEMICAL REACTIONS AS
POTENTIAL TARGETS

Class 1 : These reactions are poor targets ,
for two reasons .
First ,there is no difference between
bacteria and humans cells in the mechanism
for obtaining energy from glucose .
second , even though selective toxic to
ATP synthesis in the bacteria. It could be used
alternative sources like lactate and amino
acids .
5

 Class 2 : These reactions are good
targets because folic acid bio synthesis
pathway takes place only in bacteria not in
human cells. But folic acid is required in
the synthesis of nucleic acid in both human
cells and bacterial cells.

6

FOLIC ACID SYNTHESIS
PABA
sulfonamide Dihydropterate synthetase
DHFA
Trimethoprim Dihydrofolate reductase

THFA
5-flurouracil Thymidylate synthetase

THYMIDYLATES

DNA
7

class 3 : These reactions are particularly best
targets for selective toxicity.
There are very distinct differences between
mammalian cells and parasitic cells.
That are :
 The synthesis of peptidoglycan
 Protein synthesis
 Nucleic acid synthesis

8

What is Leprosy

 Leprosy, also known as Hansen's
disease (HD), is a chronic disease caused by
the bacteria Mycobacterium leprae

9

Signs and symptoms

 Neuropathic pain
 Skin lesions are the primary external sign.
 It causing permanent damage to the skin,
nerves, limbs, and eyes.
 Collapsed nose.

10

Depending on clinical features, leprosy
is classified as:

 Indeterminate leprosy (IL)
 Tuberculoid leprosy (TT)
 Borderline tuberculoid leprosy (BT)
 Lepromatous leprosy (LL)

12

Stages of leprosy:

1st stage: bacteria enters through skin, the skin sensation become dull and small
patches develop. In this stage the bacteria multiply in the axoplasm of nerve fibers
causing tingling sensations.

2nd stage: skin becomes thick and wrinkled, ears become swollen, nodules are
formed in skin of nose and throat. These nodules discharge fluid which is highly
infectious.

3rd stage: the bacteria burst out of the nerve cell and go to peripheral tissues and
begin to proliferarate. This results in deformities in hands, feet, face and toes etc.

13

TREATMENT

 Pre-modern treatment :
Chaulmoogra oil

 Modern treatment :
Dapsone
Rifampicin
Clofazimine

14

Chaulmoogra oil

 A common pre-modern treatment of leprosy
was chaulmoogra oil.
 The oil has long been used in India as an
Ayurvedic medicine for the treatment of
leprosy and various skin conditions. It has also
been used in China and Burma

15

DAPSONE

 Dapsone (diamino-diphenyl sulfone) is an
antibacterial most commonly used in
combination with rifampicin and
clofazimine as multidrug therapy (MDT) for
the treatment of Mycobacterium leprae
infections leprosy

16

SYNTHESIS OF DAPSONE:

4,4-Dinitrodiphenyl sulfide Dapsone
sulfone

17

MECHANISM OF ACTION

 Dapsone is chemically related to the
sulfonamides.
 It acts by inhibition of folic acid synthesis

18

PABA
DAPSONE Dihydropterate synthetase

DHFA
Dihydrofolate reductase

THFA
Thymidylate synthetase

THYMIDYLATES

DNA
19

PHARMACOKINETICS :

 Dapsone is given orally and is well absorbed
and widely distributed through body water
and all tissues.
 The plasma half-life is 24-48hrs.
 It is metabolised in the liver and excreted
through urine.

20

Unwanted effects :

 Methaemoglobinaemia
 Hepatotoxicity
 Photo sensitivity
 Haemolytic anaemia
 Nausea and vomiting.

21

RIFAMPICIN:

 Rifampicin is rapidly bactericidal to
Mycobacterium leprae .
 It can be conveniently given once a monthly.
 It is used in combination with dapsone in
multidrug therapy (MDT)
 Rifampicin given alone, bacteria develops
resistance .

22

Mechanism of action:

 Rifampicin inhibits bacterial DNA-dependent
RNA synthesis by inhibiting bacterial DNA-
dependent RNA polymerase enzyme.

23

Pharmacokinetics:
 Rifampicin is given orally and is widely
distributed in the tissues and body fluids.
 Rifampicin is easily absorbed from
the gastrointestinal tract because
its ester functional group is
quickly hydrolyzed in the bile.
 Plasma half-life is 1-5 hrs. ,
 Though urinary elimination accounts for only
about 30% of the drug excretion. About 60%
to 65% is excreted through the feces.

24

UNWANTED EFFECTS:
 Orange colour of body fluids.
 Hepatotoxicity- liver failure in severe cases
 Respiratory problems- breathlessness
 Cutaneous - flushing, , rash, redness and
watering of eyes.
 Abdominal - nausea, vomiting, abdominal
cramps with or without diarrhoea.
 Flu-like symptoms - fever, headache.

25

CLOFAZIMINE:

 Clofazimine is a fat-soluble riminophenazine
dye used in combination with rifampicin and
dapsone as multidrug therapy (MDT) for the
treatment of leprosy.
 It has been used investigationally in
combination with other antimycobacterial
drugs to treat Mycobacterium-
avium infections in AIDS patients

26

CLOFAZIMINE:

Systematic (IUPAC) name
N,5-bis(4-chlorophenyl)-3-(propan-2-ylimino)-3,5-
dihydrophenazin-2-amine

27

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.

28

Pharmacokinetics:

 Clofazimine is given orally and is widely
distributed in the tissues and body fluids.
 But clofazimine has a very long half life of
about 70 days.
 It is metabolised in the liver and excreted
through urine.

29

Unwanted effects:

 Reddish colour of urine.
 Clofazimine produces pink to brownish skin
pigmentation in 75-100% of patients within a
few weeks, as well as similar discoloration of
most body fluids and secretions.
 These discolorations are reversible but may
take months to years to disappear.

30

 H.P.RANG & M.M. DALE, TEXT BOOK OF PHARMACOLOGY,5th EDITION ,PG NO: 620-653
 K.D.TRIPATHI,TEXT BOOK OF PHARMACOLOGY,PG NO:335-41
 R.S.SATOSKAR, PHARMACOLOGY AND PHARMACOTHERAPEUTICS,21ST EDITION,PG NO:755-
59
 SALIL K BHATTACHARYA, PARANTAPA SEN, ARUNABHA RAY, PHARMACOLOGY,SECOND
EDITION,PG NO:413-416
 Padmaja Udaykumar,, textbook of Medical Pharmacology,
 Second Edition, Pg no:337-343
 http://www.Uic.edu/pharmacy
 http://www.Suite101.com
 http://www.aac.asm.org
 http://www.pathmicro.med.sc.edu

 http://www.quizlet.com
 http://www.merckmanuals.com

31

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